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Incidence and Mortality
Estimated new cases and deaths from chronic myelogenous leukemia (CML) in the United States in 2012:[1]
CML is one of a group of diseases called the myeloproliferative disorders. Other related entities include the following:
(Refer to the PDQ summary on Chronic Myeloproliferative Disorders Treatment for more information.)
CML is a clonal disorder that is usually easily diagnosed because the leukemic cells of more than 95% of patients have a distinctive cytogenetic abnormality, the Philadelphia chromosome (Ph1).[2,3] The Ph1 results from a reciprocal translocation between the long arms of chromosomes 9 and 22 and is demonstrable in all hematopoietic precursors.[4] This translocation results in the transfer of the Abelson (ABL) on chromosome 9 oncogene to an area of chromosome 22 termed the breakpoint cluster region (BCR).[4] This, in turn, results in a fused BCR/ABL gene and in the production of an abnormal tyrosine kinase protein that causes the disordered myelopoiesis found in CML. Furthermore, these molecular techniques can now be used to supplement cytogenetic studies to detect the presence of the 9;22 translocation in patients without a visible Ph1 (Ph1-negative).
Ph1-negative CML is a poorly defined entity that is less clearly distinguished from other myeloproliferative syndromes. Patients with Ph1-negative CML generally have a poorer response to treatment and shorter survival than Ph1-positive patients.[5] Ph1-negative patients who have BCR/ABL gene rearrangement detectable by Southern blot analysis, however, have prognoses equivalent to Ph1-positive patients.[6,7] A small subset of patients have BCR/ABL detectable only by reverse transcriptase–polymerase chain reaction (RT–PCR), which is the most sensitive technique currently available. Patients with RT–PCR evidence of the BCR/ABL fusion gene appear clinically and prognostically identical to patients with a classic Ph1; however, patients who are BCR/ABL-negative by RT–PCR have a clinical course more consistent with chronic myelomonocytic leukemia, which is a distinct clinical entity related to myelodysplastic syndrome.[6,8,9] Fluorescent in situ hybridization of the BCR/ABL translocation can be performed on the bone marrow aspirate or on the peripheral blood of patients with CML.[10]
At the time of diagnosis of patients with CML, splenomegaly is the most common finding on physical examination.[10] The spleen may be enormous, filling most of the abdomen and presenting a significant clinical problem, or the spleen may be only minimally enlarged. In about 10% of patients, the spleen is neither palpable nor enlarged on splenic scan.
The median age of patients with Ph1-positive CML is 67 years.[11] While the median survival used to be 4 to 6 years, with the advent of the new oral therapies, the median survival is expected to approach normal life expectancy for most patients, although it is still too soon to say this definitively.
Bone marrow sampling is done to assess cellularity, fibrosis, and cytogenetics. The Philadelphia chromosome (Ph1) is usually more readily apparent in marrow metaphases than in peripheral blood metaphases; in some cases, it may be mashed and reverse transcriptase–polymerase chain reaction (RT–PCR) or fluorescent in situ hybridization analyses on blood or marrow aspirates may be necessary to demonstrate the 9;22 translocation.
Histopathologic examination of bone marrow aspirate demonstrates a shift in the myeloid series to immature forms that increase in number as patients progress to the blastic phase of the disease. The marrow is hypercellular, and differential counts of both marrow and blood show a spectrum of mature and immature granulocytes similar to that found in normal marrow. Increased numbers of eosinophils or basophils are often present, and sometimes monocytosis is seen. Increased megakaryocytes are often found in the marrow, and sometimes fragments of megakaryocytic nuclei are present in the blood, especially when the platelet count is very high. The percentage of lymphocytes is reduced in both the marrow and blood in comparison with normal subjects, and the myeloid/erythroid ratio in the marrow is usually greatly elevated. The leukocyte alkaline phosphatase enzyme is either absent or markedly reduced in the neutrophils of patients with chronic myelogenous leukemia (CML).[1]
Transition from the chronic phase to the accelerated phase and later the blastic phase may occur gradually over a period of 1 year or more, or it may appear abruptly (blast crisis). The annual rate of progression from chronic phase to blast crisis is 5% to 10% in the first 2 years and 20% in subsequent years.[2,3] Signs and symptoms commonly indicating such a change include the following:
In the accelerated phase, differentiated cells persist, though they often show increasing morphologic abnormalities, and increasing anemia and thrombocytopenia and marrow fibrosis are apparent.[1]
Studies have suggested that certain presenting features have prognostic significance. The following are predictive of a shorter chronic phase:
Predictive models using multivariate analysis have been derived.[2,3,4,5,6,7]
Chronic-phase CML
Chronic-phase CML is characterized by bone marrow and cytogenetic findings as described above with less than 10% blasts and promyelocytes in the peripheral blood and bone marrow.[8]
Accelerated-phase CML
Accelerated-phase CML is characterized by 10% to 19% blasts in either the peripheral blood or bone marrow.[8]
Blastic-phase CML
Blastic-phase CML is characterized by 20% or more blasts in the peripheral blood or bone marrow.
When 20% or more blasts are present in the face of fever, malaise, and progressive splenomegaly, the patient has entered blast crisis.[8]
Relapsing CML
Relapsed CML is characterized by any evidence of progression of disease from a stable remission. This may include the following:
Detection of the BCR/ABL translocation by RT–PCR during prolonged remissions does not constitute relapse on its own. However, exponential drops in quantitative RT–PCR measurements for 3 to 12 months correlates with the degree of cytogenetic response, just as exponential rises may be associated with quantitative RT–PCR measurements that are closely connected with clinical relapse.[9]
Treatment of patients with chronic myelogenous leukemia (CML) is usually initiated when the diagnosis is established, which is done by the presence of an elevated white blood cell (WBC) count, splenomegaly, thrombocytosis, and identification of the BCR/ABL (breakpoint cluster region/Abelson) translocation.[1] The optimal frontline treatment for patients with chronic-phase CML is the subject of active clinical evaluation but involves specific inhibitors of the BCR/ABL tyrosine kinase.
In a randomized trial comparing imatinib mesylate with interferon plus cytarabine, with 5 years' median follow-up, imatinib mesylate induced complete cytogenetic responses in more than 80% of newly diagnosed patients; in addition, the annual rate of progression to accelerated phase or blast crisis dropped from 2% to less than 1% in the fourth year on the imatinib arm.[2][Level of evidence: 1iiDiii] However, most of these continually responding patients still showed detectable evidence of the BCR/ABL translocation by the most sensitive measurement of reverse transcriptase–polymerase chain reaction (RT–PCR).[3,4,5] The clinical implication of this finding after 10 years or more is unknown, but these results have changed clinical practice. Although evidence-based survival advantages are unavailable because of crossover in randomized trials, the overall survival rate for all patients at 5 years is 89%, with fewer than 50% of all deaths (4.5%) caused by CML.[6]
Tyrosine kinase inhibitors with greater potency and selectivity for BCR/ABL than imatinib have been evaluated in newly diagnosed patients with CML. In a randomized, prospective study of 846 patients comparing nilotinib with imatinib, the rate of major molecular response at 12 months was 43% and 44% for 2-dose schedules of nilotinib and 22% for imatinib (P < .001 for both comparisons). The rate of complete cytogenetic response at 12 months was 80% and 78% for 2-dose schedules of nilotinib and 65% for imatinib (P < .001 for both comparisons).[7][Level of evidence: 1iiDiv] Progression to accelerated phase or blast crisis occurred in 11 patients on imatinib (4%) but only occurred in 2 patients (<1%, P = . 01) and 1 patient (<1%, P = .004) for the patients on 2-dose schedules of nilotinib.[7]
Similarly, in a randomized, prospective study of 519 patients comparing dasatinib with imatinib, the rate of major molecular response at 12 months was 46% for dasatinib and 28% for imatinib (P < .0001). The rate of complete cytogenetic response at 12 months was 77% for dasatinib and 66% for imatinib (P = .007).[8][Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in nine patients (3.5%) on imatinib and in five patients (1.9%) on dasatinib (not statistically different).
Although one of these two studies showed statistically significant decreased rates of progression to accelerated or blastic phase, which may ultimately translate into improved survival, the follow-up period with nilotinib and dasatinib has not been long enough to detect and confirm this prolonged survival with these agents. The preferred initial treatment for newly diagnosed patients with chronic-phase CML could be any of these specific inhibitors of the BCR/ABL tyrosine kinase.[9]
The only consistently successful curative treatment of CML beyond 10 years' follow-up has been allogeneic bone marrow transplantation (BMT) or stem cell transplantation (SCT).[10] Long-term data beyond 10 years of therapy are available, and most long-term survivors show no evidence of the BCR/ABL translocation by any available test (e.g., cytogenetics, RT–PCR, or fluorescent in situ hybridization [FISH]). Many patients, however, are not eligible for this approach because of age, comorbid conditions, or lack of a suitable donor. In addition, substantial morbidity and mortality result from allogeneic BMT or SCT; a 15% to 30% treatment-related mortality can be expected, depending on whether a donor is related and on the presence of mismatched antigens.[10]
Long-term data are also available for patients treated with interferon alpha.[11,12,13] Approximately 10% to 20% of these patients have a complete cytogenetic response with no evidence of BCR/ABL translocation by any available test, and the majority of these patients are disease free beyond 10 years.[10] Maintenance of therapy with interferon is required, however, and some patients experience side effects that preclude continued treatment.
Newly diagnosed patients with very high levels of circulating leukocytes (WBC >100,000/mm3) require immediate therapy with imatinib mesylate to avoid cerebrovascular events or death from leukostasis. Leukophoresis and plateletpheresis are sometimes required for an even more emergent reduction of counts.
Treatment Options for Chronic-Phase Chronic Myelogenous Leukemia (CML)
Targeted therapy with tyrosine kinase inhibitors
A trial randomly assigning 1,106 previously untreated patients to imatinib mesylate or to interferon plus cytarabine documented a 76% complete cytogenetic response rate with imatinib mesylate versus 14% for interferon plus cytarabine at a median follow-up of 19 months.[1,2][Level of evidence: 1iiDiii] At 18 months, 96.7% of the imatinib group had avoided progression to accelerated-phase CML or blast crisis compared with 91.5% of the interferon plus cytarabine group (P < .001). Because 90% of the combination group had switched to imatinib by 18 months (mostly because of intolerance of side effects), a survival difference may never be observed. By the 5-year median follow-up of this trial, imatinib mesylate induced complete cytogenetic response in more than 80% of the participants, with the annual rate of progression to accelerated-phase CML or blast crisis dropping from 2% in the first year to less than 1% in the fourth year.[2] In addition, the overall survival (OS) rate for all patients at 5 years is 89%, with fewer than 50% of all deaths (4.5%) caused by CML. More than 90% of completely responding patients still show detectable evidence of the BCR/ABL translocation, usually by reverse transcription-polymerase chain reaction (RT–PCR) or by fluorescence in situ hybridization of progenitor cell cultures.[3,4,5] The clinical implication of this finding after 10 years or more is unknown, but these results have changed clinical practice. Poor compliance is the predominant reason for inadequate molecular response to imatinib.[6]
Tyrosine kinase inhibitors with greater potency and selectivity for BCR/ABL than imatinib have been evaluated in newly diagnosed patients with CML. In a randomized, prospective study of 846 patients comparing nilotinib with imatinib, the rate of major molecular response at 12 months was 43% and 44% for 2-dose schedules of nilotinib and 22% for imatinib (P < .001 for both comparisons). The rate of complete cytogenetic response at 12 months was 80% and 78% for 2-dose schedules of nilotinib and 65% for imatinib (P < .001 for both comparisons).[7][Level of evidence: 1iiDiv] Progression to accelerated-phase CML or blast crisis occurred in 11 patients on imatinib (4%) but only occurred in 2 patients (<1%, P = .01) and 1 patient (<1%, P = .004) for the patients on two-dose schedules of nilotinib.[7]
Although one of these two studies showed statistically significant decreased rates of progression to accelerated- or blastic-phase CML, which may ultimately translate into improved survival, the follow-up period with nilotinib and dasatinib has not been long enough to detect and confirm this prolonged survival with these agents. The preferred initial treatment for newly diagnosed patients with chronic-phase CML could be any of these specific inhibitors of the BCR/ABL tyrosine kinase.[9]
Higher doses of imatinib mesylate, alternative tyrosine kinase inhibitors (such as dasatinib or nilotinib, and allogeneic SCT) are implemented for suboptimal response or progression and are under clinical evaluation as frontline approaches.[10,11,12,13,14,15,16,17,18] Currently in practice, dose escalation of imatinib is usually the first step taken for suboptimal response, but clinical trials are required to establish the relative efficacy and sequencing of dose escalation, dasatinib, and nilotinib.[15,16] Two studies looked at dose escalation of imatinib in almost 200 previously untreated patients, most of whom were of intermediate Sokal risk; 63% to 73% achieved a major molecular response by 18 to 24 months and only three patients showed progression to advanced phase in these preliminary phase II results.[19,20][Level of evidence: 3iiiDiv] Until randomized studies are performed, it is unclear whether the increased response with increased dosage will translate into longer durations of response or survival advantages.[17,21]
Among the many unanswered questions are the following:
All of these issues have led to an active reappraisal of recommendations for optimal frontline therapy for chronic-phase CML.
High-dose therapy followed by allogeneic BMT or SCT
The only consistently successful curative treatment of CML has been high-dose therapy followed by allogeneic BMT or SCT.[26] Patients younger than 60 years with an identical twin or with HLA-identical siblings can be considered for BMT early in the chronic phase. Although the procedure is associated with considerable acute morbidity and mortality, 50% to 70% of patients transplanted in the chronic phase survive 2 to 3 years, and the results are better in younger patients, especially those younger than 20 years. The results of patients transplanted in the accelerated and blastic phases of the disease are progressively worse.[27,28] Most transplant series suggest improved survival when the procedure is performed within 1 year of diagnosis.[29,30,31][Level of evidence: 3iiiA] The data supporting early transplant, however, have never been confirmed in controlled trials. In a randomized, clinical trial, disease-free survival and OS were comparable when allogeneic transplantation followed preparative therapy with cyclophosphamide and total-body irradiation (TBI) or busulfan and cyclophosphamide without TBI. The latter regimen was associated with less graft-versus-host disease and fewer fevers, hospitalizations, and hospital days.[32][Level of evidence: 1iiA] Reduced-intensity conditioning allogeneic SCT is under evaluation in first or second remissions.[33,34]
About 20% of otherwise eligible CML patients lack a suitably matched sibling donor.[35] HLA-matched unrelated donors or donors mismatched at one-HLA antigen can be found for about 50% of eligible participants through the National Marrow Donor Program.[35] A retrospective review of 2,444 patients who received myeloablative allogeneic SCT showed OS at 15 years of 88% (95% confidence interval [CI], 86%–90%) for sibling-matched transplant and of 87% (95% CI, 83%–90%) for unrelated donor transplant.[36] The cumulative incidences of relapse were 8% (95% CI, 7%–10%) for sibling-matched transplant and 2% (95% CI, 1%– 4%) for unrelated donor transplant.[36]
Although the majority of relapses occur within 5 years of transplantation, relapses have occurred for as long as 15 years following BMT.[37] In a molecular analysis of 243 patients who underwent allogeneic BMT over a 20-year interval, only 15% had no detectable BCR/ABL transcript by PCR analysis.[38] The risk of relapse appears to be less in patients transplanted early in disease and in patients who develop chronic graft-versus-host disease.[28,39]
With the advent of imatinib, dasatinib, and nilotinib, the timing and sequence of allogeneic BMT or SCT has been cast in doubt.[24] Allogeneic SCT is the preferred choice for patients presenting with accelerated-phase or blast-phase disease, for patients with a T3151 mutation (resistant to currently available tyrosine kinase inhibitors), and for patients with complete intolerance to the pharmacologic options.[40]
In a prospective trial of 354 patients aged younger than 60 years, 123 of 135 patients with a matched, related donor underwent early allogeneic SCT while the others received interferon-based therapy and imatinib at relapse; some also underwent a matched, unrelated-donor transplant in remission.[41] With a 9-year median follow-up, survival still favored the drug treatment arm (P = .049), but most of the benefit was early as a result of transplant-related mortality, with the survival curves converging by 8 years.[41][Level of evidence: 2A] Among the many unanswered questions are the following:
Clinical trials and long-term results from ongoing trials will be required before these controversies are resolved.
Biologic therapy with or without chemotherapy
Long-term data are available for initial treatment with interferon alpha. A meta-analysis of seven trials that randomly assigned patients to receive interferon or conventional chemotherapy (hydroxyurea or busulfan) demonstrated a 30% reduction in the annual death rate for patients who received interferon (P < .001).[42][Level of evidence: 1iiA] The annual death rate was reduced by 26% in the trials of interferon versus hydroxyurea (P = .001) and 36% in the trials of interferon versus busulfan (P = .007). Median survival was prolonged by 1 to 2 years; 5-year survival rate was 57% for patients treated with interferon and 42% for patients treated with chemotherapy (P < .001). Further analysis of the two trials, which included a three-way randomization between interferon, hydroxyurea, and busulfan, showed hydroxyurea to be superior to busulfan, decreasing the proportional odds of death by 24% (P = .02).[42] About 20% of the chronic-phase patients treated with interferon alpha have complete cytogenetic remissions with temporary disappearance of Philadelphia chromosome (Ph1)-positive cells in the marrow, and in about 10% of the patients these cytogenetic responses are quite long lasting.[43,44,45] These data have only been published in the context of a review article, rather than a peer-reviewed research manuscript.[45]
Long-term follow-up of the interferon-treated patients from a randomized trial comparing interferon with chemotherapy showed that the median survival had not been reached at 10 years for patients who had complete or major cytogenetic responses to interferon.[46] Seventy-four percent of patients with complete cytogenetic responses and 55% of patients with major cytogenetic responses were alive and had shown no disease progression at date of publication (median follow-up time was not provided). Using molecular methods of analysis, however, small numbers of Ph1-positive cells can still be detected in the majority of patients having long-term cytogenetic remissions, and longer follow-up will be required to ascertain whether the disease will recur.
Patients older than 60 years with chronic-phase CML have a hematologic and cytogenetic response rate and duration of cytogenetic response similar to that in younger patients; however, the incidence of complications is greater in elderly patients.[47] Interferon alpha has significant toxic effects that can result in dosage modification or discontinuation of therapy in many cases. A randomized, prospective trial of 407 patients compared two doses of interferon, 5 million units/m² daily versus 3 million units/m² daily; at a median follow-up of 53 months, no difference was seen in OS, progression-free survival, or number of major cytogenetic responses.[48][Level of evidence: 1iiA] As evidenced in the CLB-9013 study, common side effects included influenza-like syndrome, nausea, anorexia, weight loss, and neuropsychiatric symptoms, all of which were completely reversible with cessation of therapy.[49] (Refer to the PDQ summaries on Nausea and Vomiting and Nutrition for information on some of these side effects.) Immune-mediated complications, such as hyperthyroidism, hemolysis, and connective tissue diseases may occur rarely after long-term treatment.[50] Interferon alpha is quite costly, and daily subcutaneous injections can be troublesome. Pegylated interferon alpha is administered weekly; a randomized, noninferiority trial of 344 newly diagnosed CML patients could not rule out the possibility that pegylated interferon alpha may be slightly inferior to daily interferon alpha.[51][Level of evidence: 1iiDiv]
Patients whose disease is in cytogenetic remission should continue therapy for at least 2 to 3 years beyond remission, and perhaps indefinitely, as suggested by some investigators. After 1 year, patients with only a partial cytogenetic response should consider alternative therapy with imatinib mesylate or allogeneic BMT or SCT (if eligible). The French Chronic Myeloid Leukemia Study Group randomly assigned 721 patients to interferon and cytarabine versus interferon alone.[52][Level of evidence: 1iiA] Patients who received the combination had significantly more major cytogenetic responses (41% vs. 24%, P < .001) and improved 3-year survival (86% vs. 80%). Another trial by the Italian Cooperative Study Group on CML did not show a survival benefit for interferon plus cytarabine versus interferon alone.[53][Level of evidence: 1iiA] Both studies showed increased toxic effects for the combination versus interferon alone.[52,53] Interferon alpha is also effective for patients who have relapsed after allogeneic BMT.[54,55]
Hydroxyurea is given daily by mouth (1–3 g per day as a single dose on an empty stomach). Hydroxyurea is superior to busulfan in the chronic phase of CML, with significantly longer median survival and significantly fewer severe adverse effects.[56] A dose of 40 mg/kg per day is often used initially and frequently results in a rapid reduction of the white blood cell (WBC) count. When the WBC count drops below 20,000 mm3, the hydroxyurea is often reduced and titrated to maintain a WBC count between 5,000 and 20,000. Hydroxyurea is currently used primarily to stabilize patients with hyperleukocytosis or as palliative therapy for patients who have not responded to other therapies.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with chronic phase chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Treatment Options for Accelerated-Phase Chronic Myelogenous Leukemia (CML)
Patients with accelerated-phase CML show signs of progression without meeting the criteria for blast crisis (acute leukemia). Symptoms and findings include the following:
Bone marrow examination shows increasing blast cell percentage (but ≤30%) and basophilia. Additional cytogenetic abnormalities occur during the accelerated phase (trisomy 8, trisomy 19, isochromosome 17Q, p53 mutations or deletions), and the combination of hematologic progression plus additional cytogenetic abnormalities predicts for lower response rates and a shorter time-to-treatment failure on imatinib mesylate.[6] At 1 year after the start of imatinib, the failure rate is 68% for patients with both hematologic progression and cytogenetic abnormalities, 31% for patients with only hematologic progression, and 0% for patients with cytogenetic abnormalities only. Before the availability of imatinib, the median survival time of accelerated-phase CML patients was less than 1 year.[6]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with accelerated phase chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Treatment Options for Blastic-Phase Chronic Myelogenous Leukemia (CML)
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with blastic phase chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Overt failure is defined as a loss of hematologic remission or progression to accelerated-phase or blast-crisis phase chronic myelogenous leukemia (CML) as previously defined. Although presumed to represent relapsing disease, a rising quantitative reverse transcriptase–polymerase chain reaction signal is a controversial finding. Prospective studies comparing resumption of therapy versus continued observation have not been performed. Similarly, there has been no prospective validation for failure to achieve certain benchmarks during initial therapy. For initial use of imatinib mesylate, the designation of relative failure has been proposed for lack of complete hematologic remission by 3 months, no cytogenetic response by 6 months, or no major cytogenetic response by 12 months.[1,2] Nilotinib and dasatinib induce such high rates of complete cytogenetic responses (93% of 155 patients in one series) and major molecular responses (87%) within several months that new benchmarks are required for responsiveness.[3] These investigators propose that a complete cytogenetic response by 3 months should define an optimal response.[3]
In case of treatment failure or suboptimal response, patients should undergo BCR/ABL kinase domain mutation analysis to help guide therapy with the newer tyrosine kinase inhibitors or with allogeneic transplantation.[4,5] Mutations in the tyrosine kinase domain can confer resistance to imatinib mesylate; alternative inhibitors such as dasatinib, nilotinib, or bosutinib, higher doses of imatinib mesylate, and allogeneic stem cell transplantation (SCT) have been studied in this setting.[6,7,8,9,10,11,12,13,14,15,16,17,18] Clinical trial participation should help establish the optimal sequence of these options.
Infusions of buffy-coat leukocytes or isolated T cells obtained by pheresis from the bone marrow transplant donor have induced long-term remissions in more than 50% of patients who relapse following allogeneic transplant.[19,20] The efficacy of this treatment is thought to be the result of an immunologic graft-versus-leukemia effect. This treatment is most effective for patients whose relapse is detectable only by cytogenetics or molecular studies and is associated with significant graft-versus-host disease. After relapse from allogeneic SCT, some patients will also respond to interferon alpha.[21] Most patients will respond to imatinib mesylate with durable (>1 year) cytogenetic and molecular responses. (These patients had not previously received imatinib.)[22,23,24]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with relapsing chronic myelogenous leukemia. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Treatment Option Overview
Added Wei et al. as reference 9.
Chronic-Phase Chronic Myelogenous Leukemia (CML)
Added Hehlmann et al. as reference 21.
Added text to state that allogeneic SCT is the preferred choice for patients presenting with accelerated-phase CML or blast-phase disease, for patients with a T3151 mutation, and for patients with complete intolerance to the pharmacologic options (cited O'Brien et al. as reference 40).
Accelerated-Phase Chronic Myelogenous Leukemia
Revised text to state that the first treatment option for this phase of CML is allogeneic bone marrow transplantation or SCT and cited a cohort study that compared imatinib as first-line therapy versus allogeneic SCT; overall survival was improved using allogeneic SCT for the Sokal high-risk patients (cited Jiang et al. as reference 1 and level of evidence: 3iiiA).
Added text to state that other tyrosine kinase inhibitors need to be evaluated as first-line therapy in accelerated-phase CML.
Relapsing Chronic Myelogenous Leukemia
Added text to state that nilotinib and dasatinib induce such high rates of complete cytogenetic responses and major molecular responses within several months that new benchmarks are required for responsiveness. These investigators propose that a complete cytogenetic response by 3 months should define an optimal response (cited Jabbour et al. as reference 3).
Added text to state that in case of treatment failure or suboptimal response, patients should undergo BCR/ABL kinase domain mutation analysis to help guide therapy with the newer tyrosine kinase inhibitors or with allogeneic transplantation (cited Soverini et al. and Parker et al. as references 4 and 5). Revised text to include bosutinib as an alternative inhibitor that has been studied (cited Cortes et al. and Khoury et al. as references 17 and 18).
This summary is written and maintained by the PDQ Adult Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of chronic myelogenous leukemia. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Chronic Myelogenous Leukemia Treatment are:
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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National Cancer Institute: PDQ® Chronic Myelogenous Leukemia Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/CML/HealthProfessional. Accessed <MM/DD/YYYY>.
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text:
In Memoriam ...rest in peace dear friends.
1 9 6 4
Many alumni have requested a listing of
their deceased classmates so as to be able to honor dear friends. This is the
list for your class. If you are aware of deceased classmates who are not on this
list, please e-mail us the details (date, city, etc.) at
email@example.com. To return to
the main directory page,
click here.

subset: commoncrawl


text:
Probably the Best Static and Radio Control Model Boat Kits in the World
Welcome to BillingBoats
Welcome Guest! Would you like to log yourself in? Or would you prefer to create an account?
Important: www.BillingBoats.co.uk of Great Britain, is an authorised reseller / dealer of Billing Boats APS, Broedsgaardsvej 70B, DK-6000, Kolding, Denmark. If you require the website of Billing Boats, please visit www.BillingBoats.com.
Important: Many Billing Boat kits are available from stock, or after a short delay. However, there are supply shortages on some kits, causing backlogs of several weeks.
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text:
All Steel is a series of stainless steel cookware designed by Finnish Pentagon Design. The frying pans, sauté pan and wok feature a ceramic Ceratec° coating that conducts heat efficiently, guarantees excellent browning and prevents food from sticking to the pans. The casseroles and saucepan have a convenient measuring scale on the inside and a steam vent on the lid. Every All Steel pan and casserole is dishwasher proof, oven proof up to 240 °C and suitable for all hobs. This high-quality series will satisfy even the most demanding domestic chef. All Steel products are manufactured in Finland.
- Manufacturer:
- Fiskars
- Design:
- Pentagon Design
- Material:
- Stainless steel
- Size:
- Diameter 26 cm


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Friday, June 15, 2012
It is a good day.
President Announces Administrative Relief to DREAMers
On June 15th theAdministrationannounced that it will stop deporting DREAM Act-eligible youth. In addition, it will use its authority to grant, on a case-by-case basis, deferred action status valid for two years. At the end of that two-year period, deferred action can be renewed. Those granted deferred action will be eligible for work authorization for the duration of deferred action. Aliens who meet the following criteria can qualify for this relief:
Entered the United States before the age of 16 and have not yet turned 30
Have continuously lived in the United States for at least five years preceding June 15, 2012 and were residing in the United States on that date
Are currently in school, have graduated from high school or obtained a GED, or have been honorably discharged from the Coast Guard or U.S. Armed Forces
Have not been convicted of a felony, a significant misdemeanor, three or more minor misdemeanors, or otherwise pose a threat to national security or public safety.
Aliens currently in removal proceedings or subject to a final order of removal can still qualify for deferred action, as are those who accepted administrative closure or whose case was terminated. Those who meet the above eligibility criteria and who are encountered by CBP or ICE officials should be able to stop further enforcement actions based on the agency's prosecutorial discretion criteria. ICE and USCIS personnel responsible for considering requests for an exercise of prosecutorial discretion will receive special training on this new process.
Possible documentation of entry to the United States before the age of 16, physical presence on June 15, 2012, and five years of residence could include financial, medical, school, employment, and military records. Possible documentation of current enrollment in school, graduation from high school, or GED could include diplomas, GED certificates, report cards, and school transcripts. Brief and innocent departures will not preclude a finding of five years of U.S. residence.
The Administration indicated that applicants for deferred action will need to complete a background check. Deferred action is a discretionary grant that does not lead to permanent resident status, but does allow the recipient to qualify for employment authorization if he or she can demonstrate "an economic necessity." It is not clear at this time whether those granted deferred action will be eligible for advance parole and thus would be able to leave and return to the United States.
There is no appeal of a denial of deferred action. Applicants will receive some form of supervisory review, however. The agency is developing protocols on that that review standard and procedure. Those who are denied will be subject to potential enforcement and issuance of a Notice to Appear if they have committed certain criminal offenses or there is a finding of fraud in their request.
Relatives of the alien granted deferred action are not eligible for any derivative benefits if they do not satisfy the criteria.
The Administration indicated that it will issue further details on the application process, the fee, and the recommended documentary proof.
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Dick and Liz Cheney have an Op-Ed over at the Wall Street Journal where they place the blame for the collapse of Iraq on the shoulders of the president. Reading it is just unbearable. I literally had to look away several times and repress my gag reflex. Is there, in all American history, a more execrable duo?
But what I wanted to single out here was one single line from their piece: "Rarely has a U.S. president been so wrong about so much at the expense of so many." Forget the fact that this line seems far more appropriate for the epitaph of George W. Bush. Forget the seemingly impossible lack of self-awareness. Forget the clinically insane immunity to shame or misgiving. The thing that is so utterly loathsome about this sentence is that it echoes one of Winston Churchill's more famous utterances: "Never was so much owed by so many to so few." The words came to Churchill as he witnessed the heroic efforts of the Royal Air Force as they battled the Nazi Luftwaffe in August of 1940. The reversal of the line, I suppose, is a particularly sharp, but cryptic, attempt to paint Obama as an appeaser, whose weakness is rivaled only by his misjudgment. But now the Nazis are played by ISIS and al Qaeda and Obama is Chamberlain in blackface.
The whole argument is so patently absurd and self-serving that I find it impossible that any thinking person would allow them space in their newspaper to make their case. The authors of the War on Terror, Torture Incorporated, Gitmo, and the disruption of the entire Middle East should be forever disqualified from the public arena.


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Shalaparni Desmodium gangeticum
Shalaparni is a small plant which grows to a maximum of four feet and which is usually only found at altitudes of above 5000 feet in India. Its flowers are a delicate purple and white and the leaves are sprinkled with tiny soft hairs.
The taste of this herb is surprisingly sweet and is most famously used in the traditional Ayurvedic 10 herb formula known as 'Dashamoola' and Mahanarayan Oil that we have made our own version of in Active Oil.


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Is Whitney Houston continuing to have problems with her comeback tour?
The R&B legend performed on Wednesday night in the UK at Birmingham's LG Arena, but the singer missed a few notes while performing… and possibly missed out with her fans too.
In video posted on YouTube, Whitney can bee seen taking a long pause during "I Will Always Love You," before belting out the song's signature hook. She then failed to hit the high notes that audiences have come to expect from her.
She also left the stage for 15 minutes for a costume change, after only having performed for about 15 minutes.
The British press had a field day with headlines like "Houston, You Have A Problem," "Send For Men In Whit Coats" and "More Nights Like This And They Won't Always Love You."
Whitney has two days off and then she heads to Dublin, Ireland for three performances, before heading back to England for shows in Newcastle and London.
Check out more video of Whitney in concert in the UK, HERE.
Related Content from AccessHollywood.com:
VIEW THE PHOTOS: Hollywood's Hottest Moms & Their Loveable Little Ones
VIEW THE PHOTOS: Daring! Dramatic! Fabulous! Hot Shots Of Hollywood's Divas
PLAY IT NOW: Whitney Houston's 'Nothing But Love World Tour': UK Opening Night
PLAY IT NOW: Access Extended: Whitney Houston & Clive Davis Talk Comeback (July 21, 2009)
MORE ACCESS ON THESE TOPICS: Whitney Houston - Tours - Music - TV One


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Republicans and Democrats in one of the few Congressional districts in Southern California where they have roughly equal numbers agree: They don't like the federal government shutdown.
And as was evidenced on a recent weekday in the 36th Congressional District, members of both parties were unimpressed at Rep. Raul Ruiz (D-Palm Springs) crossing the aisle to vote with Republicans.
Ruiz was the lone California Democrat to vote last week for a delay in the individual mandate -- a rule under the Affordable Healthcare Act that requires individuals to have health insurance through the government, work or a private insurer. The bill passed the House but failed in the Senate as both parties argued over how to end the partial government shutdown.
The 36th District includes most everything north and south of Interstate 10 in Riverside County, from the Inland Empire city of Banning east through the desert to Blythe at the California border. Republicans and Democrats each claim about 39 percent of the district's voters.
Banning's best-known eatery is The Farmhouse, a big red barn with a 15-foot chicken in the parking lot. Inside, the décor is antiques and lots of American flags put up by owner Jackie Kennedy. The mother of a Marine Corps lieutenant who was killed in 2004 in Iraq, she is deeply disappointed in Congress over the shutdown.
She says the government shutdown makes the lingering hard times in the inland region that much harder for families and small businesses like hers.
"I hear a lot of people that come in, they don't know if they're going to get their checks this month, they're afraid about that," Kennedy said. "They're just eating toast now."
Kennedy's customer base includes road-trippers headed to the Joshua Tree National Monument and federal parks in California and Arizona. She's heard from plenty of campers and tourists angry that their destinations are closed.
Kennedy is Republican. She likes former Rep. Mary Bono Mack, the Republican who lost the 2012 election in a surprise upset to Ruiz. But his vote with the Republicans to delay the requirement that individuals buy health insurance did not make Kennedy like Ruiz or Congress any better.
"I think America needs to step up and be the strong country we have been," she said.
The populated heart of the 36th District is the cluster of desert cities. Palm Springs' downtown shopping strip — where bells at a coffee shop chime the hour over passing traffic, and visitors cavort under the upblown skirt of a gigantic Marilyn Monroe sculpture — is all about attracting tourists.
At a life-sized statue of the late Congressman Sonny Bono, a group of Dutch tourists make alternate plans now that their expected visits to 10 national parks in 18 days are thwarted. Instead, Entoon Vingruthusen is taking his group to the tiny desert town of Blythe.
"In Holland, we have no desert. So, we go there," Vingruthusen said.
Up Highway 74 to the Santa Rosa and San Jacinto Mountains National Monument, the gates and visitor center are closed up tight. A park ranger sits in an air conditioned patrol SUV overlooking the entrance. He exits the truck briefly, long enough to say he's not permitted to comment on the closure. The driveway entrance is locked, but a roadside parking lot is open for those who prefer to hike in.
Farther up the mountain, Pine Cove resident Todd Hoggan horses around at an Idylwlild coffee house with his son, Quentin. Hoggan is a self-employed biologist on disability after losing part of his vision in a car crash. His wife is a federal worker on furlough, and until it's over, they risk missing a mortgage payment.
"Getting paid later doesn't really matter right now," Hoggan said. "If you live month to month, that isn't going to cut it. No one's going to cut you some slack because you say the federal government hasn't paid you."
He notes that Idyllwild's economy leans heavily on income and contracts from the Forest Service and other federal agencies, so he has a number of friends who are in the same dilemma.
"It's basically a forest town. That's who administers the forest. It's the biggest employer in this town," Hoggan said.
He supported Congressman Ruiz in the last election, but now he blames the freshman Democrat for the economic difficulties his family may soon face.
"Representative Ruiz voted Tea Party, that was a huge shock to all of us that voted him in and that will be rectified next election, I'm sure," Hoggan said.
Ruiz has explained his vote by saying individuals deserve the same delay for mandatory health insurance that was given to small businesses. He has since called the shutdown "reckless" and "unconscionable."
Hoggan, a Democrat, says he isn't quite ready to support a Republican rival next year, but he says he will explore his options.
Whether other district voters also reconsider Ruiz depends on how long their memories, and the shutdown, lasts.


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I'm a little late with this post as I'm just getting over a really bad migraine. My vision is still a little fuzzy and the laptop makes my eyes sore so it's taking me a while to catch up with a few blog posts, I'll be back in a while with my post for this weeks Critter Sketch Challenge.
Anyhoo, I'm sharing my creation for this weeks Paper Crafting Journey challenge where the theme this week is:
I have kept my card quite simple and have used a die to cut an aperture to let the backing paper show through. I was inspired by this weeks sketch challenge at Less is More and actually made my card on Saturday but due to the migraine I'm only going to make the challenge by the skin of my teeth.
Please hop over to Paper Crafting Journey and see what the rest of the DT have made.
Bye for now.
Items: Scalloped 6x6 card blank, patterned paper from a Daisy and Dandelion pad, nesties, Rich Cocoa Memento inkpad, a Penny Black Christmas Stamp set, pearls from Wild Orchid Crafts and ProMarkers.


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PC Load Letter Paper Jam
March 03, 2006
So I thought today was going to be a good day.
Unlike yesterday, Noah didn't wake up at 4 am with a hacking cough and full of righteous indignation at said hacking cough because it interrupted the flow of his screaming.
Unlike yesterday, Noah didn't throw up an entire 8 ounces of formula all over me, my bed, my pillow and Jason's ear at 4:30 am.
Unlike yesterday, I was not doing loads of vomitous laundry at 4:45 am, nor was I at work by 7:45 am, because while I'm okay with tossing a towel over a baby pee-stain on the bed, puddles of regurgitated Similac are something else entirely and FINE, I will get up and just go to work already.
Yesterday was a bad day. I was at work for 10 hours straight, had to speak in front of the entire company and I may have murdered a coworker or two. I barely made the daycare pick-up deadline and Noah's teacher informed me that all the babies had the same cough, and now seemed to be moving on to sharing a case of hand, foot and mouth disease. So you know, watch out for that.
But! Today seemed better! Noah slept until 7 and there was no screaming, just a happy baby chattering away to his hands, who are really good listeners and find Noah to be an excellent conversationalist. The cough is better, the mucus is abating and no one threw up on me, not even a little bit.
And then!
Hello! I am Amy's work computer! I greet you with happy blue screen of death! You are doomed! You are welcome!
My work computer blew the fuck up. It is "corrupted." It is "riddled with hard drive inconsistencies and bad cluster files." It is "not under warranty." It is "currently in many little pieces after I beat it to death with a baseball bat."
Helpful Network Guy: You save your stuff on your network drive, right?
Amy: Um.
Random Coworker Wondering Why I Am Weeping: But you can still get to your network drive, right?
Amy: Well, yes, but...um.
Amy's Boss: I save everything on the network drive. You do too, right?
Amy: I am going to go lie down in the parking garage for a little while.
So yes. I am really, really dumb. Four years of files are more than likely gone forever.
I sort of take a Unabomberesque approach to data management, as I simply don't trust network drives for some reason and prefer to instead create the world's most crowded and bizarrely structured My Documents folder, which is where I put EVERYTHING, in a series of folders and subfolders that only make sense to me.
Looking for a spreadsheet of stock market returns? No, that is not in the "Spreadsheets" folder, that contains the Word docs of stuff that I need to create spreadsheets for, but haven't yet. No, the actual spreadsheets are in My Pictures, in the folder labeled "Money." I mean, duh.
I am also lazy and never back anything up. If Typepad eats it, a la Diary-X, y'all will just have to remember the archives from memory.
Anyway, I looked on my network drive and found the following:
1. My Outlook Sent Items folder, circa June 2003
2. Four photos of my shoes, circa God knows when, but apparently stacked heels were really in.
3. A Word document on why Enron is the commodity stock of the future, circa July 2001
Helpful Network Guy messed around with my computer for quite some time this morning, while I paced around my office, chewing on my fingers, drinking cup after cup of coffeecoffeecoffee and texting people on my phone because the lack of email was KILLING ME, and I was even texting COWORKERS because I don't really know where people sit and have lost my list of phone extensions because WHO NEEDS IT when you have EMAIL, GLORIOUS EMAIL.
Helpful Network Guy: I'll bring you a temporary computer while I work on trying to save your data.
Amy: *thinks about all the personal crap on her work computer*
Amy: *thinks about the spare copies of her resume on her work computer*
Amy: *thinks about the baby pictures. the belly pictures. the dog pictures. the shoe pictures.*
Amy: Um. Could you maybe...you know...recover stuff without really looking at it?
Helpful Network Guy: What?
Amy: Excuse me, I need another cup of coffee.
Amy: *realizes that the Irish Creme coffee creamers are not actually getting her drunk in the slightest and considers writing Coffeemate a letter about false advertising*
Amy: Damn it, I'd really rather just send them an email.
Helpful Network Guy: What?


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Create an Account - Increase your productivity, customize your experience, and engage in information you care about.
The Office of Economic Development offers financial support to businesses of all sizes, and works closely with the business community to obtain traditional financing, venture capital and local, state, and federal loans.
Harford County will provide matching funds to its businesses to accelerate the delivery of technical training to existing employees that will contribute to expand or improve production capabilities.
Get information about, and apply for, the Economic Development Advisory Board (EDAB)/Tourism Competitive Funding Program.


text:
UNIVERSITY PARK, Pa. -- Two Penn State aerospace engineers recently won a best paper award at a rotorcraft conference.
Jianhua Zhang, a research associate in aerospace engineering, and Edward Smith, professor of aerospace engineering and director of Penn State's Vertical Lift Research Center of Excellence (VLRCOE), received the best paper award during the second annual Asian/Australian Rotorcraft Forum and fourth annual International Basic Research Conference on Rotorcraft Technology on Sept. 8 to 11 in Tianjin, China.
The two were honored for their paper "Influence of Aeroelastically Tailored Wing Extensions and Winglets on Whirl Flutter Stability."
The award is the first for either researcher and the first for a member of the VLRCOE. The work was sponsored by the National Rotorcraft Technology Center and NASA Ames Research Center.
Smith credited Ames aerospace engineer Wally Acree for the paper's original concept.
"The idea for the project was his," Smith said. "Wally also provides frequent and very wise feedback on our progress. He is an unsung engineering hero."


text:
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The Filibuster
"MLB just handed down suspensions to Joe Girardi, Dusty Baker and Wally
Joyner as a result of recent disputes with umpires. Meanwhile, the umps
blew several calls over the past week, including what should have a
been a three-run homerun by Carlos Delgado last Sunday. Are umps
earning their money and has MLB become overly sensitive to criticism of
their arbiters?"
— Allen
"Are umps earning their money…?"
Seriously, Al? You act as if baseball has never seen a controversial call or a heated argument between umpire and manager before. Ejections, game-changing calls — right or wrong — are fundamental aspects of the game, Mr. Krause. They are as natural as the infield-fly rule or the strike-em-out throw-em-out inning-ending double play.
Your questioning of recent events yet again proves your ignorance for what has always been a defining element of the grand game of baseball.
What sets baseball apart from all the rest is that it doesn't rely on the fast-paced pinpoint accuracy of machines to govern its highly relative rules. As a game that sees its best players fail 7 out of 10 times at the plate, baseball's umpiring system — which has a much higher success rate — is bound to see a mistake or two during the long season. But to introduce technology (like instant replay) to arbitrate — even if it's solely used for home run calls — would be nothing short of sacrilege in my point of view, which by the way, is the only correct point of view.
And I'm saying this as an avid proponent for burning down Don Denkinger's house — still — 23 years after he singlehandedly destroyed my childhood by calling Jorge Orta safe when he was CLEARLY OUT during the 1985 World Series. A few years ago, I was going through some personal issues and while recovering made a list of all those whom I had hurt in some way with the ultimate goal of verbalizing an apology to them. I have said a lot of awful things about Denkinger in my lifetime and I am not proud of them. But when it came time to write an apology to him, the one person whom I hold more contempt for than even Bill O'Reilly, I was unable to reverse my absolute hatred. I even did extensive background research on Denkinger's life, hoping that it would humanize him in some way that would make me feel bad about the anger I held inside.
The result?
Nothing changed.
But that's just me. As an adult, I realize that that call was just a part of the game I love so much and that if I changed it, baseball would no longer be the rhetorical love of my life. It's really as simple as that.
And while the league minimum salary for baseball players is around the $350K mark, the umpiring crews hover around $100K. The best umps in the game might make close to the player minimum, but of course, they're doing it without any fanfare. They're doing it while having to be on the road for every game, not just 81 games. They're doing it while being targeted by angry fans in Chicago, Philadelphia, New York and Detroit. They're doing it without any attention paid to how good of a game they might call and they're doing it while being singled out only when they get one wrong, which in the grand scheme of things, isn't very often.
So they've had a bad week. So what. Their bad week pales in comparison to an Eric Byrnes, who is having a terrible season while getting paid over $6.5 million this year or an Eric Gagne, who is getting $10 million for throwing like a batting practice coach. These guys are the ones who aren't earning their keep. These guys are the ones we should be talking about.
And if for some reason Bud Selig lets these idiots get to him with the whole instant replay institution, I will take to the streets French revolutionary style to ensure that the game stays just the way it is.
I may do it alone, but I will do it because it is right, because I am right. And whether I come out of it dead or alive, please don't hate me 'cuz I'm right 'cuz that's all I have in this cold, cold world.


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Bob Blumenfield, the Assembly Democrat who is a champion of the state's high-speed rail project, needs a new talking point.
Blumenfield was quoted in the New York Times this weekend as saying of "It's not putting someone on the moon, but it's a state version of making a giant leap forward."
He's right, of course. Building a high-speed rail project in California isn't the equivalent of putting someone into space.
U.S. & World
It's more expensive.
The most recent projections for phase 1 of high-speed rail -- getting you from LA to San Francisco in two-and-a-half hours, or only 90 minutes slower than in an airplane -- range from $99 billion to $118 billion, according to a new report this week from the non-partisan Legislative Analyst's Office.
The LAO report also noted that the ballot initiative authorizing bonding requires a plan for funding everything, and questions the claims in a new high-speed rail business plan about savings and economic boost from building the project.
Estimate of another manned mission to the Moon also range widely, but most fall around $20 billion. A manned trip to Mars, including return, has been estimated at $40 billion. Assuming additional costs, the high-speed rail project is two manned missions to Mars.
I don't think the space exploration comparison makes the case for the project.
In fact, it highlights the problem. And that problem is not merely one of cost. It's the combination of an extraordinary cost and an ordinary project -- a project that doesn't get us from north to south any faster than we can get now, a project that doesn't connect what needs connecting (the east and west parts of California), a project that skips Sacramento and San Diego.
Here's betting that a Californian returns to the moon before a Calfornian rides a high-speed train from LA to San Francisco.
The moon trip is cheaper, after all.
Let us know what you think. Comment below, send us your thoughts via Twitter @PropZero or add your comment to our Facebook page.


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"Harry Ironside is a great example of a preacher full of God's Word."—R. Kent Hughes
H. A. Ironside's The Four Hundred Silent Years is June's Free Book of the Month!
Henry "Harry" Allen Ironside was one of the twentieth century's greatest preachers. He held honorary degrees from Wheaton College and Bob Jones University and was frequently invited to lecture at Dallas Theological Seminary.
After serving as a Salvation Army officer for a brief period, Ironside joined the Plymouth Brethren and started what would become a highly successful itinerant ministry of preaching and teaching. He served as pastor at Moody Memorial Church from 1930 to 1948, preaching more than 7,000 sermons during his lifetime.
In The Four Hundred Silent Years, Ironside draws from sources like C. M. Grant's Between the Testaments and the Apocrypha to piece together the timeline between the prophet Malachi and the Gospel of Matthew.
You can get Ironside's book free throughout the end of June, and when you visit the Free Book of the Month page, you can enter to win the 65-volume Works of H. A. Ironside collection.
Visit the Free Book of the Month page to download your free book and enter the giveaway!


text:
In Memory of
Ralph Andrew Fletcher
son of
Herbert Ellery and Carrie Hill Fletcher
May 10, 1866 January 26, 1956 January 22, 1866 November 9, 1933
His Children
John Herbert
Samuel Hill
Rebecca Ann
His Children
Ralph Andrew
Emerson Kennard
Fairview Cemetery
Westford, Middlesex Co., Massachusetts
I was very surprised to find this family was not listed in FindAGrave with all the other 107 Fletchers. How could anybody miss this enormous cube. This is a well-known name and granite company, which had a long history, until it closed recently.


text:
Invitation to a Lecture at Emory University on American and Israeli Dance
Video: Cedar Lake Contemporary Ballet performing Ohad Naharin's Decadance
If you're in Atlanta, Georgia – or if you know someone in Atlanta – here's a heads up:
I'm happy to announce that I am speaking in the Emory Friends of Dance Lecture Series on Wednesday, February 24 at 7:00 p.m. (Eastern Standard Time). My talk, Foreign Exchange: American and Israeli Dance from Martha Graham to Ohad Naharin, will precede a performance by Cedar Lake Contemporary Ballet of Ohad Naharin's Decadance. I won't be in Atlanta in person, but I will be speaking via Skype and have an exciting presentation prepared!
Cedar Lake performing Ohad Naharin's Decadance. Photo by Paul B. Goode.
Here's the official blurb about my lecture:
Forty years ago, Israel's premiere dance company imported works by top American choreographers. Now cutting-edge American troupes like Cedar Lake Contemporary Ballet are drawing crowds with choreography by Israeli artists. In this lecture, dance scholar Deborah Friedes Galili explores the dynamic relationship between American and Israeli dance and traces the meteoric rise of Israeli contemporary dance. This lecture will be presented live from Israel via webcam prior to the performance by Cedar Lake Contemporary Ballet.
Cedar Lake performing Ohad Naharin's Decadance. Photo by Paul B. Goode.
My lecture is free and open to the public, so if you're in Atlanta, I hope you will come listen in the Chase Lobby at the Schwartz Center for Performing Arts, 1700 N. Decatur Road. I will speak for one half hour, and then there will be a question and answer session. Please let others know about this event as well!
Related Articles on Dance In Israel
- Batsheva Dance Company: From Graham to Gaga
- Americans in Israel: Cedar Lake in Tel Aviv Dance 2008
- Ohad Naharin's Deca Dance in Israel: A Cycle Completed
Related Links
- Emory Dance Program Events
- Emory Report (article about the event)
- Cedar Lake Contemporary Ballet
- Batsheva Dance Company
4 comments
Hi Deborah,
I am going to Atlanta next week to perform and then visit friends dancing in Cedar Lake; however, we arrive in Atlanta at 8pm! I am researching Israeli Contemporary dance for my senior project so I am very intrigued with your presentation! The movement was actually a collaboration with Jesse Zaritt. He referred me to your website and I have been intrigued ever since.
Will you be able to document your presentation and the following questions?
I do wish I could be there!
Thank you for all you had done!
Hi Deborah
Will it be possible to listen to your lecture or read it through the blog?
do hope so
Good luck


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"Going green" is becoming the design mantra for foodservice operators.
There is currently a lot of buzz about "going green" in noncommercial foodservice, particularly with design projects incorporating environmentally sound elements cropping up in schools, colleges hospital and corporate settings. The trend is giving operators a vocabulary of new phrases such as LEED-certified, biodiesel fuels, biodegradable disposables and waste composting.
"Sustainability is a very hot topic today," says Todd Guyette of Colburn & Guyette Consulting Partners, Inc., Rockland, MA. "There's a lot we can be doing because, from a design standpoint, foodservice is very energy-intensive. To go green can be less expensive [over time] despite the upfront costs, and can save operators money."
Universities in particular are "really getting on board," he says, often driven by student pressure, but also by government regulations. In Boston, for example, all new construction must now follow the U.S. Green Building Council's LEED (Leadership in Energy and Environmental Design) regulations, while California requires new government buildings to be LEED-certified.
At Ricca/Newmark Design in Centennial, CO, Kathleen Seelye, president, Foodservice Planning, sees a "different matrix of decisions" in planning foodservice facilities along with more new sources of funding for sustainable projects.
"Look at what can be done in the design itself to impact energy use long-term and select procedures that provide long-term sustainability," she tells operators.
Energy guzzlers: Ventilation systems, she adds, use 25% of the energy in a commercial kitchen, a number that can be halved by decisions such as hood placement. Technology that reads heat and smoke is "most important," she says, noting that a typical marketplace concept might contain nine to 11 hoods.
Refrigeration also "is a very big deal." Equipment that is self-contained has a shorter life cycle and is harder to service than remote units. Recycling and reusing water is extremely important in dish rooms. Other factors in green design might include recycled materials such as rubber tires for flooring.
"Carts and racks can be [made of] recycled aluminum instead of stainless, which has gone up in price 60% this year," she adds.
A sustainable operation is one involved in waste-to-energy programs, recycling, composting, and using oils from fryers for conversion to bio-diesel fuels. Ray Soucie, a vice president at foodservice consultant Romano-Gatland, suggests that operators create a "closed loop" from the back door through receiving, storage, prep, cooking, serving and waste handling as they design a facility, and examine how equipment can be changed for "sustainable design."
Design schools: Recently, a new, $5.7-million cafeteria at 750-student Waipahu Intermediate School in Hawaii received LEED certification for such features as 100% natural lighting of the dining area, 65% reduction in irrigation water consumption, and effective natural ventilation. The school saves $3,000 a year from a 15% reduction in energy consumption. In addition, locally made and recycled materials were used to construct the cafeteria.
The University of California at Santa Cruz received a "green business certificate" from the city for renovations to two dining operations that serve 14,000 meals a day, says Director of Dining and Hospitality Scott Berlin. The renovations save "thousands of kilowatts annually;" reduce water usage from new low-flow spray nozzles; added grease traps and include composting. "We're in a design phase now to remodel another facility and will be doing LEED certification for that, with new sensor-controlled grease hoods and new windows, starting next summer."
At the Emma Willard School in Troy, N.Y., green design was used in an adaptive renovation that united two dining facilities into one servery/dining area with energy-efficient lighting, Energy Star-compliant pumps and motors, and low-flow faucets. Parts of the kitchen were 80 to 100 years old, says Facilities Director Ian Smith.
A new dish machine recycles water, using less energy, says Kevin Boyer, foodservice director for Sodexho at the private school. He adds that the facility does more cooking to order now with less waste.
Going 'greenware': Fletcher Allen Health Care, Burlington, Vt., has been recycling for more than a decade, notes Diane Imrie, director of nutrition services. Now, her department is focusing on disposables, switching to "greenware" cups made from corn that can be composted. Composting food waste saves $18,000 a year in landfill fees, she adds.
At Concord (N.H.) Hospital, Foodservice Director Tom Serafin is working with the hospital's vice president, Ray Gerbi, on a 160,000-square-foot addition to the hospital that will expand, renovate and redecorate the cafeteria and kitchen using LEED guidelines. Gerbi estimates the project will cost $800,000.
"We'll use natural wood products, energy-efficient and natural lighting and low-VOC flooring," says Serafin.
He's seeking energy efficient retherming equipment and would like to learn more about the energy efficiency of manufacturers' products. "If Energy Star ratings were on items I need, I'd certainly buy them."
Greening of a High School
A new high school continues a history of environmental consciousness.
Becky Domokos-Bays, director of school foodservice for the Alexandria (Va.) City Public Schools, is no stranger to "going green." Her district has long been a practitioner of conservation, with one high school becoming part of an ACPS Energy Star conservation program as far back in 1992. That program saved the district more than $175,000 over the past five years alone.
In addition, over the years the 18-school system has retrofitted lighting systems, installed new double-pane windows in most buildings, replaced electric heating/cooling systems with high efficiency gas systems, used energy-efficient chillers and boilers, and picked energy-efficient roofing with four inches of insulation and reflective white surfaces.
In addition, the schools began shutting off all cafeteria lights when natural lighting could suffice, for an estimated savings of $175,000 annually.
This fall, her department will operate a cafeteria in the new T.C. Williams High School, an $88-million facility that is expected to earn at least LEED silver certification, she says.
The new facility, which was in the planning for nearly a decade, has an LCD display that shows how energy is being used in the building. "It'll help us train our staff to turn down the ovens as needed, " she declares. "We're doing really good stuff."
All lighting in the building has motion sensors that detect when people are in a room and turn lights on or off as needed. A 400-gallon cistern on the roof collects rainwater for the toilets, and a garden on the top of the building also uses rainwater. Additionally, the school is recycling glass, plastic, metal, paper and cardboard.
The new kitchen includes "all energy-efficient equipment," Domokos-Bays says. Plans call for recycling paper and cans and for composting cafeteria waste for "significant savings." A new blast chiller will allow the school's kitchen to more easily be used as a distribution center for the 17 other schools it services.
"The kitchen is designed to be more of a workhorse with a better flow of materials," says Domokos-Bays. The loading dock has security cameras, and trucks can unload directly onto pallets and take incoming products straight to coolers. When commodities arrive, they can be stored on site instead of at a distributor's, which represents another cost savings.
The 16 food 'outlets' are positioned in a food court built in a straight line. "Since 1965, this school has been an open campus and they could go off site to eat," she says. "Now, all students have to eat here."
Input from students prompted foodservice to give a "restaurant feel" to the design with mixed tables, booths and tables around columns. "They didn't want a school cafeteria feeling," Domokos-Bays says.
Voice of Experience
Ted Mayer talks about the work and the rewards of taking a "green" approach to design.
Ted Mayer, executive director of Harvard University Dining Services in Cambridge, Mass., wants his fellow foodservice operators to know first and foremost that the perception of green design as more expensive is wrong.
"It's a misconception," he declares. "The upfront costs may be somewhat higher but they are offset easily by the savings." And the savings, he points out, can be significant. At Dunster-Mather Dining Halls, part of the university's "house" system of dormitory complexes, he oversaw a major $7.1-million renovation that became the first internal foodservice kitchen to receive LEED silver certification from the U.S. Green Building Council in the summer of 2005.
"Our dish machine saved us $6,000 in soap alone in the first year. It also saved us 5,000 gallons of hot water a year, which translated into $18 million in savings. The entire focus in the project was foodservice. I funded it and controlled the process. Dunster-Mather serves 850 students a year, or 284,000 meals annually.
At Dunster-Mather, the challenges involved looking at equipment in a lot more detailed way than previously. We tried to get the biggest bang for the buck in energy savings. We built in equipment for recycling and composting kitchen waste. We put in dual flush toilets. We now collect waste oil from the fryer [which is plumbed and filtered for use in trucks that run on vegetable oil].
We recycled 95% of the construction waste through contacts that found places that could use our old equipment. It was a process of building relationships and getting everybody on board.
You get credits [in the certification process] for where the materials you're using are from. Values are given to each part of the phase such as the finishes and the lighting. It's a complicated system.
Often the people involved in a renovation aren't involved in the actual operation [of what's being renovated] so you get a sort of disconnect. You're trying to save money in the building process. We connected these two groups so we could have long-term savings.
You always weigh the value of each purchase, its use, its purpose, but you have to make compromises in a project like this. We got silver certification on Dunster-Mather because we couldn't afford gold. The more information you have up front, the better choices you can make. These kinds of projects take a lot of planning. We plan a year ahead with the LEED checklist in front of us at every step.
The renovation was the last of a series of renovations at 13 different houses in eight years. We decided to go for LEED certification. Now, Harvard has a minimum standard of gold LEED certification for all new buildings. All of Harvard's facilities going forward will be LEED certified.
The next new building will be a Science Center in Allston, MA, which will have a foodservice facility. It will be smaller than Dunster-Mather."


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FRIENDS OF Bogue Banks Library hosts guest speaker Kevin Duffus at 3 p.m. Jan. 26 at Bogue Banks Library on �How Shipwrecks shaped the Destiny of the Outer Banks.� Call 252-247-4660.
FRIENDS OF Bogue Banks Library hosts guest speaker Kevin Duffus at 3 p.m. Jan. 26 at Bogue Banks Library on �How Shipwrecks shaped the Destiny of the Outer Banks.� Call 252-247-4660.
SEASIDE LODGE No. 429 will hold a Stated Communication at 7:30 p.m. Jan. 27 with refreshments before meeting.
ONSLOW ANIMAL Services seeks foster care families for dogs displace during upcoming shelter upgrades. For more information call 9100455-0182.
LOWER CAPE FEAR Hospice seeks volunteers from Onslow County to provide respite for caregivers/families with life-limiting illnesses. Training held Jan. 27, 29 and 31 at Onslow Public Library. Call 910-976-7981.
AMERICAN Sewing Guild�s Wilmington Neighborhood Group meets at noon Jan. 27 at Fran�s Sewing Circle, Wilmington. Bring red item they have made. Asgcapefear.org.
JACKSONVILLE New River Lions Club meets at 6:30 p.m. Jan. 27 at Logan�s, Western Blvd. Call 910-346-4205.
ONSLOW COUNTY Democratic Party meets at 6:30 p.m. Jan. 27 at Kerr Street Recreation Center.
JACKSONVILLE High School student council presents �Cupid�s Ball� senior citizens prom from 7 to 9 p.m. Feb. 15 at the high school cafeteria. Open to all seniors 55 and older for music, dancing and refreshments.
HIDDEN TALENTS Craft Fair is accepting applications for its upcoming event held April 5-6 at Paradise Point Officers� Club aboard Camp Lejeune. Email firstname.lastname@example.com.
WORLD HERITAGE Student Exchange program seeks host families for high school boys/girls from abroad for the 2014/15 school year. Call 252-571-1853 or whHosts.com.
WHITE OAK High School Class of 1989 celebrates its 25th class reunion held July 25-26 with pool party, family beach day and banquet. Information at firstname.lastname@example.com or email@example.com.
JACKSONVILLE Chamber of Commerce hosts its annual State of the Community Breakfast at 8 a.m. Feb. 11 at MCAS New River Officers� Club. Reservations required at 910-347-3141.


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Backstreet Boy A.J. McLean Welcomes Baby Girl Ava Jaymes — Congrats
Backstreet Boys singer A.J. and wife Rochelle welcomed baby Ava Jaymes into the world on Nov. 27! Congrats!
The Backstreet Boys may be busy rehearsing songs for their new album, but member A.J. McLean is going to have to add some lullabies to his song list! His wife Rochelle gave birth to baby daughter Ava Jaymes on Nov. 27 in Los Angeles.
A.J., 34, wrote on his website, "Rochelle and I are thrilled to announce the birth of our baby. She arrived at 4:51 a.m. weighing 7 lbs., 7 oz. We are so in love with our bundle of joy and happy to have started our family now."
The pop star and his wife took to YouTube back in April to announce the pregnancy in a video for fans. "I just wanted to say thank you guys for all your love and support…Because we love you all so much, we wanted to share with you — for the first time — something very special. We're having a baby," A.J. said.
Just as A.J. and his BSB buddies have kept fans waiting for new music, Ava kept her parents waiting, as well. On Sunday, Nov. 25 — the expected due date — Rochelle tweeted her impatience. "Come on AVA!!! It never takes Mommy this long to get ready!" she wrote. "Being punctual is a great quality to have!! Now come out so we can see you!!"
Congrats, A.J. and Rochelle!
— Billy Nilles
More Celebrity Births:


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When will we see you in Blacktown?
Blacktown Arts is a recognised leader in the development of contemporary arts in Australia. We support artistic innovation and offers exciting, new experiences for audiences through an award-winning curated program of exhibitions, performances, workshops, residencies and events. Blacktown Arts is committed to exploring dynamic, culturally diverse work that reflects Blacktown, its history and its communities. We place Aboriginal and Torres Strait Islander artists and communities at the heart of our program to develop new work drawing on issues of local and global significance.
The Leo Kelly Blacktown Arts Centre is an innovative multi-arts hub located in the heart of Blacktown, a short walk from the railway station.
- This event has passed.
2019 Blacktown City Art Prize
04/12/2019 | 10:00 am - 5:00 pm
An event every week that begins at 10:00am on Tuesday, Wednesday, Thursday, Friday and Saturday, repeating until 25/01/2020
Now in its 24th year, the Blacktown City Art Prize is a highly valued art prize, with cash prizes of $20,000 and acquisitive awards. Local, regional and national artists are invited to submit entries in drawing, painting, sculpture, ceramics and mixed media.


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Sorry - diesmal auf Englisch: Hello Everyone, I just uploaded to the server new beta maps of Austria and Italy (Germany is still uploading, please don't download until 02:00 CET (02.Dec) - or before it has reached 405 Mbit.
Autorouting in Mapsource works around 50% better if used via car/motorcycle faster route. Now shorter Distance will actually work pretty well too - especially on longer distances and in combination with mode :bicycle. In Mapsource I would advise moving the slider a little bit to prefer highways if using "shorter distance". What I don't know is how well these maps work on your GPS - therefore this is a beta release. On my etrex Vista HCx I could notice a little bit improvement - I do think on Oregon/Dakota or other modern units Improvements will be even bigger - please report back.
Also Autorouting against the traffic flow (if cycleway=opposite; opposite_track; opposite_lane will now be tried to avoided). And Delivery only avoids Primaries/Secondaries - but does not block them (this was actually already on last map Update)
-- http://openmtbmap.x-nation.de/maps/beta/