{'fraction_non_alphanumeric': 0.032385243593353985, 'fraction_numerical': 0.009011546043368065, 'mean_word_length': 5.517431192660551, 'pattern_counts': {'":': 0, '<': 1, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
More general incorporation of hemoglobin level into response criteria for myelodysplastic syndrome and acute myeloid leukemia with increase in minimum red cell transfusion levels

In this issue of Leukemia and Lymphoma, McQuilten and colleagues [1] report determinants of healthrelated quality of life (HRQOL) in patients given azacitidine for the treatment of myelodysplastic syndrome (MDS) or low blast count (<30%) acute myeloid leukemia (AML). Two-hundred and thirty-one patients (74% MDS, 16% chronic myelomonocytic leukemia, 24% AML) received treatment in two multicenter trials. Of principal interest, higher pretreatment hemoglobin levels were associated with better global QOL and physical function, with increases in hemoglobin during therapy correlated with improvement in QOL and physical function, independent of other patient and disease-associated characteristics. These findings raise several issues. First, should we increase our minimum red blood cell (RBC) transfusion thresholds in MDS? Second, should erythroid response [2] and/or transfusion-independence gain more importance as an endpoint for drug approval in trials for higher-risk MDS (and low blast count AML), rather than just in low-risk MDS trials? Third, should assessments of QOL be more routinely be included in clinical trials? Finally, given the increasing realization of the pathogenetic and prognostic importance of genetic mutations in myeloid malignancies, is continuing reliance on a morphologic criterion to distinguish AML from MDS sensible? There is no single transfusion threshold for hemoglobin above which benefit is clear, and below which adverse outcomes become more common. Any threshold must be modified according to clinical circumstances; for example, the threshold would be expected to be higher in an older patient with coronary artery disease. Nonetheless, there appears to be a trend to set thresholds lower, driven by data in the inpatient and critical care settings [3–5], where the focus has been on shorter-term outcomes like cardiac events and thromboembolism. In outpatients with chronic anemia, data demonstrating risks of transfusion-associate iron overload [6,7] have been influential, as has concern for alloimmunization [8]. Expert panels have generally remained vague on RBC transfusion thresholds in MDS. The NCCN MDS guidelines simply recommend transfusion for “symptomatic anemia,” noting that the number of transfusions should “be kept to a minimum in non-cardiac patients.” [9] Similarly, guidelines from the European Leukemia (ELN 2013) note the “objective of RBC transfusion therapy is to improve QOL and to avoid anemia-related symptoms and ischemic organ damage” a general recommendation is that all patients with hemoglobin less than 8 g/dL or those with symptomatic anemic should receive transfusion [10]. Indeed, experience suggests 8 g/dl is the generally-accepted red cell transfusion threshold. However, several reports have now linked lower hemoglobin to poor QOL and function in MDS and AML patients [11,12]. The current study provides confirmation. We believe we should examine the value of targeting higher threshold hemoglobin levels in patients with both lower and higher-grade myeloid neoplasms. This is currently being done in a prospective, randomized trial limited, however, to low-risk MDS patients [13]. Simultaneously, efforts should be made to reduce the adverse effects of higher transfusion volumes. Possibilities include early use of iron chelation [14] or the prophylactic use of extended matching or