hematology and oncology
Chronic Myeloid Leukemia (CML)
Treatment of CML
Tyrosine kinase inhibitors Sometimes, allogeneic stem cell transplantation ) are the initial treatment choice; they are not curative but are extremely effective. Tyrosine kinase inhibitors are also sometimes used in the accelerated or blast phase. Allogeneic hematopoietic Hematopoietic Stem Cell Transplantation is reserved for patients with accelerated or blast phase CML or those with disease resistant to the available tyrosine kinase inhibitors. Asciminib(binder to the ABL pocket) is available for CML previously treated with two or more tyrosine kinase inhibitors or CML in chronic phase with the T315I mutation. Except when Hematopoietic Stem Cell Transplantation is successful, treatment is not proven to be curative. However, tyrosine kinase inhibitors prolong survival. Some patients may be able to discontinue tryrosine kinase inhibitors and remain in remission. The durability of these remissions is not yet known. Tyrosine kinase inhibitors inhibit theBCR-ABLoncogene, which is responsible for induction of CML. These drugs are dramatically effective in achieving complete hematologic and cytogenetic remissions of Ph chromosome–positive CML (Ph+ CML) and are clearly superior to other drug regimens (eg, interferon with or withoutcytarabine). Theresponse to TKI therapyis the most important prognostic factor for patients with CML. Patient's response is measured at baseline and then at 3 months, 6 months, and 1 year. The response can be assessed with either a molecular test (measurement of BCR-ABL protein) or a cytogenetic test (measurement of Ph+ chromosome cells), but both are recommended whenever possible. A major molecular response is defined as blood BCR-ABL < 1/1000th (or less) of the expected value for untreated CML. If, after 12 months, a major molecular response is achieved, the response can be monitored every 3 to 6 months by real time quantitative polymerase chain reaction of BCR-ABL protein and cytogenetic testing. Rarely, other drugs are used as palliation in CML. These drugs includehydroxyurea,busulfan, and recombinant interferon or pegylated interferon. The main benefit ofhydroxyureais reduction in distressing splenomegaly and adenopathy and control of the tumor burden to reduce the incidence of tumor lysis syndrome and gout. None of these drugs seems to prolong survival, although interferon can produce a clinical remission in about 19 % of patients. Allogeneic Hematopoietic Stem Cell Transplantation , because of its toxicity and because of the efficacy of tyrosine kinase inhibitors, is used selectively. Transplantation is reserved for patients with accelerated- or blast-phase CML resistant to BCR-ABL inhibitors. Transplantation can be curative. 