Philadelphia chromosome‐positive mixed phenotype acute leukemia in the imatinib era

Abstract

Although the introduction of imatinib dramatically improved the outcomes for patients with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph + BCP-ALL), the survival benefit of imatinib has not been assessed in the context of Ph + mixed phenotype acute leukemia (Ph + MPAL). To clarify this important issue, we studied 42 Ph+ acute leukemia (Ph + AL) patients who received intensive chemotherapy and concurrent administration of imatinib. Of the 42 Ph + AL patients, 13 (31%) patients were categorized as Ph + MPAL (positive for both myeloid and B-cell lineage), 27 (64%) were categorized as Ph + BCP-ALL, and two (5%) were categorized as Ph + acute myeloid leukemia. The complete remission rates after the initial induction therapy were not significantly different when comparing Ph + MPAL and Ph + BCP-ALL patients (100% vs. 85%, respectively, P = 0.14). Likewise, there were no significant differences in the 5-yr overall survival (OS) or disease-free survival (DFS) rates when comparing the MPAL and BCP-ALL groups (OS: 55% vs. 53%, respectively, P = 0.87, DFS: 46% vs. 42%, respectively, P = 0.94). These findings suggest that concurrent imatinib administration with chemotherapy improved the outcomes of Ph + MPAL patients to the level seen in Ph+BCP-ALL patients and should, therefore, be considered as the standard therapy for these patients.

Mixed-phenotype acute leukemia: state-of-the-art of the diagnosis, classification and treatment

“…One retrospective analysis compared treatment outcomes of 13 patients with Ph1+ MPAL and 27 patients with Ph1+ ALL. The results showed comparable probability of achieving complete remission (100% vs. 85%) as well as the overall 5-year survival (55% vs. 53%) in both groups 29 . Therapy for Ph1+ MPAL is based on an ALL protocol adjusted to the patient's age, combined with TKI and followed by allogeneic HCT (ref.…”

“…Similarly to Ph1+ ALL complete molecular remissions can be achieved even in elderly MPAL patients with only a combination of prednisolone and TKI (ref. [28][29][30]33 ). The presence of FLT3/ITD in MPAL can be a potential therapy target for inhibitors similarly to AML (ref.…”

Initial Diagnostic Workup of Acute Leukemia: Guideline From the College of American Pathologists and the American Society of Hematology

“…J Clin Epidemiol. 2011;64(4): [401][402][403][404][405][406]; copyright 2011, with permission from Elsevier. a Derived from Andrews et al 431 2013.…”

“…Although one study from our SR informed this recommendation, 140 the guideline statement is evidence based and supported by 2 additional studies outside our SR. 400,401 Mixed-phenotype acute leukemia is associated with a variety of cytogenetic abnormalities, among which, are included t(9;22)(q34.1;q11.2); BCR-ABL1 and KMT2A (MLL) translocations. 140,02 Those cytogenetic abnormalities are associated with distinctive features and define specific entities under the WHO classification: MPAL with t(9;22); BCR-ABL1 (Ph þ ) and MPAL with t(v;11q23.3); KMT2A (MLL) rearranged.…”

“…400 In a different series, which compared the outcome of 42 patients with Ph þ AL treated with imatinib-containing regimens, the 5-year OS and DFS of the 13 patients with MPAL was no different from that of the patients with Ph þ ALL, suggesting that imatinib therapy improved the outcome of the patients with Ph þ MPAL and should be considered the standard of care. 401 Similarly, KMT2A (MLL) rearrangement was associated with reduced survival. 404 Based on those data, the EP recommends testing for t(9;22)(q34.1;q11.2); BCR-ABL1 and KMT2A (MLL) translocations in MPAL.…”