How I treat mixed-phenotype acute leukemia

Abstract

Mixed-phenotype acute leukemia (MPAL) encompasses a heterogeneous group of rare leukemias in which assigning a single lineage of origin is not possible. A variety of different terms and classification systems have been used historically to describe this entity. MPAL is currently defined by a limited set of lineage-specific markers proposed in the 2008 World Health Organization monograph on classification of tumors of hematopoietic and lymphoid tissues. In adult patients, MPAL is characterized by relative therapeutic resistance that may be attributed in part to the high proportion of patients with adverse cytogenetic abnormalities. No prospective, controlled trials exist to guide therapy. The limited available data suggest that an “acute lymphoblastic leukemia–like” regimen followed by allogeneic stem-cell transplant may be advisable; addition of a tyrosine kinase inhibitor in patients with t(9;22) translocation is recommended. The role of immunophenotypic and genetic markers in guiding chemotherapy choice and postremission strategy, as well as the utility of targeted therapies in non–Ph-positive MPALs is unknown.

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

“…The published data suggest poor treatment outcomes, in terms of both the probability of achieving complete remission and overall survival (OS), as compared with AML or ALL (ref. 19,25 ). A study of treatment in 35 children with MPAL meeting the EGIL criteria showed results comparable to those in AML but worse overall survival than in pediatric ALL (ref.…”

“…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. 25 ). In patients with Ph1+ ALL, excellent short-term outcomes were achieved using dasatinib combined with corticosteroids and intrathecal chemotherapy 30 .…”

“…In patients with Ph1+ ALL, excellent short-term outcomes were achieved using dasatinib combined with corticosteroids and intrathecal chemotherapy 30 . It is assumed that MPAL arising from a hematopoietic stem cell (with strong CD34+ expression and a potential to differentiate into various lineages) will not be curable by chemotherapy alone 19,20,25 . As in Ph1+ ALL, AML arising from MDS or with adverse cytogenetics, incurable without allogeneic HCT, the role of transplantation in the first complete remission is similar in mixed-phenotype leukemia [25][26][27][28] .…”

“…It is assumed that MPAL arising from a hematopoietic stem cell (with strong CD34+ expression and a potential to differentiate into various lineages) will not be curable by chemotherapy alone 19,20,25 . As in Ph1+ ALL, AML arising from MDS or with adverse cytogenetics, incurable without allogeneic HCT, the role of transplantation in the first complete remission is similar in mixed-phenotype leukemia [25][26][27][28] . The use of a protocol for ALL with a broader spectrum of cytostatic drugs in the first cycle of chemotherapy seems to be more reasonable than of protocols for AML therapy 15,25 .…”

“…Identification of these patients is important for selecting therapy different from that for Ph1-negative patients. Treatment of Ph1+ MPAL is derived from recommendations for treating Ph1+ ALL which, until the era of tyrosine kinase inhibitors (TKIs) was thought to have rather adverse prognosis 25,28 . One retrospective analysis compared treatment outcomes of 13 patients with Ph1+ MPAL and 27 patients with Ph1+ ALL.…”