Allogeneic Hematopoietic Stem Cell Transplantation with Myeloablative Conditioning Is Associated with Favorable Outcomes in Mixed Phenotype Acute Leukemia

Abstract

Mixed phenotype acute leukemia (MPAL) represents a poorly characterized group of acute leukemias that lack an accepted therapeutic approach and are typically associated with poor outcomes. We present our experience of genomic profiling, pre-transplant therapy and transplant outcomes for 36 well characterized pediatric and adult patients with MPAL defined according to the 2016 WHO leukemia update. A predominance of ALL-associated mutations and cytogenetic abnormalities was noted. Remission rates after induction appeared comparable among adults (20/23) and children (11/13) and among those who received ALL (10/11) or AML-type (21/25) induction. Adults were transplanted in first remission while children were transplanted in the setting of relapse or MLL rearrangement. The median follow-up among the 25 patients who underwent transplantation was 39.6 months and median OS was not reached. Relapse after transplant was associated with MLL rearrangement (p=0.022), reduced intensity (p<0.001), and higher WBC at diagnosis (p=0.034). These data highlight differing therapeutic approaches between adult and pediatric MPAL and demonstrate favorable survival of adult MPAL patients consolidated with allogeneic hematopoietic cell transplantation.

PHF6 and DNMT3A mutations are enriched in distinct subgroups of mixed phenotype acute leukemia with T-lineage differentiation

“…Posttransplant outcomes of a subset of the patients were previously reported. 27 The clinical, morphologic, immunophenotypic, and cytogenetic/molecular results were independently re-reviewed by 2 hematopathologists (W.X. and M.R.).…”

“…We have recently reported overall good outcomes in a well-defined cohort of MPAL patients undergoing allogeneic transplant, in contrast to prior studies, which were confounded by the inclusion of secondary AML cases. 27 Given the rarity of the disease and the evolving definition of this entity, the mutational repertoire of MPAL has not been fully elucidated. In addition, the mutations associated with specific lineage differentiation and the enrichment of mutations in specific cellular compartments have not been studied in MPAL.…”

“…[34][35][36][37][38][39] PHF6 mutations have also been reported in rare MPAL patients. 14,27 Here, we report the clinicopathologic analysis and genomic landscape in a stringently confirmed cohort of MPAL patients from Memorial Sloan Kettering Cancer Center (MSKCC).…”

Cytogenetic aberration in mixed-phenotype acute leukemia in children: A single-center retrospective review

“…17 Reportedly, adults were transplanted in first remission, whereas children were transplanted in the setting of relapse or MLL rearrangement. 18 To date, clear distinctions are defined between strong and weak expression, as well as percentage requirements for positivity (especially, positivity for MPO). Using either definition of MPAL, ALL-therapy is associated with higher initial remission rates and is at least equivalent to more intensive AML therapy for long-term survival.…”

Concomitant Use of Blinatumomab and Donor Lymphocyte Infusion for Mixed-Phenotype Acute Leukemia: A Case Report With Literature Review

“…Matutes et al reported a better complete remission rate (85%) with ALL-type therapy when compared with AML-type therapy (41%) [3]. Recent retrospective analyses showed favorable outcomes in MPAL patients consolidated with allogeneic hematopoietic stem cell transplantation (allo-HSCT) [12][13][14][15]. Blinatumomab, a bispecific CD19-directed CD3 T-cell engager, is a US FDA-approved drug for relapse and/or refractory (R/R) CD19 expressing B-ALL [16,17].…”