Ofir Wolach1, Richard M Stone. 1. aLeukemia Service, Davidoff Cancer Center, Rabin Medical Center, Petah-Tikva, Israel bDepartment of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Abstract
PURPOSE OF REVIEW: Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL. RECENT FINDINGS: Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumor suppressors, and transcription factors. The limited available data suggest that higher remission rates are achieved with acute lymphoblastic leukemia-like induction regimens compared with acute myeloid leukemia-type approaches. Allogeneic transplantation in first remission may be associated with improved survival compared with consolidation chemotherapy. SUMMARY: Advances in understanding the genetic landscape of MPAL may allow a more biologically driven classification of this heterogeneous group of leukemias in the future that will lead to optimized therapies for individual patients. Most data that inform therapy are based on retrospective, uncontrolled studies; prospective trials that incorporate targeted approaches based on genetics and immunophenotype are needed.
PURPOSE OF REVIEW: Mixed-phenotype acute leukemia (MPAL) is a rare disease that poses many diagnostic and therapeutic challenges. Patients with MPAL are considered to have poor outcomes. The difficulties in classifying this leukemia, the lack of prospectively collected data concerning therapeutic outcomes, and rare incidence result in much uncertainty as to the best approach for patients with MPAL. RECENT FINDINGS: Recent studies demonstrated that most MPALs are associated with cytogenetic abnormalities; genetic sequencing studies disclose a high frequency of somatic mutations in genes encoding epigenetic regulators, tumor suppressors, and transcription factors. The limited available data suggest that higher remission rates are achieved with acute lymphoblastic leukemia-like induction regimens compared with acute myeloid leukemia-type approaches. Allogeneic transplantation in first remission may be associated with improved survival compared with consolidation chemotherapy. SUMMARY: Advances in understanding the genetic landscape of MPAL may allow a more biologically driven classification of this heterogeneous group of leukemias in the future that will lead to optimized therapies for individual patients. Most data that inform therapy are based on retrospective, uncontrolled studies; prospective trials that incorporate targeted approaches based on genetics and immunophenotype are needed.
Authors: Wenbin Xiao; Maheetha Bharadwaj; Max Levine; Noushin Farnhoud; Friederike Pastore; Bartlomiej M Getta; Anne Hultquist; Christopher Famulare; Juan S Medina; Minal A Patel; Qi Gao; Natasha Lewis; Janine Pichardo; Jeeyeon Baik; Brian Shaffer; Sergio Giralt; Raajit Rampal; Sean Devlin; Robert Cimera; Yanming Zhang; Maria E Arcila; Elli Papaemmanuil; Ross L Levine; Mikhail Roshal Journal: Blood Adv Date: 2018-12-11
Authors: Brianna R Murphy; Michael Roth; E Anders Kolb; Todd Alonzo; Robert Gerbing; Robert J Wells Journal: Pediatr Blood Cancer Date: 2019-03-25 Impact factor: 3.167