Clinicoepidemiologic Profile and Outcome Predicted by Minimal Residual Disease in Children With Mixed-phenotype Acute Leukemia Treated on a Modified MCP-841 Protocol at a Tertiary Cancer Institute in India

Abstract

Introduction: Mixed-phenotype acute leukemia (MPAL) accounts for 1.2% to 5% of acute leukemia across age groups with intermediate prognosis. We evaluated clinicoepidemiologic profiles and outcomes of MPAL. Methods: Records of children younger than 15 years of age with acute leukemia from January 2010 to December 2016 were reviewed on the basis of the MPAL WHO 2008 criteria. Treatment was uniform with a modified MCP-841 protocol. Descriptive analysis tools were used. Outcomes were measured by the Kaplan-Meier method on MedCalc, version 14.8.1. Results: Among 3830 children with acute leukemia in the study period, 2892 received treatment from our center, of whom 24 (0.83%) had MPAL, median age 9 years, with a male:female ratio of 3:1, and median white blood cell of 13.4×109/L. Common immunophenotypes were B/myeloid—12 (50%), T/myeloid—9 (37.5%), and B/T-lymphoid—3 (12.5%). Some B/myeloid cases had abnormal cytogenetics. Seventeen patients were evaluable for outcome. Sixteen patients underwent postinduction bone marrow and 13 (81%) achieved morphologic remission. Thirteen patients underwent flow cytometry–based minimal residual disease evaluation; 9 (69%) were <0.01% (4 postinduction, 5 postconsolidation), and 67% of these had sustained remission till the last follow-up. None underwent bone marrow transplant. The projected 3-year event-free and overall survival rates were 40% and 48%, respectively (median follow-up: 22 mo). Conclusion: MPAL represented <1% of childhood acute leukemia. acute lymphoblastic leukemia–type chemotherapy that incorporated high-dose cytarabine was effective in achieving an minimal residual disease–negativity rate of 69% in evaluated patients, which was also predictive of better outcome.

Editorial: The management of hematologic malignancies in lower-income countries

“…With little data available on this rare subtype of acute leukemias, the authors report on a series of 42 children treated for MPAL, achieving a 5-year event-free survival (EFS) of 56% and overall survival (OS) of 61%. These results are comparable to data from two pediatric MPAL series in India, highlighting the challenges in managing high-risk pediatric leukemias in resource-limited settings ( 5 , 6 ). In one of the largest reports of pediatric MPALs from LMICs, the authors highlight the difficulties of treating high-risk pediatric leukemia in resource-limited settings.…”

“…from Egypt discuss the challenges in managing mixed-phenotype acute leukemia (MPAL) in LMICs. MPAL is a relatively rarer subtype of acute leukemias, and there are limited data, especially on children from LMICs ( 5 , 6 ). With little data available on this rare subtype of acute leukemias, the authors report on a series of 42 children treated for MPAL, achieving a 5-year event-free survival (EFS) of 56% and overall survival (OS) of 61%.…”

Paediatric ambiguous lineage leukaemia with monocytic differentiation at diagnosis: case series and review of literature

“…Treatment is largely guided by MRD and bone marrow transplant is reserved for those with inadequate response to therapy 5,9 . Previous studies have shown non‐inferior outcomes in both CD19 + and CD19 − cases compared to non‐ALAL cases with MRD 0·1% or higher after induction treated on current intensified protocols 5,12,13 …”

“…5 Treatment is largely guided by MRD and bone marrow transplant is reserved for those with inadequate response to therapy. 5,9 Previous studies have shown non-inferior outcomes in both CD19 + and CD19 À cases compared to non-ALAL cases with MRD 0Á1% or higher after induction treated on current intensified protocols. 5,12,13 We conducted a multicentre retrospective study with chart and pathology review of all cases of MPAL/ALAL diagnosed and treated at University Hospital Southampton (UHS) and Sheffield Children's Hospital (SCH), UK from the year 2015 until 2020.…”

“…5,6 The outcome for MPAL is inferior to other common paediatric acute leukaemia. [7][8][9][10][11] The International Berlin-Frankfurt-M€ unster Study of Leukemias of Ambiguous Lineage (iBFM-AMBI2012) study showed a superior 5-year event-free survival (80 AE 4% vs. 36 AE 7Á2%) in those treated with acute lymphoblastic leukaemia (ALL)-type than with AMLtype or combined therapy. 5 AML-type treatment was effective in those with CD19 À or in the absence of lymphoid markers.…”