Cytogenetic Risk Remains a Major Predictor of Outcome in Pediatric AML and ALL Treated with Allogeneic Stem Cell Transplantation,
Authors: Walter Claudia Ulrike , Ayas Mouhab , Alseraihy Amal , El-Solh Hassan , Al-Jefri Abdullah , Al-Ahmari Ali , Belgaumi Asim F , Albitar Maher 
Published: October 2019

Abstract
Abstract 3524

Background:
Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) each represent a heterogeneous group of disorders resulting from diverse mechanisms of leukemogenesis. Cytogenetic abnormalities are considered reliable risk-stratification tools in both AML and ALL. Most studies assessing clinical outcome according to cytogenetic risk consider patients treated with conventional intensive chemotherapy. The impact of cytogenetics on outcome in patients treated uniformly with hematopoietic stem cell transplantation (HSCT), especially in the pediatric group, is not well studied. We evaluated whether allogeneic HSCT has an impact on outcome as predicted by cytogenetic risk at diagnosis.

Methods:
Bone marrow karyotyping and FISH data from 61 pediatric AML patients and 37 pediatric patients with ALL was reviewed and patients divided into two groups according to their cytogenetic risk: one group combined patients with favorable or intermediate risk and the second group comprised patients with adverse-risk cytogenetics. Cytogenetic risk classification was according to WHO and MRC cytogenetic criteria. The AML cohort included 47 (77%) patients treated in their first remission (CR1) while most non-CR1 AML patients were treated with HSCT in CR2. Of the ALL patients, 18 (49%) were treated with HSCT in CR1. The outcome of patients with either favorable/intermediate cytogenetic risk or adverse cytogenetics was compared for AML and ALL patients, first including all patients, then including only CR1 patients. The median age of patients was 8 years (range: 9 months to 13 years).

Results:
Patients with ALL and favorable / intermediate cytogenetics had significantly longer overall survival (OS) and event-free survival (EFS) as compared with the adverse-risk group (P=0.02 and P=0.03 for OS and EFS, respectively). A similar trend was observed when only CR1 ALL patients were evaluated, although their number is small. Notably, separation between the CR1 ALL and CR2 ALL groups was stronger when only Philadelphia chromosome positive and MLL positive patients were considered (P=0.01 for OS and EFS for all patients; P=0.003 for OS and EFS for CR1patients only). Also for pediatric AML, combined favorable / intermediate-risk cytogenetics was associated with significantly longer OS (P=0.03) and EFS (P=0.04) when all patients were included (Fig. 1). A similar trend was obtained when only CR1 AML patients were considered (P=0.03 for both OS and EFS).

Conclusions:
This study suggests that stratification of AML and ALL in pediatric patients according to their cytogenetic risk remains relevant even when treated with HSCT and irrespective if patients were treated in CR1 or CR2 after relapse. In particular, MLL gene rearrangements and the Philadelphia chromosome remain poor prognostic factors in pediatric ALL despite HSCT treatment.

Disclosures:
No relevant conflicts of interest to declare.