Acute Megakaryoblastic Leukemia (AMKL) in Children without Down Syndrome.
Authors: O'Brien Maureen , Dahl Gary , Pounds Stanley , Lacayo Norman J. , Taub Jeffrey , Chang Myron , Weinstein Howard J. , Ravindranath Yaddanapudi , Campana Dario , Pui Ching-Hon , Rubnitz Jeffrey 
Published: October 2019

Abstract
Abstract 482

Background:
Acute megakaryoblastic leukemia (AMKL) in children without Down syndrome represents approximately 10% of pediatric acute myeloid leukemia (AML). Published reports regarding prognosis of non-Down syndrome children with AMKL vary; hence, some groups treat these patients as high-risk while others as standard-risk. As a result, the optimal treatment strategy, including the role of hematopoeitic stem cell transplant (HSCT), remains unclear.

Methods:
We reviewed the treatment and outcomes of patients with AMKL treated on two pediatric AML protocols. Pediatric Oncology Group (POG) 9421 (1995-99) included two cycles of induction chemotherapy with randomization to standard or high-dose DAT (daunorubicin, cytarabine, 6-thioguanine) followed by HSCT for children in remission with matched sibling donors or three cycles of consolidation chemotherapy with or without cyclosporine for those without suitable donors. St. Jude protocol AML02 (2002-2008) randomized patients during induction to receive high- or low-dose cytarabine with daunorubicin and etoposide (ADE). Patients without complete remission (CR) received gemtuzumab ozogamicin (GO) with induction 2 chemotherapy (ADE). After induction, AMKL patients with availabel donor proceeded to HSCT while those without donors received three cycles of consolidation chemotherapy including mitoxantrone and cytarabine. Comparisons of event-free survival (EFS) and overall survival (OS) were performed by Mantel-Haenszel log-rank test. Independent effect of HSCT on EFS or OS were analyzed by Cox proportional hazard model, with HSCT as time-dependent variable.

Results:
The 49 patients with AMKL treated on POG 9421 had a median age at diagnosis of 1.8 years (range 0.13-16.2 years), and a median leukocyte count of 13.5 × 109/L (range 0.3-98.4). The patient with the t(1;22) translocation remains in CR. 39 patients had CR after induction, 5 partial response and 4 no response with no difference between standard- and high-dose DAT. The 5-year EFS for all AMKL patients was 34.7% ± 7.5%. Of the 39 patients in CR, 6 underwent matched sibling HSCT, of whom 4 remain in CR, and the other 33 patients received consolidation chemotherapy, of whom 15 remain in continuous remission. The 5-year OS for patients undergoing HSCT was 66.7% ± 19.3% compared to 36.1% ± 8.4% for those receiving consolidation chemotherapy (p = 0.2). The 26 patients with AMKL treated on SJCRH AML02 had a median age at diagnosis of 1.2 years (range 0.21-11.2 years), and a median leukocyte count of 11.8 × 109/L (range 2.3-72.9). All 5 patients with the t(1;22) translocation achieved CR after one induction cycle, with negative minimal residual disease, and remain in CR after treatment with chemotherapy only. The 3-year EFS was 35.9% ± 12.9% for the other AMKL patients, significantly lower than the 61.5% ± 4.8% for non-AMKL patients (p = 0.026). The 3-years OS estimates are 100% for patients with t(1;22), 48% ± 14.1% for other AMKL patients, and 71.8% ± 4.4% for non-AMKL patients (p = 0.03). Of the 21 patients without t(1;22), 14 received HSCT with 7 survivors (3-year EFS 46.3 ± 17%) while 7 received chemotherapy with only one long-term survivor (3-year EFS 14.3 ± 9.4%) (p=0.55).

Conclusions:
AMKL patients with the t(1;22) translocation have excellent treatment outcome with chemotherapy alone. In contrast, AMKL patients without t(1;22) fared poorly, especially when they were treated with only chemotherapy. Additional studies of larger number of patients are needed to determine if they would benefit from HSCT.

Disclosures:
No relevant conflicts of interest to declare.