Early Hematopoietic Stem Cell Transplantation in the Treatment of High-Risk Infant Leukemia
Authors: Paina Olesia V , Rakhmanova Zhemal Zarifovna , Kozhokar Polina Valerievna , Frolova Anastasia Sergeevna , Tsvetkova Luibov Alexandrovna , Borovkova Anastasia Svyatoslavovna , Ekushov Kirill Alexandrovich , Markova Inna Viktorovna , Bondarenko Sergey N. , Babenko Elena V , Alyanski Aleksandr L. , Barkhatov Ildar M. , Semenova Elena Vladimirovna , Bakin Eugene A. , Kulagin Aleksandr D. , Moiseev Ivan S. , Zubarovskaya Ludmila S 
Published: November 2021

Abstract
INTRODUCTION:
Acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are rare diseases in children less than one and two years old respectively. Infant ALL and AML demonstrates unique biological characteristics associated with aggressive clinical features, i.e. high frequency of KMT2A gene rearrangements, poor response to standard chemotherapy, and thus worse prognosis compared to older children. These patients (pts) are at high risk (HR). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative therapy for HR infant leukemia especially in 1 st CR, but proportion of these patients unable to undergo allo-HSCT due to early events, mainly relapse or treatment-related toxicity during initial therapy. We investigated the role of early allo-HSCT from different types of donors. The primary end points were overall survival (OS), transplant-relate mortality (TRM), graft-versus-host disease (GVHD) free, relapse-free survival (GRFS). Secondary end points included neutrophil engraftment and acute and chronic GVHD.
Methods:
We included 50 infants with HR ALL (n=10, of with MLLr+ n=6) and AML (n=40, of with MLLr+ n=14) in CR 1. Median age at allo-HSCT 12,5 months old (range from 4 m.o. till 35 m.o.). Median time from diagnosis to allo-HSCT was 9 months (range from 3 till 21). Donor of SCT was: MSD-10% (n=5), MUD-46% (n=23), Haplo-44% (n=22). Majority of patients, 86% received MAC based on busulfan 12-16mg/kg (n=43, including IV busulfan-20pts), 14% (n=7) received RIC based on melphalan 140 mg/m 2. GVHD prophylaxis consisted of PTCy±CNI and m-TOR inhibitor in 62% (n=31), seroprophylaxis±CNI in 38% (n=19). Median follow-up was 64,3 months (range 1-220). Patient data were censored at the time of death or last follow-up. Probabilities of OS and GRFS were estimated using Kaplan-Meier curves. TRM was defined as any death that occurred in the absence of disease relapse; relapse was a competing risk for this event.
Results:
Engraftment rate was 82%. Cumulative incidences by day 100 of TRM in Haplo were 2% vs 4% in MSD+MUD (р=0,9). Ten-year rates OS in Haplo and MSD+MUD were 77,3% (±4,7%) vs 78,6% (±9%) respectively (p=0,73). Ten-year GRFS did not differ between two study cohorts being 50% vs 57% for Haplo and MSD+MUD (p=0,76). Clinically significant aGVHD (grades 2-4) after allo-HSCT was observed in 27% (n=6) Haplo and 32% (n=9) MSD+MUD (p=0,77). A total of 12% (n = 6) patients developed severe cGVHD.
Conclusions:
Early allogeneic HSCT in 1 st CR from different types of donors, including haploidentical is associated with favorable outcomes in infant acute leukemias. This approach should be evaluated in further controlled clinical studies.

Disclosures
Kulagin: X4 Pharmaceuticals, Alexion, Apellis, Biocad: Research Funding; Novartis, Generium, Sanofi, Roche, Johnson & Johnson, Pfizer: Speakers Bureau.