Acute Lymphoblastic Leukaemia in the Youngest: Haematopoietic Stem Cell Transplantation and Beyond.

Adriana Balduzzi,Anca M Colita,Marc Bierings,Marianne Ifversen,Jochen Buechner,Jean-Hugues Dalle

doi:10.3389/fped.2022.807992

Abstract

The ALL SCTped 2012 FORUM (For Omitting Radiation Under Majority age) trial compared outcomes for children ≥4 years of age transplanted for acute lymphoblastic leukaemia (ALL) who were randomised to myeloablation with a total body irradiation (TBI)-based or chemotherapy-based conditioning regimen. The TBI-based preparation was associated with a lower rate of relapse compared with chemoconditioning. Nevertheless, the age considered suitable for TBI was progressively raised over time to spare the most fragile youngest patients from irradiation-related complications. The best approach to use for children <4 years of age remains unclear. Children diagnosed with ALL in their first year of life, defined as infants, have a remarkably poorer prognosis compared with older children. This is largely explained by the biology of their ALL, with infants often carrying a KMT2A gene rearrangement, as well as by their fragility. In contrast, the clinical presentations and biological features of ALL in children >1 year but <4 years often resemble those presented by older children. In this review, we explore the state of the art regarding haematopoietic stem cell transplantation (HSCT) in children <4 years, the preparative regimens available, and new developments in the field that may influence treatment decisions.

Highlights

Risk-adapted treatment stratification is the basis for modern paediatric acute lymphoblastic leukaemia (ALL) treatment
Results of Frontline Trials Children diagnosed with ALL in their first year of life have a remarkably poorer prognosis compared with older children; this is largely explained by the biology of their ALL, as ∼75–80% of them carry a KMT2A gene rearrangement
For 40 years, the combination of total body irradiation (TBI), usually consisting of 12 Gy divided into 6 fractions, has been considered as the standard myeloablative conditioning regimen for children with ALL, most often in combination with cyclophosphamide (120 mg/kg divided over 2 days)

Summary

Introduction

Risk-adapted treatment stratification is the basis for modern paediatric acute lymphoblastic leukaemia (ALL) treatment. AIEOP, Associazione Italiana di Ematologia e Oncologia Pediatrica; ALL, acute lymphoblastic leukaemia; AraC, cytarabine; BFM, Berlin-Frankfurt-Münster; Bu, busulfan; CIBMTR, Center for International Blood and Marrow Transplant Research; Cy, cyclophosphamide; CR1, first complete remission; CR2, second complete remission; EFS, event-free survival; Flu, fludarabine; Haplo, haploidentical donor; HSCT, haematopoietic stem cell transplantation; JPLSG, Japanese Pediatric Leukemia/Lymphoma Study Group; JSHCT, Japan Society for Hematopoietic Cell Transplantation; MD, matched donor; MEL, melphalan; MMD, mismatched donor; MSD, matched sibling donor; MUD, matched unrelated donor; MRD, minimal residual disease; NA, not applicable; TBI, total body irradiation; TRM, transplant-related mortality; TT, thiotepa; VP16, etoposide.

Results

Conclusion