Allogeneic Hematopoietic Cell Transplantation in First Remission Abrogates Poor Outcomes Associated with High-Risk Pediatric Acute Myeloid Leukemia

Abstract

Despite remission rates of approximately 85% for children diagnosed with acute myeloid leukemia (AML), greater than 40% will die from relapsed disease. Patients with poor-risk molecular/cytogenetics and/or inadequate response to upfront therapy are typically considered high-risk (HR) and historically have poor outcomes with chemotherapy alone. We investigated whether allogeneic hematopoietic cell transplantation (allo-HCT) with best available donor in first remission (CR1) would abrogate the poor outcomes associated with HR AML in chemotherapy treated children and young adults. We reviewed the outcomes of 50 consecutive children and young adults (ages 0–30 years) with AML who received a myeloablative allo-HCT between 2001 and 2010. Thirty-six patients (72%) were HR, defined as having FLT3-ITD mutations, 11q23 MLL rearrangements, chromosome 5 or 7 abnormalities, induction failure and/or having persistent disease. The majority of patients received cyclophosphamide and total body irradiation conditioning and graft-versus-host-disease (GVHD) prophylaxis was cyclosporine based. Transplant outcomes for HR patients were compared to standard-risk patients with no significant differences observed in overall survival (72% vs. 78%, p=0.72), leukemia-free survival (69% vs. 79%, p=0.62), relapse (11% vs. 7%, p=0.71) or TRM (17% vs. 14%, p=0.89). Children and young adults with HR-AML have comparable outcomes to standard-risk patients following allo-HCT in CR1.

Impact on long-term OS of conditioning regimen in allogeneic BMT for children with AML in first CR: TBI+CY versus BU+CY: a report from the Société Française de Greffe de Moelle et de Thérapie Cellulaire

“…Both chemobased and TBI-based conditioning regimens still remain administered. 12,21 In 1994, Michel et al, published a previous French study comparing two different Bu-based conditioning regimen. 5 In this study, the authors reported better results for patients who received 200 mg/kg as total dose of CY rather than those who received 120 mg/kg.…”

“…However, including those in North America, some groups still continue using TBI-based conditioning regimen. 12,13 Then, we conducted a retrospective study to analyze the impact of conditioning regimen on the longterm OS of children who underwent HSCT for AML in CR1. We report the results regarding patients o18 years who received allogeneic HSCT from either sibling or alternative donor in France from 1980 to 2004 after myeloablative TBI-based conditioning regimen or Bu-based conditioning regimen for AML in CR1.…”

Effects of Priming with Recombinant Human Granulocyte Colony–Stimulating Factor on Conditioning Regimen for High-Risk Acute Myeloid Leukemia Patients Undergoing Human Leukocyte Antigen–Haploidentical Hematopoietic Stem Cell Transplantation: A Multicenter Randomized Controlled Study in Southwest China

“…High-risk acute myeloid leukemia (HR-AML) has not been treated with the same success for favorable or intermediate acute myeloid leukemia [1]. Although the majority of patients with HR-AML achieve complete remission (CR) after intensive induction therapy, most of them will die from Biology of Blood and Marrow Transplantation j o u r n a l h o m e p a g e : w w w .…”

TCR-alpha/beta and CD19 depletion and treosulfan-based conditioning regimen in unrelated and haploidentical transplantation in children with acute myeloid leukemia

“…1,2 A 2-year overall survival (OS) of 50-70% is expected with the standard approach to GvHD prevention in recipients of allogeneic grafts if transplanted in CR. [3][4][5] The increased use of unrelated and mismatched family (haploidentical) donors became possible due to improvements in unrelated donor registries, high-resolution HLA-typing and new methods of in vivo and ex vivo graft manipulation. 6,7 The major obstacle to the success of both unrelated and haploidentical transplantation is leukemia relapse.…”