Outcome of relapse after allogeneic HSCT in children with ALL enrolled in the ALL‐SCT 2003/2007 trial

Abstract

SummaryRelapse remains the major cause of treatment failure in children with highrisk acute lymphoblastic leukaemia (ALL) undergoing allogeneic haematopoietic stem-cell transplantation (allo-SCT). Prognosis is considered dismal but data on risk factors and outcome are lacking from prospective studies. We analysed 242 children with recurrence of ALL after first allo-SCT enrolled in the Berlin-Frankfurt-Munster (BFM) ALL-SCT-BFM 2003 and ALL-SCT-BFM international 2007 studies. Median time from allo-SCT to relapse was 7Á7 months; median follow-up from relapse after allo-SCT until last follow-up was 3Á4 years. The 3-year event-free survival (EFS) was 15% and overall survival (OS) was 20%. The main cause of death was disease progression or relapse (86Á5%). The majority of children (48%) received salvage therapy without second allo-SCT, 26% of the children underwent a second allo-SCT and 25% received palliative treatment only. In multivariate analyses, age, site of relapse, time to relapse and type of salvage therapy were identified as significant prognostic factors for OS and EFS, whereas factors associated with first SCT were not statistically significant. Combined approaches incorporating novel immunotherapeutic treatment options and second allo-SCT hold promise to improve outcome in children with post allo-SCT relapse.

Second Hematopoietic Stem Cell Transplantation for Post-Transplantation Relapsed Acute Leukemia in Children: A Retrospective EBMT-PDWP Study

“…It also confirms the favorable prognostic value of remission status at the second HSCT for patients with ALL and identifies novel favorable factors, especially the presence of cGVHD before the second HSCT, which requires further investigation. These findings complement data on pediatric patients with relapsed B-precursor ALL after first HSCT, in whom factors related to the first HSCT did not impact outcomes after the second HSCT [35]. Our results are particularly relevant in the current era, which has seen an explosion of new therapies, specifically targeted therapies and immune modulators that may ultimately serve as a bridge to transplantation or an alternative to it.…”

Molecular Approaches to Treating Pediatric Leukemias

“…Yet, even nowadays, leukemia remains the leading cause of death from cancer in children and adolescents in many developed countries. Especially, outcome of refractory/relapsed (r/r) leukemia remains poor (5, 7, 8). Indeed, it becomes more and more difficult to achieve further improvement of survival.…”

Improved survival rate in T-cell depleted haploidentical hematopoietic cell transplantation over the last 15 years at a single institution

“…3 Although increased efforts in detecting and treating infections and graft-vs.-host disease (GVHD) have been made, these complications along with disease recurrence remain the primary causes of death. [4][5][6][7][8] Matched related and matched unrelated donors continue to be the standard for transplantation in patients with hematologic malignancies, however 25-60% of eligible pediatric recipients lack such donors. 9 Ex vivo T-cell depleted haploidentical donor (haplo) grafts can reliably achieve donor engraftment with manageable side effects.…”