Reduced-intensity conditioning followed by allogeneic transplantation in pediatric malignancies: a report from the Société Française des Cancers de l’Enfant and the Société Française de Greffe de Moelle et de Thérapie Cellulaire

Abstract

We report French prospective experience with reduced-intensity conditioning-allo-SCT in 46 patients (median age: 15.5 years, 4.8-20.2) presenting high-risk AL (n ¼ 11), Hodgkin's lymphoma (n ¼ 15) or solid tumors (n ¼ 20). Graft sources were BM (n ¼ 21), PBSC (n ¼ 20) and cord blood (CB; n ¼ 5) from related (n ¼ 20) or unrelated (n ¼ 26) donors. For CB grafts, only one patient out of five achieved sustained engraftment. For PBSC/BM grafts, engraftment rate was 95%, hematopoietic recovery times were not significantly different between BM, PBSC, sibling or unrelated grafts, day þ 100. Full donor chimerism was achieved in 94% of patients, and incidences of primary acute GVHD and chronic GVHD were 49% and 14%, respectively. Underlying disease was fatal in 39% of patients. TRM was 6.9%. Three-year OS was 49.15%. OS and EFS were not significantly different between patients transplanted with different grafts and with or without primary GVHD. Patients with solid tumor or measurable disease at transplant had poorer outcomes. Three-year EFS: 33.3% for ALL, 75.0% for AML, 51.8% for Hodgkin's lymphoma, 28.6% for neuroblastoma and 22.2% for sarcoma patients. This multicentre study concluded that Bu/fludarabine/anti-thymocyte globulin conditioning with PB or BM, related or unrelated grafts in patients with various malignancies at high-risk for transplantation toxicity results in high engraftment rates, low TRM and acceptable survival.

Improvement of overall survival after allogeneic hematopoietic stem cell transplantation for children and adolescents: a three-decade experience of a single institution

“…38 The median age of recipients was lower in the 2000-2010 period (8.2 years old) compared with the 1983-2009 period (11.4 years old), corresponding to broadened selection criteria related to a better understanding of the role of transplants in younger children and infants. Moreover, new conditioning regimens, such as RIC, have been recently developed for pediatric patients [39][40][41] and have enabled proposal of allo-SCT to patients with comorbidities, and also second allo-SCT.…”

A critical review of which children with acute myeloid leukaemia need stem cell procedures

“…Reduced‐intensity conditioning (RIC) regimens have shown favourable outcome in adults with AML but there have been very limited experiences in children. A French series included eight AML children considered ineligible for myeloablative transplantation due to severe infection or previous myeloablative therapy and found a 3‐year event‐free‐survival of 75% (Paillard et al , ). A recent international study comparing RIC ( n = 39) with matched cases receiving myeloablative regiments ( n = 141) found similar rates of toxicity, relapse and survival (5‐year OS 45% vs. 48%) (Bitan et al , ).…”

Reduced-toxicity myeloablative conditioning consisting of 8-Gy total body irradiation, cyclophosphamide and fludarabine for pediatric hematological malignancies

“…NMAC/RIC have been reported as the preparative regimen for allo-HSCT of pediatric patients with hematological malignancy in poor PS and for second allo-HSCT192021222324. In these days, non TBI-based RTMAC regimens have been used for first allo-HSCT of pediatric patients with hematological malignancy252627.…”

“…Graft failure is one of the major problems for CBT after an NMAC/RIC/RTMAC regimen202126. Paillard et al 20 and Bradley et al 21 reported that 4 of 5 CB and 6 of 21 CB, respectively, failed to engraft into pediatric patients, when RIC was used as the preparative conditioning.…”

“…Paillard et al 20 and Bradley et al 21 reported that 4 of 5 CB and 6 of 21 CB, respectively, failed to engraft into pediatric patients, when RIC was used as the preparative conditioning. Satwani et al 26 reported that graft failure occurred in 16 of 51 patients who received CBT after non TBI-based RTMAC regimen.…”