Transplantation Conditioning Regimens and Outcomes after Allogeneic Hematopoietic Cell Transplantation in Children and Adolescents with Acute Lymphoblastic Leukemia

Abstract

Relapse is common after hematopoietic cell transplantation for acute lymphoblastic leukemia (ALL). While 1200 cGy total body irradiation (TBI) and cyclophosphamide (Cy) is standard, attempts to lower relapse have led to the addition of a second chemotherapeutic agent and/or higher dose TBI. We examined transplantation outcomes in patients aged <18 years with ALL, in second or subsequent remission or in relapse at transplantation. Most transplants occurred in remission. Patients received grafts from an HLA-matched sibling or unrelated donor. Four treatment groups were created: 1) Cy + TBI≤1200 cGy (n=304), 2) Cy + etoposide + TBI≤1200 cGy (n=108), 3) Cy + TBI≥1300 cGy (n=327), and 4) Cy + etoposide + TBI≥1300 cGy (n=26). Neither TBI in excess of 1200 cGy nor the addition of etoposide resulted in fewer relapses. The 5-year probabilities of relapse were 30%, 28%, 35% and 31% for groups 1, 2, 3 and 4, respectively. However, transplant-related mortality was higher (35% vs. 25%, p=0.02) and overall survival lower (36% vs. 48%, p=0.03) after Cy + etoposide + TBI ≥1300 cGy compared to Cy + TBI ≥1300 cGy. Compared to the standard regimen neither TBI in excess of 1200cGy nor the addition of etoposide improves survival after HCT for ALL.

Comparison of chemotherapeutic agents as a myeloablative conditioning with total body irradiation for pediatric acute lymphoblastic leukemia: A study from the pediatric ALL working group of the Japan Society for Hematopoietic Cell Transplantation

“…Previous studies regarding HSCT for pediatric ALL suggested that intensification of the most traditional regimen, TBI‐CY, by adopting other cytotoxic agents, such as VP16, L‐PAM, or AraC, could improve the outcome . However, the results were not always consistent, and evidence of successfully improving outcome is limited . Our study, using nationwide registry data, confirmed that L‐PAM and CY + VP16 could provide better EFS, and clearly demonstrated that the advantage of L‐PAM was maximized when the HSCT was performed from a matched related donor, regardless of disease status (CR1 or CR2).…”

Umbilical Cord Blood Transplantation in Children with Acute Leukemia: Impact of Conditioning on Transplantation Outcomes

“…The inclusion of another agent in addition to cyclophosphamide may explain the observed higher non-relapse mortality risk. 23 The role of TBI-containing versus non-TBI regimens offer mixed results, with one recent report that showed no significant differences in outcome for children with AML receiving TBI with cyclophosphamide or busulfan and cyclophosphamide 24 and the other, fewer relapse with busulfan, cyclophosphamide and melphalan. 25 None of these reports included recipients of UCB transplants.…”

Single-centre experience of allogeneic haemopoietic stem cell transplant in paediatric patients in Cape Town, South Africa

“…The results for patients with RESEARCH AML (OS 44.4%) are also comparable to those from units in highincome settings. [22] Only three of the 36 surviving patients (8.3%) have experienced chronic GvHD requiring ongoing immunosuppression, suggesting that ex vivo T-cell depletion of the PBSC grafts has been effective in reducing the incidence of GvHD. Some of the literature on paediatric Allo-HSCT favours the use of bone marrow as a source of graft over PBSCs owing to the increased risk of chronic GvHD with PBSCs.…”