Use of thiotepa in haematopoietic stem cell transplantation for paediatric acute lymphoblastic leukaemia: An australian and New Zealand children's haematology/oncology group study

Abstract

Objective: Total body irradiation (TBI)/Cyclophosphamide (CY) is a standard of care conditioning regimen in allogeneic haematopoietic stem cell transplant (HSCT) for paediatric acute lymphoblastic leukaemia (ALL). This study sought to identify whether the common addition of Thiotepa (TT) to TBI/CY improves HSCT outcomes for paediatric patients with ALL. Methods: A retrospective analysis was performed on 347 paediatric ALL patients who underwent HSCT at Australian and New Zealand Children's Haematology/Oncology Group centres between 1995 and 2015, with 105 patients receiving TBI/CY and 242 receiving TBI/CY/TT. Mean age at HSCT was 9 years, and donor source was bone marrow in 62.5%, umbilical cord blood in 29% and peripheral blood stem cells in 7.8%. Complete remission (CR) status was as follows: CR1 27%, CR2 58%, CR = 3 10% and active disease 5%. Pre-HSCT minimal residual disease (MRD) was available for 128 patients (92% DNA PCR, 8% flow). There were no statistical differences in age, donor source, CR status or MRD status between the two groups. Average follow up for the cohort was years. Results: Comparison of patients who received TBI/CY versus those that received TBI/CY/TT demonstrated no difference in neutrophil (92% versus 88%, P =.28) or platelet engraftment (86% versus 88%, P =.9). There were no differences in acute Graft-Versus-Host Disease (GVHD) (51% versus 52%); chronic GVHD (31% versus 28%); or transplant related mortality at 1 year (both 11%). Relapse rate was 26% for TBI/CY versus 14% for TBI/CY/TT at 1 year, 36% versus 24% at 3 years, and 36% versus 26% at 5 years (P =.02). There was a trend for improved 5-year disease free survival (DFS) between the two groups (47% versus 59%, P =.05) but no significant effect on 5-year overall survival (53% versus 62%, P =.12). Multivariate analysis demonstrated only MRD status and year of transplant had significant independent impact on relapse risk. Discussion: This retrospective study showed a lower relapse rate and a trend towards improved DFS in ALL HSCT patients conditioned with TBI/CY/TT versus TBI/CY, although this effect may be due to other changes improving pre-HSCT MRD over time.L6218999152018-05-02 <br />