Comparison of total body irradiation plus cyclophosphamide with busulfan plus cyclophosphamide as conditioning regimens in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplant

Abstract

Conditioning regimens used during stem cell transplant provide prolonged control or cure of the disease in patients with acute lymphoblastic leukemia (ALL). In this study, we present a comparison of treatment results for 95 patients with ALL who underwent allogeneic hematopoietic stem cell transplant (AHSCT) with total body irradiation plus cyclophosphamide (TBI + Cy) or busulfan plus cyclophosphamide (Bu + Cy) as conditioning regimen. Median age was 25 (range: 9-54) years. Median follow-up was 24 (range: 3-107) months. Median overall survival (OS) was found to be 29 months. Median event-free survival (EFS) was 9 months. Median OS was 37 months in the TBI + Cy arm, while it was 12 months in the Bu + Cy arm, suggesting a significant advantage favoring the TBI + Cy arm (p = 0.003). Median EFS was 13 months in the TBI + Cy arm, while it was 4 months in the Bu + Cy arm, indicating a significant difference (p = 0.006). In univariate and multivariate analysis, it was found that high OS and EFS were significantly correlated with TBI + Cy conditioning regimen and lack of transplant-related mortality (p < 0.05). The TBI + Cy conditioning regimen was found to be superior to the Bu + Cy regimen in patients with ALL undergoing AHSCT regarding both OS and EFS.

Improving results of allogeneic hematopoietic cell transplantation for adults with acute lymphoblastic leukemia in first complete remission: an analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

“…Although comparison of TBI with myeloblative chemotherapy in a setting of ALL has never been a subject of a prospective trial, some retrospective analyses confirmed the advantage of TBI. 17,18 Results of the current study strongly support this statement. New, irradiationfree regimens based on the use of thiotepa are under development; however, their utility requires further evaluation.…”

Impact of conditioning with TBI in adult patients with T-cell ALL who receive a myeloablative allogeneic stem cell transplantation: a report from the acute leukemia working party of EBMT

“…24,25 In pediatric or adult ALL, a better outcome has been described for TBI-based regimens compared with chemotherapy-based regimen such as oral Bu-Cy. 23,[26][27][28] Meanwhile, the improved results with TBI may result from the variable pharmacokinetics reported for oral Bu and/or the increased NRM reported for oral Bu-Cy. 23,27 As IV Bu has progressively replaced oral Bu in the past decade, these unspecific ALL data may not apply in the IV Bu era or in the specific T-ALL disease.…”

The role of total body irradiation (TBI) as a conditioning regime for paediatric acute lymphoblastic leukaemia: A discussion of the evidence

“…Median EFS was 4 months in the Bu and Cy arm, while it was 13 months in the TBI and Cy arm indicating that TBI and Cy conditioning regimes to be superior to the Bu and Cy regime. 12 The larger cohort of patients within this study indicates a higher degree of certainty, but there were some flaws within the methodology such as a lack of randomisation and omission in the data of the patients' remission statuses. The median age of participants was 25 years making it hard to draw direct comparison with other studies, but was deemed worthy of inclusion within this discussion as the ages ranged from 9 years old.…”

“…A larger trial with 95 participants conducted by Eroglu et al (2013) carried out a direct comparison of Bu and Cy versus TBI and Cy as a conditioning regime for ALL. Median EFS was 4 months in the Bu and Cy arm, while it was 13 months in the TBI and Cy arm indicating that TBI and Cy conditioning regimes to be superior to the Bu and Cy regime.…”

“…4 The most common cause of treatment failure in paediatric ALL is relapse, occurring in approximately 15e20% of patients, and a combination of myeloablative Cyclophosphamide (Cy) and Total Body Irradiation (TBI) is part of the standard of conditioning regime treatment in all stages of relapse, but chemotherapy only regimes are currently being reviewed in trials. 5,11,12 TBI is defined as a specialist radiotherapy technique that is designed to deliver a uniform dose to the whole of a patient's body, and the purpose of the technique is to induce myelosupression suitable for SCT. 6 The National Cancer Survivorship Initiative, Living with and beyond cancer: Taking Action to Improve Outcomes document states that by 2021, there will be nearly 11,000 more adult survivors of childhood cancer.…”