Professor Alina Daniela Tanase* comments on the publication titled "Thiotepa-based regimens are a valid alternative to total body irradiation-based reduced-intensity conditioning regimens in patients with acute lymphoblastic leukemia: a retrospective study on behalf of the Acute Leukemia Working Party of the EBMT" published in Transplantation and Cellular Therapy.
* Alina Daniela Tanase*, MD, PhD, Professor of Medicine, Immunology of Transplant, Fundeni Clinical Institute - Bone Marrow Transplantation Program, University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania
Thiotepa-based regimens are a valid alternative to total body irradiation-based reduced-intensity conditioning regimens in patients with acute lymphoblastic leukemia: a retrospective study on behalf of the Acute Leukemia Working Party of the EBMT
Giorgia Battipaglia et al.
Published in Transplantation and Cellular Therapy October 08, 2023 DOI: https://doi.org/10.1016/j.jtct.2023.09.028
Total Body Irradiation (TBI) is described as an essential component of conditioning regimens in adult patients undergoing allo-HSCT for ALL, but TBI is also associated with short- and long-term adverse effects that can negatively impact long-term survival. There are comparative studies, in myeloablative conditioning setting, between TBI and thiotepa-containing regiments, but studies comparing transplant outcomes with either TBI or thiotepa based RIC regimens in adults undergoing allo-HSCT are lacking.
This article presents a retrospective study comparing transplant outcomes in adult patients with acute lymphoblastic leukemia (ALL) who underwent reduced-intensity conditioning (RIC) regimens containing either total body irradiation (TBI) or thiotepa. The study aimed to determine whether there were any differences in transplant outcomes between the two conditioning regimens.
The study included 265 patients aged 40 years or older who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) for ALL in first complete remission between 2000 and 2020. Of these patients, 117 received a TBI-based RIC regimen and 148 received a thiotepa-based RIC regimen.
The results of the study showed that there were no significant differences in transplant outcomes between the TBI and thiotepa groups. Specifically, there were no differences in relapse rates, non-relapse mortality, leukemia-free survival, overall survival, graft-versus-host disease (GVHD)/relapse-free survival, or grade II-IV acute GVHD. The only difference observed was a higher incidence of chronic GVHD in the TBI group (43% vs 29%, p=0.03). However, this difference was not significant in the multivariate analysis. The cumulative incidence of day 60 neutrophil engraftment (99.1% [95% CI 89.5-99.9] for TBI vs 96.4% [95% CI 91.2-98.6], p=0.30), grade II-IV acute GVHD (30% for both groups, p=0.84), and grade III-IV acute GVHD (9% [95% CI 5-16] for TBI vs 10% [95% CI 6-16], p=0.89) were similar between the two groups. However, the TBI group had a higher cumulative incidence of chronic GVHD of all grades at 2 years (43% [95%CI 32-53] vs 29% [95% CI 21-37], p<0.04). In terms of relapse and non-relapse mortality, there were no significant differences between the TBI and thiotepa groups. The cumulative incidence of relapse and non-relapse mortality were similar between the two groups (23% [95% CI 15-33] in TBI group vs 28% [95% CI 20-36], p=0.24). The main causes of death in both groups were recurrence of ALL, infections, and GVHD. Overall survival and leukemia-free survival rates were also similar between the TBI and thiotepa groups (for TBI vs THIO: overall survival, 67% vs 56%, p=0.18; leukemia-free survival, 57% vs 46%, p=0.12). Although there were slightly higher probabilities of survival in the TBI group, these differences did not reach statistical significance.
The limitations of this study result from the fact that it is retrospective, the heterogeneity of patient population (may have introduced variability in patient characteristics, comorbidities, and treatment responses), the variability in treatments protocols and lack of randomization.
This study suggests that in elderly patients undergoing RIC regimens for ALL, the use of a thiotepa-based regimen may be a valid alternative to a TBI-based regimen. The study found no significant differences in transplant outcomes between the two conditioning regimens.
References:
1. Giebel S, Marks DI, Boissel N, et al. Hematopoietic stem cell transplantation for adults with Philadelphia chromosome-negative acute lymphoblastic leukemia in first remission: a position statement of the European Working Group for Adult Acute Lymphoblastic Leukemia (EWALL) and the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant 2019; 54(6):798-809.
2. Cahu X, Labopin M, Giebel S, et al. 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. Bone Marrow Transplant 2016; 51(3):351-7.
3. Thomas O, Mahé M, Campion L, et al. Long-term complications of total body irradiation in adults. Int J Radiat Oncol Biol Phys 2001; 49(1):125-31
4. Eder S, Canaani J, Beohou E, et al. Thiotepa-based conditioning versus total body irradiation as myeloablative conditioning prior to allogeneic stem cell transplantation for acute lymphoblastic 14 leukemia: A matched-pair analysis from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Am J Hematol 2017; 92(10):997-1003.