Comparison of Two Myeloablative Total-Body Irradiation (MAC-TBI) Regimens: 1200 Cgy Vs 800 Cgy of TBI for Allogeneic Stem Cell Transplantation in Adults with Hematological Malignancies
Authors: Sanchez-Petitto Gabriela , Huang Ying , Bezerra Evandro , Brammer Jonathan E. , Choe Hannah , Denlinger Nathan , Shindiapina Polina , Penza Sam , Wall Sarah A , Behbehani Gregory K , Blachly James S. , Blaser Bradley Wayne , Borate Uma , Eisfeld Ann-Kathrin , Grieselhuber Nicole R. , Koenig Kristin L , Larkin Karilyn T. , Long Meixiao , Mims Alice , Srisuwananukorn Andrew , Saad Ayman , Vasu Sumithira , de Lima Marcos 
Published: December 2024

Introduction: Total body irradiation (TBI) is a commonly used conditioning regimen for allogeneic hematopoietic cell transplantation (alloHSCT). TBI 1200 cGy (TBI1200) has been associated with short- and long-term toxicities, while TBI 800 cGy (TBI800) regimens have been primarily used for benign hematologic disorders. Comparisons of these approaches are lacking.

Methods: We retrospectively reviewed 23 consecutive patients with hematologic malignancies undergoing their first allogeneic transplant receiving TBI-MAC between June 2016 and January 2024, of whom 12 (52%) received 800 cGy and 11 (48%) received 1200 cGy. We evaluated immediate (≤90 days post-transplant) and late (&gt;90 days) complications as well as survival data. Post-transplant complications between TBI800 vs TBI1200 groups were compared using Fisher's exact test. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). The Fine-Gray model was used to correlate acute graft-versus-host disease (aGVHD) with clinical factors.

Results: Twelve patients (52.2%) received fludarabine and TBI800, 9 patients (39.1%) received cyclophosphamide (Cy) and TBI1200, and 2 patients (8.7%) received fludarabine and TBI 1200 cGy. GVHD prophylaxis included: post-transplant Cy, mycophenolate mofetil, and tacrolimus in 5 patients (21.7%) and methotrexate and tacrolimus in 18 patients (78.3%). Palifermin was administered to 43.5% patients (25% in the TBI800 group vs 63.6% in the TBI1200 group, p=0.1). Donor sources included: matched-related donors (9, 39.1%), matched-unrelated donors (11, 47.8%), and haploidentical or mismatched-related donors (3, 13%). PBSC were used in 19 patients (82.6%) and bone marrow in 4 (17.4%). Diagnoses were AML (3, 13%), B-cell ALL (13, 56.5%), T-cell ALL (3, 13%), mixed phenotype leukemia (2, 8.7%), MPN (1, 4.4%), and NHL (1, 4.4%), p=0.51. There were similar baseline demographics between the two groups, except for remission status (TBI800 vs TBI1200 groups: CR1 41.7% vs 72.7%, CR2 and beyond 58.3% vs 9.1%, active disease 0 vs 18.2%, p=0.02, respectively).

Among the patients in the TBI800 and TBI1200 groups, time to neutrophil and platelet engraftment (16 vs 14 days, p=0.38; and 20 vs 17 days, p=0.07), incidence of engraftment syndrome (8.3% vs 9.1%, p=1.0), use of total parenteral nutrition (0 vs 9.1%, p=0.48) and patient-controlled analgesia (16.7% vs 18.2%, p=1.0), and presence of full chimerism at D+30 (77.8% vs 70%, p=1.0) were similar. The need for intensive care unit admission (≤90 days) was also comparable (8.3% vs 9.1%, p=1.0). Except for grade 2 diarrhea (66.7% vs 18.2%, p=0.05), there was a similar incidence of immediate adverse events among the patients who received TBI800 vs TBI1200: grade 1 radiation dermatitis (0 vs 9.1%, p=0.48), grade 3 febrile neutropenia (66.7% vs 54.6%, p=0.68), grade 2 lung infection (8.3% vs 0, p=1.0), ≥ grade 3 mucositis (16.7% vs 36.4%,p=0.91), and grade 3 nausea (0 vs 9.1%, p=0.8). Rates of late adverse events were also comparable among the two groups, with similar incidence of grade 2 cataracts (25% vs 0, p=0.22), grade 1 osteoporosis (8.3% vs 0, p=1.0), grade 2 hyperlipidemia (0 vs 9.1%, p=0.48), grade 3 hyperglycemia (8.3% vs 0, p=1.0), and grade 3 LVEF dysfunction (8.3% vs 9.1%, p=1.0).

Despite the TBI800 group having more patients with advanced disease (CR2 and beyond), survival outcomes were comparable. After a median follow-up of 22.2 months (range, 3.3 - 94.3 months), the 1-yr OS, PFS, and CIR for TBI800 vs TBI1200 were: 91.7% vs 77.9%, p=0.67; 81.5% vs 80.8%, p=0.48; 18.5% vs 19.2%, p=0.78, respectively. Day +100 mortality was comparable at 8.3% vs. 9.1%, p=1.0. Only one case of NRM was reported in the TBI800 group (related to infection with COVID-19), and none in the TBI1200 group. The Multivariable Fine-Gray Model showed a higher risk of aGVHD, particularly grade I-II, in the TBI1200 group (HR 6.66, 95% CI: 2.07-21.38).

Conclusion: TBI800 vs TBI1200 led to similar relapse incidence, with a lower risk of aGVHD and decreased grade 3-4 mucositis rate in the TBI800 group. Studies on a larger scale are required to establish the safety and efficacy of TBI800.