Factors Influencing Tolerance to Total Body Irradiation (400 cGy) for Hematopoietic Stem Cell Transplantation

Objective: To investigate the tolerance to 400 cGy of total body irradiation (TBI) as part of a myeloablative conditioning regimen for hematopoietic stem cell transplantation (HSCT) and to identify factors influencing tolerance to TBI.

Patients and method: We conducted a prospective study grading the tolerance to 400 cGy of TBI combined with Fludarabine and Busulfan as myeloablative-conditioning (FluBuTBI) for HSCT. FluBuTBI consists of Fludarabine 50 mg/m²/day x 5 days), Busulfan (3.2 mg/kg/day x 4 days) and total body irradiation (200 cGy/day x 2 days). We also conducted an exploratory analysis for factors affecting tolerance. Thirty-six (36) patients received FluBuTBI. We graded tolerance to TBI as Very Good (VG) – minor breaks during treatment overall treatment time not doubled, Good (G) – important breaks, treatment time at least doubled and Poor (P) – major breaks with clinical toxicity of E (emesis), D (diarrhea), or S (syncopal episode). We grouped VG and G as one category with 19 patients (VG=12 + G=7), and poor as the other category (n=16). We then analyzed age, sex, BMI, remission status, comorbidity index, Karnofsky score comparing the 2 categories. Diagnoses included AML (n=13), ALL (n=4), NHL (n=13), Hodgkin lymphoma (n=3) and CML (n=1). Twenty (20) patients underwent allogeneic and 16 autologous transplant.

Results: Median age was 45 years in the VG/G category versus 54 years in the P category (p=0.11). 74% of patients in the VG/G category were male versus 35% of patients in the P category (p= 0.02). Heavily pre-treated was 37% in VG/G category and 88% in the P category (p= 0.0009). The BMI was identical in both the groups at 30. The HCT-CI was also similar in both groups with medians of 1.6 (VG/G group) and 1.9 (P group). The Karnofsky score was 90 in both groups. 47% of patients in the VG/G group and 41% of patients in the P group were in complete remission. 74% patients in the VG/G category underwent allogeneic transplant while only 29% of patients in the P category did so (p=0.002).

CONCLUSION:  Our data shows that sex and prior therapy affect tolerance to TBI. Males tolerated TBI better than females. Patients who were heavily pretreated tolerated TBI less well. Surprisingly, Karnofsky score, HCT-CI, disease and BMI had no effect on the tolerance to TBI. Better prophylactic strategy is warranted in the at risk population. Factors affecting tolerance to TBI deserves further study in a larger cohort.