Does Total Body Irradiation Conditioning Improve Outcomes of Myeloablative Human Leukocyte Antigen–Identical Sibling Transplantations for Chronic Lymphocytic Leukemia?

Abstract

An allogeneic hematopoietic cell transplant (HCT) from an HLA-identical donor after high-dose (myeloablative) pre-transplant conditioning, is an effective therapy for some people with chronic lymphocytic leukemia (CLL). Because CLL is a highly radiosensitive cancer, we hypothesized total body irradiation (TBI) conditioning regimens may be associated with better outcomes than those without TBI. To answer this we analyzed data from 180 subjects with CLL receiving myeloablative doses of TBI (N=126) or not (N=54), transplanted from an HLA-identical sibling donor, between 1995 and 2007 and reported to the Center for International Blood & Marrow Transplant Research (CIBMTR). At 5 years, treatment-related mortality was 48% (95% CI, 39–57%) vs. 50% (95% CI, 36–64%); p=NS. Relapse rates were 17% (95% CI, 11–25%) vs. 22% (95% CI, 11–35%); p=NS. Five-year progression-free survival and overall survival was 34% (95% CI, 26–43%) vs. 28% (95% CI, 15–42%); p=NS and 42% (95% CI, 33–51%) vs. 33% (95% CI, 19–48%); p=NS, respectively. The single most common cause of death in both cohorts was recurrent/progressive CLL. No variable tested in the multivariate analysis was found to significantly affect these outcomes including having failed fludarabine. Within the limitations of this study we found no difference in HLA-identical sibling transplant outcomes between myeloablative TBI and chemotherapy pre-transplant conditioning in persons with CLL.

Outcomes of Human Leukocyte Antigen–Matched Sibling Donor Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia: Myeloablative Versus Reduced-Intensity Conditioning Regimens

“…From the recently reported MA experience comparing chemotherapy- vs. TBI-based conditioning, which included the MA cohort of patients from the current study, there were no differences in TRM, relapse, PFS or survival [31]. Investigation of novel treatment agents for conditioning as well as adoptive cellular therapy studies and post-transplant maintenance therapy may be further explored.…”

Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation

“…The 5-year EFS of 35% in this large study fits right in the middle of the reported range between 28 and 43% reported from smaller series of patients. [6][7][8]18,19 When counting from the day of allo-HCT, 28% of patients (95% CI, 25-31) maintained disease control at 10 years. For patients who passed the 2-and 5-year landmark event-free, the fraction of patients who maintained disease control at 10 years from allo-HCT increased to 56% (95% CI, 51-62) and 79% (95% CI, 73-85).…”

“…In patients who passed the 2year landmark event-free, relapse/progression and NRM continued to occur. The cumulative incidence of relapse at 8 years after the landmark was 24% (95% CI, [20][21][22][23][24][25][26][27][28] and NRM was 20% (95% CI, [16][17][18][19][20][21][22][23][24]. The probability of being alive 10 years after allo-HCT (8 years after the landmark) was 65% (95% CI, 60-70).…”

Effect of dose rate on pulmonary toxicity in patients with hematolymphoid malignancies undergoing total body irradiation

“…In previous literatures, TRM was generally defined as death from any cause without leukemia relapse [ 15 , 16 ]. Many cases of death after HSCT are due to infectious causes [ 17 ], and the risk of opportunistic infection is small after 3 months [ 18 ]. For this reason, we limited the definition of TRM to 3 months after TBI followed by HSCT.…”