Comparison of non-myeloablative conditioning regimens for lymphoproliferative disorders

Abstract

Hematopoietic cell transplantation (HCT) with non-myeloablative conditioning (NMA) for lymphoproliferative diseases (LD) includes fludarabine with and without low-dose total body irradiation (TBI). Transplant outcomes were compared among patients ≥40 years with LD who received a HCT with TBI (N=382) and no-TBI (N=515) NMA from 2001 to 2011. The groups were comparable except for donor, graft, prophylaxis for graft-versus-host disease (GVHD), disease status and year of HCT. Cumulative incidences of grades II–IV GVHD at 100 days, were 29% and 20% (p=0.001), and chronic GVHD at 1 year were 54% and 44% (p=0.004) for TBI and no-TBI, respectively. Multivariate analysis of progression/relapse, treatment failure and mortality showed no outcome differences by conditioning. Full donor chimerism at day 100 was observed in 82% vs. 64% in the TBI and no-TBI groups, respectively (p=0.006). Subset of four most common conditioning/ GVHD prophylaxis combinations demonstrated higher rates of grades II–IV acute (p<0.001) and chronic GVHD (p<0.001) among recipients of TBI-mycophenolate mofetil (MMF) compared to other combinations. TBI-based NMA conditioning induces faster full donor chimerism but overall survival outcomes are comparable to no-TBI regimens. Combination of TBI and MMF are associated with higher rates of GVHD without impact on survival outcomes in patients with LD.

Association of Reduced-Intensity Conditioning Regimens With Overall Survival Among Patients With Non-Hodgkin Lymphoma Undergoing Allogeneic Transplant

“…A Center for International Blood and Marrow Transplant Research (CIBMTR) analysis compared HCT outcomes among patients with lymphoma who underwent either a total body irradiation (TBI)-based regimen or a non-TBI-containing NMAC regimen allogeneic HCT. 10 The study found a higher risk of graft-vs-host disease (GVHD) associated with TBI-based approaches but no difference in survival. A retrospective North American and Spanish study (n = 136) showed inferior overall survival (OS) associated with use of fludarabine-melphalan, 140 mg/ m 2 (Flu-Mel140) compared with fludarabine-busulfan (Flu-Bu).…”

Higher Total Body Irradiation Dose Intensity in Fludarabine/TBI-Based Reduced-Intensity Conditioning Regimen Is Associated with Inferior Survival in Non-Hodgkin Lymphoma Patients Undergoing Allogeneic Transplantation

“…Increased doses of TBI in conditioning regimens have been associated with a higher risk of tissue injury and subsequently higher risk of GVHD. Prior CIBMTR data [7] comparing NMA allo-HCT outcomes among patients with lymphoma undergoing 2-Gy TBI-based conditioning versus non-TBI RIC approaches showed a higher risk of GVHD with TBI-containing approaches. In the current analysis, we found no increase in the risk of either acute or chronic GVHD with increasing TBI dose from 2 Gy to 4 Gy (Table 2), consistent with the data reported by the Cleveland Clinic group [17].…”

“…The RIC/NMA conditioning approach with the best risk/ benefit profile (NRM versus relapse rate) in patients with NHL remains controversial. A Center for International Blood & Marrow Transplant Research (CIBMTR) analysis [7] compared HCT outcomes among patients with lymphoma undergoing allo-HCT with either 2-Gy total body irradiation (TBI)-based or non-TBI containing NMA conditioning allo-HCT. The study found a higher risk of graft-versus-host disease (GVHD) with TBI-based approaches but no difference in relapse risk or survival outcomes between the 2 approaches.…”

The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review

“…Total body irradiation (TBI) is often incorporated into conditioning protocols to improve disease eradication, immune clearance, and donor engraftment. However, a CIBMTR analysis study of 897 patients with CLL and other lymphomas reported that the inclusion of low-dose (≤2 Gray [Gy]) TBI in NMA conditioning regimens does not appear to impact OS or PFS ( 92 ). Regarding TBI-based versus chemotherapy-only MAC, a CIBMTR study of 180 patients with CLL did not find a significant survival advantage, although there was a trend toward superior OS with TBI-based conditioning ( 93 ).…”