1.
The Dilemma of Conditioning Intensity: When Does Myeloablative Conditioning Improve Outcomes for Allogeneic Hematopoietic Cell Transplantation
Solh, M. M., Solomon, S. R., Morris, L. E., Zhang, X., Holland, H. K., Bashey, A.
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2018
Abstract
The impact of conditioning intensity on different disease risk index (DRI) groups has not been evaluated. We retrospectively analyzed AML/MDS hematopoietic cell transplantation (HCT) recipients in two groups based on DRI, to assess the impact of conditioning intensity on overall survival, disease free survival (DFS), relapse, and non-relapse mortality (NRM). A total of 380 patients with either high/very high (n = 148) or low/intermediate DRI (232) myeloid malignancy (AML 278, MDS 102) were included in the analysis. Median follow up for survivors was 35 months. Median age was 58 years (18, 75). Patient and transplant related characteristics were: 41% reduced intensity conditioning (RIC); 59% myeloablative conditioning (MAC); 13% bone marrow graft; 29% MRD, 49%MUD, 22% haploidentical donor (Haplo); 52% had HCT-CI ≥3. Among patients with high/very high DRI, there was no difference in OS, DFS, relapse and NRM between RIC and MAC conditioning groups. For low/intermediate risk DRI, recipients of MAC had better OS estimate (3-year 69% vs 57%, P = .001), DFS (3-year 65% vs 51%, P = .003) and lower relapse (3-year cumulative incidence 17% vs 32%, P = .01) but similar NRM (3-year 19% vs 17%, P = .04) to RIC recipients. On multivariable analysis, MAC was associated with better DFS (HR 0.58, 95% CI 0.39-0.88, P = .01), lower relapse (HR .56, 95% CI .32-0.97, P = .038) and similar NRM (HR1.11, 95% CI .54-2.26, P = .781) compared to RIC in the low/intermediate DRI. Intensity had no impact on HCT outcomes in the high/very high DRI group. MAC improves DFS and relapse compared to RIC among AML/MDS patients with low/intermediate DRI. The finding of no such benefit in high/very high DRI needs to be further explored in a larger cohort with a longer follow up.
2.
Myeloablative Conditioning with PBSC Grafts for T Cell-Replete Haploidentical Donor Transplantation Using Posttransplant Cyclophosphamide. [Review]
Solomon, S. R., Solh, M., Morris, L. E., Holland, H. K., Bashey, A.
Advances in Hematology. 2016;2016:9736564
Abstract
Relapse is the main cause of treatment failure after nonmyeloablative haploidentical transplant (haplo-HSCT). In an attempt to reduce relapse, we have developed a myeloablative (MA) haplo-HSCT approach utilizing posttransplant cyclophosphamide (PT/Cy) and peripheral blood stem cells as the stem cell source. We summarize the results of two consecutive clinical trials, using a busulfan-based (n = 20) and a TBI-based MA preparative regimen (n = 30), and analyze a larger cohort of 64 patients receiving MA haplo-HSCT. All patients have engrafted with full donor chimerism and no late graft failures. Grade III-IV acute GVHD and moderate-severe chronic GVHD occurred in 23% and 30%, respectively. One-year NRM was 10%. Predicted three-year overall survival, disease-free survival, and relapse were 53%, 53%, and 26%, respectively, in all patients and 79%, 74%, and 9%, respectively, in patients with a low/intermediate disease risk index (DRI). In multivariate analysis, DRI was the most significant predictor of survival and relapse. Use of TBI (versus busulfan) had no significant impact on survival but was associated with significantly less BK virus-associated hemorrhagic cystitis. We contrast our results with other published reports of MA haplo-HSCT PT/Cy in the literature and attempt to define the comparative utility of MA haplo-HSCT to other methods of transplantation.