The Dilemma of Conditioning Intensity: When Does Myeloablative Conditioning Improve Outcomes for Allogeneic Hematopoietic Cell Transplantation

Abstract

The impact of conditioning intensity on different disease risk index (DRI) groups has not been evaluated. We retrospectively analyzed acute myelogenous leukemia (AML)/myelodysplastic syndrome (MDS) hematopoietic cell transplantation (HCT) recipients in 2 groups based on DRI, to assess the impact of conditioning intensity on overall survival (OS), disease free survival (DFS), relapse, and nonrelapse mortality (NRM). A total of 380 patients with either high/very high (n = 148) or low/intermediate DRI (n = 232) myeloid malignancy (AML, n = 278; MDS, n = 102) were included in the analysis. Median follow-up for survivors was 35 months. Median age was 58 years (range, 18 to 75). Patient and transplant-related characteristics were 41% reduced-intensity conditioning (RIC), 59% myeloablative conditioning (MAC), 13% bone marrow graft, 29% matched related donor, 49% matched unrelated donor, 22% haploidentical donor, and 52% HCT-specific comorbidity index ≥ 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 3-year OS estimate (69% versus 57%, P = .001), DFS (65% versus 51%, P = .003), and lower relapse (3-year cumulative incidence, 17% versus 32%; P = .01) but similar NRM (19% versus 17%, P = .04) to RIC recipients. On multivariable analysis MAC was associated with better DFS (hazard ratio [HR], .58; 95% confidence interval [CI], .39-.88; P = .01), lower relapse (HR, .56; 95% CI, .32 to .97; P = .038), and similar NRM (HR, 1.11; 95% CI, .54 to 2.26; P = .781) compared with RIC in the low/intermediate DRI group. Intensity had no impact on HCT outcomes in the high/very high DRI group. MAC improves DFS and relapse compared with 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.

Post-Transplant Cyclophosphamide Combined with Anti-Thymocyte Globulin as Graft-versus-Host Disease Prophylaxis for Allogeneic Hematopoietic Cell Transplantation in High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

“…As previously noted, all patients that received the ATG + PTCy combination also underwent RIC, which generally is considered to be associated with an increased relapse risk, at least in the non-high-risk disease groups [8]. However, various studies have demonstrated that while disease risk at diagnosis is a significant factor in predicting AML relapse after transplantation, conditioning intensity does not seem to play a role in the high-risk disease group [7, 8, 23].…”

“…Conditioning intensity plays a significant role in post-transplant relapse risk, with reduced-intensity regimens being associated with increased relapse rates. For high-risk myeloid malignancies, however, such as those with a monosomal karyotype, the relapse risk does not seem to be overcome by increasing the conditioning intensity [7, 8].…”

Dose intensity for conditioning in allogeneic hematopoietic cell transplantation: can we recommend “when and for whom” in 2021?

“…One analysis evaluated 380 AML/MDS patients with either high/very high or low/intermediate DRI. 55 Among patients with high/very high DRI, there was no difference in outcome between the RIC and MAC groups. For low/intermediate risk DRI, recipients of MAC showed better 3-year overall survival (69% vs .…”

Human CD83-targeted chimeric antigen receptor T cells prevent and treat graft-versus-host disease

“…Despite known off-target impairment of beneficial graft-versus-leukemia (GVL) and limited tolerance induction (3), calcineurin inhibitors have been included in GVHD prophylaxis and treatment for more than 3 decades (4)(5)(6). While advances in donor and graft selection (7,8), recipient comorbidity assessment (9,10), and conditioning regimens have improved allo-HCT outcomes (11,12), the use of calcineurin inhibitors remains prevalent in GVHD prevention (1). In particular, calcineurin inhibitors are still incorporated in the popular use of posttransplant cyclophosphamide-based regimens as GVHD prophylaxis (13).…”