Acute GVHD less severe after haploidentical transplant with post-cyclophosphamide prophylaxis
ORLANDO — Acute graft-versus-host disease tended to be less severe among patients who underwent haploidentical transplantation with post-cyclophosphamide prophylaxis than those who underwent 8/8 HLA-matched unrelated donor stem cell transplant with standard prophylaxis, according to study results presented at TCT | Transplantation & Cellular Therapy Meetings.
The approach also appeared associated with less nonrelapse mortality — except for transplants from a female donor to male recipient — and the beneficial effects were consistent among older patients.
“Post-transplant cyclophosphamide GVHD prophylaxis has changed the epidemiology of GVHD,” Rima M. Saliba, PhD, associate professor in the department of stem cell transplantation and cellular therapy at The University of MD Anderson Cancer Center, said during a presentation. “Several studies have shown lower incidence of grade 3 to grade 4 acute GVHD and lower incidence of chronic GVHD. However, the pathophysiological mechanisms by which post-transplant cyclophosphamide affects GVHD are evolving ... and it is not clear how use of post-transplant cyclophosphamide alters the clinical manifestations of acute GVHD and its prognosis.”
Saliba and colleagues used Center for International Blood and Marrow Transplant Research data to compare acute GVHD characteristics and nonrelapse mortality among adults who developed grade 2 to grade 4 acute GVHD after haploidentical transplant with post-transplant cyclophosphamide (n = 264) or HLA-matched unrelated donor transplant with conventional prophylaxis (n = 1,163).
The investigators aimed to determine whether clinical manifestations and prognosis of grade 2 to grade 4 acute GVHD varied between post-transplant cyclophosphamide and conventional GVHD prophylaxis, as well as whether the differences were consistent between younger patients and older patients ( 60 years).
Most patients (46.7%) had acute myeloid leukemia, whereas 37.2% had myelodysplastic syndrome, 13.1% had acute lymphoblastic leukemia and 2.8% had chronic myeloid leukemia. More than half (54.6%) had early disease, and 33.7% had advanced disease.
Prophylaxis for haploidentical transplant included a calcineurin inhibitor, mycophenolate mofetil and post-transplant cyclophosphamide. Patients who underwent HLA-matched unrelated donor transplants received prophylaxis with a calcineurin inhibitor with mycophenolate mofetil or methotrexate.
Patients in the haploidentical group tended to be younger (less than 60 years, 65% vs. 46%) and have older donor age (median, 39 years vs. 28 years) than those in the matched unrelated group.
A lower percentage of patients in the haploidentical transplant group developed grade 2 to grade 4 acute GVHD by 6 months (35% vs. 45%; P < .001).
An analysis revealed acute GVHD was less severe in the haploidentical group than the matched unrelated group (percentage of grade 3 to grade 4 cases among all patients, 28% vs. 38%; P = .001; percentage of grade 3 to grade 4 cases among those aged 60 years or older, 25% vs. 41%; P = .003).
Fewer acute GVHD cases in the haploidentical group had more than two organs involved (26% vs. 35%; P = .008).
Results showed no significant difference between the haploidentical and HLA-matched unrelated donor groups with regard to skin involvement (66% vs. 67%), liver involvement (11% vs. 16%) or lower gastrointestinal involvement (76% vs. 78%); however, more cases in the matched unrelated group had upper gastrointestinal involvement (53% vs. 46%; P = .04).
Patients who underwent haploidentical transplant were significantly less likely to have stage III/stage IV liver involvement (4% vs. 7%; P = .04) or stage III/stage IV lower gastrointestinal involvement (14% vs. 21%; P = .009).
Rates of nonrelapse mortality among patients who developed grade 2 to grade 4 acute GVHD were lower in the haploidentical group overall (18% vs. 28%) and among the subset of patients aged 60 years or older (17% vs. 31%).
“This trend was confirmed in multivariate analysis, however multivariate analysis showed a very significant interaction effect by donor and recipient [sex],” Saliba said.
For transplants from female donors to male recipients, cumulative incidence of nonrelapse mortality at 2 years was 30% with haploidentical and 26% with matched unrelated. For other donor-recipient pairs, cumulative incidence of nonrelapse mortality at 2 years was 15% with haploidentical vs. 28% for matched unrelated (P < .01). – by Mark Leiser
Reference: Saliba RM, et al. Abstract 31. Presented at: TCT | Transplantation & Cellular Therapy Meetings; Feb. 19-23, 2020; Orlando.
Disclosures: Saliba reports no relevant financial disclosures. Please see the abstract for all other authors’ relevant financial disclosures.