In a clinical trial comparing three graft-versus-host disease (GVHD)–prevention regimens in patients undergoing hematopoietic stem cell transplants, a calcineurin inhibitor (CNI)–free strategy using CD34-selected peripheral blood stem cells (PBSCs) was associated with a nearly twofold increase in transplant-related mortality, compared with either a different CNI-free regimen or tacrolimus plus methotrexate, investigators reported.
In the phase 3 Progress II trial, patients who received CD34-selected PBSCs without post-transplant immune suppression had a hazard ratio for death of 1.74 compared with patients who received T-cell depletion with posttransplant cyclophosphamide, and a HR of 1.78, compared with patients who received tacrolimus and methotrexate after a bone marrow graft, Miguel-Angel Perales , MD, from Memorial Sloan Kettering Cancer Center, New York, reported at the Transplant & Cellular Therapies Meetings.
“CD34 selection was associated with worse overall survival, which offset any benefit from lower rates of moderate to severe chronic GVHD,” he said at the meeting held by the American Society for Blood and Marrow Transplantation and the Center for International Blood and Marrow Transplant Research.
Neither of the two CNI-free interventions were superior to tacrolimus/methotrexate with bone marrow–derived stem cells for preventing chronic GVHD, and there were no differences in the primary endpoint of chronic GVHD/relapse-free survival, Dr. Perales said.
T-cell depletion vs. CNI
The Progress II trial was designed to see whether either of two CNI-free, T-cell depletion approaches could improve chronic GVHD rates post transplant over a CNI-based regimen.
The investigators enrolled patients aged 65 years or younger with acute leukemia or myelodysplasia with fewer than 5% blasts and a HLA-matched related or unrelated donor.
The patients were randomly assigned to either bone marrow grafts with tacrolimus/methotrexate (118 patients), bone marrow with in vivo posttransplant cyclophosphamide (114), or PBSCs with ex vivo CD34-selected cells (114).
The primary endpoint of chronic GVHD/relapse-free survival (CRFS) was a time-to-event outcome defined as moderate to severe chronic GVHD according to National Institutes of Health consensus criteria, disease relapse or progression, or death from any cause.
As noted before, there were no between-arm differences in the primary CRFS endpoint, and in multivariate analysis controlling for donor type, patient characteristics, disease category and disease risk index, the only factor significantly predictive for CRFS was being aged 50 years or older.
The 2-year posttransplant survival rates were 61.6% in the CD34-selected arm, 76.7% in the posttransplant cyclophosphamide arm, and 74.2% in the tacrolimus/methotrexate arm.
As noted before, the HR for CRFS with CD34 versus tacrolimus/methotrexate was 1.74, and for CD34 versus cyclophosphamide was 1.78 (P = .02 for both comparisons). In contrast, there was no difference in CRFS between posttransplant cyclophosphamide and tacrolimus/methotrexate.
Both relapse-free survival and transplant-related mortality were worse with the CD34-selected group, compared with the other two groups, but there were no significant differences among the arms in disease relapse.
Hematologic recovery was faster in the CD34 arm, but there were no significant differences in graft failure.
In addition, the incidence of grade II-IV acute GVHD was increased in the posttransplant cyclophosphamide group, compared with the other two, while chronic GVHD and moderate to severe chronic GVHD were reduced in the CD34 group.
There were no differences in quality of life measures among the groups, Dr. Perales said.