Survival With Half-Matched Donor as Good as Full Match

Kristin Jenkins

July 04, 2016

For many patients needing a stem cell transplant, the odds of finding a fully-matched sibling donor are only 25%.

But a new analysis of outcomes in patients with lymphoma shows that the results from a related half-matched (haploidentical) donor are as good as those after a fully-matched donor, which will greatly increase the potential donor pool.

The findings come from an analysis of an observational database of almost 1000 adult patients with lymphoma from a US blood and marrow registry.

Multivariate analysis revealed no significant difference between the related haploidentical hematopoietic cell transplantation (Haplo-HCT) and fully-matched sibling donor (MSD-HCT) in terms of non-relapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34).

The research was published online June 6 in the Journal of Clinical Oncology.

Patients who received the half-matched transplant also received reduced-intensity or non-myeloablative (RIC/NMA) conditioning before the transplant, and then received post-transplantation cyclophosphamide (PT-Cy). This approach "should be considered an acceptable option for patients with lymphoma without MSDs," the authors write.

The study "greatly expands treatment options for patients with lymphoma," said lead author Nilanjan Ghosh, MD, PhD, of the Center for International Blood and Marrow Transplant Research at the Medical College of Wisconsin in Milwaukee.

"The advantage of a haploidentical transplant is that most people have at least one half-matched donor and relatives can usually be requested to donate stem cells more quickly than unrelated volunteers. This allows for timely transplants," Dr Ghosh told Medscape Medical News.

Depending on the patient's race/ethnicity, the availability of matched-related or unrelated donors varies between 15% to 65%, coauthor Mehdi Hamadani, MD, also at the Medical College of Wisconsin, said in an interview. "Not too long ago, [this] precluded a potentially curative allogeneic transplant procedure in patients with relapsed/refractory lymphomas." Now, he added, "virtually every patient has a half-matched-related donor available."

Importantly, the study revealed that Haplo-HCT using post-transplantation PT-Cy significantly reduced the risk of chronic graft-versus-host disease (GVHD) without compromising relapse and survival.

"There was some skepticism that reducing the risk of chronic graft-versus-host disease may compromise graft-versus-tumor effect and lead to increased risk of relapse," Dr Ghosh explained. "However, this large study ... shows equal efficacy with low risk of chronic graft-versus-host disease using half-matched donors compared to full-matched sibling donors."

Study Details

For the analysis, the outcomes of Haplo-HCT were compared against MSD-HCT using the observational database of the Center for International Blood and Marrow Transplant Research at the Medical College of Wisconsin. All patients were 18 years of age or older with Hodgkin and non-Hodgkin lymphoma. Between 2008 and 2013, 180 patients underwent Haplo-HCT and 807 patients underwent MSD-HCT following reduced-intensity conditioning regimens.

Haploidentical-related donors were mismatched for at least two or more HLA loci and only those Haplo-HCT recipients who received GVHD prophylaxis with PT-Cy — with or without a calcineurin inhibitor and mycophenolate mofetil (CellCept, Genentech) — were included in the analysis. Patients in the MSD group received calcineurin inhibitor-based GVHD prophylaxis.

Median follow-up was 3 years. The 28-day neutrophil recovery was similar between the Haplo-HCT and MSC-HCT groups (95% vs 97%; P = .31), although the 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% vs 91%; P = .001).

At day 100, the cumulative incidence of grade II to IV acute GVHD between the groups was similar (27% vs 25%; P = .84). At 1 year however, it was significantly lower after Haplo-HCT (12% vs 45%; P < .001), and this was confirmed in multivariate analysis (P < .001).

The 3-year rate of non-relapse mortality was 15% for Haplo-HCT and 13% for MSD-HCT (P = .41), and relapse/ progression was 37% vs 40% (P = .51). Progression-free survival was 48% in both groups (P = .96), and overall survival was 61% vs 62% (P = .82).

"The results of our study warrant confirmation in prospective, randomized, controlled trials," the study authors write.

The study is ongoing, they add, and the results will be validated in a larger international patient cohort in partnership with the European Group for Blood and Marrow Transplantation.

"Novel strategies to improve remission rates and achieve deeper remissions prior to transplants will likely improve post-transplant outcomes," Dr Ghosh said. "Targeted anti-tumor strategies and efforts to modulate the immune system post-transplant to augment the graft-versus-tumor effect will also improve post-transplant outcomes."

The Center for International Blood and Marrow Transplant Research is supported in part by the National Cancer Institute, National Heart, Lung, and Blood Institute, and National Institute of Allergy and Infectious Diseases. Dr Ghosh reported relationships with Janssen, Celgene, and AbbVie. Dr Hamadani reported relationships with Celgene, MedImmune, Celerant, and Takeda, and some coauthors also acknowledged relationships with industry, as detailed in the paper.

J Clin Oncol. Published online June 6, 2016. Full article

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