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Bone marrow harvest
Photo by Chad McNeeley

SAN DIEGO—Haploidentical bone marrow transplant (haplo-BMT) is a feasible option for patients with high-risk hematologic malignancies who don’t have timely access to an HLA-matched donor, according to a speaker at the 2015 BMT Tandem Meetings.

Haplo-BMT using myeloablative conditioning, T-cell replete grafts, and post-transplant cyclophosphamide elicited “excellent” rates of engraftment, graft-vs-host disease (GVHD), and transplant-related mortality, said Heather Symons, MD, of The Johns Hopkins University School of Medicine in Baltimore, Maryland.

Dr Symons presented these results at the meeting as abstract 6*, which was chosen as one of the meeting’s “Best Abstracts.” The research was funded by Otsuka Pharmaceuticals.

Dr Symons and her colleagues conducted a phase 2 study of 96 patients with high-risk hematologic malignancies and a median age of 42 (range, 1-65). Males made up 58% of the population.

Diagnoses included acute and chronic leukemias, lymphomas, multiple myeloma, and myelodysplastic syndromes. Some patients were in complete remission, and some were in chemo-sensitive partial remission. There was also a mix of minimal residual disease positivity and negativity.

“Given the heterogeneity of these patients, we further classified our patients by disease risk index,” Dr Symons said. “We used the revised disease risk index as published by Armand in 2013. The disease risk index, or DRI, assigned patients into overall survival risk groups based on disease type and status.”

So 6 patients had a low DRI, 61 had an intermediate DRI, and 29 had a high DRI.

For most patients (n=73), conditioning consisted of intravenous busulfan (pharmacokinetically adjusted) on days –6 to –3 and cyclophosphamide (50 mg/kg/day) on days –2 and –1. But 23 patients (those with acute lymphocytic leukemia or lymphoblastic lymphoma) received cyclophosphamide (50 mg/kg/day) on days –5 and –4 and total body irradiation (200 cGy twice daily) on days –3 to -1.

All patients received T-cell-replete bone marrow from haploidentical, related donors. The median number of HLA mismatches was 4.

Post-transplant immunosuppression consisted of cyclophosphamide (50 mg/kg/day) on days 3 and 4, followed by mycophenolate mofetil for 30 days and tacrolimus for 6 months.

‘Excellent’ outcomes

The median follow-up was 18 months (range, 3-59). The median time to neutrophil engraftment was 24 days, and the median time to platelet engraftment was 29 days. Ninety-one percent of patients had donor chimerism greater than 95% at day 60.

The cumulative incidence of acute GVHD was 17% for grades 2-4 and 7% for grades 3-4. The cumulative incidence of chronic GHVD was 15%. For moderate-to-severe chronic GVHD, it was 5%.

Twenty-four percent of patients had CMV reactivation, and 22% had hemorrhagic cystitis.

The rate of relapse was 36% at 1 year and 44% at 3 years. The transplant-related mortality rate was 6% at 100 days and 11% at 1 year.

Ten patients died—2 from GVHD, 1 of cardiomyopathy, 2 of veno-occlusive disease, 1 of drug-induced liver injury, 2 due to infection, and 2 of unknown causes.

Overall survival was 72% at 1 year, 57% at 2 years, and 51% at 3 years. Event-free survival was 56% at 1 year, 51% at 2 years, and 47% at 3 years.

A multivariate analysis revealed that overall survival decreased with increasing age and increasing DRI.

Compared to patients younger than 20, the hazard ratio (HR) was 6.3 for patients ages 20 to 50 (P=0.02) and 4.7 for patients older than 50 (P=0.04). Compared to patients with a low or intermediate DRI, the HR was 2.2 for those with a high DRI (P=0.03).

The analysis also indicated that increasing age and donor CMV-positivity conferred worse event-free survival.

Compared to patients younger than 20, the HR was 3.6 for patients ages 20 to 50 (P=0.04) and 4.0 for patients older than 50 (P=0.03). Compared to patients who had a CMV-negative donor, the HR was 2.2 for patients who had a CMV-positive donor (P=0.01).

“In conclusion, myeloablative haploidentical bone marrow transplantation with post-transplantation cyclophosphamide for high-risk hematologic malignancies has excellent rates of engraftment, graft-vs-host disease, and transplant-related mortality, with results that are similar to those described in myeloablative HLA-matched bone marrow transplantation,” Dr Symons said.

“Overall, this seems a feasible option for high-risk patients who lack timely access to an HLA-matched donor and warrants continued study. We are soon to start enrolling patients on a Pediatric Blood & Marrow Transplant Consortium trial using myeloablative conditioning, haploidentical donors, and post-transplantation cyclophosphamide.” end hematology article

*Information in the abstract differs from that presented at the meeting.

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