Transplant approach feasible for high-risk leukemia

Mesenchymal stem cells

A new approach to transplant can improve outcomes for patients with high-risk leukemia, according to results of a recent study.

Researchers in China designed a haploidentical hematopoietic stem cell transplant regimen that resulted in a superior rate of donor engraftment and a lower incidence of severe graft-versus-host disease (GVHD) than those typically observed in high-risk patients.

Huisheng Ai, MD, of Affiliated Hospital of the Academy of Military Medicine Sciences in Beijing, and colleagues incorporated several approaches to transplant that have proven successful in previous studies. The resulting regimen consisted of haploidentical peripheral blood stem cell transplant, combined with intrabone marrow injection of donor-derived mesenchymal stem cells, modified nonmyeloablative conditioning, and GVHD prophylaxis.

The researchers enrolled 33 patients ranging in age from 7 years old to 43 years old. Sixteen patients had acute lymphocytic leukemia, 14 had acute myeloid leukemia, and 3 patients had chronic myeloid leukemia in accelerated phases.

None of the patients had an HLA identical donor. Nineteen donor/patient pairs were mismatched at 3 loci, 10 were mismatched at 2 loci, and 4 were mismatched at 1 locus.

The nonmyeloablative conditioning regimen consisted of fludarabine, total body irradiation, cyclophosphamide, cytarabine, and rabbit ATG. As GVHD prophylaxis, patients received intravenous cyclosporine A, oral mycophenolate mofetil, and an anti-CD25 antibody.

The rates of overall and severe GVHD were much lower in this group of patients than those observed in previous studies. Fifteen patients (45.5%) developed acute GVHD between day 27 and day 82 following transplant. Seven of these patients developed grade 1 acute GVHD, 6 developed grade 2 acute GVHD, and 2 developed grade 3 or 4 acute GVHD. Nine patients developed chronic GVHD.

Patients also experienced superior rates of hematopoietic recovery and donor chimerism. All of the patients achieved full donor chimerism, including 6 who progressed from mixed chimerism between 30 days and 60 days posttransplant. The median time to neutrophil recovery (0.5 x 109/L) was 11 days, and the median time to platelet recovery (30 x 109/L) was 14 days.
 
Six patients relapsed between 2 months and 7.5 months after transplant. Four of these patients later underwent chemotherapy but did not respond. The remaining 2 achieved a second complete remission after another transplant or following the withdrawal of immunotherapy agents. One of these patients survived; the other died of severe pulmonary infection.

Follow-up ranged from 1.5 months to 60 months. Twenty patients (60.6%) remained alive during this time period. The probability of 3-year leukemia-free survival was 57.2%.

Based on these results, Dr Ai and colleagues concluded that their transplant regimen is a feasible treatment option for patients with high-risk leukemia. A full account of this study can be found in the August issue of Biology of Blood and Marrow Transplantation.

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