Long-Term Survival after HLA-Haploidentical Stem Cell Transplantation from Non-Inherited Maternal Antigen-Mismatched Family Donors: Impact of Chronic Graft-Versus-Host Disease.

Background: We previously reported that T-cell-replete HLA-haploidentical hematopoietic stem cell transplantation (SCT) from a microchimeric noninherited maternal HLA antigen (NIMA)-mismatched related donor offers a feasible treatment option in patients with poor-risk hematologic malignancies who lack an immediately available stem cell source (

Methods: We studied 16 patients who had survived more than 3 years after T-cell-replete HLA-haploidentical NIMA-mismatched SCT to evaluate the impact of late complications on morbidity and mortality. The patients received bone marrow (n=5) or peripheral blood stem cell (n=11) between 01/2001 and 07/2004 at 11 centers with a median age of 19 years (range, 2 to 56) as treatment for acute myeloid leukemia (n=6), acute lymphoblastic leukemia (n=3), chronic myeloid leukemia (n=4), and other B-cell neoplasms (n=3). At the time of SCT, 6 patients had a chemosensitive disease and 10 had a chemorefractory disease. Type of donor was NIMA-mismatched sibling in 9, mother in 6, and daughter in 1; all patient-donor pairs had two or three serologic mismatches at HLA-A, −B, and −DR in the graft-versus-host direction. Organ-specific symptoms related to chronic graft-versus-host disease (cGVHD) and their severity were evaluated by clinical scoring system proposed by the National Institutes of Health consensus development project.

Results: At a median follow-up of 56 months (range, 38 to 74), 13 (81%) of 16 patients were alive and free of their primary disease. One patient was alive with relapsed disease; 2 died from bronchiolitis obliterans at 51 and 52 months in continuous remission. Karnofsky or Lansky performance score among 14 survivors was 100% in 6 (43%), 80–90% in 5 (36%), 70% in 2 (14%), and less than 70% in 1 (7%). Thirteen (81%) patients developed extensive cGVHD and eleven of them experienced organ symptoms corresponding to the consensus score greater than 1. The commonly involved organs (score>1) were lungs (n=5), skin (n=4), eyes (n=3), and liver (n=3). Seven patients were successfully withdrawn from immunosuppressive agents between 3 and 46 months (median, 19) after transplantation.

Conclusions: T-cell-replete HLA-haploidentical SCT from a microchimeric NIMA-mismatched donor confers long-term survival in selected patients without compromising their performance status, although a high incidence of moderate to severe cGVHD may limit its usefulness as compared with conventional SCT.