Work

221: A submyeloablative regimen of Campath-1H and Fludarabine for patients with graft failure following allogeneic transplantation from MHC identical or near identical donors

Year: 2007

Type: article

Abstract: Primary or secondary graft failure or the persistence or reappearance of mixed chimerism (MC) are potentially serious causes of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). In a phase I/II pilot study we combined Fludarabine with the lympho-depleting humanized anti-CD52 antibody Campath-1H as a non-myeloablative therapy designed to overcome donor-anti-recipient T cell responses and to permit complete and successful donor engraftment following re-infusion of donor stem cells. This study evaluated the safety, feasibility, and rate of donor engraftment for twenty-two patients at our institution from September 2000 to June 2006 (median age 3.5 years; range 7 months to 69 years; 14 males) with engraftment failure or mixed chimerism (range 8-61% donor cell chimerism). All patients had previously received one or more transplants for lympho-hematologic malignancies (n=14), immunodeficiency syndromes (n=5) or metabolic diseases (n=3). Twelve patients were enrolled for graft failure (55%) and ten for mixed chimerism (45%). Seven patients were transplanted in relapse (3 with graft failure and 4 with mixed chimerism). The conditioning regimen consisted of Fludarabine and Campath-1H (30mg/m2/day and 10mg/day, respectively) given on days –5 to –3. Twelve patients received transplants from a single antigen mismatched family donor (55%), nine from a matched unrelated (41%) and one from an HLA-identical sibling. Donors were the same used for the primary transplant. Twenty-one evaluable patients (>95%) achieved sustained neutrophil engraftment, and complete donor chimerism by day 28. Regimen-related toxicities were tolerable. Nine patients (41%) never experienced neutropenia. The median time to neutrophil engraftment for those who experienced neutropenia was 10 days (range 2 to 20). The overall survival for non-malignant transplant recipients was 100 % and 43 % for patients with malignant disease, at a median follow-up of 32 months (range, 4 to 73 months). Of the 8 patients who died, 5 succumbed to relapse, while 1 died from infection, 1 from pulmonary and 1 from cardiac toxicity. Only one patient had mild (grade I) acute graft-versus-host disease (aGVHD). We conclude that this reduced-intensity regimen enabled satisfactory engraftment and achievement of rapid complete donor chimerism with minimal toxicities. It was associated with a low incidence of aGHVD. The disease status was the main determinant of treatment failure in this study.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2006.12.226