Work

Non-myeloablative allogeneic transplantation with alemtuzumab, fludarabine and cyclophosphamide using 3-6/6 HLA matched donors

Year: 2006

Type: article

Abstract: To broaden the proportion of patients able to undergo allogeneic therapy, we have investigated the use of 3-6/6 HLA matched family member donors in combination with donor T cell depletion in a non-myeloablative preparative regimen. Methods: Seventy five matched and 63 mismatched patients received fludarabine 30 mg/m2 IV qd × 4, cyclophosphamide 500 mg/m2 IV qd × 4, and alemtuzumab 20 mg IV qd × 5 followed by infusion of donor stem cells. In those with a matched donor, no other GVHD prophylaxis was used. In those with a 3-5/6 HLA matched donor, mycophenolate 1000 mg po BID was given to the first 35 and cyclosporine was added to the subsequent 28 for 6-8 weeks following transplantation. Results: Patient diagnoses included lymphoma/myeloma n = 36, leukemia/MDS n = 63, myelofibrosis/aplasia n = 10, metastatic solid tumors n = 29. The median age was 48 (17-70) with a median follow up of approximately 20 months. Engraftment occurred in 100% of matched recipients and 92% of mismatched patients. Eight percent had secondary graft failure as well. Forty six patients with a matched donor and 23 with a mismatched donor also had a DLI (range 105-107 CD3+ cells/kg). Grade III-IV acute GVHD occurred in only 7/75 (7%) in the matched setting and 8/63 (13%) of patients. Four percent of matched and 15% of the mismatched patients developed chronic GVHD and CMV reactivation was common. One hundred day treatment related mortality for both groups was <10%. Combining both matched and mismatched patients, only 12% entered in remission, though 76% attained a CR. The most common cause of death remained progressive disease (42%) and GVHD (8%). Despite the high risk nature of this group, 21 had aplastic anemia/myelofibrosis or leukemia in first or second CR and no other available donor other than their mismatched family member. This group had an encouraging 50% 3 year median survival. Phenotypic, spectratype and TRECs analysis reveals robust recovery by 6 months following transplantation from peripheral expansion of residual transplanted T cells Conclusions: The results demonstrate reasonable tolerance and reliable engraftment using T cell depleted, 3-6/6 HLA matched family member donors in a non-myeloablative setting with low treatment related mortality and severe GVHD. The future challenge will to be to develop strategies to improve immune recovery to enhance immune-mediated graft-versus-tumor effect and to minimize the risk of infections.

Source: Transplantation and Cellular Therapy

DOI: 10.1016/j.bbmt.2005.11.104