Non-Myeloablative Allografting for Patients with Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukaemia (AML).

Taussig, David C. Jamie D. Cavenagh, Andrew J. Davies, Heather Oakervee, Denise Syndercombe-Court, Stephen M. Kelsey, Michael J. Barnett, Ama Rohatiner, Andrew Lister.

Author address: 

Cancer Research UK Department of Medical Oncology, St. Bartholomew's Hospital, London, United Kingdom; Department of Haematology, St. Bartholomew's Hospital, London, United Kingdom; Department of Haematology, Royal London Hospital, London, United Ki

Abstract: 

Allogeneic stem cell transplantation (SCT) is the treatment of choice for selected patients with myelodysplastic syndrome and acute myeloid leukaemia The efficacy of SCT is due in part to the graft-versu-leukaemia (GvL) effect. Most patients with MDS are too old or unfit to tolerate conventional SCT. The concept of non-myeloablative SCT (NSCT) is based on conditioning that is immunosuppressive but not ablative of recipient myelopoiesis. This study was designed to assess the feasibility and efficacy of a fludarabine and cyclophosphamide based regimen in a group of patients with AML or MDS for whom conventional SCT was deemed inappropriate. Between April 1999 and October 2001, 21 patients with MDS (Primary=4, therapy related=4) or AML (de novo=5, therapy related=3, arising out of primary MDS=5) underwent NSCT from either family (n=16) or unrelated donors (UD, n=5). 11 patients had poor risk disease by cytogenetic criteria. 8 patients with AML were in complete remission (CR) 1 at transplant and 2 were in CR2. None of 8 patients with MDS were in CR. Peripheral blood was the source of stem cells in 15 patients. Conditioning was with fludarabine (25mg/m2 on days -6 to -2) and cyclophosphamide (1g/m2 on days -3 and -2) with the addition of CAMPATH 1H (10mg on days -10 to -6) for those with UD. Graft-versus-host disease (GvHD) prophylaxis comprised methotrexate and cyclosporin. Median age of patients=52 years (37-66). Median CD34 dose=3.4 X 106/kg of recipient weight (0.6-7.3). The median duration of neutropenia=15 days (7-35). The median Bearman toxicity grade=0 (0-II). Primary graft failure was seen in 1 patient. 2 patients had cytomegalovirus (CMV) reactivation but neither developed CMV disease. There were no treatment related deaths within 100 days. Acute GVHD occurred in three patients (Grade I=1, Grade II=2). Chronic extensive GVHD occurred in 9 patients. Donor lymphocyte infusions (DLI) were not administered to the recipients of family donors. 2 recipients of UD grafts were given DLI of whom one developed grade IV GvHD. At a median follow up of 19 months (8-38) 13 patients are alive, 11 in continuous CR and 2 with disease. 7 of 11 with poor risk cytogenetics are in continuous CR. 1 patient is in CR 14 months after a second NSCT given for disease relapse. 7 patients have died, 6 of disease and 1 of aspergillosis. In conclusion NSCT with fludarabine and cyclophosphamide conditioning (+ CAMPATH for UD grafts) allowed successful engraftment with acceptable toxicity in a group of patients with AML or MDS for whom conventional SCT would have been extremely hazardous. Continuing remission in those patients with poor risk disease suggests that the efficacy of the GvL effect has been retained.
2002

abstract No: 

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Full conference title: 

44th Amercian Society of Hematology Annual Meeting
    • ASH 44th (2002)