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Journal of Clinical Oncology, Vol 21, Issue 16 (August), 2003: 3060-3065
© 2003 American Society for Clinical Oncology

Durable Remissions of Myelodysplastic Syndrome and Acute Myeloid Leukemia After Reduced-Intensity Allografting

D.C. Taussig, A.J. Davies, J.D. Cavenagh, H. Oakervee, D. Syndercombe-Court, S. Kelsey, J.A.L. Amess, A.Z.S. Rohatiner, T.A. Lister, M.J. Barnett

From the Division of Haematological Oncology, St Bartholomew’s Hospital, London, United Kingdom.

Address reprint requests to Michael Barnett, BM, Department of Medical Oncology, 45 Little Britain, St Bartholomew’s Hospital, London EC1A 7BE, United Kingdom; email: Michael.Barnett{at}cancer.org.uk.

Purpose: To evaluate the use of reduced-intensity (RI) conditioning with allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-identical family donors in patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML).

Patients and Methods: Sixteen patients (median age, 54 years; range, 37 to 66 years) underwent RI-HSCT using a conditioning regimen of fludarabine 25 mg/m2 daily for 5 days and either cyclophosphamide 1 g/m2 daily for 2 days (14 patients) or melphalan 140 mg/m2 for 1 day (two patients). The median number of CD34+ cells and CD3+ cells infused per kilogram of recipient weight was 4.5 x 106 (range, 1.8 to 7.3 x 106 cells) and 2.9 x 108 (range, 0.1 to 9.6 x 108 cells), respectively.

Results: There was no transplant-related mortality (TRM) within 100 days of HSCT. Grade 1 to 2 acute graft-versus-host disease (GVHD) occurred in three patients, but neither grade 3 nor grade 4 disease was observed. Chronic GVHD occurred in 10 patients. One patient had cytomegalovirus (CMV) reactivation but did not develop CMV disease. With a median follow-up of 26 months (range, 15 to 45 months), 11 patients are alive (nine in continuous complete remission and one in complete remission after a second transplantation), and five have died (four from disease progression and one from bone-marrow aplasia induced by cyclosporine withdrawal). The 2-year actuarial overall and event-free survival rates were 69% (95% confidence interval [CI], 40% to 86%) and 56% (95% CI, 30% to 68%), respectively.

Conclusion: This strategy of RI-HSCT resulted in reliable engraftment with low incidence of acute GVHD and TRM. Durable remissions were observed in patients with MDS and AML consistent with a graft-versus-leukemia effect.

Supported by Cancer Research UK.

Presented in part at the American Society of Hematology annual meeting, Philadelphia, PA, December 2002.


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