Originally published as JCO Early Release 10.1200/JCO.2008.17.3328 on December 8 2008

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Favorable Long-Term Survival After Reduced-Intensity Allogeneic Transplantation for Multiple-Relapse Aggressive Non-Hodgkin's Lymphoma

Kirsty J. Thomson, Emma C. Morris, Adrian Bloor, Gordon Cook, Don Milligan, Anne Parker, Fiona Clark, Lynny Yung, David C. Linch, Ronjon Chakraverty, Karl S. Peggs, Stephen Mackinnon

From the Royal Free and University College Medical School; Guys Hospital; London; Christie Hospital, Manchester; Leeds General Infirmary, Leeds; Birmingham Heartlands Hospital; Queen Elizabeth Hospital, Birmingham; and Glasgow Royal Infirmary, Glasgow, United Kingdom

Corresponding author: Kirsty Thomson, MBChB, Department of Haematology, University College Hospital, 1st Floor Central, 250 Euston Rd, London, NW1 2PQ; e-mail: kirsty.thomson{at}uclh.nhs.uk

Purpose The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, with relatively little published data. We report the outcome of reduced-intensity transplantation (RIT) in a cohort of 48 consecutive patients with relapsed/refractory DLBCL (30 patients with de novo disease and 18 patients with transformed follicular lymphoma) who underwent transplantation with an alemtuzumab-containing regimen, with a median follow-up of 52 months.

Patients and Methods Patients had experienced treatment failure with a median of five lines of prior therapy, including autologous transplantation in 69%, and 17% of patients were chemotherapy refractory at transplantation. Median age was 46 years, and 38% of patients had matched/mismatched unrelated donors. Conditioning was with alemtuzumab, fludarabine, and melphalan, and additional graft-versus-host disease (GVHD) prophylaxis was with cyclosporine.

Results All patients were successfully engrafted. Only 17% of patients developed grade 2 to 4 acute GVHD, with 13% experiencing extensive chronic GVHD. Four-year estimated nonrelapse mortality was 32%, and relapse risk was 33%. Twelve patients received donor lymphocyte infusions ± chemoimmunotherapy for relapse, and five patients obtained durable remissions, giving current progression-free survival (PFS) and overall survival (OS) rates at 4 years of 48% and 47%, respectively. Patients who had chemotherapy-sensitive disease before RIT had current PFS and OS rates at 4 years of 55% and 54%, respectively. Chemotherapy-refractory patients had a poor outcome.

Conclusion The encouraging survival rates with extended follow-up suggest a role for RIT in chemotherapy-sensitive relapsed DLBCL, even in patients who have previously experienced treatment failure with autologous transplantation. Future studies will be required to determine whether any subset of patients with relapsed DLBCL should be considered for RIT versus autologous transplantation.

published online ahead of print at www.jco.org on December 8, 2008.

UCLH/UCL received a proportion of funding from the United Kingdom Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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