T-Cell–Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma

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BlankJournal of Clinical Oncology, Vol 28, No 23 (August 10), 2010: pp.

3695-3700

T-Cell–Depleted Reduced-Intensity Transplantation Followed by Donor Leukocyte

Infusions to Promote Graft-Versus-Lymphoma Activity Results in Excellent

Long-Term Survival in Patients With Multiply Relapsed Follicular Lymphoma

Kirsty J. Thomson, Emma C. , Don Milligan, Anne N. , Ann E. Hunter,

Gordon Cook, J.C. Bloor, Fiona , Majid Kazmi, C. Linch, Ronjon

Chakraverty, Karl S. Peggs, Mackinnon

From the University College London; Guy's Hospital, London; Birmingham

Heartlands Hospital, Birmingham; Beatson West of Scotland Cancer Centre,

Glasgow; Leicester Royal Infirmary, Leicester; Leeds Teaching Hospitals Trust,

Leeds; Christie Hospital, Manchester; and Queen Hospital, Birmingham,

United Kingdom.

Corresponding author: Kirsty J. Thomson, MD, Department of Haematology,

University College Hospital, 1st floor central, 250 Euston Rd, London, NW1 2PQ,

United Kingdom; e-mail: Kirsty.thomson@... .

Purpose Follicular lymphoma (FL) is an indolent disorder that is treatable but

considered incurable with chemotherapy alone. The curative potential of

allogeneic transplantation using conventional myeloablative conditioning has

been demonstrated, but this approach is precluded in the majority of patients

with FL because of excessive toxicity. Thus, reduced-intensity conditioning

regimens are being explored.

Patients and Methods This study reports the outcome of 82 consecutive patients

with FL who underwent transplantation using fludarabine, melphalan, and

alemtuzumab for in vivo T-cell depletion. Patients were heavily pretreated,

having received a median of four lines of prior therapy, and 26% had experienced

treatment failure with previous autologous transplantation. Median patient age

was 45 years, and 52% of patients received stem cells from unrelated donors.

Results With a median follow-up time of 43 months, the nonrelapse mortality was

15% at 4 years (8% for sibling and 22% for unrelated donor transplantations),

acute grade 2 or 3 graft-versus-host disease (GVHD) occurred in 13%, and the

incidence of extensive chronic GVHD was only 18%. Although relapse risk was 26%,

this was significantly reduced where mixed chimerism had been converted to full

donor chimerism by the use of donor lymphocyte infusion (DLI; P = .03). In

addition, 10 (77%) of 13 patients given DLI for relapse after transplantation

experienced remission, with nine of these responses being sustained. Current

progression-free survival at 4 years was 76% for the whole cohort (90% for those

with sibling donors and 64% for those with unrelated donors).

Conclusion The excellent long-term survival with associated low rates of GVHD

and the frequency and durability of DLI responses make this an extremely

encouraging strategy for the treatment and potential cure of FL.