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. Morris, Don Milligan, Anne N. Parker, Ann E. Hunter, Gordon Cook, Adrian J. C. Bloor, Fiona Clark, Majid Kazmi, David C. Linch, Ronjon Chakraverty, Karl S. Peggs, Stephen Mackinnon

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    120 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)3695-3700
    Number of pages6
    JournalJournal of Clinical Oncology
    Volume28
    Issue number23
    DOIs
    Publication statusPublished - 10 Aug 2010

    Keywords

    • BONE-MARROW-TRANSPLANTATION
    • NON-HODGKINS-LYMPHOMA
    • ALLOGENEIC HEMATOPOIETIC TRANSPLANTATION
    • CHRONIC LYMPHOCYTIC-LEUKEMIA
    • LOW-GRADE LYMPHOMA
    • AUTOLOGOUS TRANSPLANTATION
    • ADOPTIVE IMMUNOTHERAPY
    • HOST-DISEASE
    • TOXICITY
    • MORTALITY

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