Abstract Introduction In most patients with chronic lymphocytic leukemia (CLL) the disease follows an indolent course for which aggressive therapies are not warranted. However, a significant minority of patients with rapidly progressive CLL exists who are very likely to die of this dis- ease even with conventional chemo-immunotherapy. It is possible to identify patients with poor-risk features at diagnosis, or early in their disease course, so that alternative strategies incorporating stem cell transplantation (SCT) can be considered. Despite widespread enthusiasm for this approach, there have been no randomized tri- als comparing the outcome of SCT with standard chemotherapy for patients with CLL. Recruitment of appropriate patients into well-designed clinical trials is vital in evaluating the role of SCT in CLL, particularly in light of promising results with novel chemo- immunotherapy combinations alone. Phase II studies of autologous stem cell transplantation have demonstrated feasibility but disease relapse appears inevitable. The optimal strategy for allogeneic SCT in CLL is not clear. A graft- versus-leukemia (GVL) effect in CLL has been demonstrated, with encouraging responses seen to reduced-intensity conditioning SCT and to donor lymphocyte infusions. Myeloablative conditioning results in very high transplantation-related mortality (TRM) and is inappropriate for many patients with CLL. In the absence of any other treatment modalities currently capable of improving survival, the treatment of choice for younger patients with poor-risk CLL may well be allogeneic SCT. Management Strategies in Chronic Lymphocytic Leukemia Evidence of a survival benefit from treatment is available only for patients with advanced-stage CLL (Rai III and IV or Binet B and C). The decision to treat is also guided by the presence of symptoms and the disease activity. Initiating treatment for early-stage CLL is only justified by the presence of disease-associated morbidity such as troublesome lymphadenopathy or constitutional symptoms. Traditionally, treatment was based on alkylating agents such as chlorambucil alone, cyclophosphamide, doxorubicin, and predni- sone (CAP), or cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP). Three large randomized trials have demon- strated that monotherapy with the purine analogue fludarabine produces superior overall response, higher response rates, and longer duration of response compared with alkylating agent–based therapy. 1-3 However, this has not translated into a survival advan- tage because of the relatively high response rates to salvage therapy with purine analogues for patients treated initially with alkylating agents. The combination of fludarabine with cyclophosphamide (FC) has been shown in randomized trials to result in increased response rates and produce a longer duration of response than fludarabine alone. 4,5 As a single agent the anti-CD20 monoclonal antibody rituximab has less activity in CLL than in follicular lym- phoma. However, the addition of rituximab (R) to chemotherapy appears to improve response rates and duration of responses com- pared with fludarabine, 6 or fludarabine and cyclophosphamide using the FCR regimen. 7 Transplantation in Chronic Lymphocytic Leukemia: Timing and Expectations Simon Hallam, John G. Gribben Stem cell transplantation in chronic lymphocytic leukemia (CLL) is an evolving field. Younger patients with high-risk disease might derive the greatest benefit from this approach and the availability of reduced-intensity conditioning regi- mens has made allogeneic stem cell transplantation more relevant to patients with CLL. Patient selection, timing of transplantation, and method of conditioning, stem cell delivery and immunosuppression appear to influence outcomes. We collect and review the available data to assist clinical decision-making in this field. Clinical Lymphoma & Myeloma, Vol. 9, Suppl. 3, S186-S193, 2009; DOI: 10.3816/CLM.2009.s.010 Keywords: Allogeneic transplantation, Autologous transplantation, Donor lymphocyte infusion, Myeloablative, Reduced-intensity conditioning CLL Leukemia 2008 Proceedings Institute of Cancer, Bart’s and the London School of Medicine, Charterhouse Square, London, UK Submitted: May 8, 2009; Revised: Jul 2, 2009; Accepted: Jul 29, 2009 Address for correspondence: John G. Gribben, MD, DSc, FRCP, Institute of Cancer, Bart’s and the London School of Medicine, Charterhouse Square, London, EC1M 6BQ, UK Fax: 44-0-20-7882-6126; e-mail: john.gribben@cancer.org.uk This summary may include the discussion of investigational and/or unlabeled uses of drugs and/or devices that may not be approved by the FDA. Electronic forwarding or copying is a violation of US and International Copyright Laws. Authorization to photocopy items for internal or personal use, or the internal or personal use of specific clients, is granted by CIG Media Group, LP, ISSN #1557-9190, provided the appropriate fee is paid directly to Copyright Clearance Center, 222 Rosewood Drive, Danvers, MA 01923 USA. www.copyright.com 978-750-8400. S186 | Clinical Lymphoma, Myeloma & Leukemia Supplement September 2009