Cancer Treatment Today

Patients with low-grade non-Hodgkin’s lymphoma (NHL) and CLL have a median survival of 4-8 years from diagnosis and a cause-specific survival of about 10 years. Allogeneic transplantation has been increasingly utilized in patients with lymphoid malignancies but is associated with high toxicity. Recently, reduced-intensity conditioning regimens have shown encouraging results, attributed to graft-versus-lymphoma effects. The use of recently introduced reduced-intensity and truly nonmyeloablative conditioning regimens has shifted some or all of the burden of tumor-cell kill from the conditioning regimens to the graft-versus-tumor effects. These regimens are less toxic than conventional regimens and allow for the treatment of older patients and patients with comorbid conditions. Early experience with high-dose chemoradiotherapy and allogeneic SCT in patients with heavily pretreated disease demonstrated high non-relapse mortality rates (10% to 40%), but the suggestion of plateau on survival curves. Recent data available on 38 patients who had undergone transplantations from unrelated donors from the National Marrow Donor Program revealed a 5-year failure-free survival rate of 32%.  Sorror et al recently reported the outcome of 64 patients with advanced CLL who were treated with nonmyeloablative conditioning consisting of 2 Gy of total body irradiation with (n = 53) or without (n = 11) fludarabine from related (n = 44) or unrelated (n = 20) donors. The median age was 56 years, and the median interval between diagnosis and transplantation was 4.4 years. There was a median of 4 prior treatment regimens, and chemotherapy resistance to pretransplantation salvage treatment was present in 53% of patients. The incidence of acute II–IV GVHD was 61%. The 2-year estimated OS and DFS rates were 60% and 52%, respectively.

It would stand to reason that patients with poor prognostic features benefit more from transplantation. However, a recent retrospective analysis show that alloSCT leads to the best outcome in the subgroup of patients with good risk profile CLL, contradicting their conclusions and leaving the debate open as to why this aggressive strategy did not translate into improved outcome in the high-risk patients. Thus, this remains a controversial and debated topic. A recent guideline states: “The possibility of an allogeneic transplant procedure should be considered for younger patients with good performance status who have been previously treated and have poor risk disease. Suitable patients should be discussed with a transplant centre at an early stage in their disease before the development of drug resistant disease for inclusion into a clinical research protocol (grade B recommendation, level III evidence).”  NCCN  lists considering an allogeneic transplant as a standard option in patients without comorbidities (CSLL-5). NCCN does not recommend transplantation.

Luca Laurenti, Michela Tarnani, Patrizia Chiusolo, Federica Sor� and Simona Sica. Allogeneic Transplantation for Chronic Lymphocytic Leukemia Mediterranean Journal of hematology and infectious disease. Vol 2, No 2(2010)

C. Nabhan and J. D. Bitran Chronic Lymphocytic Leukemia: To Transplant or Not to Transplant… That Is the Question? . Clin. Oncol., November 1, 2005; 23(31): 8126 – 8127.

Oscier D, Fegan C, Hillmen P, Illidge T, Johnson S, Maguire P, Matutes E, Milligan D, Guidelines Working Group of the UK CLL Forum, British Committee for Standards in Haematology. Guidelines on the diagnosis and management of chronic lymphocytic leukaemia. Br J Haematol 2004 May;125(3):294-317. [169 references]

nccn.org, CLL 2012

Michallet M, Dreger P, Sutton L, et al. Autologous hematopoietic stem cell transplantation in chronic lymphocytic leukemia: results of European intergroup randomized trial comparing autografting versus observation. Blood. Feb 3 2011;117(5):1516-1521

Gribben JG. How I treat CLL up front. Blood. Jan 14 2010;115(2):187-97.

Oscier D, Fegan C, Hillmen P, Illidge T, Johnson S, Maguire P, Matutes E, Milligan D, Guidelines Working Group of the UK CLL Forum, British Committee for Standards in Haematology. Guidelines on the diagnosis and management of chronic lymphocytic leukaemia. Br J Haematol 2004 May;125(3):294-317. [169 references]

Johan Aschan Allogeneic haematopoietic stem cell transplantation: current status and future outlook Medical Bulletin 2006 77-78(1):23-36;