1.
Prognostic score and cytogenetic risk classification for chronic lymphocytic leukemia patients: Center for International Blood and Marrow Transplant Research report
Kim, H. T., Ahn, K. W., Hu, Z. H., Davids, M. S., Volpe, V., Antin, J. H., Sorror, M., Shadman, M., Press, O. W., Pidala, J., et al
Clinical cancer research : an official journal of the American Association for Cancer Research. 2019
Abstract
PURPOSE To develop a prognostic model and cytogenetic risk classification for previously treated patients with chronic lymphocytic leukemia (CLL) undergoing reduced intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (HCT). EXPERIMENTAL DESIGN We performed a retrospective analysis of outcomes of 606 CLL patients who underwent RIC allogeneic HCT between 2008 and 2014 reported to the Center for International Blood and Marrow Transplant Research. RESULTS Based on multivariable models, disease status, comorbidity index, lymphocyte count and white blood cell count at HCT were selected for the development of prognostic model. Using the prognostic score, we stratified patients into low, intermediate, high, and very high risk (4-year progression-free survival (PFS) 58%, 42%, 33%, and 25%, respectively, p<0.0001; 4-year overall survival (OS) 70%, 57%, 54%, and 38%, respectively, p<0.0001). We also evaluated karyotypic abnormalities together with del(17p) and found that del(17p) or ≥5 abnormalities showed inferior PFS. Using a multivariable model, we classified cytogenetic risk into low, intermediate, and high (p<0.0001). When the prognostic score and cytogenetic risk were combined, patients with low prognostic score and low cytogenetic risk had prolonged PFS (61% at 4-year) and OS (75% at 4-year). CONCLUSIONS In this large cohort of previously treated CLL patients who underwent RIC HCT, we developed a robust prognostic scoring system of HCT outcomes and a novel cytogenetic based risk stratification system. These prognostic models can be used for counseling patients, comparing data across studies, and providing a benchmark for future interventions. For future study, we will further validate these models for patients receiving targeted therapies prior to HCT.
2.
Reduced intensity is preferred over myeloablative conditioning allogeneic HCT in chronic lymphocytic leukemia whenever indicated: A systematic review/meta-analysis
Kharfan-Dabaja, M. A., Moukalled, N., Reljic, T., El-Asmar, J., Kumar, A.
Hematology/Oncology & Stem Cell Therapy. 2017
Abstract
Despite availability of new and more effective therapies for chronic lymphocytic leukemia, presently this disease remains incurable unless eligible patients are offered an allogeneic hematopoietic cell transplant. Recent published clinical practice recommendations on behalf of the American Society for Blood and Marrow Transplantation relegated the role of for allogeneic hematopoietic cell transplantation to later stages of the disease. To our knowledge, no randomized controlled trial has been performed to date comparing myeloablative versus reduced intensity conditioning regimens in chronic lymphocytic leukemia patients eligible for the procedure. We performed a systematic review/meta-analysis to assess the efficacy of allogeneic hematopoietic cell transplantation when using myeloablative or reduced intensity conditioning regimens. We report the results in accordance to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Based on lower non-relapse mortality and slightly better overall survival rates, reduced intensity conditioning regimens appear to be the most desirable choice whenever the procedure is indicated for this disease. It appears highly unlikely that a RCT will be ever performed comparing reduced intensity vs. myeloablative allogeneic hematopoietic cell transplantation in chronic lymphocytic leukemia. In the absence of such a study, results of this systematic review/meta-analysis represent the best available evidence supporting this recommendation whenever indicated in patients with chronic lymphocytic leukemia.
3.
Clinical Practice Recommendations for Use of Allogeneic Hematopoietic Cell Transplantation in Chronic Lymphocytic Leukemia on Behalf of the Guidelines Committee of the American Society for Blood and Marrow Transplantation. [Review]
Kharfan-Dabaja, M. A., Kumar, A., Hamadani, M., Stilgenbauer, S., Ghia, P., Anasetti, C., Dreger, P., Montserrat, E., Perales, M. A., Alyea, E. P., et al
Biology of Blood & Marrow Transplantation. 2016;22(12):2117-2125
Abstract
We sought to establish clinical practice recommendations to redefine the role of allogeneic hematopoietic cell transplantation (allo-HCT) for patients with chronic lymphocytic leukemia (CLL) in an era of highly active targeted therapies. We performed a systematic review to identify prospective randomized controlled trials comparing allo-HCT against novel therapies for treatment of CLL at various disease stages. In the absence of such data, we invited physicians with expertise in allo-HCT and/or CLL to participate in developing these recommendations. We followed the Grading of Recommendations Assessment, Development and Evaluation methodology. For standard-risk CLL we recommend allo-HCT in the absence of response or if there is evidence of disease progression after B cell receptor (BCR) inhibitors. For high-risk CLL an allo-HCT is recommended after failing 2 lines of therapy and showing an objective response to BCR inhibitors or to a clinical trial. It is also recommended for patients who fail to show an objective response or progress after BCR inhibitors and receive BCL-2 inhibitors, regardless of whether an objective response is achieved. For Richter transformation, we recommend allo-HCT upon demonstration of an objective response to anthracycline-based chemotherapy. A reduced-intensity conditioning regimen is recommended whenever indicated. These recommendations highlight the rapidly changing treatment landscape of CLL. Newer therapies have disrupted prior paradigms, and allo-HCT is now relegated to later stages of relapsed or refractory CLL. Copyright © 2016 The American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
4.
Systematic review of high dose chemotherapy and autologous haematopoietic stem cell transplantation for chronic lymphocytic leukaemia: what is the published evidence?
Kharfan-Dabaja, M. A., Kumar, A., Behera, M., Djulbegovic, B.
British Journal of Haematology. 2007;139(2):234-42
Abstract
Despite improved responses, chronic lymphocytic leukaemia (CLL) remains incurable with conventional chemotherapy. Patients with poor-risk factors or who fail conventional chemoimmunotherapy are offered autografts, preferably after achieving remission. This report presents the totality of evidence through a systematic review that assessed the efficacy of autografts in CLL. A search of MEDLINE databases from 1966-2006 and hand-search of references identified 82 prospective-randomized, non-randomized comparisons or single-arm trials, of which only nine met our inclusion criteria: two trials were funded by public/government, one by private foundations, one jointly by private/public, and was unclear in five. No randomized controlled trials comparing autografts versus conventional chemotherapy (or chemoimmunotherapy) were found. Six studies were single-arm and three were non-randomized with a control-arm (autologous versus allogeneic). Overall, 361 patients were enrolled, but only 292 were transplanted. Transplant-related mortality ranged from 0% to 9%. Complete responses ranged from 74% to 100% and molecular responses ranged from 57% to 88%. Overall survival ranged from 68% at 3 years to 58% at 6 years. It is uncertain whether autograft is superior to conventional therapy. The high incidence of myelodysplastic syndrome (9-12%) is particularly concerning in CLL, where median survival is 9 years.