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Allogeneic hematopoietic cell transplantation for patients with TP53 mutant or deleted chronic lymphocytic leukemia: Results of a prospective observational study
Schetelig, J., Hoek, J., Stilgenbauer, S., Middeke, J. M., Andersen, N. S., Fox, C. P., Lenhoff, S., Volin, L., Shimoni, A., Schroyens, W., et al
Bone marrow transplantation. 2020
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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.
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Chronic lymphocytic leukemia patients with HLA-B27 referred for allogeneic hematopoietic stem cell transplantation do not have worse outcomes: Results of a population-based case series analysis in British Columbia, Canada
Huang, S. J., Chan, J., Bruyere, H., Allan, L. L., Gerrie, A. S., Toze, C. L.
Leukemia research. 2019;84:106193
Abstract
Human leukocyte antigen B27 (HLA-B27), associated with spondyloarthritis, was suggested to be protective against chronic lymphocytic leukemia (CLL). It is hypothesized that HLA-B27 patients may have worse outcome in part related to their other comorbidities. OBJECTIVES We sought to compare the clinical characteristics and outcomes of CLL and small lymphocytic lymphoma (SLL) patients referred for allogeneic hematopoietic stem cell transplantation (allo-HSCT) based on their HLA-B27 status. METHODS This retrospective population-based case series analyzed CLL/SLL patients who were HLA-typed for potential allo-HSCT in British Columbia, Canada. RESULTS of 279 CLL/SLL patients referred for potential allo-HSCT, 34 patients were HLA-B27 positive. For HLA-B27 patients, median age at CLL diagnosis was 53.5 years (range, 27-67) and 71% were male. Seven patients had 11q deletion and nine patients had 17p deletion detected prior to first CLL therapy or at relapse. Eleven HLA-B27 patients received allo-HSCT. Two patients developed acute myeloid leukemia. One patient with ankylosing spondylitis had Richter's transformation prior to any CLL therapy. Spondyloarthritis-related disorders were diagnosed in 12 HLA-B27 patients but there was no temporal correlation with development of CLL. Overall survival (OS) and treatment-free survival (TFS) were not significantly different between HLA-B27 patients with or without spondyloarthritis-related disorders. There were no significant differences in clinical characteristics at CLL diagnosis or OS/TFS between HLA-B27 positive and negative patients referred for allo-HSCT. CONCLUSIONS HLA-B27 positivity does not appear to influence outcome for CLL/SLL patients referred for allo-HSCT. Further studies are needed to evaluate the clinical significance of HLA-B27 in a general CLL population.
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Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopoietic Cell Transplantation in Young Patients With High Cytogenetic Risk Chronic Lymphocytic Leukemia - A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT
van Gelder, M., Ziagkos, D., de Wreede, L., van Biezen, A., Dreger, P., Gramatzki, M., Stelljes, M., Andersen, N. S., Schaap, N., Vitek, A., et al
Clinical lymphoma, myeloma & leukemia. 2017;17(10):667-675.e2
Abstract
BACKGROUND Patients with genetically high-risk relapsed/refractory chronic lymphocytic leukemia have shorter median progression-free survival (PFS) with kinase- and BCL2-inhibitors (KI, BCL2i). Allogeneic hematopoietic stem cell transplantation (alloHCT) may result in sustained PFS, especially in younger patients because of its age-dependent non-relapse mortality (NRM) risk, but outcome data are lacking for this population. PATIENTS AND METHODS Risk factors for 2-year NRM and 8-year PFS were identified in patients < 50 years in an updated European Society for Blood and Marrow Transplantation registry cohort (n = 197; median follow-up, 90.4 months) by Cox regression modeling, and predicted probabilities of NRM and PFS of 2 reference patients with favorable or unfavorable characteristics were plotted. RESULTS Predictors for poor 8-year PFS were no remission at the time of alloHCT (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.1-2.5) and partially human leukocyte antigen (HLA)-mismatched unrelated donor (HR, 2.8; 95% CI, 1.5-5.2). The latter variable also predicted a higher risk of 2-year NRM (HR, 4.0; 95% CI, 1.4-11.6) compared with HLA-matched sibling donors. Predicted 2-year NRM and 8-year PFS of a high cytogenetic risk (del(17p) and/or del(11q)) patient in remission with a matched related donor were 12% (95% CI, 3%-22%) and 54% (95% CI, 38%-69%), and for an unresponsive patient with a female partially HLA-matched unrelated donor 37% (95% CI, 12%-62%) and 38% (95% CI, 13%-63%). CONCLUSION Low predicted NRM and high 8-year PFS in favorable transplant high cytogenetic risk patients compares favorably with outcomes with KI or BCL2i. Taking into account the amount of uncertainty for predicting survival after alloHCT and after sequential administration of KI and BCL2i, alloHCT remains a valid option for younger patients with high cytogenetic risk chronic lymphocytic leukemia with a well-HLA-matched donor.Copyright © 2017 Elsevier Inc. All rights reserved.
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Impact of telomere length on the outcome of allogeneic stem cell transplantation for poor-risk chronic lymphocytic leukaemia: results from the GCLLSG CLL3X trial
Scheffold, A., Jebaraj, B. M., Jaramillo, S., Tausch, E., Steinbrecher, D., Hahn, M., Bottcher, S., Ritgen, M., Bunjes, D., Zeis, M., et al
British Journal of Haematology. , 2016 Jul 08. 2016