Michel van Gelder1, Dimitris Ziagkos2, Liesbeth de Wreede3, Anja van Biezen2, Peter Dreger4, Martin Gramatzki5, Matthias Stelljes6, Niels Smedegaard Andersen7, Nicolaas Schaap8, Antonin Vitek9, Dietrich Beelen10, Vesa Lindström11, Jürgen Finke12, Jacob Passweg13, Matthias Eder14, Maciej Machaczka15, Julio Delgado16, William Krüger17, Luděk Raida18, Gerard Socié19, Pavel Jindra20, Boris Afanasyev21, Eva Wagner22, Yves Chalandon23, Anja Henseler2, Stefan Schoenland4, Nicolaus Kröger24, Johannes Schetelig25. 1. Department of Internal Medicine, University Medical Center Maastricht, Maastricht, the Netherlands. Electronic address: m.van.gelder@mumc.nl. 2. Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands. 3. Department of Medical Statistics and Bioinformatics, Leiden University Medical Center, Leiden, the Netherlands; DKMS Clinical Trials Unit, Dresden, Germany. 4. Department of Medicine V, University of Heidelberg, Heidelberg, Germany. 5. Division of Stem Cell Transplantation and Immunotherapy, University Hospital Schleswig-Holstein, Kiel, Germany. 6. Department of Medicine A/Hematology and Oncology, University of Muenster, Muenster, Germany. 7. BMT Unit, Department of Hematology, Rigshospitalet, Copenhagen, Denmark. 8. Department of Hematology, Radboud University-Nijmegen Medical Center, Nijmegen, the Netherlands. 9. Department of Clinical Hematology, Institute of Hematology and Blood Transfusion, Prague, Czech Republic. 10. Department of Bone Marrow Transplantation, University Hospital, Essen, Germany. 11. Stem Cell Transplantation Unit, HUCH Comprehensive Cancer Center, Helsinki, Finland. 12. Department of Medicine-Hematology, Oncology, University of Freiburg, Freiburg, Germany. 13. Department of Hematology, University Hospital, Basel, Switzerland. 14. Department of Haematology, Hemostasis, Oncology, and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany. 15. Department of Hematology, Karolinska University Hospital, Stockholm, Sweden. 16. Department of Hematology, Hospital Clinic-Institute of Hematology and Oncology, Barcelona, Spain. 17. Klinik für Innere Medizin C, Hämatologie, und Onkologie, Transplantationszentrum, Palliativmedizin, Universitätsmedizin Greifswald, Germany. 18. Department of Haemato-Oncology, University Hospital, Olomouc, Czech Republic. 19. Department of Hematology - BMT1, Hopital St. Louis, Paris, France. 20. Department of Hematology/Oncology, Charles University Hospital, Pilsen, Czech Republic. 21. First State Pavlov Medical University of St Petersburg, Raisa Gorbacheva Memorial Research Institute for Paediatric Oncology, Hematology, and Transplantation, Petersburg, Russia. 22. Department of Hematology, Oncology, and Pneumology, University Medical Center Mainz, Mainz, Germany. 23. Département des Spécialités de Médecine, Service d'Hématologie, Hôpitaux Universitaires de Genève, Geneva, Switzerland. 24. Department of Stem Cell Transplantation, University Hospital Eppendorf, Hamburg, Germany. 25. DKMS Clinical Trials Unit, Dresden, Germany; Medizinische Klinik und Poliklinik I, University Hospital of the Technical University Dresden, Dresden, Germany.
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.
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.
Authors: Mauricette Michallet; Peter Dreger; Mohamad Sobh; Linda Koster; Jennifer Hoek; Ariane Boumendil; Christof Scheid; Christopher P Fox; Gerald Wulf; William Krüger; Michel van Gelder; Paolo Corradini; Domenico Russo; Jakob Passweg; Hélène Schoemans; Wolfgang Bethge; Nicolaas Schaap; Jan Cornelissen; Paul Browne; Nadira Durakovic; Lutz Muller; Silvia Montoto; Nicolaus Kroger; Johannes Schetelig Journal: Bone Marrow Transplant Date: 2019-11-07 Impact factor: 5.483