Page 104 - 2021_07-Haematologica-web

O. Tournilhac et al.
driven immune-intervention following ATG-based RIC allogeneic HSCT in CLL. These data highlight the impor- tance to repeatedly monitor post-HSCT MRD to guide early CsA discontinuation in patients with D90 MRDpos and without GvHD. However, as we report the results of this study in 2020, we must emphasize that the entry cri- teria were based on the EBMT 2007 recommendations, which no longer represent current practice. Particularly, this is the case for untreated patients with del(17p) and/or TP53 mutation who represent 26% of the study's enroll- ment. A presentation of post-transplant outcome exclud- ing these 11 patients is shown in the Online Supplementary Appendix (Online Supplementary Figure S3). Allogeneic HSCT indications have evolved in 2014 under the impulse of the European Research Initiative on CLL (ERIC) and EBMT with of a new decisional algorithm according to patient biology and prior treatment with BCR and BCL-2 inhibitors,42 the feasibility of which has just been reported in a recent analysis.43 The pre-emptive immune modula- tion based on post-transplant MRD, as described in our study in patients who were 90% naive of BCR and/or BCL-2 treaments, should also be effective in patients pre- treated with such agents, but this will have to be demon- strated.
Disclosures
OT has received travel grant, scientific support, and honorarium
for board participation from Amgen, Roche, Jansen, Abbevie and Gilehead; MLGT has receieved honorarium for board participa- tion from Alexion; VL has received board participation, speaker bureau, honorarium from Roche, Abbevie, Gilehead, Amgen and Janssen.
Contributions
OT and ND designed and performed research including patients’ care, coordinated the study and wrote the paper; MLGT and CQ performed MRD flow cytometry assessment; PC per- formed molecular chimerism; SNGQ, EF, PC, FLI, GLD, DM, CT, CB, CO, PT, RR, GG, LV, CS, JOB, VL performed research especially patients’ care; RL, LC, and AC worked on study design, study application and national coordination and BP performed sta- tistical data analysis.
Acknowledgments
The study was supported by a National Grant from the Fondation ARC. Logistic support was provided through the Fonds de recherche clinique en hématologie Force Hémato. Les Laboratoires Pierre Fabre provided financial research support for the study, but did not participate in the conduct of the study or data and results analysis.
The authors thank Dr Reza Tabrizi and Dr Oumeladi Reman for their devoted implication in patient care and the clinical research assistants of the FILO group for the onsite monitoring process per- formed during the study.
References
1.Byrd JC, Furman RR, Coutre SE, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32-42.
2. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chronic lymphocytic leukemia. N Engl J Med. 2014;370(11):997-1007.
3. Roberts AW, Davids MS, Pagel JM. et al. Targeting BCL2 with venetoclax in relapsed chronic lymphocytic leukemia. N Engl J Med. 2016;374(4):311-322.
4. Gribben JG. How and when I do allogeneic transplant in CLL. Blood 2018; 132(1):31-39. 5. Hallek M. Chronic lymphocytic leukemia: 2017 update on diagnosis, risk stratification, and treatment. Am J Hematol.
2017;92(9):946-965.
6.Hahn M, Böttcher S, Dietrich S, et al.
Allogeneic hematopoietic stem cell trans- plantation for poor-risk CLL: dissecting immune-modulating strategies for disease eradication and treatment of relapse. Bone Marrow Transplant. 2015;50(10):1279-1285.
7.Khouri IF, Bassett R, Poindexter N, et al. Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chron- ic lymphocytic leukemia. Cancer. 2011;117(20):4679-4688.
8.Michallet M, Socié G, Mohty M, et al. Rituximab, fludarabine, and total body irra- diation as conditioning regimen before allo- geneic hematopoietic stem cell transplanta- tion for advanced chronic lymphocytic leukemia: long-term prospective multicenter study. Exp Hematol. 2013;41(2):127-133.
9. Sorror ML, Storer BE, Sandmaier BM, et al. Five-year follow-up of patients with advanced chroniclLymphocytic leukemia treated with allogeneic hematopoietic cell transplantation after nonmyeloablative con-
ditioning. J Clin Oncol. 2008;26(30):4912-
4920.
10.Dreger P, Döhner H, Ritgen M, et al.
Allogeneic stem cell transplantation pro- vides durable disease control in poor-risk chronic lymphocytic leukemia: long-term clinical and MRD results of the German CLL Study Group CLL3X trial. Blood. 2010;116(14):2438-2447.
11. Algrin C, Golmard J-L, Michallet M, et al. Flow cytometry minimal residual disease after allogeneic transplant for chronic lym- phocytic leukemia. Eur J Haematol. 2017; 98(4):363-370.
12.Farina L, Carniti C, Dodero A, et al. Qualitative and quantitative polymerase chain reaction monitoring of minimal resid- ual disease in relapsed chronic lymphocytic leukemia: early assessment can predict long- term outcome after reduced intensity allo- geneic transplantation. Haematologica. 2009;94(5):654-662.
13.Logan AC, Zhang B, Narasimhan B, et al. Minimal residual disease quantification using consensus primers and high-through- put IGH sequencing predicts post-transplant relapse in chronic lymphocytic leukemia. Leukemia. 2013;27(8):1659-1665.
14. Moreno C, Villamor N, Colomer D, et al. Clinical significance of minimal residual dis- ease, as assessed by different techniques, after stem cell transplantation for chronic lymphocytic leukemia. Blood. 2006;107(11):4563-4569.
15. Ritgen M, Böttcher S, Stilgenbauer S, et al. Quantitative MRD monitoring identifies distinct GVL response patterns after allo- geneic stem cell transplantation for chronic lymphocytic leukemia: results from the GCLLSG CLL3X trial. Leukemia. 2008;22(7):1377-1386.
16. Dreger P, Corradini P, Kimby E, et al. Indications for allogeneic stem cell trans-
plantation in chronic lymphocytic leukemia: the EBMT transplant consensus. Leukemia. 2007;21(1):12-17.
17.Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HSCT)- specific comorbidity index: a new tool for risk assessment before allogeneic HSCT. Blood. 2005;106(8):2912-2919.
18. Blaise D, Devillier R, Lecoroller-Sorriano AG, et al. Low non-relapse mortality and long-term preserved quality of life in older patients undergoing matched related donor allogeneic stem cell transplantation: a prospective multicenter phase II trial. Haematologica. 2015;100(2):269-274.
19. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute–Working Group 1996 guidelines. Blood. 2008;111(12):5446-5456.
20. Rawstron AC, Villamor N, Ritgen M, et al. International standardized approach for flow cytometric residual disease monitoring in chronic lymphocytic leukaemia. Leukemia. 2007;21(5):956-964.
21. Rawstron AC, Böttcher S, Letestu R, et al. Improving efficiency and sensitivity: European Research Initiative in CLL (ERIC) update on the international harmonised approach for flow cytometric residual dis- ease monitoring in CLL. Leukemia. 2013;27(1):142-149.
22. Rawstron AC, Fazi C, Agathangelidis A, et al. A complementary role of multiparameter flow cytometry and high-throughput sequencing for minimal residual disease detection in chronic lymphocytic leukemia: an European Research Initiative on CLL study. Leukemia. 2016;30(4):929-936.
23. Glucksberg H, Storb R, Fefer A, et al. Clinical
1874
haematologica | 2021; 106(7)