Sinem CİVRİZ BOZDAĞ, Muhit ÖZCAN, Pervin TOPÇUOĞLU, Erden ATİLLA, Meltem Kurt YÜKSEL, Gültekin PEKCAN, Önder ARSLAN, Osman İLHAN, Günhan GÜRMAN, Pınar ATACA ATİLLA, Sinem CİVRİZ BOZDAĞ, Selami Koçak TOPRAK

Kronik Lenfositik Lösemi’de Allojeneik Kök Hücre Nakli Deneyimi*

Amaç: Kronik lenfositik lösemi (KLL) erișkinlerde en sık görülen lösemidir. Tedavi seçeneği kısıtlı kötü prognozu olan hastalarda, allojeneik kök hücre nakli (AKHN) tedavi alternatifidir. KLL’de allojeneik nakil; tedaviye yan ıtısız veya pürin analogları sonras ında erken nükste (12 aydan kısa), pürin analogları veya otolog kök hücre nakli ile yanıta ulașmıș hastalarda 24 ay içinde nüks geli-șiminde veya p53 anomalisi olanlarda önerilmekteyken günümüzde hedefe yönelik tedavilerin baș arısıyla AKHN endikasyonları güncellenmiștir. Bu çalıșmada, allojeneik kök hücre nakli yapı-lan KLL hastalarımızın değerlendirilmesi amaçlanmıștır.Gereç ve Yöntem: 2007 -2015 tarihleri arasında Ankara Üniversitesi Tıp Fakültesi Hematoloji Bi-lim Dalı’nda tanı alan ve sonrasında Kök Nakil Ünitemizde AKHN yapılmıș yüksek riskli 7 KLL has-tası retrospektif olarak değerlendirilmiștir.Bulgular: Nakil sonrası hastalık değerlendirmesinde; 4/7 hastada (%57) tam remisyon, 3/7 has-tada (%43) yanıtsızlık gözlenmiștir. Akut graft versus host hastalığı 2/7 (%29) hastada görülür-ken, 3/7 (%43) hasta kronik graft versus host hastalığı tanısı almıștır. Genel sağkalım 69 aydır (aralık, 19-121 ay).Sonuç: Yüksek riskli KLL hastalarında AKHN ile uzun süreli ve sürdürülebilir yanıt oranlarına ula-șılabilmektedir.

Allogeneic Stem Cell Transplantation Experience in Chronic Lymphocytic Leukemia

Objective: Chronic lymphocytic leukemia (CLL) is the most common leukemia in adults. In pa-tients with poor prognosis, allogeneic stem cell transplantation (ASCT) treatment is an alterna-tive. ASCT indications in CLL: Patients with refractory disease or early relapse (shorter than 12 months) after treatment with purine analogues, relapse within 24 months after achieving re-sponse with purine analogues/autologous stem cell transplantation or in patients with p53 anomalies. However, the indications have been revised after novel therapies reached successful results in relapsed/refractory setting. In this study, we aimed to evaluate our CLL patients who underwent ASCT.Materials and Methods: Seven high-risk patients with CLL who were diagnosed at Ankara Uni-versity School of Medicine Department of Hematology between 2007-2015 and subsequently underwent ASCT at our Bone Marrow Transplantation Unit were evaluated retrospectively.Results: In post-transplant disease evaluation, 4/7 patients (57%) achieved complete remission and 3/7 patients (43%) did not respond. Acute graft versus host disease was detected in 2/7 (29%) patients while 3/7 (43%) patients were diagnosed with chronic graft versus host disease. Overall survival was 69 months (range, 19-121 months).Conclusion: Sustained response rates can be achieved with ASCT in high-risk CLL patients in long-term.

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28. Schetelig J, Wreede LC, Gelder van M et al. Risk factors for treatment failure after allogeneic transplantation of patients with CLL: a report from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2017;52: 552-560.
27. Van Gelder M, Ziagkos D, Wreede L, et al. Baseline Characteristics Predicting Very Good Outcome of Allogeneic Hematopo-ietic Cell Transplantation in Young Pati-ents With High Cytogenetic Risk Chronic Lymphocytic Leukemia-A Retrospective Analysis From the Chronic Malignancies Working Party of the EBMT. Clin Lymp-homa Myeloma Leuk. 2017;17:667-675.
26. van Gelder M, de Wreede LC, Bornhauser M, et al. Long-term survival of patients with CLL after allogeneic transplantation: a report from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2017; 52:372-380.
25. Cwynarski K, van Biezen A, de Wreede L, et al. Autologous and allogeneic stem-cell transplantation for transformed chronic lymphocytic leukemia (Richter’s synd-rome): a retrospective analysis from the Chronic Lymphocytic Leukemia Subcom-mittee of the Chronic Leukemia Working Party and Lymphoma Working Party of the European Group for Blood and Mar-row Transplantation. J Clin Oncol. 2012;30: 2211-2217.
24. Khouri IF, Saliba RM, Admirand J, et al. Graft-versus-leukaemia effect after non-myeloablative haematopoietic transplanta-tion can overcome the unfavourable expression of ZAP-70 in refractory chro-nic lymphocyte leukaemia. Br J Haematol. 2007;137:355-363.
23. Schetelig J, van Biezen A, Brand R, et al. Allogeneic hematopoietic stem-cell transplantation for chronic lymphocytic leukemia with 17p deletion: a retrospective European Group for Blood and Marrow Transplantation analysis. J Clin Oncol. 2008;26:5094-5100.
22. Khouri IF, Bassett R, Poindexter N, et al. Nonmyeloablative allogeneic stem cell transplantation in relapsed/refractory chronic lymphocytic leukemia: long-term follow-up, prognostic factors, and effect of human leukocyte histocompatibility an-tigen subtype on outcome. Cancer. 2011;117:4679-4688.
21. Kharfan-Dabaja MA, Moukalled N, Reljic T, et al. Reduced intensitiy is preferred over myeloablative conditioning alloge-neic HCT in chronic lymphocytic leuke-mia whenever indicated: A systemic re-view/meta-analysis. Hematol Oncol Stem Cell Ther. 2017 Nov 26.
20. Brown JR, Kim HT, Armand P, et al. Long-term follow-up of reduced-intensity allogeneic stem cell transplantation for chronic lymphocytic leukemia: prognostic model to predict outcome. Leukemia. 2013 ;27:362-369.
19. Kharfan-Dabaja MA, El-Asmar J., Awan FT, et al. Current state of hematopoietic cell transplantation in CLL as smart thera-pies emerge. Best Pract Res Clin Haema-tol. 2016;29:54-66.
18. Jain P, Keating M, Wierda W, et al. Out-comes of patients with chronic lymphocy-tic leukemia after discontinuing ibrutinib. Blood. 2015;125:2062-2067.
17. Shanafelt TD, Borah BJ, Finnes HD, et al. Impact of ibrutinib and idelalisib on the pharmaceutical cost of treating chronic lymphocytic leukemia at the individual and societal levels. J Oncol Pract 2015 ;11:252-258.
16. Jones J, Choi MY, Mato AR, et al. Vene-toclax (VEN) monotherapy for patients with chronic lymphocytic leukemia (CLL) who relapsed after or were refractory to ibrutinib or idelalisib. Blood 2016; 128:637.
15. Stilgenbauer S, Eichhorst B, Schetelig J, et al. Venetoclax in relapsed or refractory chronic ymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study. Lancet Oncol. 2016;17:768-778.
14. Burger JA, Keating MJ, Wierda WG, et al. Safety and activity of ibrutinib plus rituximab for patients with high-risk chro-nic lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol, 2014;15:1090-1099.
13. Shustik C, Bruckler IB, Delage R, et al. Ad-vances in the treatment of relapsed/refrac-tory chronic lymphocytic leukemia. Ann Hematol. 2017;96:1185-1196.
12. Bacigalupo A, Ballen K, Rizzo D et al. De-fining the intensity of conditioning regi-mens: working definitions. Biol Blood and Marrow Transplant. 2009;15: 1628-1633.
11. 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;111:5446-5456.
10. Gratwohl A, Stern M, Brand R, et al. Risk score for outcome after allogeneic hema-topoietic stem cell transplantation: a ret-rospective analysis. Cancer. 2009;115: 4715-4726.
9. Sorror ML, Storer BE, Sandmaier BM, et al. Five-year follow-up of patients with ad-vanced chronic lymphocytic leukemia tre-ated with allogeneic hematopoietic cell transplantation after nonmyeloablative conditioning. J Clin Oncol 2008; 26:4912-4920.
8. Kharfan-Dabaja MA, Kumar A, Hama-dani M, et al. Clinical practice recommen-dations for use of allogeneic hematopoie-tic cell transplantation in chronic lymp-hocytic leukemia on behalf of the guideli-nes Committee of the American Society for blood and marrow transplantation. Biol Blood Marrow Transplant. 2016; 22:2117-2125.
7. Stilgenbauer S, Zenz T. Understanding and managing ultra high-risk chronic lymphocytic leukemia. Hematology Am Soc Hematol Educ Program. 2010;2010:481-488.
6. Roberts AW, Davids MS, Pagel JM, et al. Targeting BCL2 with venetoclax in relap-sed chronic lymphocytic leukemia. N Engl J Med. 2016;374:311-322.
5. Furman RR, Sharman JP, Coutre SE, et al. Idelalisib and rituximab in relapsed chro-nic lymphocytic leukemia. N Engl J Med. 2014; 370:997-1007.
4. Byrd JC, Brown JR, O’Brien S, et al. Ibru-tinib versus ofatumumab in previously tre-ated chronic lymphoid leukemia. N Engl J Med. 2014;371:213-223.
3. Chao MP. Treatment challenges in the ma-nagement of relapsed or refractory non-Hodgkin’s lymphoma - novel and emer-ging therapies. Cancer Manag Res. 2013;5:251-269.
2. Bazargan A, Tam CS, Keating MJ. Predic-ting survival in chronic lymphocytic leuke-mia. Expert Rev Anticancer Ther. 2012; 12:393–403.
1. National Cancer Institute. Surveillance, Epidemiology, and End Results Program (SEER). Cancer Statistics Review: 1975-2010, November 21, 2013; 1975-2010