Relaps/Refrakter Hodgkin Lenfoma Hastalarının Otolog Hematopoetik Kök Hücre Nakil Sonuçları ve Risk Faktörü Etkilerinin Retrospektif Değerlendirilmesi

Yıl 2022, Cilt: 48 Sayı: 2, 231 - 237, 15.09.2022

Ezel Elgun , Vildan Gürsoy , Tuba Ersal , İbrahim Ethem Pınar , Fahir Özkalemkaş , Vildan Ozkocaman

https://doi.org/10.32708/uutfd.1062468

Öz

Otolog hematopoetik kök hücre nakli (OHKHN) relaps/refrakter Hodgkin lenfoma (HL) için kurtarma tedavisi sonrasında uygulanılan standart bir tedavidir. Çalışma ile merkezimizdeki relaps/refrakter HL tanılı OHKHN uygulanılan hastaların hastalıksız (DFS) ve genel sağkalım (OS) saptamasını ve risk faktörlerinin sağkalım üzerindeki etkisini incelenmeyi amaçladık. Merkezimizde Ocak 2009–Mart 2020 tarihleri arasında takipli OHKHN uygulanılan 314 hastanın 35 (%11)’i HL tanılıydı. Çalışmaya relaps/refrakter HL tanılı 18 yaşından büyük OHKHN uygulanılan 35 hasta dahil edildi. Hastaların %46’sı kadındı. Medyan tanı yaşı 29 (14-62) ve nakil yaşı 33 (22-62)’idi. Primer kemoterapi sonrasında hastaların %66’sında remisyon sağlanırken %34’ü refrakter kaldı. Relaps/refrakter HL’ye uygulanılan kurtarma tedavisi sonucunda %6 parsiyel yanıt, %26 tam yanıt, %68 refrakter kabul edildi. OHKHN sonrası hastaların %49’unda remisyon sağlanırken, %51’inde relaps gelişti. OHKHN sonrasında relaps olan hastaların tedavi yanıtında %39’u remisyon, %17’si refrakter, %44’ü hayatını kaybetti. Hayatını kaybeden hastaların %88'i lenfoma kaynaklı, %12’si lenfoma harici nedenden kaybedildi. OHKHN sonrası hastaların ortalama OS 99(±8,9) ay; DFS 60(±10,7) aydı. OHKHN sonrası relaps süresi 12 ay altında (p=0,033) ve relaps anındaki sedimentasyon düzeyinin normal olması (p=0,021) DFS için anlamlı; relaps anında LDH düzeyinin normal olması (p=0,022) OS için anlamlı olduğu saptandı. Çok değişkenli analizde OS üzerinde etkili prognostik risk faktörü saptanmadı. Diğer taraftan DFS üzerinde; hemoglobin düzeyinde bir birimlik artışın relaps riskini 1,67 kat arttırdığı, nötrofil engraftmanında bir birimlik artışın relaps riskini %30 ve relaps süresi 12 ay üzerinde olmasının relaps riskini %85 düzeyinde azalttığı saptandı. Çalışmamızda hastaların birkaç risk faktörünün OHKHN sağkalımı ve süresi üzerinde etkili olduğunu saptadık. Ancak daha anlamlı sonuçlar için çalışmaların örneklem grubunun genişletilmesi ve takip süresinin uzatılması gerekmektedir.

Anahtar Kelimeler

Otolog Hematopoetik Kök Hücre Nakli, Relaps/Refrakter Hodgkin Lenfoma, Sağkalım, Risk Faktörleri

Retrospective Evaluation of the Results of Autologous Hematopoietic Stem Cell Transplantation and the Effects of Risk Factors in Patients With Relaps/Refractory Hodgkin Lymphoma

Öz

Autologous hematopoietic stem cell transplantation (AHSCT) is a standard treatment applied after rescue treatment for relapse/refractory Hodgkin's lymphoma (HL). In our study, we aimed to determine the disease-free (DFS) and overall survival (OS) of patients diagnosed relapse/refractory HL who applied AHSCT in our center and to examine the effect of risk factors on survival. Thirty-five (11%) of 314 patients who underwent AHSCT between January 2009 and March 2020 and followed up in our center were defined HL. 46% of the patients were female. The median age of diagnosis was 29(14-62), and the transplantation age was 33(22-62). After primary chemotherapy; 66% of patients remained in remission, 34% refractory. The rescue treatment’s result applied to relapse/refractory HL, 68% refractory. 26% complete and 6% partial response. After AHSCT, the patients accomplished remission of 49% and developed relapsed 51%. The result of the treatment applied to patients who relapsed after AHSCT was accomplished remission in 39%, considered refractory at 17%, and died at 44%. The patients who died after AHSCT died 88% from lymphoma and died 12% from causes other. After AHSCT, the mean OS of patients was 99(±8.9); the mean DFS was 60(±10.7) months The time-to-relapse being less than 12 months (p=0.033) and normal sedimentation at relapse (p=0.021) were found to be substantial on DFS, and normal LDH at relapse (p=0.022) was found to be substantial on OS. In multivariate analysis, no prognostic risk factor was detected affecting OS. On the other hand, that was found that the increase in hemoglobin at diagnosis on PFS increased the risk of relapse 1.67 times; increase in one-unit neutrophil engraftment decreased the risk of relapse by 30%, and the time-to-relapse being over 12 months decreased the risk of relapse by 85%. In our study, we could validate several risk factors affecting survival and duration of patients who underwent AHSCT. However, that ıs necessary to expand the sample group of the studies and extend the follow-up period for more meaningful results.

Anahtar Kelimeler

Autologıcal stem cell transplantation, Relaps/ refrakter Hodgkin Disease, Survival, Rısk Factors

Kaynakça

• 1.Dufour M, Enric CC. The EBMT Handbook;Hematopoietic Stem Cell Transplantation and Cellular Therapies. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. 2018. 688 p.
• 2.Appelbaum FR, Forman SJ et al. Thomas’ Hematopoietic Cell Transplantation: Stem Cell Transplantation, Fourth Edition. Thomas’ Hematopoietic Cell Transplantation: Stem Cell Transplantation, Fourth Edition. 2009. 1–1718 p.
• 3.Broccoli A, Zinzani PL. The role of transplantation in Hodgkin lymphoma. British Journal of Haematology. 2019;184(1):93–104.
• 4.Maccario R, Moretta A et al. Human mesenchymal stem cellsand cyclosporin a exert a synergistic suppressive effect on in vitro activation of alloantigen-specific cytotoxic lymphocytes.Biology of Blood Marrow Transplant. 2005;11(12):1031–2.
• 5.Shanbhag S, Ambinder R. Hodgkin Lymphoma: a review andupdate on recent progress. HHS Public Access; available PMC 2019 March 01. 2019;68(2):116–32.
• 6.Storer BE, Gopal AK et al. Comorbidities, Alcohol Use Disorder, and Age Predict Outcomes after AutologousHematopoietic Cell Transplantation for Lymphoma. 2017;22(9):1582–7.
• 7.Arat M, Arpaci F, et al. Turkish Transplant Registry: Acomparative analysis of national activity with the EBMT European Activity Survey. Bone Marrow Transplant. 2008;42(SUPPL.1):142–5.
• 8.Bröckelmann PJ, Müller H et al. Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma. Annals of Oncology. 2017;28(6):1352–8.
• 9.Moskowitz CH, Walewski J et al. Five-year PFS from the AETHERA trial of brentuximab vedotin for Hodgkin lymphoma at high risk of progression or relapse. Blood
• 10.Alsuliman BC. Autologous hematopoietic stem-cell transplant in small-sized and peripheral centers : a 10-year experiment. Therapeutic Advances in Hematology Original. 2019;10: 1–7:1–7.
• 11.Radford J, Illidge T et al. Results of a trial of PET-directed therapy for early-stage Hodgkin’s lymphoma. New EnglandJournal of Medicine. 2015;372(17):1598–607.
• 12.Puig N, Pintilie M et al. High-dose chemotherapy and auto-SCT in elderly patients with Hodgkin’s lymphoma. Bone Marrow Transplant. 2011;46(10):1339–44.
• 13.Morschhauser F, Brice P et al. Risk-adapted salvage treatment with single or tandem autologous stem-cell transplantation for first relapse/refractory Hodgkin’s lymphoma: Results of the prospective multicenter H96 trial by the GELA/SFGM study group. Journal of Clinical Oncology. 2008;26(36):5980–7.
• 14.Cortez AJP, Dulley FL et al. Autologous hematopoietic stemcell transplantation in classical hodgkin’s lymphoma. Revista Brasileira Hematolgia Hemoter. 2011;33(1):10–4.
• 15.Arai S, Fanale M et al. Defining a hodgkin lymphoma population for novel therapeutics after relapse from autologoushematopoietic cell transplant. Leukemia and Lymphoma. 2013;54(11):2531–3.
• 16.Scott DR, Nademanee A et al. Quality of life results from aphase 3 study of brentuximab vedotin consolidation following autologous haematopoietic stem cell transplant for persons with Hodgkin lymphoma Scott. HHS Public Access. 2016;175(1):139–48.
• 17.Lazarus HM, Loberiza FR et al. Autotransplants for Hodgkin’s disease in first relapse or second remission: A report from the autologous blood and marrow transplant registry. Bone Marrow Transplant. 2001;27(4):387–96.
• 18.Constans M, Sureda A et al. Autologous stem celltransplantation for primary refractory Hodgkin’s disease: Results and clinical variables affecting outcome. Annals ofOncology.
• 19.Martínez C, Salamero O et al. Autologous stem celltransplantation for patients with active Hodgkin’s lymphoma: Long-term outcome of 61 patients from a single institution. Leukemia and Lymphoma. 2007;48(10):1968–75.
• 20.Perz JB, Giles C et al. LACE-conditioned autologous stem cell transplantation for relapsed or refractory Hodgkin’s lymphoma: Treatment outcome and risk factor analysis in 67 patients from a single centre. Bone Marrow Transplant. 2007;39(1):41–7.
• 21.Czyzc J, Dziadziuszko R et al. Two autologous transplants inthe treatment of patients with Hodgkin’s lymphoma: Analysisof prognostic factors and comparison with a single procedure. Leuk Lymphoma. 2007;48(3):535–41.
• 22.Stamatoullas A, Brice P et al. Autologous stem cell transplantation for patients aged 60 years or older withrefractory or relapsed classical Hodgkin’s lymphoma: A retrospective analysis from the French Society of Bone MarrowTransplantation and Cell Therapies. Bone Marrow Transplant. 2016;51(7):928–32.
• 23.Shah GL, Moskowitz CH. Transplant strategies in relapsed/refractory Hodgkin lymphoma. Blood. 2018;131(15):1689–97.
• 24.Sharma A, Kayal S et al. Comparison of BEAM vs. LEAMregimen in autologous transplant for lymphoma at AIIMS.Springerplus. 2013;2(1):1–6.