Lenfomada Otolog Kök Hücre Nakli Hazırlama Rejimi Olarak Beam ve Bucye Protokollerinin Karşılaştırılması

Yıl 2020, Cilt: 42 Sayı: 5, 489 - 495, 15.09.2020

Eren Gunduz , Hava Üsküdar Teke , Cengiz Bal , Tuba Bulduk

https://doi.org/10.20515/otd.566305

Öz

Otolog kök hücre nakli, immünokemoterapi sonrası relaps Hodgkin ve non-Hodgkin lenfomada uzun süreli sağkalımı arttıran standart bir tedavi şeklidir. Başarıyı etkileyen en önemli faktör hastalığın kemosensitif ya da kemorezistan olmasıdır. Ancak transplant ilişkili morbidite/mortalite işlem başarısını halen önemli ölçüde etkilemektedir. Transplant ilişkili morbidite/mortalite açısından minimal kalıntı hastalığın yok edilmesi ile toksisite arasında bir denge sağlanması önemlidir. Bu amaçla yüksek doz rejimlerin terapötik penceresini arttırmaya yönelik çabalar devam etmektedir. Bununla birlikte bir yüksek doz tedavinin diğerine üstünlüğünden bahsetmek için kesin kanıtlar mevcut değildir. Farklı rejim arayışları devam etmekle birlikte özellikle karmustin temininde bir dönem yaşanan sıkıntı rejim değişikliğini zorunlu kılmıştır. Bu süreçte merkezimizde BEAM yerine BuCyE protokolü tercih edilmiştir. Çalışmamızda BuCyE’nin BEAM’a kalıcı bir alternatif olma potansiyelinin değerlendirilmesi amaçlanmıştır. Çalışmaya otolog nakil işlemleri 2006-2017 yılları arasında gerçekleştirilen 20 hasta dahil edildi.Hastalar 2 gruba ayrılarak demografik, klinik ve laboratuvar özellikleri açısından değerlendirildi. BuCyE uygulanan hasta sayısı 10 idi. Karşılaştırma amacıyla kullanılan BEAM grubuna seçilen hastalar verilerine ulaşılması mümkün olan hastalara ait isim listesinden rastgele seçildi. Sağkalım süresi; kaybedilen hastalar için nakil günü ile ölüm tarihi arası, yaşayan hastalar için nakil günü ile değerlendirme tarihi arası olarak hesaplandı. Çalışmamızda birçok parametre için veriler 2 grupta da benzer olmakla birlikte sağkalım BEAM lehine bulundu (55.25±15.29 vs 12.12±4.02 ay, p=0.02). Hasta sayısı ve takip süresi kesin sonuçlar çıkarmak için yetersiz olmakla birlikte verilerimiz sağkalım süresi ve merkezimizin mevcut tecrübesi itibariyle BEAM protokolünün lenfoma için BuCyE’ye tercih edilecek hazırlama rejimi olduğunu düşündürmüştür. Ancak prospektif karşılaştırmalı çalışmaların yokluğunda bir hazırlama rejimini tavsiye etmek mevcut kanıt düzeyleri düşük olduğundan güçtür. Devam eden klinik çalışmalara katılım önemlidir.

Anahtar Kelimeler

lenfoma, otolog kök hücre nakli

Comparison of Beam and Bucye Protocols as a Conditioning Regimen for Autologous Stem Cell Transplantation in Lymphoma

Öz

Autologous stem cell transplantation is a type of standard therapy which increases the long term survival in post immunochemotherapy relapsed Hodgkin and non-Hodgkin lymphoma. Success is most commonly affected by the presence of chemosensitive or chemoresistant disease. However, transplant related morbidity/mortality still affects the success of the procedure. In the era of transplant related morbidity/mortality it is important to provide a balance between minimal residual disease and toxicity. To manage this goal trials on increasing the therapeutic window of high dose regimens are continuing. Unfortunately, we do not have conclusive evidence to say that one high dose regimen is better than the other. Different regimen trials are still going on but lack of carmustine for a while led to a compulsory change in regimen preference. During this period BuCyE was preferred instead of BEAM in our center. In this study, our aim was to decide whether BuCyE can be a permanent alternative to BEAM. Twenty patients who underwent autologous transplantation between 2006-2017 were included in the study. Patients were divided into 2 groups demographic, clinical and laboratory characteristics were evaluated. The number of patients in BuCyE group was 10. BEAM group which is used for comparison was chosen randomly from the list of patients with accessible data. Survival was calculated as the time between day of transplantation and data collection or exitus. Many of the parameters were similar between 2 groups in our study but survival was longer in favor of BEAM group (55.25±15.29 vs 12.12±4.02 months, p=0.02). Despite number of patients and follow up period is not enough to make definitive conclusions our data suggested that BEAM was superior to BuCyE in lymphoma in terms of survival and center experience. In the absence of prospective trials it is difficult to suggest a conditioning regimen due to low level of evidence. It is important to participate in ongoing clinical trials.  

Anahtar Kelimeler

Lymphoma; autologous stem cell transplantation

Kaynakça

• 1) Isidori A, Clissa C, Loscocco F, Guiducci B, Barulli S, Malerba L, Gabucci E, Visani G. Advancement in high dose therapy and autologous stem cell rescue in lymphoma. World J Stem Cells. 2015;7(7):1039-46.
• 2) Fernandez HF, Escalón MP, Pereira D, Lazarus HM. Autotransplant conditioning regimens for aggressive lymphoma: are we on the right road? Bone Marrow Transplant. 2007;40(6):505-13.
• 3) Chen YB, Lane AA, Logan B, Zhu X, Akpek G, Aljurf M, Artz A, Bredeson CN, Cooke KR, Ho VT, Lazarus HM, Olsson R, Saber W, McCarthy P, Pasquini MC. Impact of conditioning regimen on outcomes for patients with lymphoma undergoing high-dose therapy with autologous hematopoietic cell  transplantation. Biol Blood Marrow Transplant. 2015;21(6):1046-53.
• 4) Caballero MD, Rubio V, Rifon J, Heras I, Garcia-Sanz R, Vazquez L, Vidriales B, del Canizo MC, Corral M, Gonzalez M, Leon A, Jean-Paul E, Rocha E, Morelada JM, San Miguel JF. BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors. Bone Marrow Transplant. 1997;20(6):451-8.
• 5) Damaj G, Cornillon J, Bouabdallah K, Gressin R, Vigouroux S, Gastinne T, Ranchon F, Ghesquieres H, Salles G, Yakoub-Agha I, Gyan E. Carmustine replacement in intensive chemotherapy preceding reinjection of autologous HSCs in Hodgkin and non-Hodgkin lymphoma: a review. Bone Marrow Transplant. 2017;52(7):941-9.
• 6) Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, Di Bartolomeo P, Crescimanno A, Perrone T, Pinto A. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010;45(7):1147-53.
• 7) Garciaz S, Coso D, Schiano de Collela JM, Broussais F, Stoppa AM, Aurran T, Chabannon C, Helvig A, Xerri L, Blaise D, Bouabdallah R. Bendamustine-based conditioning for non-Hodgkin lymphoma autologous transplantation: an increasing risk of renal toxicity. Bone Marrow Transplant. 2016;51(2):319-21.
• 8) Kim JW, Lee HJ, Yi HG, Kim BS, Bang SM, Kim JS, Kim I, Yoon SS, Lee JS, Kim CS, Park S, Kim BK. Mitoxantrone, etoposide, cytarabine, and melphalan (NEAM) followed by autologous stem cell transplantation for patients with chemosensitive aggressive non-Hodgkin lymphoma. Am J Hematol. 2012;87(5):479-83.
• 9) Sharma A, Kayal S, Iqbal S, Malik PS, Raina V. Comparison of BEAM vs. LEAM regimen in autologous transplant for lymphoma at AIIMS. Springerplus. 2013;2:489.
• 10) Krishnan AY, Palmer J, Nademanee AP, Chen R, Popplewell LL, Tsai NC, Sanchez JF, Simpson J, Spielberger R, Yamauchi D, Forman SJ. Phase II Study of Yttrium-90 Ibritumomab Tiuxetan Plus High-Dose BCNU, Etoposide, Cytarabine, and Melphalan for Non-Hodgkin Lymphoma: The Role of Histology. Biol Blood Marrow Transplant. 2017;23(6):922-9.
• 11) Briones J, Novelli S, García-Marco JA, omás JF, Bernal T, Grande C, Canales MA, Torres A, Moraleda JM, Panizo C, Jarque I, Palmero F, Hernández M, González-Barca E, López D, Caballero D; GELTAMO. Autologous stem cell transplantation after conditioning with yttrium-90 ibritumomab tiuxetan plus BEAM in refractory non-Hodgkin diffuse large B-cell lymphoma: results of a prospective, multicenter, phase II clinical trial. Haematologica. 2014;99(3):505-10.
• 12) Voegeli M, Rondeau S, Berardi Vilei S, Lerch E, Wannesson L, Pabst T, Rentschler J, Bargetzi M, Jost L, Ketterer N, Bischof Delaloye A, Ghielmini M. Y90 -Ibritumomab tiuxetan (Y90 -IT) and high-dose melphalan as conditioning regimen before autologous stem cell transplantation for elderly patients with lymphoma in relapse or resistant to chemotherapy: a feasibility trial (SAKK 37/05). Hematol Oncol. 2017;35(4):576-83.
• 13) Gilli S, Novak U, Taleghani BM, Baerlocher GM, Leibundgut K, Banz Y, Zander T, Betticher D, Egger T, Rauch D, Pabst T. BeEAM conditioning with bendamustine-replacing BCNU before autologous transplantation is safe and effective in lymphoma patients. Ann Hematol. 2017;96(3):421-9.
• 14) William BM, Allen MS, Loberiza FR Jr, Bociek RG, Bierman PJ, Armitage JO, Vose JM. Phase I/II study of bortezomib-BEAM and autologous hematopoietic stem cell transplantation for relapsed indolent non-Hodgkin lymphoma, transformed, or mantle cell lymphoma. Biol Blood Marrow Transplant. 2014;20(4):536-42.15) Berber I, Erkurt MA, Nizam I, Koroglu M, Kaya E, Kuku I, Bag HG. Can BuCyE conditioning regimen be an alternative treatment to BEAM at autologous transplantation in malignant lymphoma patients?: a single center experience. Int J Clin Exp Med. 2015;8(9):16308-14.
• 16) Sakellari I, Mallouri D, Batsis I, Apostolou C, Konstantinou V, Abela EM, Douka V, Marvaki A, Karypidis K, Iskas M, Baliakas P, Kaloyannidis P, Yannaki E, Sotiropoulos D, Kouvatseas G, Smias C, Anagnostopoulos A. Carmustine, etoposide, cytarabine and melphalan versus a newly designed intravenous busulfan-based Busulfex, etoposide and melphalan conditioning regimen for autologous hematopoietic cell transplant: a retrospective matched-pair analysis in advanced Hodgkin and non-Hodgkin lymphomas. Leuk Lymphoma. 2015;56(11):3071-81.
• 17) Sellner L, Boumendil A, Finel H, Choquet S, de Rosa G, Falzetti F, Scime R, Kobbe G, Ferrara F, Delmer A, Sayer H, Amorim S, Bouabdallah R, Finke J, Salles G, Yakoub-Agha I, Faber E, Nicolas-Virelizier E, Facchini L, Vallisa D, Zuffa E, Sureda A, Dreger P. Thiotepa-based high-dose therapy for autologous stem cell transplantation in lymphoma: a retrospective study from the EBMT. Bone Marrow Transplant. 2016;51(2):212-8.
• 18) Krishnan AY, Palmer J, Nademanee AP, Chen R, Popplewell LL, Tsai NC, Sanchez JF, Simpson J, Spielberger R, Yamauchi D, Forman SJ. Phase II Study of Yttrium-90 Ibritumomab Tiuxetan Plus High-Dose BCNU, Etoposide, Cytarabine, and Melphalan for Non-Hodgkin Lymphoma: The Role of Histology. Biol Blood Marrow Transplant. 2017;23(6):922-9.
• 19) Esbah O, Tekgündüz E, Şirinoğlu Demiriz I, Civriz Bozdağ S, Kaya A, Tetik A, Kayıkçı Ö, Durgun G, Kocubaba Ş, Altuntaş F. Finding the Optimal Conditioning Regimen for Relapsed/Refractory Lymphoma Patients Undergoing Autologous Hematopoietic Cell Transplantation: A Retrospective Comparison of BEAM and High-Dose ICE. Turk J Haematol. 2016;33(3):209-15.
• 20) Khattry N, Gupta A, Jain R, Gore A, Thippeswamy R, Jeevangi N, Kannan S, Nair R, Saikia T. LACE versus BEAM conditioning in relapsed and refractory lymphoma transplant: retrospective multicenter analysis of toxicity and efficacy. Int J Hematol. 2016;103(3):292-8.
• 21) Saleh K, Danu A, Koscielny S, Legoupil C, Pilorge S, Castilla_Llorente C, Ghez D, Lazarovici J, Michot JM, Khalife-Saleh N, Lapierre V, Alenxandrova K, Arfi-Rouche J, Bourhis JH, Ribra V. A retrospective, matched paired analysis comparing bendamustine containing BeEAM versus BEAM conditioning regimen: results from a single center experience. Leuk Lymphoma 2018;59(11):2580-7.
• 22) Joffe E, Rosenberg D, Rozovski U, Perry C, Kirgner I, Trestman S, Gur O, Aviv F, Sarid N, Kolomansky A, Gepstein L, Herishanu Y, Naparstek E. Replacing carmustine by thiotepa and cyclophosphamide for autologous stem cell transplantation in Hodgkin's and non-Hodgkin's B-cell lymphoma. Bone Marrow Transplant. 2018;53(1):29-33.