Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study

Yıl: 2022 Cilt: 39 Sayı: 3 Sayfa Aralığı: 152 - 159 Metin Dili: İngilizce DOI: 10.4274/tjh.galenos.2022.2021.0680 İndeks Tarihi: 02-10-2022

Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study

Öz:
Objective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up. Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse. Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787). Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.
Anahtar Kelime:

Akut Lenfoblastik Lösemili Erişkin Hastalarda Profilaktik Santral Sinir Sistemi Işınlaması Vazgeçilmez Değildir: Çok Merkezli Retrospektif Kohort Çalışması

Öz:
Amaç: Erişkin akut lenfoblastik lösemi (ALL) hastalarında, santral sinir sistemi (SSS) tutulumuna karşı kullanılan profilaktik rejimlerin etkinlik ve güvenliğini karşılaştıran çalışma bulunmamaktadır. Bu çok merkezli retrospektif çalışmada, profilakside SSS ışınlamayı içeren ve içermeyen rejimlerin etkinliklerinin karşılaştırılması amaçlanmıştır. Gereç ve Yöntemler: Bu çalışma, karşılaştırmalı retrospektif kohort çalışması olup; Türkiye’de dört farklı üçüncü basamak merkeze başvuran 203 hastayla yapılmıştır. Hastalar, SSS ışınlaması alanlar ve almayanlar olarak iki gruba ayrılmıştır. Gruplar, takipte SSS tutulumu gelişimi temelinde hastaların ve ALL’nin özelliklerine göre karşılaştırılmıştır. Bulgular: Yüz beş hasta sadece kemoterapi bazlı profilaksi alırken, 98 hasta ek olarak SSS ışınlaması almıştır. SSS ışınlama grubundaki hastaların medyan yaşı daha küçüktür ve kök hücre nakli oranı daha yüksektir. Bunlar haricinde gruplar, demografik özellikler ve SSS tutulumu risk faktörleri açısından benzer dağılım göstermektedir. Medyan 23,8 (11,1-62,4) aylık takipte, SSS tutulumsuz sağkalım açısından iki grup arasında fark saptanmamıştır (log-rank p=0,787). Sonuç: Pediatrik hastalarda kanıtlandığı gibi erişkin ALL hastalarında da SSS ışınlaması, çok yüksek riskli hastalar dışında profilakside yer almayabilir. Özellikle yüksek yaşam süresi beklenen hastalarda, ışınlamanın nörolojik toksisitesinden kaçınılması da günümüzde amaçlar arasında olmalıdır. Işınlamanın, SSS tutulumu gelişmiş hastalarda terapötik amaçla sınırlandırılması, çok yüksek riskli hastalar dışında iyi bir risk/fayda oranına sahiptir.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. Hollender A, Kvaloy S, Nome O, Skovlund E, Lote K, Holte H. Central nervous system involvement following diagnosis of non-Hodgkin’s lymphoma: a risk model. Ann Oncol 2002;13:1099-1107.
  • 2. Frishman-Levy L, Izraeli S. Advances in understanding the pathogenesis of CNS acute lymphoblastic leukaemia and potential for therapy. Br J Haematol 2017;176:157-167.
  • 3. Pui CH, Howard SC. Current management and challenges of malignant disease in the CNS in paediatric leukaemia. Lancet Oncol 2008;9:257-268.
  • 4. Gökbuget N, Hoelzer D. Meningeosis leukaemica in adult acute lymphoblastic leukaemia. J Neurooncol 1998;38:167-180.
  • 5. Evans AE, Gilbert ES, Zandstra R. The increasing incidence of central nervous system leukemia in children. (Children’s Cancer Study Group A). Cancer 1970;26:404-409.
  • 6. Bleyer WA, Poplack DG. Prophylaxis and treatment of leukemia in the central nervous system and other sanctuaries. Semin Oncol 1985;12:131- 148.
  • 7. Surapaneni UR, Cortes JE, Thomas D, O’Brien S, Giles FJ, Koller C, Faderl S, Kantarjian H. Central nervous system relapse in adults with acute lymphoblastic leukemia. Cancer 2002;94:773-779.
  • 8. Krull KR, Zhang N, Santucci A, Srivastava DK, Krasin MJ, Kun LE, Pui CH, Robison LL, Hudson MM, Armstrong GT. Long-term decline in intelligence among adult survivors of childhood acute lymphoblastic leukemia treated with cranial radiation. Blood 2013;122:550-553.
  • 9. Cortes J, O’Brien SM, Pierce S, Keating MJ, Freireich EJ, Kantarjian HM. The value of high-dose systemic chemotherapy and intrathecal therapy for central nervous system prophylaxis in different risk groups of adult acute lymphoblastic leukemia. Blood 1995;86:2091-2097.
  • 10. Lazarus HM, Richards SM, Chopra R, Litzow MR, Burnett AK, Wiernik PH, Franklin IM, Tallman MS, Cook L, Buck G, Durrant IJ, Rowe JM, Goldstone AH; Medical Research Council (MRC)/National Cancer Research Institute (NCRI) Adult Leukaemia Working Party of the United Kingdom and the Eastern Cooperative Oncology Group. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993. Blood 2006;108:465-472.
  • 11. Gajjar A, Harrison PL, Sandlund JT, Rivera GK, Ribeiro RC, Rubnitz JE, Razzouk B, Relling MV, Evans WE, Boyett JM, Pui CH. Traumatic lumbar puncture at diagnosis adversely affects outcome in childhood acute lymphoblastic leukemia. Blood 2000;96:3381-3384.
  • 12. Bürger B, Zimmermann M, Mann G, Kühl J, Löning L, Riehm H, Reiter A, Schrappe M. Diagnostic cerebrospinal fluid examination in children with acute lymphoblastic leukemia: significance of low leukocyte counts with blasts or traumatic lumbar puncture. J Clin Oncol 2003;21:184-188.
  • 13. Richards S, Pui CH, Gayon P; Childhood Acute Lymphoblastic Leukemia Collaborative Group (CALLCG). Systematic review and meta-analysis of randomized trials of central nervous system directed therapy for childhood acute lymphoblastic leukemia. Pediatr Blood Cancer 2013;60:185-195.
  • 14. Stock W, La M, Sanford B, Bloomfield CD, Vardiman JW, Gaynon P, Larson RA, Nachman J; Children’s Cancer Group; Cancer and Leukemia Group B Studies. What determines the outcomes for adolescents and young adults with acute lymphoblastic leukemia treated on cooperative group protocols? A comparison of Children’s Cancer Group and Cancer and Leukemia Group B studies. Blood 2008;112:1646-1654.
  • 15. Kantarjian H, Stein A, Gökbuget N, Fielding AK, Schuh AC, Ribera JM, Wei A, Dombret H, Foà R, Bassan R, Arslan Ö, Sanz MA, Bergeron J, Demirkan F, Lech-Maranda E, Rambaldi A, Thomas X, Horst HA, Brüggemann M, Klapper W, Wood BL, Fleishman A, Nagorsen D, Holland C, Zimmerman Z, Topp MS. Blinatumomab versus chemotherapy for advanced acute lymphoblastic leukemia. N Engl J Med 2017;376:836-847.
  • 16. Kantarjian HM, DeAngelo DJ, Stelljes M, Martinelli G, Liedtke M, Stock W, Gökbuget N, O’Brien S, Wang K, Wang T, Paccagnella ML, Sleight B, Vandendries E, Advani AS. Inotuzumab ozogamicin versus standard therapy for acute lymphoblastic leukemia. N Engl J Med 2016;375:740-753.
  • 17. Kantarjian HM, Walters RS, Smith TL, Keating MJ, Barlogie B, McCredie KB, Freireich EJ. Identification of risk groups for development of central 159 nervous system leukemia in adults with acute lymphocytic leukemia. Blood 1988;72:1784-1789.
  • 18. Larson RA. Managing CNS disease in adults with acute lymphoblastic leukemia. Leuk Lymphoma 2018;59:3-13.
  • 19. Pui CH, Campana D, Pei D, Bowman WP, Sandlund JT, Kaste SC, Ribeiro RC, Rubnitz JE, Raimondi SC, Onciu M, Coustan-Smith E, Kun LE, Jeha S, Cheng C, Howard SC, Simmons V, Bayles A, Metzger ML, Boyett JM, Leung W, Handgretinger R, Downing JR, Evans WE, Relling MV. Treating childhood acute lymphoblastic leukemia without cranial irradiation. N Engl J Med 2009;360:2730-2741.
  • 20. Schuitema I, Deprez S, Van Hecke W, Daams M, Uyttebroeck A, Sunaert S, Barkhof F, van Dulmen-den Broeder E, van der Pal HJ, van den Bos C, Veerman AJ, de Sonneville LM. Accelerated aging, decreased white matter integrity, and associated neuropsychological dysfunction 25 years after pediatric lymphoid malignancies. J Clin Oncol 2013;31:3378-3388.
  • 21. Krull KR, Brinkman TM, Li C, Armstrong GT, Ness KK, Srivastava DK, Gurney JG, Kimberg C, Krasin MJ, Pui CH, Robison LL, Hudson MM. Neurocognitive outcomes decades after treatment for childhood acute lymphoblastic leukemia: a report from the St Jude lifetime cohort study. J Clin Oncol 2013;31:4407-4415.
  • 22. Greene-Schloesser D, Robbins ME, Peiffer AM, Shaw EG, Wheeler KT, Chan MD. Radiation-induced brain injury: a review. Front Oncol 2012;2:73. 23. Meyers CA, Smith JA, Bezjak A, Mehta MP, Liebmann J, Illidge T, Kunkler I, Caudrelier JM, Eisenberg PD, Meerwaldt J, Siemers R, Carrie C, Gaspar LE, Curran W, Phan SC, Miller RA, Renschler MF. Neurocognitive function and progression in patients with brain metastases treated with whole-brain radiation and motexafin gadolinium: results of a randomized phase III trial. J Clin Oncol 2004;22:157-165.
  • 24. Matloub Y, Lindemulder S, Gaynon PS, Sather H, La M, Broxson E, Yanofsky R, Hutchinson R, Heerema NA, Nachman J, Blake M, Wells LM, Sorrell AD, Masterson M, Kelleher JF, Stork LC; Children’s Oncology Group. Intrathecal triple therapy decreases central nervous system relapse but fails to improve event-free survival when compared with intrathecal methotrexate: results of the Children’s Cancer Group (CCG) 1952 study for standard-risk acute lymphoblastic leukemia, reported by the Children’s Oncology Group. Blood 2006;108:1165-1173.
  • 25. Gökbuget N, Hartog CM, Bassan R, Derigs HG, Dombret H, Greil R, Hernández-Rivas JM, Huguet F, Intermesoli T, Jourdan E, Junghanss C, Leimer L, Moreno MJ, Reichle A, Ribera J, Schmid M, Serve H, Stelljes M, Stuhlmann R, Hoelzer D; German Multicenter Study Group for Adult ALL and the European Working Group for Adult ALL. Liposomal cytarabine is effective and tolerable in the treatment of central nervous system relapse of acute lymphoblastic leukemia and very aggressive lymphoma. Haematologica 2011;96:238-244.
  • 26. Jabbour E, O’Brien S, Kantarjian H, Garcia-Manero G, Ferrajoli A, Ravandi F, Cabanillas M, Thomas DA. Neurologic complications associated with intrathecal liposomal cytarabine given prophylactically in combination with high-dose methotrexate and cytarabine to patients with acute lymphocytic leukemia. Blood 2007;109:3214-3218.
  • 27. National Comprehensive Cancer Network. Acute Lymphoblastic Leukemia Version 4.2021. Available at https://www.nccn.org/professionals/physician_ gls/pdf/all.pd
APA Çınar O, Göker H, Fidan K, Aydın Ö, Pashayev T, Malkan U, Velet M, Büyükaşık Y, Aksu S, Özcebe O, Haznedaroglu I, Sayinalp N, vural f, TURGUT M, ÜNAL A, Demiroglu H (2022). Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. , 152 - 159. 10.4274/tjh.galenos.2022.2021.0680
Chicago Çınar Olgu Erkin,Göker Hakan,Fidan Kemal,Aydın Öznur,Pashayev Tural,Malkan Umit Yavuz,Velet Mustafa,Büyükaşık Yahya,Aksu Salih,Özcebe Osman,Haznedaroglu Ibrahim C.,Sayinalp Nilgun,vural filiz,TURGUT Mehmet,ÜNAL ALİ,Demiroglu Haluk Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. (2022): 152 - 159. 10.4274/tjh.galenos.2022.2021.0680
MLA Çınar Olgu Erkin,Göker Hakan,Fidan Kemal,Aydın Öznur,Pashayev Tural,Malkan Umit Yavuz,Velet Mustafa,Büyükaşık Yahya,Aksu Salih,Özcebe Osman,Haznedaroglu Ibrahim C.,Sayinalp Nilgun,vural filiz,TURGUT Mehmet,ÜNAL ALİ,Demiroglu Haluk Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. , 2022, ss.152 - 159. 10.4274/tjh.galenos.2022.2021.0680
AMA Çınar O,Göker H,Fidan K,Aydın Ö,Pashayev T,Malkan U,Velet M,Büyükaşık Y,Aksu S,Özcebe O,Haznedaroglu I,Sayinalp N,vural f,TURGUT M,ÜNAL A,Demiroglu H Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. . 2022; 152 - 159. 10.4274/tjh.galenos.2022.2021.0680
Vancouver Çınar O,Göker H,Fidan K,Aydın Ö,Pashayev T,Malkan U,Velet M,Büyükaşık Y,Aksu S,Özcebe O,Haznedaroglu I,Sayinalp N,vural f,TURGUT M,ÜNAL A,Demiroglu H Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. . 2022; 152 - 159. 10.4274/tjh.galenos.2022.2021.0680
IEEE Çınar O,Göker H,Fidan K,Aydın Ö,Pashayev T,Malkan U,Velet M,Büyükaşık Y,Aksu S,Özcebe O,Haznedaroglu I,Sayinalp N,vural f,TURGUT M,ÜNAL A,Demiroglu H "Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study." , ss.152 - 159, 2022. 10.4274/tjh.galenos.2022.2021.0680
ISNAD Çınar, Olgu Erkin vd. "Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study". (2022), 152-159. https://doi.org/10.4274/tjh.galenos.2022.2021.0680
APA Çınar O, Göker H, Fidan K, Aydın Ö, Pashayev T, Malkan U, Velet M, Büyükaşık Y, Aksu S, Özcebe O, Haznedaroglu I, Sayinalp N, vural f, TURGUT M, ÜNAL A, Demiroglu H (2022). Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. Turkish Journal of Hematology, 39(3), 152 - 159. 10.4274/tjh.galenos.2022.2021.0680
Chicago Çınar Olgu Erkin,Göker Hakan,Fidan Kemal,Aydın Öznur,Pashayev Tural,Malkan Umit Yavuz,Velet Mustafa,Büyükaşık Yahya,Aksu Salih,Özcebe Osman,Haznedaroglu Ibrahim C.,Sayinalp Nilgun,vural filiz,TURGUT Mehmet,ÜNAL ALİ,Demiroglu Haluk Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. Turkish Journal of Hematology 39, no.3 (2022): 152 - 159. 10.4274/tjh.galenos.2022.2021.0680
MLA Çınar Olgu Erkin,Göker Hakan,Fidan Kemal,Aydın Öznur,Pashayev Tural,Malkan Umit Yavuz,Velet Mustafa,Büyükaşık Yahya,Aksu Salih,Özcebe Osman,Haznedaroglu Ibrahim C.,Sayinalp Nilgun,vural filiz,TURGUT Mehmet,ÜNAL ALİ,Demiroglu Haluk Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. Turkish Journal of Hematology, vol.39, no.3, 2022, ss.152 - 159. 10.4274/tjh.galenos.2022.2021.0680
AMA Çınar O,Göker H,Fidan K,Aydın Ö,Pashayev T,Malkan U,Velet M,Büyükaşık Y,Aksu S,Özcebe O,Haznedaroglu I,Sayinalp N,vural f,TURGUT M,ÜNAL A,Demiroglu H Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. Turkish Journal of Hematology. 2022; 39(3): 152 - 159. 10.4274/tjh.galenos.2022.2021.0680
Vancouver Çınar O,Göker H,Fidan K,Aydın Ö,Pashayev T,Malkan U,Velet M,Büyükaşık Y,Aksu S,Özcebe O,Haznedaroglu I,Sayinalp N,vural f,TURGUT M,ÜNAL A,Demiroglu H Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study. Turkish Journal of Hematology. 2022; 39(3): 152 - 159. 10.4274/tjh.galenos.2022.2021.0680
IEEE Çınar O,Göker H,Fidan K,Aydın Ö,Pashayev T,Malkan U,Velet M,Büyükaşık Y,Aksu S,Özcebe O,Haznedaroglu I,Sayinalp N,vural f,TURGUT M,ÜNAL A,Demiroglu H "Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study." Turkish Journal of Hematology, 39, ss.152 - 159, 2022. 10.4274/tjh.galenos.2022.2021.0680
ISNAD Çınar, Olgu Erkin vd. "Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study". Turkish Journal of Hematology 39/3 (2022), 152-159. https://doi.org/10.4274/tjh.galenos.2022.2021.0680