Solid Organ Tümörlü Hastalarda Yüksek Doz Kemoterapi Eşliğinde Otolog Hematopoietik Kök Hücre Naklinin Tek Merkezli Sonuçları

Year 2025, Volume: 9 Issue: 1, 19 - 35, 01.04.2025

Ünal Ataş , Ayşe Tan Doğruel , Orhan Kemal Yücel , Utku Iltar , Sema Sezgin Göksu , Ozan Salim , Levent Ündar

Abstract

Amaç: Hematopoetik kök hücre naklinin (HCT), hematolojik hastalıkların aksine, solid organ tümörlerinde kullanımı sınırlı olup, öneriler bazı seçilmiş tanılarda ve seçilmiş olgularda mevcuttur.

Method: Solid organ tümörü tanısıyla, 2006-2023 yılları arasında HCT yapılan 16 erişkin hastanın verisi analiz edildi.

Bulgular: Hastaların ortanca yaşı 36.5 (21-46) olup, 13’ü (%81.2) erkekti. Hastaların 7’sinde (%43.7) testis kaynaklı germ hücreli tümör (GCT), 4’ünde (%25) Ewing sarkomu ve 5’inde ise diğer (%31.3) solid organ tümörü tanısı vardı. Otolog HCT, 14 (%87,5) hastaya relaps/refrakter hastalık nedeni ile uygulandı ve sadece 5 (%31.3) hasta nakil öncesi kurtarma tedavisine tam yanıtlıydı. Nakil sonrası relaps %92.8 hastada görülürken, ortanca progresyonsuz sağkalım süresi (PFS) süresi 6.5 (2-32) aydı. Hastalardan, 2’si nakilde olmak üzere, 14’ü (%87.5) öldü ve hastaların ortanca genel sağkalım süresi (OS) süresi 53.0 (9–213) aydı. Testis GCT hastalarının otolog HCT sonrası ortanca PFS’si diğerlerine göre daha uzun olsa da (12.0 ve 4.5 ay; p=0.04), ortanca OS’si benzerdi (90.0 ve 46.0 ay; p=0.52).

Sonuç: Solid organ tümörlerinde HCT’nin yerine dair literatür bilgileri genellikle eski tedavi yaklaşımların uygulandığı döneme ve retrospektif verilere dayanmaktadır. Günümüzde kullanımları ön plana çıkan immunoterapi ve hedefe yönelik tedavilerle birlikte, HCT’nin hem gerekliliği hem de hangi aşamada yapılmasının daha fazla sorgulanmalıdır ve bu yönde yeni çalışmalar gerekmektedir.

Keywords

Solid organ tümörleri, Germ hücreli tümör, Ewing sarkomu, Otolog hematopoietik kök hücre nakli

Single-Center Outcomes of Autologous Hematopoietic Stem Cell Transplantation Accompanied by High-Dose Chemotherapy in Patients with Solid Organ Tumors

Abstract

Aim: In contrast to hematologic diseases, the use of hematopoietic stem cell transplantation (HCT) for solid organ tumors is limited, with recommendations available only for certain selected diagnoses and cases.

Methods: Data from 16 adult patients who underwent HCT with a diagnosis of solid organ tumor between 2006-2023 were analyzed.

Results: The median age of the patients was 36.5 years (21–46), and 13 (81.2%) were male. Seven patients (43.7%) had testicular germ cell tumors (GCT), four (25%) had Ewing sarcoma, and five (31.3%) had other solid organ tumors. Autologous HCT was performed in 14 patients (87.5%) due to relapsed/refractory disease, and only five patients (31.3%) achieved a complete response to salvage therapy prior to transplantation. Post-transplant relapse occurred in 92.8% of patients, with a median progression-free survival (PFS) of 6.5 (2-32) months. Fourteen patients (87.5%) died, including two during transplantation, with a median overall survival (OS) of 53.0 (9–213) months. Although the median PFS for testicular GCT patients after autologous HCT was longer than that of other patients (12.0 vs. 4.5 months; p=0.04), the median OS was similar (90.0 vs. 46.0 months; p=0.52).

Conclusion: The literature regarding the role of HCT in solid organ tumors is generally based on retrospective data and periods when older treatment approaches are employed. With the current use of immunotherapy and targeted therapies, both the necessity and stage at which HCT should be performed should be further investigated, and new studies are needed to address this issue.

Keywords

Solid organ tumors, Germ cell tumors, Ewing sarcoma, Autologous hematopoietic stem cell transplantation

Ethical Statement

In this study, national and international ethical rules are observed. Akdeniz University Faculty of Medicine Clinical Research Ethics Committee (Date: 30/05/2024 and Number: TBAEK-343).

Supporting Institution

The authors declare that this study has received no financial support.

References

• 1. Sureda A, Bader P, Cesaro S, Dreger P, Duarte RF, Dufour C, et al. Indications for allo- and auto-SCT for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant. 2015;50(8):1037–56. doi: 10.1038/bmt.2015.6.
• 2. Spitzer G, Dunphy FR, Bowers CE, Adkins DR. High-dose therapy with stem cell support in solid tumors. Ann Oncol. 1994;11(2):53-62. doi: 10.1007/BF02988831.
• 3. Pedrazzoli P, Ledermann JA, Lotz JP, Leyvraz S, Aglietta M, Rosti G, European Group for Blood and Marrow Transplantation (EBMT) Solid Tumors Working Party, et al. High-dose chemotherapy with autologous hematopoietic stem cell support for solid tumors other than breast cancer in adults. Ann Oncol. 2006;17(10):1479–88. doi: 10.1093/annonc/mdl044.
• 4. Banna GL, Simonelli M, Santoro A. High-dose chemotherapy followed by autologous hematopoietic stem-cell transplantation for the treatment of solid tumors in adults: a critical review. Curr Stem Cell Res Ther. 2007;2(1):65-82. doi: 10.2174/157488807779316964.
• 5. Pedrazzoli P, Rosti G, Secondino S, Carminati O, Demirer T; European Group for Blood and Marrow Transplantation; Solid Tumors Working Party; Gruppo Italiano per il Trapianto di Midollo Osseo, Cellule Staminali Emopoietiche e Terapia Cellulare. High-dose chemotherapy with autologous hematopoietic stem cell support for solid tumors in adults. Semin Hematol. 2007;44(4):286-95. doi: 10.1053/j.seminhematol.2007.08.009.
• 6. Snowden JA, Sanchez-Ortega I, Corbacioglu S, Basak GW, Chabannon C, de la Camara R, et al. Indications for hematopoietic cell transplantation for hematological diseases, solid tumors, and immune disorders: current practice in Europe, 2022. Bone Marrow Transplant. 2022;57(8):1217–39. doi: 10.1038/s41409-022-01691-w.
• 7. Sureda A, Corbacioglu S, Greco R, Kröger N, Carreras E. The EBMT Handbook, Hematopoietic Cell Transplantation and Cellular Therapies. In: Ladenstein R, Pedrazzoli P, Rosti G editors. Solid Tumours. Springer; 2024. p. 849-62. doi: 10.1007/978-3-031-44080-9.
• 8. Matthay KK, Reynolds CP, Seeger RC, Shimada H, Adkins ES, Haas-Kogan D, et al. Long-term results for children with high-risk neuroblastoma treated on a randomized trial of myeloablative therapy followed by 13-cis-retinoic acid: a children’s oncology group study. J Clin Oncol. 2009;27(7):1007–13. doi: 10.1200/JCO.2007.13.8925.
• 9. Whelan J, Le Deley MC, Dirksen U, Le Teuff G, Brennan B, Gaspar N, Euro-E.W.I.N.G.99 and EWING-2008 Investigators, et al. High-dose chemotherapy and blood autologous stem cell rescue compared with standard chemotherapy in localized high-risk Ewing sarcoma: results of Euro-E.W.I.N.G.99 and Ewing-2008. J Clin Oncol. 2018;36(31):JCO2018782516. doi: 10.1200/JCO.2018.78.2516.
• 10. Nitz UA, Mohrmann S, Fischer J, Lindemann W, Berdel WE, Jackisch C, et al. Comparison of rapidly cycled tandem high-dose chemotherapy plus peripheral-blood stem-cell support versus dose-dense conventional chemotherapy for adjuvant treatment of high-risk breast cancer: results of a Multicenter phase III trial. Lancet. 2005;366(9501):1935–44. doi: 10.1016/S0140-6736(05)67784-7.
• 11. Pedrazzoli P, Martino M, Delfanti S, Generali D, Rosti G, Bregni M, et al. High-dose chemotherapy with autologous hematopoietic stem cell transplantation in high-risk breast cancer patients. J Natl Cancer Inst. 2015;2015(51):70–5. doi: 10.1093/jncimonographs/lgv010.
• 12. Berry DA, Ueno NT, Johnson MM, Lei X, Caputo J, Smith DA, et al. High-dose chemotherapy with autologous hematopoietic stem-cell transplantation in metastatic breast cancer: overview of six randomized trials. J Clin Oncol. 2011;29(24):3224–31. doi: 10.1200/JCO.2010.32.5936.
• 13. Steenbruggen TG, Steggink LC, Seynaeve CM, van der Hoeven JJM, Hooning MJ, Jager A, et al. High-dose chemotherapy with hematopoietic stem cell transplant in patients with high-risk breast cancer and 4 or more involved axillary lymph nodes—20-year follow-up of a phase 3 randomized clinical trial. JAMA Oncol. 2020;6(4):528–34. doi: 10.1001/jamaoncol.2019.6276.
• 14. Ultimescu F, Hudita A, Popa DE, Olinca M, Muresean HA, Ceausu M, et al. Impact of Molecular Profiling on Therapy Management in Breast Cancer. J Clin Med. 2024;13(17):4995. doi: 10.3390/jcm13174995.
• 15. Cheng L, Albers P, Berney DM, Feldman DR, Daugaard G, Gilligan T, et al. Testicular cancer. Nat Rev Dis Primers. 2018;4(1):29. doi: 10.1038/s41572-018-0029-0.
• 16. Lorch A, Bascoul-Mollevi C, Kramar A, Einhorn L, Necchi A, Massard C, et al. Conventional-dose versus high-dose chemotherapy as first salvage treatment in male patients with metastatic germ cell tumors: evidence from a large international database. J Clin Oncol. 2011;29(16):2178–84. doi: 10.1200/JCO.2010.32.6678.
• 17. Feldman DR, Sheinfeld J, Bajorin DF, Fischer P, Turkula S, Ishill N, et al. TI-CE high-dose chemotherapy for patients with previously treated germ cell tumors: results and prognostic factor analysis. J Clin Oncol. 2010;28(10):1706-113. doi: 10.1200/JCO.2009.25.1561.
• 18. De Giorgi U, Richard S, Badoglio M, Kanfer E, Bourrhis JH, Nicolas-Virelizier E, et al. Salvage high-dose chemotherapy in female patients with relapsed/refractory germ-cell tumors: a retrospective analysis of the European Group for Blood and Marrow Transplantation (EBMT). Ann Oncol. 2017;28(8):1910–6. doi: 10.1093/annonc/mdx259.
• 19. Agrawal V, Abonour R, Abu Zaid M, Althouse SK, Ashkar R, Albany C, et al. Survival outcomes and toxicity in patients 40 years old or older with relapsed metastatic germ cell tumors treated with high-dose chemotherapy and peripheral blood stem cell transplantation. Cancer. 2021;127(20):3751–60. doi: 10.1002/cncr.33771.
• 20. Albany C, Einhorn LH. Extragonadal germ cell tumors: clinical presentation and management. Curr Opin Oncol. 2013;25(3):261-5. doi: 10.1097/CCO.0b013e32835f085d.
• 21. De Giorgi U, Demirer T, Wandt H, Taverna C, Siegert W, Bornhauser M, et al. Second-line high-dose chemotherapy in patients with mediastinal and retroperitoneal primary non-seminomatous germ cell tumors: the EBMT experience. Ann Oncol. 2005;16(1):146-51. doi: 10.1093/annonc/mdi017.
• 22. Heilig CE, Badoglio M, Labopin M, Fröhling S, Secondino S, Heinz J, et al. Hematopoietic stem cell transplantation in adult soft-tissue sarcoma: an analysis from the European Society for Blood and Marrow Transplantation. ESMO Open. 2020;5(5):e000860. doi: 10.1136/esmoopen-2020-000860.
• 23. Haveman LM, van Ewijk R, van Dalen EC, Breunis WB, Kremer LC, van den Berg H, et al. High-dose chemotherapy followed by autologous hematopoietic cell transplantation for children, adolescents, and young adults with first recurrence of Ewing sarcoma. Cochrane Database Syst Rev. 2021;9(9):CD011406. doi: 10.1002/14651858.CD011406.pub2.
• 24. Spreafico F, Massimino M, Gandola L, Cefalo G, Mazza E, Landonio G, et al. Survival of adults treated for medulloblastoma using pediatric protocols. Eur J Cancer. 2005;41(9):1304–10. doi: 10.1016/j.ejca.2005.02.022.
• 25. Huo G, Liu W, Zhang S, Chen P. Efficacy of PD-1/PD-L1 plus CTLA-4 inhibitors in solid tumors based on clinical characteristics: a meta-analysis. Immunotherapy. 2023;15(3):189-207. doi: 10.2217/imt-2022-0140.
• 26. Bregni M, Badoglio M, Pedrazzoli P, Lanza F. Is allogeneic transplant for solid tumors still alive? Bone Marrow Transplant. 2016;51(5):751–2. doi: 10.1038/bmt.2015.345.