Mantle Hücreli Lenfomada Kemoterapi Rejimlerinin Etkinliği: Tek Merkez Deneyimi

Öz

Bu tek merkezli çalışma, Mantle Hücreli Lenfoma (MHL) hastalarının klinik özelliklerini, tedavi yanıtlarını ve sağkalım sonuçlarını değerlendirmektedir. Ocak 2000 ile Aralık 2014 tarihleri arasında Bursa Uludağ Üniversitesi Tıp Fakültesi Hematoloji bölümünde tedavi edilen 25 MCL hastasını retrospektif olarak analiz ettik. Hastaların median takip süresi 37 (min-max=6-132) aydı. Kohortun çoğunluğu erkekti (%84) ve %92’si ileri evre hastalıkla başvurdu. Birinci basamak kemoterapiye genel yanıt oranı %72 idi ve 9 (%36) hastada tam remisyon sağlanmıştı. Progresyonsuz sağkalım (PFS) medyan 17 (min-max=2–39 ay) aydı ve 3 ve 5 yıllık genel sağkalım (OS) oranları sırasıyla %52 ve %28 idi. İkinci basamak tedavi gerektiren dokuz hastadan üçü (%33) kısmi remisyonda iken, üçü (%33) yanıtsızdı; kalan üç hasta ise yanıt değerlendirmesi yapılmadan önce hayatını kaybetmişti. İkinci basamak tedavi ile medyan progresyonsuz sağkalım (PFS) 6 ay olarak saptandı. Yedi (%28) hastaya otolog hematopoietik kök hücre nakli (OHKHN) yapılmıştı. OHKHN uygulanan grup, nakil yapılmayan hastalara kıyasla anlamlı derecede daha gençti (p=0,047) ve medyan genel sağkalım (OS) süresi anlamlı olarak daha uzundu (p<0,05). Bu gerçek yaşam verileri, terapötik ilerlemelere rağmen MHL’nin nüks sonrası kötü prognoza sahip olan zorlu bir malignite olmaya devam ettiğini doğrulamaktadır.

Anahtar Kelimeler

• mantle hücreli lenfoma
• kemoterapi
• otolog hematopoietik kök hücre nakli

Efficacy of Chemotherapy Regimens in Mantle Cell Lymphoma: A Single Center Experience

Öz

This single-center study evaluates the clinical characteristics, treatment responses, and survival outcomes of patients with Mantle Cell Lymphoma (MCL). We retrospectively analyzed 25 patients with MCL treated at the Hematology Department of Bursa Uludag University between January 2000 and December 2014. The median follow-up was 37 months min-max=6-132). The cohort was predominantly male (84%), with 92% presenting with advanced-stage disease. The overall response rate to first-line chemotherapy was 72%, with 9 patients (36%) achieving complete remission. The median progression-free survival (PFS) was 17 months (range, 2–39), and the 3- and 5-year overall survival (OS) rates were 52% and 28%, respectively. Among nine patients requiring second-line therapy, three (33%) achieved partial remission, while three (33%) had no response; the remaining three patients died before response assessment. The median PFS with second-line treatment was 6 months. Seven (28%) patients underwent autologous hematopoietic stem cell transplantation (AHSCT). The AHSCT cohort was significantly younger (p=0.047) and demonstrated a significantly longer median OS (p<0.05) compared to non-transplanted patients. These real-life data confirm that despite therapeutic advances, MCL remains a challenging malignancy with poor outcomes after relapse.

Anahtar Kelimeler

• Mantle Cell Lymphoma
• Chemotherapy
• autologous hematopoietic stem cell transplantation

Kaynakça

1. 1. Cortelazzo S, Ponzoni M, Ferreri AJ, Dreyling M. Mantle cell lymphoma. Crit Rev Oncol Hematol 2012; 82(1):78-101.
2. 2. Wiestner A, Tehrani M, Chiorazzi M, et al. Point mutations and genomic deletions in CCND1 create stable truncated cyclin D1 mRNAs that are associated with increased proliferation rate and shorter survival. Blood. 2007 Jun 1;109(11):4599-606.
3. 3.Bernard M, Gressin R, Lefrère F, et al. Blastic variant of mantle cell lymphoma: a rare but highly aggressive subtype. Leukemia 2001;15: 1785-1791.
4. 4.Mozos A, Royo C, Hartmann E, et al. SOX11 expression is highly specific for mantle cell lymphoma and identifies the cyclin D1-negative subtype. Haematologica. 2009 Nov;94(11):1555-62.
5. 5.Smith MR. Should there be a standard therapy for mantle celllymphoma?. Future Oncol. 2011 Feb;7(2):227-37.
6. 6.Dreyling M. Therapy of mantle cell lymphoma: new treatment options in an old disease or vice versa?. Semin Hematol. 2011 Jul;48(3):145-7.
7. 7.Smith A, Howell D, Patmore R, et al. İncidence of haematological malignancy by sub-type: report from the Haematological Malignancy Research Network. Br J Cancer 2011;105:1684-92.
8. 8.Cortelazzo S, Ponzoni M, Ferreri AJ, Dreyling M. Mantle cell lymphoma. Crit Rev Oncol Hematol 2012;82:78-101.

9. 9.Pileri SA, Falini B. Mantle cell lymphoma. Haematologica 2009 Nov;94(11):1488-92.
10. 10.Hoster E, Dreyling M, Klapper W, et al. German Low GradeLymphoma Study Group (GLSG); European Mantle Cell Lymphoma Network. A new prognostic index (MIPI) forpatients with advanced-stage mantle cell lymphoma. Blood. 2008 Jan 15;111(2):558-65.
11. 11.Hoster E, Rosenwald A, Berger F, et al. Prognostic Value of Ki-67 Index, Cytology, and Growth Pattern in Mantle-Cell Lymphoma: Results From Randomized Trials of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2016 Apr 20;34(12):1386-94.
12. 12.Shah JJ, Fayad L, Romaguera J. Mantle Cell International Prognostic Index (MIPI) not prognostic after R-hyper-CVAD.Blood. 2008 Sep 15;112(6):2583.
13. 13.Andersen NS, Jensen MK, Brown PN, Geisler CH. A Danish population-based analysis of 105 mantle cell lymphoma patients: incidences, clinical features, response, survival and prognostic factors. European Journal of Cancer. Volume 38, Issue 3, 2002, 401-408.
14. 14.Dreyling M, Campo E, Hermine O, et al. ESMO Guidelines Committee. Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):62-71.
15. 15.Hermine O, Hoster E, Walewski J, et al. European Mantle Cell Lymphoma Network. Addition of high-dose cytarabine to immunochemotherapy before autologous stem-celltransplantation in patients aged 65 years or younger withmantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network. Lancet. 2016 Aug 6;388(10044):565-75.
16. 16.Kluin-Nelemans HC, Hoster E, Hermine O, et al. Treatment of Older Patients With Mantle Cell Lymphoma (MCL): Long-Term Follow-Up of the Randomized European MCL Elderly Trial. J Clin Oncol. 2020 Jan 20;38(3):248-256.
17. 17.Eskelund CW, Dahl C, Hansen JW, et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017 Oct 26;130(17):1903-1910.
18. 18.Zelenetz AD, Gordon LI, Abramson JS, et al. NCCN Guidelines® Insights: B-Cell Lymphomas, Version 6.2023. J Natl Compr Canc Netw. 2023 Nov;21(11):1118-1131.
19. 19.Martin P, Chardbun A, Christos P, et al. Outcome of deferredinitial therapy in mantle-cell lymphoma. J Clin Oncol. 2009 Mar 10;27(8):1209-13.
20. 20.Chihara D, Cheah CY, Westin JR, et al. Rituximab plus hyper-CVAD alternating with MTX/Ara-C in patients with newly diagnosed mantle cell lymphoma: 15-year follow-up of a phase II study from the MD Anderson Cancer Center. Br J Haematol.2016 Jan;172(1):80-8.
21. 21.Cencini E, Calomino N, Franceschini M, et al. Survival Outcomes of Patients with Mantle Cell Lymphoma: A Retrospective, 15-Year, Real-Life Study. Hematol Rep. 2024 Jan 18;16(1):50-62.
22. 22.Dreyling M, Doorduijn J, Giné E, et al. Ibrutinib combined with immunochemotherapy with or without autologous stem-celltransplantation versus immunochemotherapy and autologous stem-cell transplantation in previously untreated patients withmantle cell lymphoma (TRIANGLE): a three-arm, randomised, open-label, phase 3 superiority trial of the European Mantle Cell Lymphoma Network. Lancet. 2024 May 25;403(10441):2293-2306.
23. 23.Munshi PN, Hamadani M, Kumar A, et al. American Society ofTransplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and European Society for Blood and Marrow Transplantation Clinical Practice Recommendations for Transplantation and Cellular Therapiesin Mantle Cell Lymphoma. Transplant Cell Ther. 2021 Sep;27(9):720-728.
24. 24.Eskelund CW, Kolstad A, Jerkeman M, et al. 15-year follow-up of the Second Nordic Mantle Cell Lymphoma trial (MCL2): prolonged remissions without survival plateau. Br J Haematol. 2016 Nov;175(3):410-418.
25. 25.Liu H, Shi X, Fang H, et al. First-Line Autologous Stem Cell Transplantation for Mantle Cell Lymphoma: A Systematic Analysis and Treatment Recommendation. Front Oncol. 2022 May 11;12:881346.
26. 26.Zoellner AK, Unterhalt M, Stilgenbauer S, et al. European Mantle Cell Lymphoma Network. Long-term survival of patients with mantle cell lymphoma after autologoushaematopoietic stem-cell transplantation in first remission: a post-hoc analysis of an open-label, multicentre, randomised, phase 3 trial. Lancet Haematol. 2021 Sep;8(9):e648-e657.
27. 27.Robak T, Huang H, Jin J, et al. Bortezomib-based therapy fornewly diagnosed mantle-cell lymphoma. N Engl J Med. 2015 Mar 5;372(10):944-53.
28. 28.Lyman GH, Poniewierski MS, Culakova E. Risk ofchemotherapy-induced neutropenic complications when treating patients with non-Hodgkin lymphoma. Expert Opin Drug Saf. 2016;15(4):483-92.
29. 29.Ohmoto A, Fuji S. Infection profiles of different chemotherapy regimens and the clinical feasibility of antimicrobial prophylaxis in patients with DLBCL. Blood Rev. 2021 Mar;46:100738.