Miyelodisplastik sendrom tanili hastalarin retrospektif değerlendirilmesi

Yıl 2023, , 508 - 513, 30.09.2023

Ferda Can , İmdat Dilek

https://doi.org/10.18663/tjcl.1342609

Öz

Amaç: Miyelodisplastik sendrom (MDS); ileri yaşta görülen, kemik iliği yetmezliği ile karakterize bir hematopoetik kök hücre hastalığıdır. Hastalığın seyri ve tedavisi hastalarda farklılık göstermekle birlikte yeni tedavilere rağmen hala allojeneik kök hücre nakli dışında küratif tedavisi olmayan bir hastalıktır. Bu çalışmanın amacı MDS serimizi geriye yönelik incelemek, hastaların demografik özelliklerini, prognostik seyirlerini, tedavilerini ve yanıtlarını incelemektir.
Gereç ve Yöntemler: Merkezimizde MDS tanısı ile takipli 56 hastanın verileri geriye yönelik incelendi. Hastaların demografik ve tanısal özellikleri, prognostik skorları, tedavileri, sağkalım bilgileri geriye yönelik olarak değerlendirildi.
Bulgular: Hastaların 25’i (%44) kadın, 31’i (%56) erkek, ortanca yaş 63 (29-85) idi. Dünya Sağlık Örgütü (DSÖ) 2022 morfolojik sınıflamasına göre hastaların 26’ si (%47) düşük blastlı MDS, 12’ si (%21) artmış blastlı MDS 1, 7’ si (%13) artmış blastlı MDS 2, 4’ ü (%7) fibrozisli MDS, 3’ ü hipoplastik MDS, 1’i izole 5q delesyonlu MDS, 3’ ü ise TP53 inaktivasyonu MDS olarak sınıflandırıldı. Hastaların 33’ ünde (%59) en az bir eşlik eden hastalık mevcuttu. 17 (%30) hastanın ECOG performans durumu ≥2 bulundu. Hastalar risk skorlamalarına göre WPSS risk skorlamalasında çoğu yüksek riskte, R-IPSS risk skorları için çoğu orta risk grubunda, IPSS risk skorlamasında ise çoğu orta 1 risk grubunda idi. Tedavisiz izlem süresi ortalama 7,8 (0-95) aydı. Birinci basamak tedavi olarak hastaların 12 (%22) hipometile edici ajan, 13 (%23) eritropoetin tedavisi, 7 (%12) steroid ve danazol tedavisi, 4 (%7) talidomid tedavisi, 4 (%7) konvansiyonel kemoterapi, bir hasta lenalidomid, 1 hasta siklosporin ile antitimosit globulin almıştı. Üç hastaya allojeneik kök hücre nakli yapılmış, 11 (%20) hasta tedavisiz veya destek tedavi ile izlenmişti. Birinci basamak tedavi yanıt oranı 12 (%26) hastada tam yanıt, 10 (%23) hastada transfüzyon azalması ile kısmi yanıt iken 23 (%51) hastada yanıt yok idi. Diğer tedavi basamakları dahil edildiğinde toplam 7 hastaya kök hücre nakli yapılmıştı. Takipte 10 (%18) hastada akut lösemi dönüşümü izlendi. Takip süresi sonunda hayatta kalan hasta sayısı 22 (%40) iken 27 (%48) hasta hayatını kaybetmişti. 7 hasta takipten çıkmış olması nedeniyle sağkalım durumu bilinmiyordu. Ölüm nedeni bilinen 27 hastadan 5 tanesi hastalık ilerlemesi, 12’ si enfeksiyon, 2 tanesi kanama nedeniyle, 6 tanesi nakil ilişkili komplikasyonlar, 2 tanesi diğer nedenlerden dolayı kaybedilmişti. Ortalama toplam sağkalım 38,6 (1-123) ay olarak tespit edildi. Yaş, ECOG performans durumu, 2016 ve 2022 DSÖ alt sınıfı, kemik iliği blast oranı, kemik iliği fibrozis durumu, IPSS-WPSS-R IPSS skoru, tedavi verilen hastalarda tedaviye yanıt durumu, şelasyon tedavisi, akut lösemi dönüşüm durumu ve allojeneik kök hücre nakli sağkalım ile ilişkili bulundu.
Sonuç: Miyelodisplastik sendrom; 2022 yılında tanı alt sınıf güncellemesi yapılması, tedavideki yeniliklerin devam etmesi nedeniyle merkezimizde izlenen hastaların verilerinin toplandığı bu çalışmada hastalığın epidemiyolojik verileri literatür ile uyumlu bulunmuştur. Güncel sınıflama ile birlikte hastaların dağılım özellikleri tespit edilmiş olup tedavi-prognoz süreçleri için ilerisi için yön gösterici olacaktır. İleri yaş hastalığı da olsa merkezimizde hastaların çoğunluğuna uygun bir tedavi seçeneği verildiği görülse de literatürde uyumlu olarak bu tedavilerin yanıtları yüksek ve kalıcı değildir. Sağkalım üzerien etkili faktörler literatürle uyumlu bulunmuştur. MDS hastalarının uygun olanları için küratif tek seçenek olan allojeneik kök hücre naklinin uygun zaman ve nakil kriterleri ile yapılması sağlansa da maalesef hala nakil ilişkili mortalite büyük bir sorun olarak görünmektedir. Çalışmamız yeni DSÖ sınıflamasının değerlendirilmesine de yer vermesi açısından literatüre katkı sağlayacaktır.

Anahtar Kelimeler

Miyelodisplastik Sendromlar;, sınıflandırma, prognoz, sağkalım

Retrospective evaluation of patients diagnosed with myelodysplastic syndrome

Öz

Aim: Myelodysplastic syndrome (MDS) is a hematopoietic stem cell disease characterized by bone marrow failure that usually occurs at an advanced age. The prognosis and treatment of the disease vary in patients, despite new treatments and it is still a disease that has no curative treatment rather than allogeneic stem cell transplantation. The aim of this study is to evaluate our MDS patients retrospectively in terms of demographic characteristics, prognostic score, treatments and responses of patients.
Material and Methods: Fifty six MDS patient's data was analyzed retrospectively. Demographic and diagnostic characteristics of the patients, prognostic scores, treatments, survival information were evaluated retrospectively.
Results: 25 (44%) of the patients were female, 31 (56%) were male. The median age was 63 (29-85). According to the World Health Organization (WHO) 2022 classification, 26 (47%) of the patients were classified as MDS with low blasts, 12 (21%) MDS with increased blasts 1, 7 (13%) MDS with increased blasts 2, 4 (7%) MDS with fibrosis, 3 with hypoplastic MDS, 1 MDS with low blasts and isolated 5q deletion, and 3 MDS with biallelic TP53 inactivation. 33 of the patients (59%) had at least one concomitant disease. ECOG performance status of 17 (30%) patients was found to be ≥2. According to the risk scoring, most of the patients were at high risk in the WPSS risk scoring, most of them were in the medium risk group for R-IPSS risk scores, and most of them were in the medium 1 risk group in the IPSS risk scoring.The mean duration of follow-up without treatment was 7.8 (0-95) months. As first-line treatment, 12 (22%) patients received hypomethylating agent, 13 (23%) erythropoietin stimulating treatment, 7 (12%) steroid and danazole treatment, 4 (7%) thalidomide treatment, 4 (7%) conventional chemotherapy, one patient received lenalidomide, 1 patient received antithymocyte globulin with cyclosporine. Three patients underwent allogeneic stem cell transplantation, and 11 (20%) patients were treated with supportive care without medical treatment. The first-line treatment response rate was complete response in 12 (26%) patients, partial response with transfusion reduction in 10 (23%) patients, and no response in 23 (51%) patients. A total of 7 patients had undergone stem cell transplantation when other treatment steps were included. During the follow-up, acute leukemia transformation was observed in 10 (18%) patients. At the end of the follow-up period, the number of surviving patients was 22 (40%), while 27 (48%) patients had died. The survival status was unknown for 7 patients due to the withdrawal of the follow-up. Of the 27 patients whose cause of death was known, 5 patients died due to disease progression, 12 due to infection, 2 patients due to bleeding, 6 due to transplant-related complications, and 2 due to other causes. The median total survival was found to be 38.6 (1-123) months. Age, ECOG performance status, 2016 and 2022 WHO classification, bone marrow blast ratio, bone marrow fibrosis status, IPSS-WPSS-R IPSS score, response status to treatment in treated patients, iron chelation therapy, acute leukemia transformation and allogeneic stem cell transplantation was statistically associated with survival.
Conclusion: Epidemiological data of the disease were found to be compatible with the literature in this study, in which the data of the patients monitored at our center were collected due to the introduction of a diagnostic classification update in MDS 2022 and the continuation of improvements in treatment. Together with the current classification, the distribution characteristics of the patients have been determined and will be a guide for the treatment-prognosis processes in the future. Although it is seen that a suitable treatment option is given to the majority of patients in our center, even though MDS is an advanced age disease, the responses of these treatments are not high and not permanent in accordance with the literature. The most effective factors on survival were found to be consistent with the literature. Although allogeneic stem cell transplantation, which is the only curative option for eligible MDS patients, is provided with the appropriate time and transplantation criteria, unfortunately, transplant-related mortality still seems to be a big problem. Our study will contribute to the literature in terms of providing a place for the evaluation of the new WHO classification.

Anahtar Kelimeler

Myelodysplastic Syndromes; classification; prognosis; survival

Kaynakça

• Rotter LK, Shimony S, Ling K, Chen E, Shallis RM, Zeidan AM, et al. Epidemiology and Pathogenesis of Myelodysplastic Syndrome. 2023;29(3):111-21.
• Barone P, Patel S. Myelodysplastic syndrome: Approach to diagnosis in the era of personalized medicine. Seminars in diagnostic pathology. 2023;40(3):172-81.
• Baidurin S, Akhmetzhanova S, Ilmalieva A, Sagyndykova G, Orazbekova A. Myelodysplastic syndrome: diagnosis, treatment and prognosis (literature review). Georgian medical news. 2023(334):103-7.
• Xu ML, Hasserjian RP. Updates in Classification of Myelodysplastic Syndrome. Cancer journal (Sudbury, Mass). 2023;29(3):122-9.
• Khoury JD, Solary E, Abla O, Akkari Y, Alaggio R, Apperley JF, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703-19.
• Arber DA, Orazi A, Hasserjian RP, Borowitz MJ, Calvo KR, Kvasnicka HM, et al. International Consensus Classification of Myeloid Neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200-28.
• Arslan S, Khaled S, Nakamura R. Current Management and New Developments in the Treatment of Myelodysplastic Syndrome. Cancer treatment and research. 2021;181:115-32.
• Fenaux P, Platzbecker U, Ades L. How we manage adults with myelodysplastic syndrome. British journal of haematology. 2020;189(6):1016-27.
• Dotson JL, Lebowicz Y. Myelodysplastic Syndrome. StatPearls. Treasure Island (FL) ineligible companies. Disclosure: Yehuda Lebowicz declares no relevant financial relationships with ineligible companies.: StatPearls Publishing Copyright © 2023, StatPearls Publishing LLC.; 2023.
• Hellström-Lindberg E, Tobiasson M, Greenberg P. Myelodysplastic syndromes: moving towards personalized management. Haematologica. 2020;105(7):1765-79.
• Can F, Atalay F. Miyelodisplastik sendromda klasik ve yeni prognostik modeller ve risk sınıflandırması. Çetiner M, editör Miyelodisplastik Sendrom 1 Baskı Ankara: Türkiye Klinikleri; 2021 p8-14. 2021.
• Gyan E, Thépot S. [Myelodysplastic syndrome : prognostic factors]. Bulletin du cancer. 2023.
• Myelodysplastic syndromes (MDS), SEER incidence rates by age at diagnosis, 2015–2019 Available at:https://seercancergov/statistics-network/explorer/applicationhtml?site=409&data_type=1&graph_type=3&compareBy=sex&chk_sex_1=1&hdn_rate_type=1&race=1&advopt_precision=1&advopt_show_ci=on&advopt_show_count=on&hdn_view=0&advopt_show_apc=on&advopt_display=2#graphArea.
• Porta MG, Tuechler H, Malcovati L, Schanz J, Sanz G, Garcia-Manero G, et al. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia. 2015;29.
• Kanagal-Shamanna R, Hidalgo Lopez JE, Milton DR, Kim HR, Zhao C, Zuo Z, et al. Validation of the 2016 revisions to the WHO classification in lower-risk myelodysplastic syndrome. American journal of hematology. 2017;92(8):E168-e71.
• Zhang Y, Wu J, Qin T, Xu Z, Qu S, Pan L, et al. Comparison of the revised 4th (2016) and 5th (2022) editions of the World Health Organization classification of myelodysplastic neoplasms. Leukemia. 2022;36(12):2875-82.
• Della Porta MG, Tuechler H, Malcovati L, Schanz J, Sanz G, Garcia-Manero G, et al. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia. 2015;29(7):1502-13.
• Beris P, Georgiou G. Overview of myelodysplastic syndromes. Seminars in hematology. 2012;49(4):287-94.
• Sauta E, Robin M, Bersanelli M, Travaglino E, Meggendorfer M, Zhao LP, et al. Real-World Validation of Molecular International Prognostic Scoring System for Myelodysplastic Syndromes. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2023;41(15):2827-42.
• Volpe VO, Garcia-Manero G, Komrokji RS. SOHO State of the Art & Next Questions: Myelodysplastic Syndromes: A New Decade. Clinical Lymphoma, Myeloma and Leukemia. 2022;22(1):1-16.
• Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al. International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079-88.
• Voso MT, Fenu S, Latagliata R, Buccisano F, Piciocchi A, Aloe-Spiriti MA, et al. Revised International Prognostic Scoring System (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO Prognostic Scoring System: validation by the Gruppo Romano Mielodisplasie Italian Regional Database. Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2013;31(21):2671-7.