Ahmet ŞEYHANLI, Muhammed EROGLU, Şerife SOLMAZ, Zeynep YÜCE, Sermin ÖZKAL, Oğuz ALTUNGÖZ, İnci ALACACIOĞLU

Myelodisplastik Sendrom Tanılı Olguların Sitogenetik / Fish ve Demografik Verilerinin İncelenmesi

Amaç: Myelodisplastik sendrom (MDS) kemik iliğinde anormal selüler proliferasyon, çevre kanında, bir veya daha fazla hücre dizisinde sitopeni, kemik iliğinde displazi ve akut myeloid lösemi (AML) gelişme riski ile karakterize heterojen bir hastalık grubudur. Bu çalışmanın amacı MDS hastalarında demografik veriler, konvansiyonel sitogenetik, Florasan in situ hibridizasyon (FİSH) ve prognostik özelliklerini değerlendirmektir. Yöntemler: Bu çalışmaya Ocak 2010 - Ocak 2020 tarihleri arasında DEÜTF Hematoloji Bölümü’nde takip edilen 18 yaş ve üzerindeki MDS tanılı hastalar dahil edildi. Hastaların verileri geriye dönük arandı. Herhangi bir zamanda tanı alan hastaların hemogram, biyokimya, sitogenetik ve FİSH sonuçları, sağ kalımları, almış oldukları tedaviler, sitopeni dereceleri, kemik iliği blast yüzdeleri, kemik iliği biyopsi sonuçları incelendi. Bulgular: Çalışmaya Ocak 2010-Ocak 2020 tarihleri arasında MDS tanısı almış ve izlemde olan 18 yaş ve üzerindeki 205 hasta alındı. Kadın/Erkek oranı 0,8/1 olarak bulundu. Ortanca yaş 70,7 (27-92) idi. Ortanca hemoglobin değeri 9,4 (4.8-14.5) idi. MDS olguları, 2016 Revize-WHO Sınıflaması’na göre sınıflandırıldıklarında; en fazla 78 hasta (%38) ile MDS-SLD grubunda saptandı. Konvansiyonel sitogenetik analiz yapılabilen 141 hastanın 112’sinde (%79,4) normal karyotip saptandı ve bu yöntem ile en fazla saptanan sitogenetik anomali komplex karyotipti (n=9, %6,3). FİSH paneli ile bakılan 135 hastanın genetik anomalilerine göre medyan sağkalımlarına bakıldı. FİSH sonucuna göre 7q delesyonu ve P53 mutasyonu olan hasta popülasyonlarında, mutasyon olmayan gruba göre azalmış ortanca sağkalım süreleri istatistiksel olarak anlamlı saptanmıştır (p-değeri

Anahtar Kelimeler:

Myelodisplastik sendrom, Kemik iliği biyopsisi, Sitogenetik analiz, Floresan in situ hibridizasyon

Retrospective Comparison of Chemotherapy Plus Anti-HER2 Therapies at First-line Treatment in Patients with Metastatic Gastric Adenocarcinoma

Aim: We aimed to compare the efficacy and the safety of cisplatin plus 5-FU plus trastuzumab and mFOLFOX-6 plus trastuzumab at first-line treatment in HER2-positive metastatic gastric cancer. Method: It was a retrospective observational monocentric study. Patients diagnosed with HER2-positive metastatic gastric adenocarcinoma between January 2013 and December 2020 in Dr AY Ankara Oncology TRH were screened. Patients treated at least one cycle of treatment with either CF-T or mFOLFOX-T were included. Survival outcomes and treatment compliance of patients were compared between groups. Results: Of 52 patients, 55.8% (n=29) of patients were treated with CF-T, and 44.2% (n=23) with mFOLFOX-T. The median age at diagnosis was 60 years (IQR: 52-70) in the CF-T and 64 years (IQR: 59-70) in the mFOLFOX-T groups. De novo metastatic disease comprised 96.6% (n=28) of patients in the CF-T and 69.6% (n=16) in the mFOLFOX-T groups (p=0.016). Both IHC3+ and ISH positivity were observed 82.8% (n=24) of patients in the CF-T and 56.5% (n=13) in mFOLFOX-T groups (p=0.038). The mPFS was 10.4 months (95% CI 8.7-12.2) in the CF-T and 6.5 months (95% CI 5.5-7.6) in the mFOLFOX-T groups (p=0.532). The mOS was 12.2 months (95% CI 11.3-13.2) in the CF-T and 12.5 months (95% CI 9.8-15.5) in the mFOLFOX-T groups (p=0.974). No statistically significant difference regarding at least one dose reduction (31.0% vs 21.7%, p=0.453) and at least one dose delay (24.1% vs 21.7%, p=0.838) was observed between groups. Conclusion: It was revealed that CF-T and mFOLFOX6-T had similar efficacy and tolerability in patients with HER2-positive metastatic gastric adenocarcinoma.

Keywords:

metastatic gastric cancer, anti-HER2 FOLFOX, CF, FOLFOX, CF,

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1.Zeidan AM, Shallis RM, Wang R, Davidoff A, Ma X.Epidemiology of myelodysplastic syndromes: whycharacterizing the beast is a prerequisite to tamingit. Blood Rev. 2019;34:1-15.
2.Mittelman M, Oster HS, Hoffman M, Neumann D.The lower risk MDS patient at risk of rapidprogression. Leuk Res. 2010;34(12):1551-5.
3.Keng MK, Sekeres MA. The race for survival inmyelodysplastic syndromes. Leuk Lymphoma.2013;54(2):219-20.
4.Young NS. Aplastic anemia, myelodysplasia, andrelated bone marrow failure syndromes. HarrisonsPrinciples of Internal Medicine. 2005;16(1):617.
5.Williamson P, Kruger A, Reynolds P, Hamblin T,Oscier D. Establishing the incidence ofmyelodysplastic syndrome. Br J Haematol.1994;87(4):743-5.
6.Aul C, Gattermann N, Schneider W. Age relatedincidence and other epidemiological aspects ofmyelodysplastic syndromes. Br J Haematol.1992;82(2):358-67.
7.Greenberg P, Cox C, LeBeau MM, et al.International scoring system for evaluatingprognosis in myelodysplastic syndromes. Blood, TheJournal of the American Society of Hematology.1997;89(6):2079-88.
8.Weisdorf DJ, Oken MM, Johnson GJ, Rydell RE.Chronic myelodysplastic syndrome: short survivalwith or without evolution to acute leukaemia. Br JHaematol. 1983;55(4):691-700.
9.Greenberg PL. The smoldering myeloid leukemicstates: clinical and biologic features. Blood,1983;61:1035.
10.Nösslinger T, Tüchler H, Germing U, et al.Prognostic impact of age and gender in 897untreated patients with primary myelodysplasticsyndromes. Ann Oncol. 2010;21(1):120-5.
11.Morita K, Ali A, Coutinho D, Mushtaq MU, Raza A.Prognostic significance of bone marrow cellularityin myelodysplastic syndromes: a retrospectiveanalysis. J Clin Oncol. 2016;34(15S):e18550.
12.Della Porta MG, Malcovati L, Boveri E, et al.Clinical relevance of bone marrow fibrosis andCD34-positive cell clusters in primarymyelodysplastic syndromes. J Clin Oncol.2009;27(5):754-62.
13.Greenberg PL, Tuechler H, Schanz J, et al. Revisedinternational prognostic scoring system formyelodysplastic syndromes. Blood, The Journal ofthe American Society of Hematology.2012;120(12):2454- 65.
14.Schanz J, Tüchler H, Solé F, et al. Newcomprehensive cytogenetic scoring system forprimary myelodysplastic syndromes (MDS) andoligoblastic acute myeloid leukemia after MDSderived from an international database merge. J ClinOncol. 2012;30(8):820.
15.Mądry K, Machowicz R, Waszczuk-Gajda A, et al.Demographic, Hematologic, and clinical features ofmyelodysplastic syndrome patients: results fromthe first polish myelodysplastic syndrome registry.Acta Haematol. 2015;134(2):125-34.
16.Gonzalez Porras JR, Cordoba I, Such E, et al.Prognostic impact of severe thrombocytopenia inlow risk myelodysplastic syndrome. Cancer.2011;117(24):5529-37.
17. Mahmood R, Altaf C, Ahmed P, Khan SA, Malik HS.Myelodysplastic Syndrome in Pakistan:Clinicohematological Characteristics, CytogeneticProfile, and Risk Stratification. Turkish Journal ofHematology. 2018;35(2):109.
18.Tekinalp A, Demircioglu S, Celik AF, Ceneli O. TheEffects of Genetic Characteristics on the Survival inMyelodysplastic Syndrome/MyelodisplastikSendromda Genetik Ozelliklerin Sagkalim UzerineEtkisi. Bezmialem Science. 2022;10(1):24-9.
19.Rashid A, Khurshid M, Shaikh U, Adil S.Chromosomal abnormalities in primarymyelodysplastic syndrome. JCPSP: Journal of theCollege of Physicians and Surgeons Pakistan.2014;24(9):632.
20.Raza A, Galili N. The genetic basis of phenotypicheterogeneity in myelodysplastic syndromes.Nature Reviews Cancer. 2012;12(12):849-59.
21.Papaemmanuil E, Cazzola M, Boultwood J, et al.Somatic SF3B1 mutation in myelodysplasia withring sideroblasts. N Engl J Med. 2011;365(15):1384-95.
22.Walter MJ, Shen D, Ding L, et al. Clonalarchitecture of secondary acute myeloid leukemia. NEngl J Med. 2012;366(12):1090-8.
23.Yoshida K, Sanada M, Shiraishi Y, et al. Frequentpathway mutations of splicing machinery inmyelodysplasia. Nature. 2011;478(7367):64-9.
24.Bejar R, Stevenson K, Abdel-Wahab O, et al.Clinical effect of point mutations in myelodysplasticsyndromes. N Engl J Med. 2011;364(26):2496-506.
25.Mills KI, Kohlmann A, Williams PM, et al.Microarray-based classifiers and prognosis modelsidentify subgroups with distinct clinical outcomesand high risk of AML transformation ofmyelodysplastic syndrome. Blood, The Journal of theAmerican Society of Hematology.2009;114(5):1063-72.
26.Pellagatti A, Cazzola M, Giagounidis A, et al.Deregulated gene expression pathways inmyelodysplastic syndrome hematopoietic stemcells. Leukemia. 2010;24(4):756-64.