Cell of Origin Limfosit B pada Diffuse Large B-Cell Lymphoma Sebagai Faktor Prognosis Kesintasan

WIWIEK PROBOWATI, dr.Mardiah Suci Hardianti,Ph.D,Sp.PD,KHOM; Dr.dr.Ibnu Purwanto,Sp.PD,KHOM

2021 | Tesis-Subspesialis | SUBSPESIALIS ILMU PENYAKIT DALAM

Diffuse large B cell Lymphoma adalah penyakit yang bersifat agresif dengan karakteristik yang heterogen, baik secara histologis, morfologi, imunofenotipik sitogenetik dan prognosis. Gene expression profilling dari Diffusse Large B Cell Lymphoma (DLBCL) dibedakan menjadi dua subtipe molekuler yang penting secara prognostik, yaitu Germinal Center B Cell (GCB) dan non GCB. Selama ini peran prognostik dari cell of origin masih bervariasi hasilnya. Tujuan Penelitian ini adalah untuk mengevaluasi subtipe molekuler atau cell of origin dengan pendekatan imunohistokimia dengan menerapkan algoritme Hans dalam mengklasifikasikan subtipe molekuler melalui pemeriksaan imunohistokimia antibodi spesifik seperti CD10, B cell lymphoma 6 (BCL6), dan multiple myeloma oncogene 1 (MUM1) termasuk mengamati nilai prognostik kedua subtipe DLBCL yang mendapat kemoterapi. Metode Kami mengidentifikasi secara kohort retrospektif 60 pasien dengan DLBCL yang didiagnosis antara 2012 hingga 2016 yang menerima kemoterapi dengan atau tanpa rituximab. Kriteria algoritme Hans menggunakan CD10, Bcl6, dan Mum1 untuk mengklasifikasikan cell of origin (COO) dan membandingkan masing-masing subtipe dalam hal karakter klinis dan laboratorium serta keluaran terapi selama 2 tahun. Hasil Dari 60 pasien yang dilibatkan dalam penelitian ini, non GCB sebagai subtipe terbanyak (76,7% 95% CI 64,6% - 85,6%) dengan rasio GCB dan non GCB sekitar 1:3. Tidak ada perbedaan ciri klinis antara kedua subtipe yang diamati dalam penelitian ini seperti usia, jenis kelamin, stadium klinis, status kinerja, jumlah ekstranodal dan kadar LDH. Tidak ada perbedaan yang signifikan antara GCB dan non GCB pada semua kelompok perlakuan (p = 0,695) atau pada subkelompok rituximab (p = 0,751). COO berdasarkan kriteria IHC gagal memprediksi perbedaan keluaran terapi yang signifikan antara subtipe dengan Hazard Ratio (HR) non GCB sebesar 1,36 (95% CI 0,29 - 6,31). Kesimpulan Subtipe non GCB adalah subtipe DLBCLyang paling banyak. Tidak ada perbedaan signifikan dari aspek klinis dan parameter laboratorium antara subtipe GC dan non GC dari DLBCL. Status performa merupakan fraktor prognostik independent pada DLBCL (HR 4,72 (1,16-19,13). Pada subtipe non GCB cenderung memiliki kesintasan luaran yang lebih buruk meskipun tidak bermakna secara statistik. Kata kunci Cell of origin, Hans algorithm, Diffuse large B cell lymphoma, keluaran terapi

The predictor factors of DLBCL therapy include traditional factors including clinical factors (age, performance status, stage, number of nodal involvement) and laboratory factors, namely lactate dehydrogenase (LDH) levels. The second factor is disease biologic factors such as cell of origin (COO) which may play an important role in the prognosis of therapeutic outcomes Objective Diffuse Large B Cell Lymphoma (DLBCL) has been known heterogeneous clinically and morphologically which was simply classified as Germinal Center B cell (GCB) and non Germinal Center B-cell (non GCB) using immunohistochemistry (IHC) method. However, the prognostic value regarding this subtyping methods was conflicting in Asian. Moreover, in Indonesia, the study to elucidate the remarkable clinical characteristics and survival of each DLBCL subtype is still limited. We retrospectively investigated the clinical phenotypes and laboratory markers among GCB and non-GCB, including observing the prognostic value of IHC-based subtyping from Hans algorithm for DLBCL treated in a single-center involved of Indonesian sub-population. Methods A single-center retrospective analysis of 60 DLBCL diagnosed on 2012-2016 with or without rituximab was performed. Hans IHC criteria using CD10, Bcl6, and Mum1 were used to classify cell of origin (COO), and compare each subtype in terms of clinical phenotypes, laboratory markers, and 2 years Overall Survival (OS). Result Among 60 patients included in the study, non-GCB was appeared as the predominant subtype (76,7% 95% CI 64,6% - 85,6%) with the ratio of GCB and non GCB was about 1:3. No difference in clinical features among both subtype was observed in this study such as age, gender, clinical stage, performance status, extranodal mass, and LDH level. No significant difference was observed between GCB and non GCB in all treated group (p = 0,695) or in rituximab subgroup (p = 0,751). COO based on IHC criteria failed to predict significantly different OS between subtype with Hazard Ratio (HR) of non-GCB was 1,36 (95% CI 0,29-6,31). Conclusion The non GCB subtype is the most frequent DLBCL subtype. There were no significant differences in clinical and laboratory parameters between GC and non GC subtypes of DLBCL. Performance status is an independent prognostic factor in DLBCL (HR 4.72 (1,16 - 19,13). Non GCB subtypes tend to have worse outcome survival, although it is not statistically significant. Keywords Cell of origin, Hans algorithm, diffuse large B cell lymphoma, progression free survival

Kata Kunci : Keywords Cell of origin, Hans algorithm, diffuse large B-cell lymphoma, progression-free survival