Single Center Experience in Diagnosis of Hepatosplenic T-cell Lymphoma

Abstracts Sequencing revealed that mutation in BRAF gene detected in 100% of patients HCL and demonstrate constitutive activation of RAF-MEK-ERK-cascade. These findings make a significant contribution to the diagnosis of issues and allow distinguishing HCL from similar B-cell lymphomas, such as SMZL. Objective: The aim of our study was to identify BRAF and MAP2K1 genes mutations and their diagnostic importance in HCL and SMZL. Patients: The study included 40 patients with the diagnosis of HCL and 24 patients with SMZL. Diagnosis was based on standard WHO criteria. In all cases, it was detected clonal rearrangement of IGHV. Mutation V600E BRAF gene was determined by allele-specific real-time PCR. Mutations in 11, 15 exons of BRAF gene and 2, 3, 11 exons of MAP2K1 gene was investigated by direct sequencing by Sanger. Results: Mutation of BRAF V600E was detected in 39 of 40 cases of HCL and none of the cases of SMZL. In addition, sequencing of exon 11, 15 of the BRAF gene in all patients don’t found activating mutations. Sequencing of the 2, 3, 11 exons of MAR2K1 gene was observed in one patient with HCL. As a result, determining the mutation status of the immunoglobulin genes, it was found VH3-34 family genes in that HCL patient. In this HCL case had an atypical picture of bone marrow: morphologically identified only scattered lymphoid cells, but immunohistochemical studies revealed pronounced interstitial lymphoid infiltration with a characteristic immunophenotype. None of the 24 patients with SMZL was detected mutations of MAR2K1 gene. Conclusions: It was shown that the BRAF V600E mutation occur in 98% (39/40) HCL cases. It was confirmed that the in BRAF V600E-negative cases could be detected activating mutations in other genes coding of protein kinases of MAP kinase cascade components, such as MAR2K1. The study of the IgHV mutation status revealed the tumor clone with IGHV4-34. These data support the fact that it is the activation of RAF-MEK-ERK-cascade underlies the pathogenesis of HCL.

approaches to the diagnosis of HSTL, to assess overall patient survival depending on the variant of the T-cell receptor (TCR). Patients: Clinical outcomes of 18 patients with newly diagnosed HSTL treated between 2005-2015 we retrospectively analyzed. Diagnosis was based on standard WHO criteria. Among the 18 patients (6 men and 12 women) were included with a median age of 52 (range, 24-76). Results: All patients had hepatosplenomegaly (sizes of spleen varied 14 - 25 cm). LDH activity was increased in 65% of pts, alkaline phosphatase e in 100% cases. Bone marrow involvement was detected in 14 of 18 cases by histological investigation. Splenectomy and liver biopsy were performed in 17 of 18 patients. Lymphoid infiltration was found in spleen in 17 cases, in liver e in 13 pts. CD3ε expression was in all cases, CD4 was positive in 3 pts, CD8 was positive in 6 pts, other cases showed double negative phenotype. An expression of CD2, CD5, CD7, CD16, CD56, CD57 varied. Tumor cell expressed Granzyme B in 100% cases. Ab-type of HSTL was identified in 67% of pts, gd-type e in 33% cases. An expression of Ki67 ranged from 5 to 30%. Clonal rearrangements TCRG genes were detected in 16 from 16 studied cases. Clonal rearrangements TCRD genes were detected in 7 from 16 studied pts. Three patients had difference clonal TCRB gene products in the spleen and bone marrow. Clonal rearrangements TCR were identified in bone marrow in 3 of the 4 cases without morphology. Treatment was carried out on the protocols of current clinical trials. The 3-year overall survival (OS) of 17 patients was 12%, median overall survival - 26 months, data of one patient absent. 2-year OS pts was depending on the variant TCR: ab e 70%, gd e25%. Conclusions: Hepatosplenic T-cell lymphoma is a heterogeneous group of disorders distinguished by the clinical course, clonal rearrangements TCR, phenotype and OS.

NHL-087 Treatment of Pediatric B-cell Non-Hodgkin Lymphoma in Croatia

NHL-083 Single Center Experience in Diagnosis of Hepatosplenic T-cell Lymphoma 1

Jelena Roganovic ,1 Ernest Bilic,2 Ljubica Rajic,2 Ranka Femenic2 1

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Natalya Chernova, Hunan Julhakyan , Yulia Vinogradova,2 Yulia Sidorova,1 Marina Sinitsyna,1 Alla Kovrigina,1 Evgeniy Zvonkov,1 Elena Parovichnikova,1 Valeriy Savchenko1 1

National Research Center for Hematology of the Ministry of Health2

care of the Russian Federation, Moscow, Russia; The State Education Institution of Higher Professional Training The First Sechenov Moscow State Medical University under Ministry of Health of the Russian Federation, Moscow, Moscow, Russia

Context: Hepatosplenic T-cell lymphoma (HSTL) is a rare form of non-Hodgkins lymphoma with involvement of the liver, spleen and bone marrow. Diagnosis and treatment of HSTL are still difficult. Objective: The aim of our study to define rational

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Clinical Lymphoma, Myeloma & Leukemia September 2016

Clinical Hospital Centre Rijeka, Department of Pediatrics, Division of Hematology and Oncology, Rijeka, Croatia; 2Clinical Hospital Centre Rijeka, Department of Pediatrics, Division of Hematology and Oncology, Rijeka, Croatia

Context: The feasibility of treating children in Croatia with Bcell non-Hodgkin lymphoma (B-NHL) according to very intensive BFM NHL protocols has not been investigated. Objective: The outcome of pediatric B-NHL has dramatically improved over the last decade with the introduction of shortterm repeated intensive chemotherapy courses. The activity of rituximab in pediatric B-NHL lymphoma has not yet been determined. The aim of this nationwide study was to evaluate and compare therapeutic efficacy of standard chemotherapy and the combination of rituximab and chemotherapy. Design: