Minimal residual disease in multiple myeloma: Benefits of flow cytometry.

Over the last 20 years, the approaches to the treatment of multiple myeloma (MM) have changed considerably, which led to an increase in remission rate. Using new diagnostic methods has made it possible to assess the response to treatment more reliably and forecast disease recurrence: allele-specific polymerase chain reaction, new-generation sequencing and multicolor flow cytometry enable minimal residual disease (MRD) detection of with sensitivity of 10-5 to 10-6 . MRD assessment with flow cytometry using is a rapidly developing area of research. The goal of multicenter groups that use flow cytometry as a tool to detect MRD in patients with MM is achieving standardization and increasing sensitivity and specificity of this method. This article provides data about the methods used for MRD monitoring and describes the advances in the field of flow cytometry.

[Experience in investigating splenic red pulp lymphoma]. / Opyt izucheniya limfomy krasnoi pul'py selezenki.

AIM: To generalize hematologists' experience of the diagnosis and differential diagnosis of splenic red pulp lymphoma (SRPL). MATERIAL AND METHODS: Eighty-seven splenic biopsy specimens taken from patients with different B-cell lymphoproliferative diseases were examined in the Hematology Research Center in 2013-2014. The diagnosis of SRPL was based on the morphological, immunohistochemical, immunophenotypic, and molecular examinations of the splenic biopsy specimens, blood and bone marrow (BM) tests in 4 (4.6%) cases. RESULTS: There was significant splenomegaly in all SRPL cases, lymphocytosis in 56 to 94% (leukocytes, 55 and 75·109/l in 2 cases), circulation of hairy lymphocytes with the phenotypes CD20+ (markedly), CD11c+/±, CD103+/± (weakly), LAIR-1+, CD25-, CD5-, CD10-, and CD23-, which did not contain tartate-resistant acid phosphatase, without BRAFV600E mutation, BM with insignificant lymphoid infiltration of CD20+, CD25-, Annexin 1-, and Cyclin D1-. The weight of the spleen averaged 3900 g (1450-9500 g); its tissue exhibited lymphoid infiltration of the red pulp with the phenotypes CD20+, DBA.44+, CD25-, Annexin1-, Cyclin D1-, CD103-, CD123-, CD27-, focal СD11c±, and TRAP±. Four patients (2 after splenectomy (SE) and 2 after SE and chemotherapy with cladribine and rituximab) are being followed up in remission. CONCLUSION: SRPL is a rare disease that should be presumed to be in significant splenomegaly and lymphocytosis with hairy lymphocytes, which have only some markers for classical hairy cell leukemia (HCL), in minor BM lesion. SE is the standard for diagnosis and treatment. The differential diagnosis of SRPL with HCL has clear criteria and that with HCL-v is undetected.

[Hepatosplenic T-cell lymphoma: The problems of diagnosis and treatment]. / Gepatolienal'naia T-kletochnaia limfoma: problemy diagnostiki i lecheniia.

In the past decade, a notable advance has been made in the understanding of the pathogenesis of NK/T-cell lymphomas; however, their diagnosis remains difficult because of their rarity and clinical and morphological variabilities. The paper generalizes the ten-year experience of the Hematology Research Center, Ministry of Health of Russia, in diagnosing and treating hepatosplenic T-cell lymphoma (HSTL), considers the problems of differential diagnosis with other hematological diseases occurring with similar clinical and laboratory symptoms, and lays down current approaches to the diagnosis and treatment of this condition. A clinician's view of the problem of diagnosis and treatment of this disease is given. HSTL is shown to be a heterogeneous group of diseases differing in a T-cell receptor chain gene rearrangement, the clinical course of the disease, and overall survival (OS). According to our data, 3-year OS was 12%; the median survival was 26 months. Two-year OS for γδ and αß HSTL was equal to 25 and 70%, respectively. The difference in OS for the variants of HSTL failed to reach statistical significance (because the sample might be insufficient).

Clonal rearrangements and Malignant Clones in Peripheral T-cell Lymphoma.

AIM: To assess the feasibility and informative value of T-cell clonality testing in peripheral T-cell lymphoma (PTCL). PATIENTS AND METHODS: Biopsies of involved sites, blood, and bone marrow samples from 30 PTCL patients are included in the study. Rearranged TCRG and TCRB gene fragments were PCR-amplified according to the BIOMED-2 protocol and analyzed by capillary electrophoresis on ABI PRISM 3130 (Applied Biosystems). RESULTS: TCRG and TCRB gene clonality assay was valuable in confirming diagnosis in 97% of PTCL patients. T-cell clonality assay performed on blood or bone marrow samples reaffirmed lymphoma in 93% of cases, whereas morphological methods were informative in 73% of cases only. We observed multiple TCRG and TCRB gene rearrangements, loss of certain clones in the course of the disease, as well as acquisition of new clones in 63% of PTCL cases, which can be attributed to the genetic instability of the tumor. CONCLUSION: TCRG and TCRB gene clonality assay is beneficial for the diagnosis of PTCL. However, the presence of multiple clonal rearrangements should be considered. Clonal evolution in PTCL, particularly acquisition of new clones, should not be treated as a second tumor. Multiple TCRG and TCRB gene rearrangements may interfere with minimal residual disease monitoring in PTCL.