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.
Clonal instability of a tumor cell population in acute lymphoblastic leukemia (ALL) may complicate the monitoring of a minimal residual disease (MRD) by means of patient-specific targets identified at the disease onset. Most of the data concerning the possible instability of rearranged clonal TCR and IG genes during disease recurrence were obtained for ALL in children. The appropriate features of adult ALL, which are known to differ from those of childhood ALL in certain biological characteristics and prognosis, remain insufficiently studied. The aim of this study was to assess the stability of IG and TCR gene rearrangements in adult ALL. Rearrangements were identified according to the BIOMED-2 protocol (PCR followed by fragment analysis). Mismatch in clonal rearrangements at onset and relapse was identified in 83% of patients, indicating clonal instability during treatment. Clonal evolution and diversity of IG and TCR gene rearrangements may be one of the tumor progression mechanisms. New rearrangements may emerge due to residual VDJ-recombinase activity in tumor cells. Also, many clonal IG and TCR gene rearrangements may be present at different levels at a diagnosis, but less abundant clones may be “invisible” due to limited detection sensitivity. Later, major clones may disappear in the course of chemotherapy, while others may proliferate. Investigation of clonal evolution and heterogeneity in ALL and their impact on the treatment efficacy will contribute to the identification of new prognostic factors and the development of therapeutic approaches.
Introduction: Peripheral T-cell lymphoma, unspecified (PTCL, NOS) is a tumor of mature T-lymphocytes characterized by aggressive course and low response rate to CHOP-like therapy. Bone marrow involvement in PTCL, NOS is detected by histological investigation in about 20-40% of patients and it is considered to be a poor prognostic factor. Importance of T-cell clonality examination in bone marrow as a prognostic and staging factor has been insufficiently studied. Aim: In order to evaluate the significance T-cell receptor gene γ- and β-chains (TCRG and TCRB) rearrangements for identification of bone marrow involvement; to estimate its value for staging and prognosis; to evaluate the significance of T-cell clonality persistence in bone marrow after initial therapy in patients with PTCL, NOS. Patients and methods: Bone marrow samples of 27 patients with primary PTCL, NOS (median age 62 years, range 32-77) have been obtained from 2006 till 2014 and were analyzed retrospectively. Morphological examination was performed for all bone marrow samples. Detection of T-cell clonality by revealing rearrangements of TCRB and TCRG were performed by PCR in bone marrow samples of patients before and after initial chemotherapy. Results: Bone marrow involvement was revealed by histological investigation in 22 (81%) of patients. T-cell clonality was detected by rearrangements of TCRG or TCRB in 26 (96%) patients, including 4 of 5 patients without bone marrow involvement by histology. Rearrangements of TCRG and TCRB were detected in 24 (89%) and 26 (96%) of patients, respectively. Rearrangements of TCRB were observed without rearrangements of TCRG in 2 cases. Interestingly, we detected more than 2 clonal rearrangements present simultaneously in 33% of cases. For monitoring minimal residual disease the examination of T-cell clonality in bone marrow samples was performed in 15 of 27 patients after initial therapy; all these 15 patients achieved complete remission. Persistence of T-cell clonality was observed in 14 of 15 patients after treatment, disease progression was noted in 1-3 months in all these cases. Conclusion: The examination of T-cell clonality in the bone marrow seems to be important and necessary for staging, monitoring minimal residual disease. Detection of T-cell clonality in bone marrow allows revealing its involvement even without morphological features in primary patients with PTCL, NOS. Persistence of clonal rearrangements in bone marrow after initial therapy shows continuing lesion and necessity for timely therapy escalation for patients with PTCL, NOS. Disclosures No relevant conflicts of interest to declare.
The paper presents experience in following up and treating hairy cell leukemia (HCL) during pregnancy. The combination of HCL and pregnancy was observed in 5 patients. The patients' median age was 35 years (range, 28-42 years). The diagnosis of HCL was based on a conventional examination protocol: clinical blood analysis with the morphological assessment of lymphocytes, a myelogram and trepanobiopsy, immunophenotypic analysis of lymphocytes or bone marrow (in all the patients), cytochemical determination of tartrate-resistant acid phosphatase in 3 patients, and identification of BRAFV600E mutation in 3 patients. Three pregnant women were treated for HCL in the postpartum period. In one patient with HCL, pregnancy was seen in remission after treatment with cladribine. In one patient with HCL detected at 11 weeks' gestation, interferon-α therapy during the second trimester of pregnancy was performed for increased cytopenia, which was followed by cladribine therapy after delivery. Pregnancy and delivery were uncomplicated in all the patients; 3 patients had vaginal delivery and 2 patients underwent cesarean section. All infants were healthy, with no developmental abnormalities during a follow-up period of 6-140 months (median 30 months). All the patients with HCL are currently in remission: 4 patients in first remission at a follow-up of 10 to 48 months (median 15 months) and one patient in second remission at a follow-up of 88 months. Possible observational tactics is possible when HCL is detected during pregnancy. Treatment of HCL during pregnancy is necessary in cases of deep or progressive cytopenia and/or splenomegaly. The use of interferon-α or splenectomy is preferable.
Angioimmunoblastic T-cell lymphoma (AITL) is a T-cell lymphoma, characterized by abundant polymorphocellular infiltrate of lymph nodes with the small number of tumor CD4+ Tfh-cells. AITL could often be misdiagnosed as reactive processes and other lymphomas, including Hodgkin's lymphoma and diffuse large B-cell lymphoma (DLBCL). We used quantitative allele-specific PCR with LNA (locked nucleotide acid) modified primers (qAS-PCR-LNA) for RHOA G17V mutation assay. Sensitivity of determination (0.02%) was sufficient for minimal residual disease (MRD) monitoring and evaluation of tumor cell number in different tissues. Method proposed demonstrated sensitivity superior to histology and PCR-based clonality determination. RHOA G17V mutation in lymph nodes was detected in 53% (32 of 62) patients with AITL. In control group (n-110) we have revealed RHOA G17V mutation in 3 patients with Hodgkin’s lymphoma (HL) and 1 patient with diffuse large B-cell lymphoma (DLBCL). Three patients with HL had clonal CD4+ T-lymphocytes population with aberrant immunophenotype in blood and clonal rearrangements of TCRG and/or TCRB genes in lymph nodes. We have shown that RHOA G17V can be used as a screening marker for patients with lymphadenopathy to exclude AITL or PTCL NOS. The persistence of tumor cells with RHOA G17V mutation was shown in most patients (12 of 16 -75%) with AITL after the induction chemotherapy and during the maintenance therapy (5 of 7 - 71.4%). Therefore qAS-PCR-LNA can be enrolled into standard protocols for management of patients with AITL to assess the effectiveness and the duration of antitumor therapy.
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