Non-Hodgkin lymphoma with t(14;18): clonal evolution patterns and cytogenetic–pathologic–clinical correlations

Purpose The pattern and frequency of secondary chromosome abnormalities in t(14;18)-carrying non-Hodgkin lymphomas (NHL) were evaluated for differences in relation to histologic NHL subtype and patients’ outcome. Methods One hundred and forty-nine NHL patients with t(14;18) and complete cytogenetic, morphologic, and clinical information were selected. Results One hundred and twelve cases were follicular lymphoma (FL) and 37 were diffuse large B-cell lymphoma (DLBCL). One hundred and forty cases showed secondary aberrations (94%, median = 6.0). The most frequent were losses from chromosome arms 1p and 6q and +7 (26%). Loss from 1q, +7, and +12 were more frequent in DLBCL than in FL. Loss from 1p, Xp, and −16 were more frequent in FL grade 3 than in FL grades 1 and 2. Patients with <6.0 secondary cytogenetic aberrations had better prognosis than did those with a higher number of aberrations. Trisomy 21 was associated with shorter patient survival. FLIPI score, the number of secondary chromosomal aberrations, and +21 were all of independent prognostic value in Cox multivariate analysis. FL grade 1-3a patients that had received chemotherapy, showed a higher frequency of i(6p) and loss from 6q. Conclusion Secondary chromosomal aberrations showed some correlation with the morphologic subgroups of t(14;18)-NHL. Trisomy 21 and the presence of >6.0 secondary cytogenetic aberrations both correlated with shorter overall survival.     

Epstein–Barr virus-positive diffuse large B-cell lymphoma carrying a t(9;14)(p13;q32) translocation

We, herein, report a 75-year-old man with lymphoma who initially presented with disseminated disease involving the lung, followed by temporal regression, and finally died of disease progression. Lymph-node biopsy showed a morphology of diffuse large B-cell lymphoma (DLBCL), containing CD30⁺ Reed–Sternberg-like cells. The lymphoma cells were stained by in situ hybridization (ISH) for Epstein–Barr virus (EBV)-encoded RNA, and the presence of the EBV genome was confirmed by the polymerase chain reaction. A cytogenetic study showed that the lymphoma cells carried a t(9;14)(p13;q32) translocation, and rearrangement of the PAX5 gene was determined by fluorescence ISH using a split signal probe. This case report is the first to identify t(9;14)(p13;q32) in EBV⁺ DLBCL of the elderly, which was very recently listed among subtypes of DLBCL.     

Protein–protein interaction networks and different clustering analysis in Burkitt’s lymphoma

Objective: Burkitt's lymphoma (BL) is a highly aggressive malignant lymphoma, its molecular biological mechanism has not been fully investigated. The construction of protein-protein interaction (PPI) networks and the identification of complexes through a cluster analysis are important research directions in the post-genome era. However, different cluster analysis algorithms have their own characteristics, and a single analysis has some limitations. In this study, we obtained the target and pathway information of BL using different clustering analyses.

Material and Methods: First, we obtained 50 BL genes by screening the Online Mendelian Inheritance in Man (OMIM) database; their related genes were further extracted from the literature. The PPI network was constructed with the Search Tool for Retrieval of Interacting Genes/Proteins (STRING). Afterward, the interaction data were input in Cytoscape3.4.0 software and related plug-ins were used to implement topology analysis and clustering analysis. Functional analysis based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to characterize the biological importance of the clusters.

Results: We constructed a PPI network consisting of 459 nodes (proteins) and 1399 sides (interactions), 12 genes and 8 signaling pathways were found to be closely related to BL.

Conclusion: In this study, the use of combined algorithms to analyse gene interactions provides a new perspective for network-based analysis. The results of this study reveal new insights into the molecular mechanisms underlying BL, which may be novel therapeutic targets for disease management and may provide a bioinformatic basis for the further understanding of BL.     

Posttransplant monomorphic Burkitt’s lymphoma: clinical characteristics and outcome of a multicenter series

Burkitt’s monomorphic posttransplant lymphoproliferative disorder (B-PTLD) is an uncommon subtype of PTLD. Owing to the paucity of this complication, clinical characteristics and outcome has not been fully described. Clinical characteristics and outcomes of 20 patients diagnosed with B-PTLD from 10 transplant centers belonging to the GEL/TAMO group were reviewed. Median time from transplant to B-PTLD was 7.2 years. All the cases fulfill the morphologic and genetic criteria of B-PTLD, whereas Epstein-Barr virus (EBV) was detected in 70% of cases. Patients were treated with different chemotherapy combinations, and three patients received upfront rituximab monotherapy. The great majority of patients receiving CHOP-like regimens attained a complete response (CR) (73%), similar to that obtained with dose-intensive chemotherapy (83% CR). In contrast, patients receiving upfront rituximab monotherapy required subsequent chemotherapy. Two patients (10%) died during treatment due to infection. The median progression-free survival and overall survival (OS) were 16 months and 139 months, respectively. When analyzing variables predicting for OS, we found that patients with bone marrow involvement had an adverse prognosis, with a median OS of 6 months (p?=?0.008). In conclusion, B-PTLD is an uncommon complication usually associated with EBV infection and with an aggressive clinical course, particularly in patients with bone marrow involvement. High-dose chemoimmunotherapy obtained similar responses to R-CHOP, suggesting that R-CHOP could be an adequate alternative for these patients. In contrast, rituximab monotherapy does not seem to be effective enough to control the disease.     

t(8;21) (q22;q22) Acute myelogenous leukemia in México: A single institution experience

We analyze the prevalence and clinical features of a group of patients with t(8;21) (q22;q22) acute myeloblastic leukemia, identified in a single institution in México over a 10-year period. Fifteen patients presented at the Centro de Hematología y Medicina Interna de Puebla from February 1995 to August 2005; only nine were treated and followed in the institution. Median age was 24 years, (range 7–49); there was only one male. According to the French–American–British (FAB) morphological classification of leukemia, the morphology was M2 in four cases, M4 in three cases, M3 in one case and M0 in one. In addition to the myeloid markers, lymphoid markers were identified in 6 patients. Patients were induced to remission with combined chemotherapy and three subsequently underwent bone marrow transplantation (BMT). The median overall and disease-free survival has not been reached, being above 3390 days, the probability of survival at this time was 73%. In this single-center experience in México, we found that the t(8;21) (q22;q22) variant of leukemia was more frequent than in Caucasian populations, that the co-expression of lymphoid markers in the blast cells is very frequent and that this malignancy is associated with a relatively good prognosis.     

Frequency and evaluation of t(14;18) translocation in Sjögren's syndrome

In most cases of follicular lymphoma, t(14;18) chromosomal translocation can be detected in lymphocytes of peripheral blood and bone marrow. Nevertheless, certain other types of diseases can also be characterised by the presence of the translocation. Patients of Sjögren's syndrome have an increased frequency of developing non-Hodgkin's lymphoma, e.g. follicular lymphoma; in turn, they may have translocation-bearing cells. One hundred Sjögren's syndrome patients were screened using a nested polymerase chain reaction technique to identify whether they had the translocation in their peripheral blood lymphocytes. Five percent of that population revealed a temporary or long-lasting presence of the translocation, sometimes even in the lymphocytes from bone marrow. Our results indicate that in addition to the conventional diagnostic methods of lymphoma, there are certain other factors, e.g. the duration of the presence of t (14; 18) translocation and the source of lymphocytes, that should be considered for successful early diagnoses and perhaps for treatment of the lymphoma in the Sjögren's patients.     

Interaction between cisplatin,5-fluorouracil and vincristine on human hepatoma cell line (7721)

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复杂易位t(2;8;21)(p12;q22;q22):变异型t(8;21)急性粒细胞白血病1例报告并文献复习

目的：探讨急性髓系白血病（AML）伴有t（2;8;21）（p12;q22;q22）复杂易位的实验室和临床特点。方法：取患者骨髓液,进行形态学检查及流式细胞术检测;用逆转录聚合酶链反应（RTPcR）方法检测AML1／ETO融合基因转录本;G显带分析染色体核型。结果：患者诊断为急性粒细胞白血病部分分化型（AML-M2）,PT—PCR检测到阳性AML1／ETO融合基因,染色体核型分析有t（2;8;21）（p12;q22;q22）复杂易位。结论：变异型t（8;21）累及染色体2p12区,可能对白血病的临床表现、预后等因素产生影响,但仍需要积累更多的病例以明确其临床与预后的特点。     

Acute myeloid leukemia M2 and t(8;21)(q22;q22) with an unusual phenotype: myeloperoxidase (+), CD13 (–), CD14 (–), and CD33 (–)

 Cases of myeloid surface antigen-negative acute myeloid leukemia (AML) are rare. We describe the morphological, cytochemical, immunologic, and cytogenetic features of two patients with AML with maturation (FAB M2) and the phenotype MPO+, CD13 (–), CD33(–), CD56(+). Cytogenetic studies demonstrated t(8;21)(q22;q22). These findings suggest an association between the lack of CD13 and CD33 in myeloperoxidase-positive AML and the presence of t(8;21). Received: August 8, 1998 / Accepted: January 27, 1999     

Characteristics of patients with systemic lupus erythematosus (SLE) and non-Hodgkin’s lymphoma (NHL)

Patients with systemic lupus erythematosus (SLE) are at increased risk of developing non-Hodgkin’s lymphoma (NHL), but features of SLE associated with NHL are not well described. The objective of this study was to describe SLE characteristics, laboratory serologies, and medication histories in patients who subsequently develop NHL. Two thousand twenty patients with SLE were identified using the online Partners’ patient database research tool between October 1992 and June 2005. We confirmed the diagnoses of SLE and NHL and sought details of medical history and treatment by medical record review. Eleven patients with NHL without coexisting rheumatoid arthritis, Sjögren’s, or HIV were identified; seven of these (64%) had a diffuse large B cell lymphoma subtype, and 83% of those stained were Epstein–Barr virus (EBV) negative. The mean duration of SLE at NHL diagnosis was 17.8 years (range 1.6–41.8), and the mean Systemic Lupus International Collaborative Clinics/American College of Rheumatology damage index was 1.9. Seven patients (64%) had SLE hematologic involvement, four had anti-dsDNA antibodies, and four had anti-phospholipid antibodies. One patient had significant renal disease. All patients had arthritis and had received antimalarial therapy. Five of 11 patients had received other treatments for SLE, including cyclophosphamide, imuran, methotrexate, and/or sulfasalazine. Diffuse large B cell lymphoma was the most common subtype of NHL, and most were EBV negative. Although disease duration was fairly long and end organ damage moderately severe in this group of patients, renal disease and the use of immunosuppressive chemotherapeutic agents were rare and did not appear to confer an increased risk of NHL development.     

Adult patients with t(8;21) acute myeloid leukemia had no superior treatment outcome to those without t(8;21): a single institution’s experience

Clinical features and treatment outcome of 31 patients over 16 years of age with t(8;21) acute myeloid leukemia (AML) were compared with 60 patients without t(8;21). Among 31 patients with t(8;21), 15 patients were classified as AML-M2 and 11 and 5 patients as AML-M4 and M1, respectively. Of these patients, 28 patients (90.3%) achieved complete remission and 22 patients received consolidative treatment: intermediate-dose cytarabine (IDAC) 11, high-dose cytarabine (HDAC) 6, and allogeneic bone marrow transplantation (BMT) 5. When compared with patients without t(8;21), we could not demonstrate better treatment outcome for t(8;21) AML [median event-free survival (EFS) and overall survival (OS) 10.3 and 12.5 months in AML with t(8;21) vs 11.5 and 15.6 months in AML without t(8;21)]. In the t(8;21) AML group, patients who received HDAC consolidation did not show superior treatment outcome to those who received other consolidative treatment [median EFS: IDAC 11.9 months vs HDAC 9.2 months vs allogeneic BMT 38.1 months (P=NS) and median OS: IDAC 17.8 months vs HDAC 12.0 months vs allogeneic BMT 47.3 months (P=NS)]. Similar treatment outcome between patients with and without t(8;21) and non-superior treatment outcome of HDAC consolidative chemotherapy in the t(8;21) AML group in our study is contradictory to previous reports.These two authors equally contributed to this study: K.-W. Lee and I. S. ChoiSupported by a grant CRI-01-07 from the Cancer Research Institute, Seoul National University College of Medicine, and a grant 05-2001-002 from the S.N.U.H. Research Fund     

Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma: results of a randomised phase III trial (OSHO# 19)

Purpose: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin’s lymphoma (NHL) and mantle cell lymphoma. Methods: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m² (days 1–5) + bendamustine 60 mg/m² (days 1–5) or + cyclophosphamide 400 mg/m² (days 1–5) for a total of eight 21-day cycles. Results: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P=0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P=0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. Conclusions: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP Funding support: Supported by a grant from ribosepharm GmbH, Clinical Research, Munich.     

Central nervous system lymphoma in a patient with Sjogren’s syndrome and autoimmune thyroiditis (Hashimoto’s thyroiditis)

We present a case of central nervous system (CNS) lymphoma in a patient with Sjogren’s syndrome (SS) and autoimmune thyroiditis (Hashimoto’s thyroiditis) overlap. A 60-year-old woman, who had the diagnosis of SS for 16 years, had been admitted for visual loss, fever, weight and appetite loss for 3 months. Cranial magnetic resonance imaging was in accordance with CNS lymphoma, and biopsy from right parietal region showed diffuse large B-cell lymphoma of the CNS. This is the first report of diffuse large B-cell lymphoma of the CNS in SS and autoimmune thyroiditis (Hashimoto’s thyroiditis) overlap.