Phase 1/2 multicenter trial of acalabrutinib in Chinese patients with relapsed/refractory mantle cell lymphoma.

Acalabrutinib studies have limited Asian participation. This phase 1/2 study (NCT03932331) assessed acalabrutinib in Chinese patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). Primary endpoint was blinded independent central review (BICR)-assessed overall response rate (ORR). Overall, 34 patients were enrolled. Most patients were men (88%); median age was 63 years and 59% had ≥3 prior treatments. Median treatment duration was 14 months (range, 1-24). Any-grade adverse events (AEs) and grade ≥3 AEs occurred in 85.3% and 44.1% of patients, respectively. AEs causing treatment discontinuation were aplastic anemia, thrombocytopenia, and gastrointestinal infection (n = 1 each). Fatal AEs occurred in 2 patients (aplastic anemia and multiple organ dysfunction syndrome [n = 1 each]). BICR-assessed ORR was 82.4% (95% confidence interval [CI]: 65.5, 93.2); 12 (35.3%) patients achieved complete response. Estimated 12-month OS was 84.5% (95% CI: 66.6, 93.3). Acalabrutinib yielded tolerable safety and high response rates in Chinese patients with R/R MCL.

Diagnostic analysis of seven subtypes of mature small B-cell lymphoma involving the bone marrow and peripheral blood / 中国基层医药

Objective:To investigate the diagnosis and differential diagnosis methods of chronic mature small B-cell lymphoma involving the bone marrow and peripheral blood.Methods:The clinical data of 27 patients with mature small B-cell lymphoma involving the bone marrow and peripheral blood (seven subtypes phase IV) who received treatment in the Kunshan Third People's Hospital from February 2015 to June 2021 were retrospectively analyzed. The application value of different detection methods in the diagnosis of mature small B-cell lymphoma involving the bone marrow and peripheral blood was analyzed.Results:The majority of patients' peripheral blood was mainly characterized by an increase in the ratio or absolute value of lymphocytes. In terms of cell morphology, mature lymphocytes were mainly small to medium in size. A few bone marrow smears or peripheral blood smears show characteristic changes in cell morphology. Flow cytometry results showed that among the cohort of 15 patients presenting CD5 expression, 11 patients had chronic lymphocytic leukemia, 1 patient had mantle cell lymphoma, 1 patient had splenic diffuse red pulp small B-cell lymphoma, and 2 patients had B-cell chronic lymphoproliferative disorders (unclassified). Among 12 patients presenting no CD5 expression, 8 had Waldenstr?m's macroglobulinemia, 3 had splenic marginal zone lymphoma, and 1 had follicular lymphoma. Among the 2 patients presenting CD5-CD10 expression, 1 patient had follicular lymphoma, and 1 patient had Waldenstr?m's macroglobulinemia. One patient with splenic diffuse red pulp small B-cell lymphoma expressed CD5, CD11c, and CD103 in addition to pan-B-cell markers, while BRAF V600E mutation detection and immunohistochemical staining for tartrate-resistant acid phosphatase and annexin-1A showed negative expression.Conclusion:This type of lymphoproliferative disease is a general term for lymphoma that has various different molecular and biological characteristics. Its diagnosis and differential diagnosis need to comprehensively consider the clinical characteristics of the patient, relevant laboratory tests, cell morphology, flow cytometry detection results, reasonable use of fluorescence in situ hybridization, molecular biology, special chemistry, and bone marrow immunohistochemistry. In a few cases, diagnosis of the lymphoproliferative disease still relies on non-bone marrow involvement and tissue biopsy.

Progress of correlation of Epstein-Barr virus with acute lymphoblastic leukemia and chronic lymphoblastic leukemia / 白血病·淋巴瘤

Epstein-Barr virus (EBV) is a kind of virus commonly infected in human, most of which is latent infection, and only a few people develop malignant diseases. EBV is the pathogen of infectious mononucleosis (IM). EBV is associated with a variety of lymphatic and epithelial malignancies. Lymphatic system malignancies associated with EBV are mainly B-cell lineage lymphoma. Burkitt lymphoma (BL) and Hodgkin lymphoma (HL) are more studied, while acute lymphoblastic leukemia (ALL) and chronic lymphoblastic leukemia (CLL) are relatively less studied. This article reviews the biological structure, gene expression of EBV and its correlation with ALL and CLL.

Diagnostic efficacy comparison between CLLflow score and Moreau score for chronic lymphocytic leukemia / 中华检验医学杂志

Objective:To explore the diagnostic efficacy difference and clinical diagnostic value of chronic lymphocytic leukemia flow (CLLflow) score and Moreau score (MS) in the diagnosis of chronic lymphocytic leukemia (CLL).Methods:According to the latest international and national diagnosis criteria for CLL, 133 patients with B-cell chronic lymphoproliferative diseases and uncertain immunophenotypes (B-CLPD), diagnosed by Zhengzhou Jinyu Comprehensive Haematological Pathology Diagnosis Centre from March 2020 to May 2021, were included in this study. Above patients were divided into the CLL group ( n=83) and non-CLL group ( n=50). The expression of clusters of differentiation (CD)5, CD10, CD20, CD19, κ light chain, λ light chain, FMC7, CD23, CD22, surface immunoglobulin M, CD200 and CD79 were detected by flow cytometry, and CLLflow score and MS score were calculated respectively according to the scoring rules. A fourfold table was used to compare the diagnostic efficacy of the two scoring systems, and the Kappa test and McNemar test were used to compare the consistency and superiority of the systems. Results:The rate of negative and positive CLLflow score were 4.8% (4/83) and 95.2% (79/83) in the CLL group and were 80.0% (40/50) and 20.0% (10/50) in the non-CLL group, and respectively (both P<0.001). The MS score (≤2, =3 and≥4) was 1.2% (1/83), 10.8% (9/83) and 88.0% (73/83) in the CLL group and was 86.0% (43/50), 14.0% (7/50) and 0 in the non-CLL group, there were significant statistical difference between the two groups ( P<0.001). The sensitivity, specificity, positive predictive value and negative predictive value of the CLLflow score were 95.2% (79/83), 80.0% (40/50), 88.8% (79/89) and 90.9% (40/44), respectively and those of MS score were 98.8% (82/83), 86.0% (43/50), 92.1% (82/89) and 97.7% (43/44) respectively. The overall coincidence rate, positive and negative coincidence rate between the CLLflow score and MS score were 91.0% (121/133), 93.3% (83/89) and 86.4% (38/44) respectively. Besides, the McNeamr dominance test presented no significant difference ( P>0.05) and high consistency (Kappa=0.796) between the two scoring systems. With MS≤2 and MS≥4, the sensitivity and the specificity of the MS score were 100% (73/73) and 97.7% (43/44) respectively, and for the CLLflow score, the sensitivity and the specificity were 97.3% (71/73) and 86.4% (38/44) in this MS range. With MS = 3, the sensitivity and specificity of the MS score were 100% (9/9) and 0 (0/7), and CLLflow was 88.9% (8/9) and 57.1% (4/7). Conclusions:The diagnostic efficacy is similar and presents high consistency between the CLLflow score and MS score in CLL diagnosis. For CLL patients with MS = 3, the specificity of MS is relatively low, combined assessment with CLLflow score could improve the diagnosis efficacy for CLL in these patients.

Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia / 中华血液学杂志

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Linfocitosis monoclonal de células B en familiares de pacientes colombianos con síndromes linfoproliferativos crónicos B

Introducción. La linfocitosis monoclonal de células B, generalmente, precede la leucemia linfocítica crónica y afecta alrededor del 12 % de la población adulta sana. Esta frecuencia se incrementa en familiares de pacientes con síndromes linfoproliferativos crónicos de células B. Objetivo. Determinar la frecuencia de linfocitosis monoclonal B en familiares de pacientes con síndromes linfoproliferativos crónicos B, sus características inmunofenotípicas y citogenéticas, posible relación con agentes infecciosos, y seguimiento a corto plazo de población colombiana. Materiales y métodos. Se estudiaron 50 adultos sanos con antecedentes familiares de síndromes linfoproliferativos crónicos de célula B, empleando citometría de flujo multiparamétrica, pruebas citogenéticas y serológicas, encuesta de hábitos de vida y seguimiento a dos años. Resultados. La frecuencia encontrada de linfocitosis monoclonal B fue del 8 %, con predominio del sexo femenino y edad avanzada, incrementándose al 12,5 % en individuos con antecedentes familiares de leucemia linfocítica crónica. Tres de cuatro individuos presentaron inmunofenotipo de tipo leucemia linfocítica crónica, todas con bajo recuento. A su vez, en estos individuos se observa de manera significativa un mayor número de células/ µl en subpoblaciones linfocitarias T, junto con mayor predisposición a la enfermedad. Las poblaciones clonales descritas aumentan a lo largo del tiempo de manera no significativa. Conclusiones. La frecuencia y comportamiento de la linfocitosis monoclonal de célula B en pacientes con antecedentes familiares de síndromes linfoproliferativos crónicos B es similar a lo encontrado en estudios relacionados, lo que sugiere que no existe afectación de genes de mayor relevancia que puedan desencadenar una proliferación clonal descontrolada, pero que generan desregulación inmunológica que podría indicar un mayor riesgo de infección grave en estos individuos.

Introduction. Monoclonal B-cell lymphocytosis generally precedes chronic lymphocytic leukemia, affecting about 12% of the healthy adult population. This frequency increases in relatives of patients with chronic B-cell lymphoproliferative disorders. Objective. To determine the frequency of monoclonal B-cell lymphocytosis in relatives of patients with chronic B-cell lymphoproliferative disorders, their immunophenotypic/ cytogenetic characteristics, a possible relationship with infectious agents, and short-term follow-up in the Colombian population. Materials and methods. Fifty healthy adults with a family history of chronic B-cell lymphoproliferative disorders were studied using multiparametric flow cytometry, cytogenetic/serological testing, lifestyle survey, and 2-year follow-up. Results. The frequency of monoclonal B-cell lymphocytosis found was 8%, with a predominance of female gender and advanced age, increasing to 12.5% for individuals with a family history of chronic lymphocytic leukemia. Three out of four individuals presented chronic lymphocytic leukemia-type immunophenotype, all with low counts. In turn, a significantly higher number of cells/µΙ is observed in these individuals in T lymphocyte subpopulations, together with a greater predisposition to the disease. The described clonal populations increase over time in a non-significant manner. Conclusions. The frequency and behavior of monoclonal B-cell lymphocytosis in patients with family history of chronic B-cell lymphoproliferative disorders are like those found in related studies, which suggests that there is no involvement of more relevant genes that can trigger uncontrolled clonal proliferation, but that generates immunological deregulation that could justify a greater risk of serious infection in these individuals.

[Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia].

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Chronic lymphocytic leukemia with nephrotic syndrome as the initial manifestation: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To investigate the clinical manifestation, diagnosis and treatment of chronic lymphocytic leukemia patients with renal involvement.Methods:The clinical data of a chronic lymphocytic leukemia patient with nephrotic syndrome as the initial manifestation in Fujian Provincial People's Hospital in October 2020 were retrospectively analyzed, and the related literature was reviewed.Results:The patient was a 68-year-old male with recurrent edema and foam urine as the initial manifestations, and he was diagnosed as nephrotic syndrome in the nephrology department. After treatment, the symptoms showed no significant improvement, and the lymphocyte count gradually increased. The patient was diagnosed as chronic lymphocytic leukemia in the hematology department. After ibrutinib monotherapy, the lymphocyte count and urine protein gradually decreased to normal levels, and the clinical efficacy evaluation of the patient was complete remission at the end of follow-up.Conclusions:Chronic lymphocytic leukemia with nephrotic syndrome as the initial manifestation is rare, and the clinical presentations are variable. Early diagnosis is the guarantee of successful treatment. The efficacy and safety of first-line Bruton tyrosine kinase inhibitor monotherapy are good.

Diagnostic value of 18F-FDG PET/CT for Richter syndrome of chronic lymphocytic leukemia / 中华核医学与分子影像杂志

Objective:To explore the value of 18F-FDG PET/CT in detecting Richter syndrome (RS) in chronic lymphocytic leukemia (CLL) patients. Methods:From August 2010 to November 2019, 101 histologically confirmed CLL patients (62 males, 39 females; age (58.0±12.7) years) who underwent PET/CT in Nanjing Drum Tower Hospital and the First Affiliated Hospital of Nanjing Medical University were retrospectively included. ROI was drawn and PET/CT images were semi-quantitatively examined by estimating SUV max. Mann-Whitney U test was used to compare the SUV max of RS and non-RS patients. ROC curve analysis was utilized to analyze the optimal cut-off value of SUV max in detecting RS. Results:RS was histologically confirmed in 27 CLL patients. The SUV max of RS patients was 13.7(11.0, 20.1), which was significantly higher than that of non-RS patients (4.1(3.1, 5.8); z=-6.48, P<0.001). ROC curve analysis identified the optimal cut-off value of SUV max was 10.0 and the AUC was 0.923, with accuracy of 94.1%(95/101), sensitivity of 85.2%(23/27), specificity of 97.3%(72/74), positive predictive value of 92.0%(23/25) and negative predictive value of 94.7%(72/76). Conclusion:As the semi-quantitative index measured by 18F-FDG PET/CT, SUV max can help to diagnose RS and provide important information for clinical use.

Diagnostic and prognostic value of ROR1 antigen in patients with chronic lymphocytic leukemia / 中华检验医学杂志

Objective:To detect the expression of receptor tyrosine kinase-like orphan receptor 1 (ROR1) antigen in chronic lymphocytic leukemia (CLL) and evaluate its diagnostic value and explore its correlation with the abnormalities of genetics and molecular biology.Methods:All of 209 newly diagnosed B-cell chronic lymphoproliferative disorders (B-CLPD) patients who were admitted to the First Affiliated Hospital of Nanjing Medical University (Jiangsu Provincial People′s Hospital) from November 2020 to November 2021 were collected retrospectively, including 70 cases of CLL with typical phenotype, 16 cases of CLL with atypical phenotype, 14 cases of MCL, and 109 cases of other types of B-CLPD. Multi-parameter flow cytometry (FCM) was used to detect the expression levels of ROR1 in tumor cells of 209 patients. And then the diagnostic value of ROR1 in CLL patients and its correlation with the genetic and molecular biological abnormalities were analyzed by c2 test and fourfold table assessment.Results:The positive expression rate of ROR1 in CLL patients was significantly higher than that in non-CLL patients (78%>11%, P<0.001); there was no significant difference of ROR1 expression between typical phenotype CLL and atypical phenotype CLL (81%>63%, P>0.05). The positive expression rate of ROR1 in atypical phenotype CLL was significantly higher than that in MCL (63%>21%, P<0.05). Additionally, there was significant difference in detection rate of chromosomal abnormalities between ROR1 +CLL group and ROR1 -CLL group. The detection rate of complex karyotype in ROR1 +CLL group was higher than that in ROR1 -CLL group (34%>14%, P<0.05). The CLL patients over 60 years old had higher ROR1 positive rate ( P<0.05). Conclusions:ROR1 can be helpful in the diagnosis of CLL, especially in the differential diagnosis of atypical phenotype CLL, MCL and other types of B-CLPD. Patients with ROR1 positive expression were older and more likely to detect complex chromosomal karyotypes.

Leucemia linfocítica crónica y deleción del gen TP53: reporte de un caso y revisión de la literatura / Chronic lymphocytic Leukemia and deletion of the TP53 gene: Case report and literature review

RESUMEN Las alteraciones genéticas en el gen TP53 están presentes entre el 5 al 8 % de los pacientes de leucemia linfocítica crónica (LLC) en el momento del diagnóstico. Estos casos se relacionan con un mal pronóstico debido a su resistencia al tratamiento estándar. Presentamos el caso de un paciente masculino de 52 años diagnosticado con LLC, expresión del marcador CD38 y una deleción en el gen TP53 (17p13.1). Tras la evaluación posterior del tratamiento, se observó enfermedad mínima residual lo que llevó a un trasplante haploidéntico de progenitores hematopoyéticos. Debido al alto riesgo de recaída, su edad y la ausencia de comorbilidades, era la única opción curativa hasta la fecha para la LLC. El objetivo de este trabajo es realizar una revisión de la literatura que sirva como base para analizar el caso clínico presentado, en el marco de las implicaciones clínicas, pronóstico y respuesta al tratamiento en los individuos con LLC que presentan alteraciones en el gen TP53.

SUMMARY Genetic alterations in the TP53 gene are present in 5 to 8% of chronic lymphocytic leukemia (CLL) cases at the time of diagnosis. These cases are typically associated with poor prognosis due to their resistance against standard CLL treatment. In our report a 52-yearold male patient was diagnosed with CLL, CD38 expression and a deletion in the TP53 gene (17p13.1). Upon evaluation post-treatment, minimal residual disease (MDR) was observed, and a haploidentical stem cell transplant was performed. Because of the high risk of relapse, his age, and the absence of comorbidities it was the only curative option to date for CLL. The purpose of this article is to complete a literature review that will give a basis to analyze the clinical case presented, within the framework of the clinical implications, prognosis, and response to treatment in patients with CLL who present with aberrations of the TP53 gene.

[Cytological analysis of lymphoblastic lymphoma/acute lymphoblastic leukemia in serous effusion].

Objective: To study the diagnostic clues and significance in serous effusion cytology associated with lymphoblatic lymphoma/acute lymphoblastic leukemia (LBL/ALL). Methods: Forty-five serous effusion specimens with final diagnosis of LBL/ALL were collected from August 2011 to December 2019 at the First Affiliated Hospital of Zhengzhou University. All cases were reviewed for their clinical profiles, cytomorphologic features and ancillary studies. Cell blocks and immunocytochemistry were prepared in 22 cases; flow cytometric immunophenotyping was performed in three cases and gene rearrangement analysis (T-cell recepter, TCR and immunoglobulin, Ig) was performed in five cases. Results: Among the 45 cases, there were 35 males and 10 females with male to female ratio of 3.5∶1.0. The median age was 15 years. Mediastinal mass was the initial presentation in 39 patients (86.7%) and high LDL level were observed in 34 patients (75.6%). Microscopically, the majority of the specimens (86.7%) were hypercellular. The smears demonstrated dispersed lymphoblasts that were predominantly small to intermediate in size with scanty basophilic cytoplasm and irregular or convoluted nuclei with fine chromatin condensation and inconspicuous nucleoli. Mitoses were frequently observed. Karyorrhexis and apoptosis were seen in all cases. By immunophenotyping, TdT was expressed in 19 cases (86.4%) and CD99 in 20 cases (90.9%). Ki-67 expression varied from 65% to 95%. Flow cytometry in three cases demonstrated positivity for TdT, CD2, CD3 and CD7. Monoclonal TCR gene rearrangement was found in 4 of 5 cases, and both monoclonal TCR and Igκ gene were found in 1 case. Conclusions: In LBL/ALL, primary diagnosis could be made basing on clinical features (younger male patients with a mediastinum mass) and cytomorphology (monotonous, small to medium sized lymphoid cells with prominent irregular nuclei, fine chromatin and frequent mitoses, karyorrhexis and apoptosis). If immunocytochemistry and other ancillary studies are performed, the accuracy and reliability of the results could be improved.

Treatment progress of chronic lymphocytic leukemia / 白血病·淋巴瘤

Chronic lymphocytic leukemia (CLL) is a kind of B-cell chronic lymphoproliferative disease. At present, the common clinical treatment regimens (such as FCR, BR, ibrutinib, etc.) have showed good therapeutic effects, but recurrence and progression still occur in some patients. In order to further improve the efficacy, the new combination therapies for CLL are continuously emerging. This article summarizes the treatment progress of CLL in combination with the related reports at the 62nd American Society of Hematology Annual Meeting.

Progress of immunotherapy in chronic lymphocytic leukemia / 白血病·淋巴瘤

Chronic lymphocytic leukemia (CLL) is a heterogeneous, mature B-cell clonal malignancy that mainly affects the senior. The immunotherapies such as chimeric antigen receptor T cell therapy, bi/tri-specific cell binding agent, immune check point therapy, etc., pave several new avenues for CLL treatment, especially the combined applications of new and existing therapies have shown improved efficacy and safety. This article attempts to review the immunotherapies and their combinatorial applications in CLL.

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study.

BACKGROUND/AIMS: Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. METHODS: We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. RESULTS: Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/µL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). CONCLUSION: Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

Promoter DNA Methylation Frequency and Clinicopathological Role of miR-129-2 Gene in Patients with Chronic Lymphocytic Leukemia.

OBJECTIVES: Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of apparently mature B-type lymphocytes in the lymphohematopoietic organs. Methylation in promoters of tumor suppressor genes is one of the mechanisms that causes blood malignancy. In this study, we evaluated the promoter DNA methylation status of miR-129-2 tumor suppressor gene and its association with clinical and laboratory parameters of patients with CLL. METHODS: We studied the promoter DNA methylation frequency of the miR-129-2 gene in 50 patients with CLL and 50 healthy controls using methylation-specific polymerase chain reaction methods. Statistical analysis was performed using SPSS-18 software, and a p-value < 0.050 was considered statistically significant. RESULTS: The frequency of promoter DNA methylation of the miR-129-2 gene was significantly higher in the CLL group compared with control group (38.0% vs. 0.0%, p < 0.001; χ2 = 23.457). The promoter DNA methylation frequency of miR-129-2 gene was not significantly different between the two sexes (p = 0.236). A significant but weak correlation was seen between the methylated state of the miR-129-2 gene and organomegaly (p = 0.019, r = 0.330) as well as hemoglobin levels (p = 0.020, r = -0.233). However, binary logistic regression analysis indicated organomegaly as the only clinical biomarker with a statistically significant association with the hypermethylated miR-129-2 gene state (p = 0.046). CONCLUSIONS: The high frequency of promoter DNA methylation of the miR-129-2 gene in the CLL group compared to the control group, as well as its significant association with organomegaly, suggests the importance of this epigenetic biomarker in the pathogenesis and prognosis of CLL disease.

Acquired reactive perforating collagenosis in association with prostate adenocarcinoma, chronic lymphocytic leukemia, and Graves disease

Abstract Acquired reactive perforating collagenosis is a rare skin disorder characterized by the presence of umbilicated pruritic papules and nodules. Transepidermal elimination of altered and perforating bundles of basophilic collagen from the epidermis is a characteristic histologic feature of acquired reactive perforating collagenosis. Along with its well-known association with systemic diseases such as diabetes mellitus, chronic renal failure, and dermatomyositis, there are reports of acquired reactive perforating collagenosis being associated with malignancies. Herein, we present a case of acquired reactive perforating collagenosis associated with chronic lymphocytic leukemia, prostate adenocarcinoma, and Graves's disease. Clinicians are required to be more vigilant in evaluating patients with acquired reactive perforating collagenosis due to its unique association with malignancies and other systemic diseases.

Acquired reactive perforating collagenosis in association with prostate adenocarcinoma, chronic lymphocytic leukemia, and Graves' disease.

Acquired reactive perforating collagenosis is a rare skin disorder characterized by the presence of umbilicated pruritic papules and nodules. Transepidermal elimination of altered and perforating bundles of basophilic collagen from the epidermis is a characteristic histologic feature of acquired reactive perforating collagenosis. Along with its well-known association with systemic diseases such as diabetes mellitus, chronic renal failure, and dermatomyositis, there are reports of acquired reactive perforating collagenosis being associated with malignancies. Herein, we present a case of acquired reactive perforating collagenosis associated with chronic lymphocytic leukemia, prostate adenocarcinoma, and Graves's disease. Clinicians are required to be more vigilant in evaluating patients with acquired reactive perforating collagenosis due to its unique association with malignancies and other systemic diseases.

Chronic lymphocytic leukemia complicated with multiple myeloma: report of one case and review of literature / 白血病·淋巴瘤

Objective@#To investigate the clinical features, diagnosis, occurrence sequence and clonal origin of chronic lymphocytic leukemia complicated with multiple myeloma.@*Methods@#The diagnosis and treatment of one patient with multiple myeloma and chronic lymphocytic leukemia who was admitted to the First Hospital of Jilin University in May 2018 was retrospectively analyzed, and the related literatures were reviewed.@*Results@#This patient began with lumbosacral pain, and he was diagnosed as chronic lymphocytic leukemia complicated with multiple myeloma after bone marrow aspiration, flow cytometry, and blood and urine immunofixation electrophoresis. It is recommended that Rd (lenalidomide + dexamethasone) or MPV (melphalan + prednisone + bortezomib) regimen, but the patient did not receive chemotherapy and died of infectious diarrhea 1 month later.@*Conclusions@#The occurrence of multiple myeloma and chronic lymphoblastic leukemia may originate from the same clone or different new clone. It is very rare that multiple myeloma and chronic lymphoblastic leukemia can co-occur. Therapeutic options tend to be more aggressive multiple myeloma-based regimen.

High-grade B-Cell lymphoma with MYC and BCL6 rearrangements associated with Richter transformation of chronic lymphocytic leukemia

Richter transformation (RT), or Richter syndrome, is defined as the transformation of chronic lymphocytic leukemia (CLL) to an aggressive B-cell lymphoma. The vast majority, up to 99%, transform into diffuse large B-cell lymphoma (DLBCL), with a small subset (<1%) becoming classical Hodgkin lymphoma. Approximately half of RT cases progress through a pathway involving dysregulation of C-MYC. High-grade B-cell lymphoma (HGBL) is a recent diagnostic category of aggressive B-cell lymphomas set forth in the updated 2017 WHO Classification of Hematopoietic and Lymphoid Tissues. HGBL with MYC and BCL2 and/or BCL6 rearrangements, formerly "double-hit" and "triple-hit" lymphomas, comprise the majority of HGBL cases. Patients with HGBL have a worse prognosis than those with diffuse large B-cell lymphoma. We present a case of RT with rearrangements of MYC and BCL6. To our knowledge, there are no reported cases of RT with a "double-hit" lymphoma genotype.