Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

OBJECTIVETo study the clinicopathologic features of primary thymic extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT).

METHODSThe clinical and pathologic findings were evaluated in 3 cases of biopsy confirmed thymic MALT lymphoma. The clincopathologic features, treatment and prognosis were discussed and literatures reviewed.

RESULTSOne male and two female patients presented with asymptomatic mediastinal masses with a history of Sjögren syndrome. They were aged 36, 35 and 41 years respectively, and only one patient had B symptoms. Grossly, all three tumors were encapsulated and had multiple variable-sized cysts on cut-surface. Histopathologically, the normal thymic lobular architecture was effaced by abnormal dense lymphoid infiltration. Prominent lymphoepithelial lesions were formed by centrocyte-like cells infiltrating and expanding Hassall's corpuscles and epithelial cyst lining. All cases showed apparent plasmacytic differentiation. Immunohistochemically, the tumor cells were positive for CD20, CD79a, bcl-2 and negative for CD3, CD5, cyclin D1, CD43, CD10, bcl-6, and CD23. The plasma cells showed kappa light chain restriction. Immunoglobulin heavy chain rearrangement in three cases was confirmed by PCR. All patients were at early stage and received routine chemotherapy with or without radiotherapy after surgical removal. All patients achieved complete remission with 24, 18 and 3 months follow-up, respectively.

CONCLUSIONSPrimary thymic MALT lymphoma may be a rare distinctive lymphoma. It can be diagnosed by HE and immunohistochemical study and should be differentiated from reactive lymphoid proliferation, other types of lymphoma and mediastinal thymoma.

Adult ; Antibodies, Monoclonal, Murine-Derived ; therapeutic use ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Keratin-19 ; metabolism ; Lymphoma, B-Cell, Marginal Zone ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Male ; Prednisone ; therapeutic use ; Pseudolymphoma ; pathology ; Thymus Hyperplasia ; pathology ; Thymus Neoplasms ; drug therapy ; genetics ; metabolism ; pathology ; surgery ; Vincristine ; therapeutic use

OBJECTIVETo explore detection of immunoglobulin heavy chain gene (IgH) rearrangement by real-time quantitative polymerase chain reaction (RQ-PCR) for minimal residual disease (MRD) monitoring in adult B-lineage acute lymphoblastic leukemia (B-ALL) patients.

METHODSDNA samples of fifteen newly diagnosed adult B-ALL patients were collected. The IgH gene rearrangements were detected by PCR followed by sequencing and subsequent blasting for monoclonal PCR products. Allele-specific oligonucleotides (ASO) were designed based on the sequence of junction regions, using PRIMER 5.0 software. MRD targets were detected in 115 bone marrow samples by RQ-PCR, in which ASO upstream primers in combination with the consensus JH probes and downstream primers were used. Transcripts copies of bcr-abl fusion gene were also measured in 7 Ph(+) ALL cases.

RESULTSThe detection sensitivity of ASO-PCR varied between 10(-3) and 10(-5) leukemia cells in 15 adult ALL patients. The background and nonspecific amplification was detectable at a low level. Quantification monitoring MRD showed that high-risk adult ALL patients in complete remission (CR) had a higher MRD level than those of standard-risk. Patients with MRD > 10(-3) had a higher relapse rate and a shorter survival time. Besids, the dynamic curves of the quantified level of respective IgH rearrangement were consistent with the expression levels of bcr-abl fusion genes in seven Ph(+) patients during follow-up.

CONCLUSIONSThe individual quantification of IgH rearrangement by RQ-PCR using ASO primers was a sensitive, specific and reliable method for accurate evaluation of malignant clones. These data indicates a close correlation between the level of rearranged IgH and the treatment response and prognosis in adult ALL patients. It may be a helpful method for monitoring MRD in clinical trials.

Adult ; DNA Primers ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Immunoglobulins ; therapeutic use ; Neoplasm, Residual ; diagnosis ; Polymerase Chain Reaction ; Precursor B-Cell Lymphoblastic Leukemia-Lymphoma ; genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; genetics

OBJECTIVETo explore the feasibility of semi-nested PCR technique for detection of immunoglobulin heavy chain (IgH) clonal rearrangement in bone marrow of B-cell lymphoma patient and to further evaluate its clinicopathological value.

METHODSGene clonal rearrangement of IgH was detected by semi-nested PCR using primers of FR2 & FR3A in 105 bone marrow samples of patients with B-cell lymphoma. The PCR detection results were compared with the cytomorphology of bone marrow aspiration biopsy. The correlation between PCR detection results and clinicopathological factors were evaluated.

RESULTSAmong 105 cases of B-cell lymphoma, bone marrow involvement was detected by PCR technique in 48 cases (45.7%), while only 22 cases (21.0%) were detected by bone marrow cytological analysis. There was a significant difference between two methods (P < 0.05), and the concordance rate was 71.4%. The incidence of bone marrow involvement at the time of initial diagnosis detected by PCR technique was 30.8% for diffuse large B cell lymphoma (DLBCL), 25.0% for follicular lymphoma (FL), and 100.0% for small lymphocytic lymphoma (SLL), respectively. Bone marrow involvement detected by PCR detection correlated with Ann Arbor stage. Rate of clonal IgH gene rearrangement by PCR in early B-cell lymphoma was lower than that in advanced stage B-cell lymphoma patients (P = 0.02). There was no statistically significant difference in efficacy between patients with positive and negative results detected by PCR (P > 0.05). But difference in complete response (CR) rate (23.3% and 46.3%) had significant difference (P = 0.019).

CONCLUSIONSemi-nested PCR analysis may be an effective method for detection of abnormalities in bone marrow in patients with B-cell lymphoma and is superior to cytomorphology. The positive rate in patients with advanced Ann Arbor stage is higher than that in patients with early Ann Arbor stage, and patients with PCR negative result have more chances to achieved CR after treatment.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Biopsy ; methods ; Bone Marrow ; pathology ; Female ; Gene Rearrangement, B-Lymphocyte, Heavy Chain ; Humans ; Immunoglobulin Heavy Chains ; genetics ; Leukemia, Lymphocytic, Chronic, B-Cell ; drug therapy ; genetics ; pathology ; Lymphoma, Follicular ; drug therapy ; genetics ; pathology ; Lymphoma, Large B-Cell, Diffuse ; drug therapy ; genetics ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Polymerase Chain Reaction ; methods ; Remission Induction

OBJECTIVETo evaluate the molecular mechanism and prognostication of bcl-2 protein expression in different subgroups of diffuse large B-cell lymphoma(DLBCL) in Guangxi Zhuang Autonomous Region, China.

METHODSImmunohistochemical stains for CD10, bcl-6, MUM-1, bcl-2 and NF-κB were performed in 214 cases of DLBCL. The Hans immunologic classification was applied to classify DLBCL into GCB and non-GCB subgroups. Using a dual-probe fluorescence in-situ hybridization (FISH) assay, IgH/bcl-2 gene translocation and bcl-2 amplification were analyzed.

RESULTSIn 214 cases of DLBCL, 30.8% (66/214) of cases were GCB and 69.2% (148/214) were non-GCB. Twenty-seven point three percent (18/66) of GCB subgroups and 59.5% (88/148) of non-GCB subgroups had bcl-2 protein expression, with a significant difference (P < 0.01). IgH/bcl-2 translocation was positive in 3.7% (8/214) of cases, even majority of them (6/8) was found in GCB subgroup, while represented only 9.1% of GCB case. There was a significant difference (P = 0.02) in bcl-2 gene amplification between GCB (27/66, 40.9%) and non-GCB subgroup (86/148, 58.1%). Among non-GCB cases, the expression of bcl-2 was correlated with that of NF-κB expression and bcl-2 gene amplification (r = 0.216 and 0.219, respectively, P < 0.05). No similar correlation was observed in GCB cases. The overall survival time of bcl-2-positive patients (31.4 ± 3.8) months was shorter than that of bcl-2-negative patients (40.2 ± 4.2) months. In conjunction with immunophenotypes and clinical stages, the bcl-2 positive patients had a 1.89 times higher risk than that of the bcl-2 negative patients.

CONCLUSIONSMajority of the cases were prognostically unfavorable non-GCB subgroups among DLBCL, which were characterized by high frequency of bcl-2 gene amplification and low frequency of IgH/bcl-2 translocation. The anti-apoptotic gene bcl-2 was frequently expressed in non-GCB subgroups and closely related to the gene amplification and NF-κB activation. bcl-2 positive patients had more short overall survival times, would face significant higher risk of death, these results suggested that bcl-2 could be a prognostic marker independent to clinical staging and immunophenotyping.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Cyclophosphamide ; therapeutic use ; Doxorubicin ; therapeutic use ; Female ; Gene Amplification ; Gene Expression Regulation, Neoplastic ; Genes, bcl-2 ; Humans ; Immunoglobulin Heavy Chains ; genetics ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse ; classification ; drug therapy ; genetics ; metabolism ; pathology ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Prednisone ; therapeutic use ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Survival Rate ; Translocation, Genetic ; Vincristine ; therapeutic use ; Young Adult