45例慢性淋巴组织增生性疾病临床资料分析

目的:研究慢性淋巴组织增生性疾病的诊断和鉴别诊断方法。方法:对45例慢性淋巴组织增生性疾病(CLPD)的临床资料,包括临床征象、细胞形态学、免疫学标记等进行分析。结果:45例CLPD患者中慢性淋巴细胞白血病35例,幼淋细胞白血病8例,带有绒毛样淋巴细胞原发性淋巴瘤及毛细胞白血病各1例。35例CLL均为B细胞,其中CD5和CD19均阳性,而CD10均阴性,临床首发表现以血淋巴细胞增高为多见。8例PLL,6例为B细胞型,骨髓中以幼淋细胞为主,免疫表现CD5均阴性,CD19均阳性。结论:依据临床征象、细胞形态学和免疫表型分析,可诊断CLPD的各个类型。     

Blood stem cell mobilization and collection in patients with lymphoproliferative diseases: practical issues

More than 15,000 autologous stem cell transplants (ASCT) were reported to European Blood and Bone Marrow Transplantation registry in 2005, most commonly for multiple myeloma (MM) and lymphomas. In 98% of the cases high-dose therapy was supported by blood stem cells. Thus stem cell mobilization and collection are integral parts of ASCT protocols. We give here a practical approach to blood stem cell mobilization and collection in patients with various lymphoproliferative diseases. While mobilization is usually easy and straightforward in patients with MM, about 10-20% of patients with non-Hodgkin's lymphoma or Hodgkin's lymphoma are hard-to-mobilize. There seems to be even more disease-specific issues in blood stem cell mobilization in patients with chronic lymphocytic leukaemia and in patients with light chain amyloidosis. We also discuss options in hard-to-mobilize patients.     

A case of rheumatoid arthritis with methotrexate related lymphoproliferative diseases of the knee

Methotrexate (MTX) is the first choice disease-modifying antirheumatic drug (DMARD) for rheumatoid arthritis (RA) and is referred to as an “anchor drug”; its use has been steadily increasing annually. However, MTX-related lymphoproliferative diseases (MTX-LPDs) have emerged as important complications in the patients with RA. There have been no reports of intra-articular MTX-LPDs of the patients with RA.

Atypical cells were found in the patient’s joint fluid by cytological examinations, and MTX-LPDs were suspected. The patient discontinued MTX and open synovectomy was performed. The histological findings and immunohistochemical staining of the specimens confirmed the diagnosis of diffuse large B-cell lymphoma (DLBCL) of MTX-LPDs. After the operation of the patient’s left knee joint, pains and swollen joint disappeared with no relapse. The cytological examinations of the synovial fluid followed by knee operation were effective for early diagnosis of MTX-LPD. MTX discontinuation with no chemotherapy followed up with a knee operation improved the recovery of the MTX-LPD.     

Hepatitis C virus infection and lymphoproliferative diseases: prospective study on 1,576 patients in France

CONTEXT: Discordant data have been reported about the prevalence of hepatitis C virus (HCV) infection in patients with lymphoproliferative diseases and the putative role of HCV in lymphomagenesis. OBJECTIVE: To assess the prevalence of HCV infection in patients admitted to a hematology department in Paris, France. DESIGN: Prospective, controlled study. SETTING: University medical center. PATIENTS: 813 patients admitted to the Hematology department (164 B-cell non-Hodgkin's lymphoma, 34 Hodgkin's diseases, 107 chronic lymphocytic leukemia, 54 multiple myeloma, 12 Waldenstr?m's macroglobulinemia, 17 acute lymphoblastic leukemia, 6 hairy cell leukemia, 189 myeloproliferative diseases, 6 solid organ tumors, and 224 nonmalignant diseases) and 694 patients admitted to the Internal Medicine department (control group). MEASUREMENTS: All patients were tested for antibodies to HCV by a third-generation enzyme-linked immunosorbent assay. RESULTS: HCV antibodies were detected in 20 of 813 (2.46%) patients in Hematology including 11 of 394 (2.79%) patients with lymphoproliferative diseases, 3 of 164 (1.83%) B-cell non-Hodgkin's lymphoma, 2 of 107 (1.87%) chronic lymphocytic leukemia, 1 of 54 (1.85%) multiple myeloma, 1 of 189 (0.5%) myeloproliferative diseases, and 8 of 224 (3.57%) nonmalignant hematologic diseases. HCV antibodies were detected in 3 of 694 (0.43%) patients in the control group. HCV contamination preceded B-cell non-Hodgkin's lymphoma only in 2 of 3 HCV-positive patients. CONCLUSION: The prevalence of HCV infection was low (1.83%) in patients with B-cell non-Hodgkin lymphoma. HCV seems not to play a major role in the pathogenesis of B-cell lymphoma in France. Cofactors should be stressed to explain geographical discrepancies.     

Lymphocyte volume and conductivity indices of the haematology analyser Coulter® GEN.STM in lymphoproliferative disorders and viral diseases

The haematology analyser Coulter^® GEN.S^TM gives a set of data –‘positional parameters’– defining white blood cell (WBC) populations by mean of index values (mean and standard deviation of volume, conductivity and scatter, used to identify the WBC populations). The volume and conductivity parameters related to the lymphocytes were analysed at diagnosis in patients suffering from chronic B‐lymphocytic leukaemia (B‐CLL), other non‐CLL lymphoproliferative disorders (OLPD) and viral diseases. The standard deviation of volume index (SDVI) is significantly higher in the three groups, whereas the mean volume index (MVI) is significantly lower in B‐CLL, and increased in OLPD and viral diseases. These two groups could be distinguished by their mean conductivity index (MCI), which is significantly lower in viral disease group. Cut‐offs were calculated for each parameter by the mean of Receiver Operating Characteristic (ROC) analysis. The study of the detection performances showed that the combination of lymphocyte count with SDVI, MVI and MCI could be used with a good sensitivity and specificity to discriminate between the most frequent lymphocyte pathologies, even in patients with normal lymphocyte count.     

Multiplex PCR for rapid detection of T-cell receptor-gamma chain gene rearrangements in patients with lymphoproliferative diseases

We describe a multiplex polymerase chain reaction (PCR) method suitable for the detection of all T-cell receptor (TCR) γ-chain gene rearrangements in patients with lymphoproliferative diseases. 40 patients with various lymphoproliferative disorders and 40 healthy individuals were tested. Clonal TCRγ rearrangements were identified in all patients with malignant disorders, and in one of 10 cases with established reactive lymphocytosis but not in normal controls. In all individuals testing positive, the patient's specific V and J segment involved in the rearrangement could be determined by simply splitting the multiplex primer mix. Our data show that the multiplex PCR technique enables rapid, simple and sensitive screening for clonal TCRγ chain gene rearrangements.     

Treatment of postrenal transplantation lymphoproliferative disease manifesting as plasmacytoma with nonmyeloablative hematopoietic stem cell transplantation from the same kidney donor

Posttransplantation lymphoproliferative disease (PTLD) presenting as an Epstein-Barr-virus (EBV)-related nasal plasmacytoma developed in a renal-allograft recipient 13 years after transplantation. Systemic dissemination occurred despite immunosuppression withdrawal, surgery, irradiation, and chemotherapy. A nonmyeloablative hematopoietic-stem-cell-transplantation (HSCT) with peripheral blood HSC from the kidney donor was performed. With the onset of graft-versus-host disease, resolution of the systemic disease was demonstrated clinically and molecularly by serial quantification of plasma EBV-DNA. Isolated relapse occurred in the central nervous system (CNS), a known tumour sanctuary site, ultimately leading to death. Nonmyeloablative HSCT might be considered a cellular therapy for PTLD, but possible CNS relapse must be effectively tackled.     

正常核型和异常核型骨髓增生异常综合征的细胞形态学特点比较

目的:比较正常核型和异常核型骨髓增生异常综合征(MDS)的细胞形态学的特点。方法:回顾分析82例MDS患者,通过对正常核型和异常核型MDS患者的细胞形态进行观察,分析二者形态学的差别。结果:核型异常组31例,占37.8%,核型正常组51例,占62.2%,2组外周血比较,核型异常组易出现原粒细胞、早幼红细胞、大红细胞,P<0.05;骨髓细胞形态比较,核型异常组三系病态造血比例高(>30%),P<0.05;原粒、淋巴样小巨核和畸形血小板比例高,P<0.05;核型异常组红系病态造血易见子母核、奇数核和多核,P<0.05;核型异常组有6例转为急性白血病。结论:异常核型MDS较正常核型组细胞病态造血发生率明显增高,原始细胞比例增高,转为白血病的比例高,预后差。     

三镜(腹腔镜、十二指肠镜、胆道镜)联合治疗胰胆疾病

目的探讨内镜联合、微创治疗在胰胆疾病中的应用。方法病例筛查,一镜应用(ERCP)、二镜联合、三镜联合应用的指征,术中应注意事项,术后观察并发症等。一镜26例即十二指肠镜(ERCP);二镜方案I:腹腔镜及十二指肠镜7例;二镜方案Ⅱ:腹腔镜+胆道镜17例;三镜方案10例:十二指肠镜、腹腔镜、胆道镜三者联合应用。结果 ERCP 26例,其中2例插管未成功,成功率92.6%。1例2次取石。并发症:2例乳头切开处少量渗血,2例并发高淀粉酶血症。二镜方案I,二镜方案Ⅱ,三镜均操作成功,未出现并发症。结论内镜联合微创治疗取长补短,成功率高,降低了并发症,疗效确切,安全性高,经济实用,体现了微创治疗的优越性。     

Anti-B cell and anti-cytokine therapy for the treatment of post-transplant lymphoproliferative disorder: past, present, and future

Abstract: Epstein–Barr virus (EBV)-induced post-transplant lymphoproliferative disorder (PTLD) is a rare but severe complication of solid organ and bone-marrow transplantation. When possible, reduction of immunosuppressive treatment or surgery for localized disease may cure PTLD. Therapeutic approaches using chemotherapy or antiviral drugs have limited effects on survival. Adoptive immunotherapy with donor T cell infusions has shown promising results in bone-marrow transplantation. The use of anti-B cell monoclonal antibodies is herein reported as a safe and efficient therapy for severe PTLD. Because IL6 has been described as a growth factor for EBV-infected B cells, anti-IL6 monoclonal antibody therapy was also tested in a phase I–II clinical trial, the results of which are summarized.     

Application of contrast-enhanced ultrasound in the diagnosis of post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation: A case report

Introduction:Post-transplant lymphoproliferative disease (PTLD) is a series of proliferative diseases of the lymphatic system. Among patients receiving hematopoietic stem cell transplantation (HSCT), PTLD is a prevalent complication that severely affects rates of survival. Ultrasound plays an essential role in the early diagnosis of PTLD. Contrast-enhanced ultrasonography (CEUS) and CEUS-guided biopsy are critical procedures for tumor diagnosis.Patient concerns:Herein, we report the case of a 40-year-old male patient with acute lymphoblastic leukemia who received HSCT more than 1 year ago. Sonography revealed a small hypoechoic nodule in the liver four months after HSCT. Eight months after HSCT, larger and more nodules were observed via ultrasound; CT was used to identify the lesions.Diagnoses:CEUS and CEUS-guided biopsy were performed, and the pathological diagnosis was PTLD.Interventions:The final clinical diagnosis was PTLD, and cyclophosphamide, epirubicin, and dexamethasone were administered as chemotherapy.Outcomes:The patient was discharged after his condition improved.Conclusion:Ultrasound can be used to effectively detect lesions of PTLD early after HSCT. Furthermore, CEUS and CEUS-guided biopsy were effective for early confirmatory diagnoses of PTLD after HSCT.     

Recommendations on the clinical use of bendamustine in lymphoproliferative syndromes and multiple myeloma

Bendamustine is an increasingly used hybrid alkylating agent that is active in lymphoid neoplasias via a novel mechanism of action. There are some pending questions about its use in clinical practice because of its developmental features. A consensus panel of several leading Spanish hematologists with broad experience in the clinical use of bendamustine has established recommendations for the management and treatment of hematological patients with bendamustine based on available clinical data and the experience of the participants. These recommendations address the dose and treatment regimen for different clinical indications, the management of toxicity, and support therapy. This article contains the conclusions of this consensus panel, which are intended to serve as guidelines for the use of bendamustine.     

供者淋巴细胞输注治疗异基因造血干细胞移植后EB病毒相关的淋巴细胞增殖性疾病的疗效和安全性

目的 采用控制数量的供者淋巴细胞输注(DLI)治疗EB病毒(EBV)相关的淋巴细胞增殖性疾病(PTLD),观察其有效性和安全性.方法 2006年11月到2009年11月移植的患者,临床或病理诊断EBV相关的PTLD采用DLI治疗者纳入研究.采用COBE血球分离机应用淋巴细胞程序采集白细胞,首选原供者,次选直系亲缘供者,冻存外周血采集物(G-PB)与移植时输入的外周血干细胞(PBSC)组分相同.控制输入的单个核细胞(PBMC)在(0.5～1.0)×108/kg.原基础免疫抑制剂预防移植物抗宿主病(GVHD),观察疗效及其副作用.结果 PTLD患者9例,输注13例次,输入外周血PBMC 0.8(0.16～1.03)× 108/kg,CD3+T淋巴细胞4.2(1.6～5.7)×107/kg.7例半相合移植患者采用了原供者,有效率为7/7,完全缓解率为6/7,退热中位时间2(1～5)d,淋巴结缩小中位时间6(1～14)d;7例中6例发生GVHD,均为轻中度,得到控制.至今无病存活3例.2例非亲缘HSCT采用了半相合供者的外周血白细胞,仅获得短暂部分疗效.结论 在配型不合/半相合移植中,采用原供者控制细胞数量的DLI并免疫抑制剂预防GVHD治疗EBV相关的PTLD安全有效.最佳方案尚需进一步研究.     

Flow cytometry in the diagnosis of mature B‐cell lymphoproliferative disorders

B‐lineage lymphoproliferative disorders (LPD) are rather frequent diseases, associated with specific clinical or biological features but also sometimes of fortuitous discovery. Multiparameter flow cytometry plays a major role for a rapid diagnostic indication, on peripheral blood or bone marrow samples in most instances, guiding complementary analyses and allowing for the proper therapeutic management of patients. After describing the important pre‐analytical precautions required for an adequate assessment, the immunophenotypic features of small‐cell and large‐cell lymphomas are described in this review. The ubiquitous expression of CD19 is a first mandatory gating step. A possible clonal proliferation is then suspected by the demonstration of surface immunoglobulin light chain restriction. The aberrant presence of CD5 allows to segregate chronic lymphocytic leukemia and mantle cell lymphoma in most cases. Other LPD exhibit specific immunophenotypic features. A table of useful markers and a decision tree are provided. Of note, immunophenotypic data should as much as possible be interpreted in an integrated manner, involving the patient's clinical and other biological features, and be completed by further chromosomal and/or molecular investigations.     

Pain in individuals with idiopathic inflammatory myopathies,other systemic autoimmune rheumatic diseases,and without rheumatic diseases: A report from the COVAD study

Objectives

To compare pain intensity among individuals with idiopathic inflammatory myopathies (IIMs), other systemic autoimmune rheumatic diseases (AIRDs), and without rheumatic disease (wAIDs).

Methods

Data were collected from the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study, an international cross-sectional online survey, from December 2020 to August 2021. Pain experienced in the preceding week was assessed using numeral rating scale (NRS). We performed a negative binomial regression analysis to assess pain in IIMs subtypes and whether demographics, disease activity, general health status, and physical function had an impact on pain scores.

Results

Of 6988 participants included, 15.1% had IIMs, 27.9% had other AIRDs, and 57.0% were wAIDs. The median pain NRS in patients with IIMs, other AIRDs, and wAIDs were 2.0 (interquartile range [IQR] = 1.0–5.0), 3.0 (IQR = 1.0–6.0), and 1.0 (IQR = 0–2.0), respectively (P < 0.001). Regression analysis adjusted for gender, age, and ethnicity revealed that overlap myositis and antisynthetase syndrome had the highest pain (NRS = 4.0, 95% CI = 3.5–4.5, and NRS = 3.6, 95% CI = 3.1–4.1, respectively). An additional association between pain and poor functional status was observed in all groups. Female gender was associated with higher pain scores in almost all scenarios. Increasing age was associated with higher pain NRS scores in some scenarios of disease activity, and Asian and Hispanic ethnicities had reduced pain scores in some functional status scenarios.

Conclusion

Patients with IIMs reported higher pain levels than wAIDs, but less than patients with other AIRDs. Pain is a disabling manifestation of IIMs and is associated with a poor functional status.