硝酸甘油单用与联用治疗不稳定性心绞痛疗效的Meta分析

背景：在治疗不稳定性心绞痛时,联硝酸甘油合用药的疗效是否要优于单用,尚缺乏相关的循证医学证据。 目的：评估硝酸甘油单用与联用治疗不稳定性心绞痛的疗效。 方法：通过计算机和手工系统检索Cochrane图书馆(2010年第2期)、Medline、Embase、Science Direct、SIGLE、GreyNet、中国生物医学文献数据库(CBMdisc)、中文科技期刊全文数据库(VIP)、中国期刊全文数据库(CNKI)和万方数据库,纳入硝酸甘油单用与联用比较用于治疗不稳定性心绞痛的临床随机对照试验,评价其方法学质量后采用RevMan 5.0软件,对其疗效进行Meta分析。 结果与结论：纳入8个单中心临床随机对照试验,共715例患者,方法学质量均为B级。Meta分析结果显示：硝酸甘油联用的临床疗效和心电图疗效优于单独应用(RR =0.79,95%CI：1.56~3.08,P < 0.01;RR =0.72,95%CI：0.64~0.81,P < 0.01)。但上述结果可能存在各种偏倚,建议根据临床症状及循证医学证据选用恰当的联用药物而非滥用。     

Synchronous breast carcinoma and chronic lymphocytic leukemia in a Chinese young female: a rare combination

Chronic lymphocytic leukemia (CLL) is one of the most common lymphoid malignancies in western countries, however, infrequent in Eastern countries. We report on a rare case of synchronous breast carcinoma and chronic lymphocytic leukemia in a Chinese female patient. A 47-year-old female patient who presented with right breast lump for three month was admitted to our hospital. An ultrasound scan showed two mass in right breast and axillary swollen lymph node. Then, this patient was given right mastectomy and axillary lymph node dissection. Histology report showed invasive ductal carcinoma of the breast (grade I) and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). Bone marrow was infiltrated by CLL cell. To the best of our knowledge, this is the first report of a Chinese patient suffering from breast carcinoma and chronic lymphocytic leukemia.     

Interleukin-2 priming chemotherapy: A strategy to improve the remission of refractory/relapsed T cell acute lymphoblastic leukemia

Regardless of the salvage therapy used, primary induction failure in acute lymphoblastic leukemia (refractory ALL) and relapse after a complete remission (CR) are associated with dismal outcomes. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) may be the best treatment option for relapsed/refractory ALL. However, the outcome of allo-HSCT is very poor when a patient is not in CR. Quiescent leukemia cells protect them from the commonly used cell cycle-specific chemotherapeutic agents. Interleukin-2 (IL-2), a very well characterized T cell growth factor, is responsible for the progression of T lymphocytes from the G0 to the S phase of the cell cycle. IL-2 receptors are present on malignant T cells. Interaction of IL-2 with the IL-2 receptor triggers T cell proliferation, but T cells must change from a resting to an activated state, which leads to the de novo synthesis of IL-2 and expression of the IL-2 receptor. Thus, exogenous IL-2 administration is pivotal for the activation of T cells. Based on the findings above mentioned, we hypothesized that IL-2 priming chemotherapy improves the remission of refractory/relapsed T cell acute lymphoblastic leukemia.     

Therapy-related acute nonlymphocytic leukemia with inversion of chromosome 16 and a sustained remission

Acute nonlymphocytic leukemia, apparently without a preleukemic phase, developed in a 48-year-old male who had received oral cyclophosphamide and razoxane in succession. Inversion of chromosome #16 was present in association with the morphologic features typically seen with this abnormality in de novo acute leukemia. Conventional chemotherapy resulted in complete remission, which lasted for 13 months. The importance of performing cytogenetic studies in cases of secondary leukemia is emphasized.     

Different distribution of NOTCH1 mutations in chronic lymphocytic leukemia with isolated trisomy 12 or associated with other chromosomal alterations

Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in Western countries. Chromosomal abnormalities commonly found using conventional cytogenetics and FISH are del(11)(q22-23), trisomy 12, del(13)(q14), and del(17)(p13). Trisomy 12 is the most frequent numerical abnormality in CLL. It can appear isolated or associated with other chromosomal aberrations, including t(14;18)(q32;q21) and trisomy 18. The aim of this study was to determine whether CLL patients with isolated trisomy 12 or associated with other chromosomal alterations have different clinico-pathological features, including a different distribution NOTCH1 mutation. Patients were classified into four groups: Group 1, isolated trisomy 12 (n=14); Group 2, trisomy 12 plus trisomy 18 (n=4); Group 3, trisomy 12 plus t(14;18) (n=8); and Group 4: patients with trisomy 12 plus other abnormalities not involving BCL2 (n=28). The Binet stage and expression of ZAP70 were significantly different among cytogenetic groups. NOTCH1 mutations were detected in 6/12 (50%) patients from Group 1, 4/25 (16%) patients from Group 4, and in no patient from groups 2 and 3 (P=0.020). Patients in Group 2 had a more rapid disease progression (median Treatment-free Survival 2 months) as against patients from Groups 1 (50 months), 3 (69 months), or 4 (68 months; P=0.001). These findings indicate that the distribution of NOTCH1 mutations in CLL with trisomy 12 is heterogeneous and that the presence of additional chromosomal abnormalities such as trisomy 18 could change the prognosis of these patients.     

Case report and literature review: a rare patient with chronic myeloid leukemia and chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the most common leukemias of the elderly. However, the sequential occurrence of CML followed by CLL in the same patient is extremely rare. In the present report, a 71-yr-old man was diagnosed with Philadelphia (Ph) chromosome positive CML and treated with imatinib mesylate. He went into morphologic, cytogenetic, and molecular remission. Seven years after the diagnosis of CML, he developed CLL. We describe the morphologic, immunophenotypic, cytogenetic, and molecular findings in this patient.     

Phenotypic heterogeneity of B cells in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma

Although some studies have examined the expression of aberrant markers such as CD2, CD7, CD10, CD13, CD33, and CD34 on B cells in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), a uniform multiparametric analysis of the frequency of expression of these markers using stringent criteria is lacking. By using 3-color flow cytometry, we analyzed 117 cases (bone marrow, 71; blood, 31; lymph nodes, 15) for coexpression of aberrant markers with CD19. Marker expression was considered positive when present on at least 20% of CD19+ cells. Of 117 cases, 40 (34.2%) showed expression of 1 or more aberrant markers. Expression of 4 aberrant markers was seen in 1 case, 3 in 4 cases, 2 in 15 cases, and 1 in 20 cases. Kaplan-Meier survival curves and the log-rank test revealed that the group with aberrant markers showed significantly shortened overall survival compared with the group without aberrant markers (P < .001). There is considerable phenotypic heterogeneity in CLL/SLL, and expression of aberrant markers indicates aggressiveness.     

Granulomatous reactions cause symptoms or clinically imitate treatment resistance in small lymphocytic lymphoma/chronic lymphocytic leukaemia more frequently than in other non-Hodgkin lymphomas

AIMS: The electronic database of the institute of pathology, Medical University of Innsbruck, was reviewed and patient histories studied to analyse systematically the coincidence of granulomatous reactions and lymphomas in a large patient collective, and to find distinct clinicopathological correlations. Five cases of small lymphocytic lymphoma/chronic lymphocytic leukaemia (CLL) associated with granulomatous reactions in lymph nodes and bone marrow were identified, all clinically associated with signs of progressive disease. METHODS: Cases were acquired by reviewing an electronic database comprising approximately 715,000 patients diagnosed between 1993 and 2003. Histochemical, immunohistochemical, and molecular techniques were used to verify diagnosis and associated infectious diseases. Clinical data were obtained from reviewing the charts. RESULTS: Of 2044 bone marrow and 411 lymph node non-Hodgkin lymphoma biopsy samples, CLL was most frequently associated with bone marrow (two cases) and lymph node granulomas (three cases). These granulomas were mostly composed of epithelioid cells, with or without giant cells, and in all but one case did not show necrosis. All patients with CLL had clinical symptoms primarily caused by the granulomatous disease: two suffered from acid fast bacilli infections (Mycobacterium tuberculosis and mycobacteria other than tuberculosis) and three presented with clinical manifestations of sarcoidosis (the reason a diagnostic biopsy was performed). CONCLUSIONS: Granulomatous reactions in patients with CLL might obscure diagnosis and imitate disease progression and Richter's transformation. Careful histological examination, exclusion of infectious agents, and a detailed clinical history are essential for correct diagnosis.     

Proliferation centers in bone marrows involved by chronic lymphocytic leukemia/small lymphocytic lymphoma: a clinicopathologic analysis

ObjectivesProliferation centers (PCs) are a characteristic finding in chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) lymph nodes, and their presence and extent in this site are not currently felt to be related to clinical course. In contrast, detailed clinicopathologic analyses of bone marrow (BM) PCs have not been previously reported.MethodsThe PCs in 88 CLL/SLL BMs from 45 patients (pts) were graded (0-4) and were correlated with other morphologic, immunophenotypic, cytogenetic, and laboratory features.ResultsProliferation centers were present in 69 BMs (78%) from 32 pts (71%) and were distinct/prominent (grades 2-4) in 21 pts (47%), with the latter more commonly found in follow-up BMs (1/7 diagnostic BMs vs 49/81 follow-up BMs; P = .04). When present, PCs were most commonly graded as distinct nodules easily visible on ×10. No relationships were identified between PCs and any complete blood count parameter, serum lactate dehydrogenase or IgG levels, degree or pattern of BM involvement, blood morphology, CD38 and FMC7 expression by flow cytometry, or fluorescence in situ hybridization results, when the first encountered BM was considered for each patient.ConclusionsThis represents the first detailed analysis of PCs in CLL/SLL BMs. In our tertiary center, PCs were seen frequently, in approximately three-fourths of cases. There were no statistical associations identified between PCs and cytogenetic, immunophenotypic, or other laboratory and morphologic findings.     

The influence of amifostine used alone or in combination with 2-chlorodeoxyadenosine on normal and chronic myelogenous leukemia granulocyte-macrophage progenitor cells in vitro

We evaluated the influence of amifostine used alone or in combination with 2-chlorodeoxyadenosine (2-CdA) on the colony growth of normal and chronic myeloid leukemia (CML) granulocyte-macrophage progenitor cells (CFU-GM) in semisolid culture in vitro. Amifostine at a concentration of 1 mg/ml was either added directly to the culture medium of normal and CML CFU-GM, or mononuclear cells (MNCs) were first preincubated with amifostine at the same concentration, washed in Iscove's modified Dulbecco minimum essential medium (IDMEM) and then added to the culture medium. Amifostine used alone inhibited the growth of CML CFU-GM colonies to a higher degree than those of normal CFU-GM, but the differences were not statistically significant. Amifostine preincubated with MNCs and used together with the highest concentration of 2-CdA significantly inhibited the colony growth of CML CFU-GM as compared to 2-CdA alone (p<0.05). In contrast, the colony growth inhibition of normal CFU-GM was not significantly lower compared to 2-CdA used alone. Our studies suggest that 2-CdA used together with amifostine is more toxic to leukemic CFU-GM than to their normal counterparts.     

Therapy-related refractory anemia with ringed sideroblasts in chronic lymphocytic leukemia. involvement of 3q21 region

Therapy-related myelodysplastic syndrome/acute myelogenous leukemia (t-MDS/AML) is extremely rare in chronic lymphocytic leukemia (CLL) despite extensive use of alkylating agents. We present a case of heavily treated CLL with resultant therapy-related refractory anemia with ringed sideroblasts (RARS). A complex cytogenetic abnormality including involvement of 3q21 was detected and to our knowledge, is the first report of a RARS case with a 3q21 abnormality.     

Toward a comprehensive prognostic scoring system in chronic lymphocytic leukemia based on a combination of genetic parameters

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with a variable clinical course. The aim of this study was to evaluate whether a combination of genetic parameters can improve prediction of outcome irrespective of clinical stage. The prognostic impact of chromosome banding analysis (CBA) in addition to FISH and IgVH mutation status was evaluated. In total, 482 patients were analyzed, but evaluation of prognostic factors was restricted to 399 untreated cases. The prognostic significance of age, white blood cell (WBC) count, IgVH status, and TP53 and ATM deletions was confirmed. In addition, a prognostic impact of translocations involving the IGH@ locus (t(IgH)) and of a complex aberrant karyotype was found. On the basis of these results, we propose a scoring system for overall survival (OS) based on: age ≥65 years, WBC ≥20 × 10⁹/l, unmutated IgVH status, TP53 deletion, t(IgH), and the number of chromosome aberrations observed with CBA. Three risk groups showed considerable differences in OS (94.5% vs. 64.3% vs. 41.1% surviving at 5 years, P < 0.0001). Time to treatment (TTT) can be predicted best by unmutated IgVH status, ATM deletion, t(IgH), and number of chromosome aberrations. Four distinct subgroups were separated with median TTT of 110.7 months, 39.8 months, 19.5 months, and 3.8 months, respectively (P < 0.0001). In conclusion, cytogenetic data from CBA add prognostic information. The proposed scoring systems for OS and TTT based on a combination of genetic markers improve the separation of prognostic subgroups in CLL already early in the course of the disease. © 2010 Wiley‐Liss, Inc.     

地西他滨联合CAG方案治疗老年性及复发难治性急性髓细胞白血病的疗效分析

目的：本研究旨在观察地西他滨联合CAG方案治疗老年及复发难治性急性髓细胞白血病(acute myeloid leukemia,AML)的临床疗效及不良反应。方法：回顾性分析了我科2015年1月至12月收治的15例老年性及复发难治性AML,应用地西他滨联合CAG方案(地西他滨15 mg·m?2·d?1,d1~5;阿克拉霉素10 mg/d,d3~6;阿糖胞苷10 mg/m2,q12 h,d3~9;G-CSF 300 mg/d,d0~9),观察其治疗效果及不良反应。结果：老年患者6例,完全缓解(complete response,CR)4例,部分缓解(partial response,PR)1例,总有效率(overall response rate,ORR)：83.3%,复发难治患者9例,CR 3例, PR 2例,ORR 55.5%。所有患者中位总生存时间7(1~12)个月,中位无进展生存时间4(0~10)个月。血液学不良反应发生率为100%,严重出血发生率为10.5%,感染发生率为73.3%,无Ⅲ~Ⅳ级肝肾损害,无Ⅲ~Ⅳ级恶心、呕吐。结论：地西他滨联合CAG方案治疗老年性及复发难治性急性髓细胞白血病效果肯定,但感染及血液血反应的发生率较高,需注意检测并予以相应的支持治疗。     

Ofatumumab in the treatment of low-grade non-Hodgkin's lymphomas and chronic lymphocytic leukemia

Ofatumumab is a novel anti-CD20 monoclonal antibody recently approved for the treatment of chronic lymphocytic leukemia refractory to alemtuzumab and fludarabine. Ofatumumab has also demonstrated activity in other low-grade non-Hodgkin's lymphomas. However, the optimal time to use ofatumumab and in what patient population is debatable. This article will review some of the key clinical studies that led to the drug's approval, current recommended usage of the drug and significant future directions.     

Composite chronic lymphocytic leukemia/small lymphocytic lymphoma and follicular lymphoma are biclonal lymphomas: a report of two cases

Composite lymphomas (CLs) consisting of 2 indolent B-cell lymphomas are rare. We present 2 CL cases composed of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), each with unique clinicopathologic features. In the first case, the FL was negative for IGH-BCL2 and harbored a novel IGH-associated translocation; in the second case, the CL manifested in the skin. The individual components in both CLs were derived from different B-cell clones. This is the first complete characterization, including molecular analysis, of CLs composed of leukemic CLL and FL and the first report of a cutaneous CL derived from 2 low-grade B cell lymphomas. Our results provide additional supporting evidence that CLs of indolent B-cell lymphomas are biclonal and suggest that they are pathogenetically different from CLs composed of a low-grade B-cell lymphoma and an aggressive B-cell lymphoma or Hodgkin lymphoma, which are usually clonally related.     

The effect of cyclosporin A used alone and in combination with either 2-chlorodeoxyadenosine or fludarabine on normal and chronic myelogenous leukemia progenitors in vitro

We evaluated the influence of cyclosporin A (CsA) used alone or together with the new purine nucleoside analogues (PNAs) 2-chlorodeoxyadenosine (2-CdA) and fludarabine (F-ara-A) on the colony growth of normal and chronic myelogenous leukemia (CML) granulocyte-macrophage progenitor cells (CFU-GM) in cultures in vitro. The assay was based on the Iscove's method in our modification. Specimens of bone marrow were collected from 15 patients with CML in the chronic phase and from 10 hematologically normal patients. CsA at the concentrations of 1, 2 and 4 microg/ml was used alone and, at the concentration of 4 microg/ml, was preincubated with mononuclear cells (MNCs) and, after 30 min PNAs were added to the culture medium. Concentrations of 5, 10, and 20 nM 2-CdA and 0.4, 0.8 and 1.6 microM F-ara-A were used. After 14 days of incubation, the colonies were scored under an inverted microscope. We observed that CsA used alone at all three concentrations inhibited the colony growth of CML CFU-GM to a statistically significant degree compared with the control (p < 0.02) and that it did not significantly influence normal colony growth. The IC50 for CsA was 3.9 microg/ml in the case of normal CFU-GM and 2.7 microg/ml in the case of CML CFU-GM. After the use of CsA in combination with either the highest concentrations of 2-CdA or F-ara-A, statistically significant differences compared with CsA used alone were observed (p = 0.008, p = 0.03 for CsA with 2-CdA, and p = 0.0007, p = 0.005 for CsA with F-ara-A, respectively, for normal and CML CFU-GM). However, there were no significant differences between the combinations of drugs and PNAs used alone. In the case of the combination of CsA with the highest concentrations of both PNAs, significant differences in colony growth inhibition between normal and CML CFU-GM were observed (p = 0.002 and p = 0.005, respectively, for 2-CdA and F-ara-A). In conclusion, at the concentrations of the drugs used, a subadditive action was observed either between CsA and 2-CdA or between CsA and F-ara-A.     

Composite lymphoma: association of a follicular lymphoma and a chronic lymphocytic leukemia

We report the case of a 71-year-old woman presenting with composite lymphoma (CL) composed of a follicular lymphoma and a B-cell chronic lymphocytic leukemia. CL is a rare lymphoproliferative disorder, characterized by two distinct morphological and immunophenotypical patterns in the same anatomical site, most frequently of biclonal origin. This entity must be distinguished from transformation of low-grade lymphoma into high-grade lymphoma and from lymphoma with differentiation such as follicular lymphoma with marginal differentiation. In this context, molecular analysis including immunoglobulin rearrangement, sequencing and FISH analyses is determinant and can be improved by tissue microdissection. Routinely, CL must not be misdiagnosed because of its prognosis and treatment implication.