Tienan Zhu

The clinical spectrum of IgM monoclonal gammopathy: A single center retrospective study of 377 patients.

OBJECTIVES We retrospectively evaluated the clinical features, serum levels of IgM, and prevalence of IgM related diseases in patients with serum immunofixation electrophoresis (sIFE) confirmed IgM monoclonal gammopathy at our center. METHODS We included patients with sIFE confirmed IgM monoclonal gammopathy between January 2008 and December 2014 in this retrospective study. We evaluated clinical data, sIFE, serum IgM levels, and diagnosis. RESULTS In total, 7107 patients had sIFE confirmed monoclonal gammopathy, with 377 (5.3%) patients having the IgM type. The median age was 62 years (range, 19-105 years). The median level of serum IgM is 8.3g/L (range, 0.24-150g/L). The diagnosis included monoclonal gammopathy of undetermined significance (MGUS, 157 patients, 41.6%), Waldenstrom macroglobulinemia (WM, 105 patients, 27.9%), B cell non-Hodgkins lymphoma (69 patients, 18.3%), primary cold agglutinin disease (pCAD, 16 patients, 4.2%), primary amyloidosis (14 patients, 3.7%), cryoglobulinaemia (six patients, 1.6%), IgM MGUS associated neuropathy (five patients, 1.3%), multiple myeloma (three patients, 0.8%), and POEMS syndrome (two patients, 0.5%). Levels of serum IgM>15.5g/L were 80.6% sensitive and 89.2% specific for the diagnosis of WM. Kappa type light chain indicated the diagnosis of WM, pCAD, IgM MGUS associated neuropathy and cryoglobulinaemia, while lambda type light chain indicated POEMS and amyloidosis. There were 41/157 (26.1%) MGUS patients diagnosed with complications due to IgM-unrelated autoimmune diseases. CONCLUSION IgM monoclonal gammopathy contains a broad spectrum of diseases. Levels of serum IgM and the type of light chain can be used to help with differential diagnosis. The association between MGUS and some autoimmune diseases requires further investigation.

Long-term follow-up study of porcine anti-human thymocyte immunoglobulin therapy combined with cyclosporine for severe aplastic anemia.

Immunosuppressive therapy with antithymocyte immunoglobulin (ATG) and cyclosporine A is the first treatment option for severe aplastic anemia (SAA) patients without transplantation. Horse ATG is not marketed in China. Because the price of porcine ATG (pATG) is only about one‐third of the price of rabbit ATG (rATG), long‐term follow‐up studies of pATGs efficacy will help provide valuable insights into the treatment of SAA. Retrospective studies were performed to analyze the clinical information of 102 SAA patients treated with pATG and cyclosporine A from 1999 to 2014 in Peking Union Medical College Hospital. The median age was 29 years old (range 12–72). Median follow‐up time was 59.6 months (0.2–176.8). The overall response rate was 74.5% (CR 42.1%, PR 32.4%). The recurrence rate was 9.9%. The mortality rate was 16.7%. The median survival time has not been reached, and the 5‐year survival rate was 81.8%. Other hematologic abnormalities were observed in 7.8% of patients, including symptomatic PNH, MDS, and AML. Multivariate analysis revealed there was no significant effect on survival by factors such as gender, age, severity of disease, treatment time, and PNH clone (P > 0.05). These data have indicated pATG therapy combined with cyclosporine A has significant long‐term efficacy and high overall survival in SAA.

The performance of age-adjusted D-dimer cut-off in Chinese outpatients with suspected venous thromboembolism

BACKGROUND D-dimer testing has been widely used in the exclusion of venous thromboembolism (VTE), but its clinical usefulness is limited in older patients because of a lower specificity. OBJECTIVE To evaluate the diagnostic performance of STA-Liatest D-dimer assay and validate the age-adjusted cut-off value in Chinese outpatients with suspected VTE in a prospective non-interventional study. METHODS Symptomatic patients suspected of having deep venous thrombosis or pulmonary embolism were recruited from 2 participating centers. STA-Liatest D-dimer assay, clinical pretest probability assessment and diagnostic imaging test including complete compression ultrasonography or computed tomography pulmonary angiography were performed among all participants. The performance of D-dimer test was assessed with an age-adjusted D-dimer cut-off (age×0.01μg/ml in patients aged>50years) and with conventional cut-off (0.5μg/ml at all ages). RESULTS A total of 594 eligible outpatients were included in this study and VTE was diagnosed in 195 (32.8%) patients. In those patients with a low or moderate pretest probability (n=373), the increase in the proportion of patients with a D-dimer below the age-adjusted cut-off value compared with the conventional cut-off value was 5.9% (95% confidence interval; 3.8%-8.7%). The sensitivity, specificity and negative predictive value of STA-Liatest D-dimer test were 95.0% (83.5% - 98.6%), 84.1%(79.8%-87.6%) and 99.3%(97.5% - 99.8%), respectively, using the age-adapted diagnostic strategy. CONCLUSIONS The application of age-adjusted cut-off of D-dimer test combined with clinical probability greatly increases the proportion of Chinese older outpatients in whom VTE can be safely excluded.

A novel mutation in the porphobilinogen deaminase gene in an extended Chinese family with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disorder caused by a partial deficiency of porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthetic pathway. Establishing accurate diagnoses of the patient and asymptomatic family members with AIP involves identifying the PBGD enzyme mutations directly. Genetic testing provides a precise diagnosis for the patient and other asymptomatic family members, and thereby proper treatments can be initiated to prevent the disease from progressing. In this study, we report a novel PBGD missense mutation, A G-to-C, at the position 988 resulting in Alanine to Proline (Ala330Pro), in a Chinese family.

Autologous stem cell transplantation as frontline strategy for peripheral T-cell lymphoma: A single-centre experience

Objective To determine the efficacy and prognosis of autologous hematopoietic stem cell transplantation (ASCT) as frontline treatment for peripheral T cell lymphoma (PTCL). Methods Clinical data from 46 PTCL patients who achieved complete (CR) or partial remission (PR) after ASCT from October 1996 to July 2014 were analysed retrospectively. Results Median patient age was 32 (range: 15–68) years. Disease types included PTCL, unspecified type, in 23 patients, anaplastic large cell lymphoma in eight, angioimmunoblastic lymphoma in eight, extranodal NK/T-cell lymphoma in five, and hepatosplenic T-cell lymphoma and enteropathy associated T-cell lymphoma in one each. Of these patients, 80% had Prognostic Index for Peripheral T-cell Lymphoma scores ≥1. Thirty-four patients had pre-transplantation CR and 12 had PR. Median follow up was 37 (6–176) months. The 5-year overall survival (OS) and progression-free survival (PFS) rates were 77.1% and 61.9%, respectively. Multivariate analysis showed that pre-transplantation CR was an independent risk factor for survival, and CR was more common than PR (OS 81% vs 59.3%; PFS 71.8% vs 17.8%). Conclusion Frontline consolidation treatment with ASCT was associated with favourable outcomes in patients with PTCL. Pre-transplantation CR was a prognostic factor for survival, suggesting that ASCT may be favoured as front-line consolidation therapy after first complete remission.

Comparison of vindesine and prednisone and cyclophosphamide, etoposide, vindesine, and prednisone as first-line treatment for adult Langerhans cell histiocytosis: A single-center retrospective study

OBJECTIVE We compared the efficacy and clinical outcomes of vindesine and prednisone (VP) and cyclophosphamide, etoposide, vindesine, and prednisone (CEVP) regimens as first-line treatment for multisystem (MS) or multifocal single system (SS-m) adult Langerhans cell histiocytosis (LCH). METHOD Clinical features, treatment response, and survival of adults with Langerhans cell histiocytosis treated at our center from January 2001 to January 2015 were reviewed retrospectively. RESULTS Forty-five adult MS or SS-m LCH patients were treated (N=31, CEVP group; N=14, VP group). Both treatment groups had similar gender distributions, patient ages, and extent of disease. The non-active disease rate for both groups was 70.0% and 64.3% (P=0.775), respectively. Median follow-up was 74.9 (range: 2.8-183.6) months and recurrence rates were 71.0% and 78.6% (P=0.593), respectively. The need for second-line therapy was 64.5% and 71.4% (P=0.649), respectively, and mortality rates were 9.7% and 15.4% (P=0.586), respectively. Neutropenia occurred in 48.4% of CEVP-treated patients and 7.1% of VP-treated patients (P=0.008). CONCLUSIONS CEVP or VP regimens for the treatment of adult SS-m or MS LCH showed similar efficacies, and both regimens were associated with high disease recurrence and the need for second-line therapy.

Clinical analysis of 14 cases with primary breast lymphoma

OBJECTIVE To analyze the clinical features, prognostic factors, diagnostic methods and treatment outcomes of primary breast lymphoma (PBL). METHODS The clinical data of 14 patients diagnosed with PBL between 2000.1 and 2013.6 were analyzed retrospectively. RESULTS The 14 patients were diagnosed with PBL, which comprised 0.24% and 0.54% of all breast malignancies and lymphoma, respectively. The median age was 43(20-77) years. All but one was female. The median course before diagnosis was 1(0.17-12) month. There were 9 patients with international prognostic index (IPI) 0 and 5 with IPI 1. The most common histological subtypes were diffuse large B cell lymphoma (DLBCL) with total 11 cases (78.6%), there was 1 case (7.1%) in each of extranodal margin zone lymphoma, peripheral T cell lymphoma(PTCL) and small lymphocytic lymphoma (SLL), respectively. Patients treated with radical operation versus local mass removing or needle biopsy were 6(42.9%) and 8(57.1%), respectively, there were 2 relapses in each group. Patients treated with or without rituxinmab combined with chemotherapy were 6(42.9%) and 7(50.0%), respectively, there were 3 and 1 relapses in each group, respectively. Three (21.4%) patients received intrathecal injection (IT). There were 3(21.4%) cases of central nervous system (CNS) relapse, who were not received IT. After the median follow-up of 45.2 (10.7-116.1) months, two patients died of disease progression. The median overall survival did not reach and median progression free survival was 73 (11- 116) months. CONCLUSION The most common histological subtype in patients with PBL was DLBCL, the role of rituxinmab in the treatment was not sure, CNS relapse should be monitored closely.

Efficacy and safety of HD-MTX based systemic chemotherapy regimens: retrospective study of induction therapy for primary central nervous system lymphoma in Chinese

We performed a retrospective study of 49 patients with newly diagnosed primary central nervous system lymphoma (PCNSL), to compare the efficacy and safety of different high-dose methotrexate (HD-MTX) based systemic chemotherapy regimens as induction therapy. 25 patients received AB ± R alternative regimen (consist methotrexate, ifosfamide, vindesine, dexamethasone, carmustine and teniposide), while others received HD-MTX ± R regimen. The complete response rate and overall response rate of AB ± R group and HD-MTX ± R group were 36.83% vs. 33.33%, and 68.42% vs. 71.43%, while the 2-year OS and PFS rate were 71.43% vs. 74.62%, and 42.86% vs. 54.64%, respectively. In Age > 60 subgroup, the 2-year OS and PFS rate of AB ± R group and HD-MTX ± R group were 81.82% vs. 33.33%, and 54.55% vs. 33.33%. No significant differences were found in grade 3 or 4 toxicity rate. Generally, HD-MTX ± R regimen was not inferior to AB ± R alternative regimen, but AB ± R alternative regimen seemed achieving more survival benefits in the elderly. We suggest to adjust HD-MTX ± R regimen by changing the dose-reduction strategy especially in elderly patients and adding other powerful drugs that can well penetrate blood-brain barrier to improve the efficacy.

Clinical and Laboratory Features of Acute Porphyria: A Study of 36 Subjects in a Chinese Tertiary Referral Center

Porphyria is a group of eight metabolic disorders characterized by defects in heme biosynthesis. The presentation of porphyria is highly variable, and the symptoms are nonspecific, which accounts in part for delays in establishing a diagnosis. In this study, we report the characteristics of 36 Chinese acute porphyria patients. Most of them were female (33/36), and the median age was 25.3 years (range 18–45 years). The most frequent presenting symptom was abdominal pain (32/36). Hyponatremia was the most common electrolyte abnormality (29/36), and the serum sodium concentration was significantly negatively correlated with convulsion (p = 0.00). Genetic testing provided a precise diagnosis of the patients. Genetic analysis of the porphobilinogen deaminase (PBGD) gene was performed for 10 subjects. Of them, 9 were found to harbor a mutation in the PBGD gene, proving a diagnosis of acute intermittent porphyria, and, in 1 case, a novel Cys209Term mutation was found.

Clinical characteristics and outcome of patients with primary central nervous system lymphoma

目的 探讨原发中枢神经系统淋巴瘤(PCNSL)的临床特征、治疗方案以及预后相关因素。 方法 回顾性总结北京协和医院自1999年6月至2012年6月收治的37例PCNSL患者临床资料，对患者临床特征、治疗以及预后相关因素进行分析。 结果 全部37例PCNSL患者中位发病年龄57(17~78)岁，男女比为2.7:1。以颅内高压和智能障碍为最常见临床表现，起病至诊断中位时间1.5(1~24)个月。肿瘤累及部位以大脑半球为主，且多灶病变更为常见。36例经治患者无进展生存(PFS)时间为18.0 (95%CI 9.1~26.9)个月，总生存(OS)时间为36.0 (95%CI 21.7~50.3)个月，3年累计OS率为46.9%。放化疗联合治疗与单纯化疗组PFS时间[16.0 (95%CI 8.9~23.1)个月对26.0(95% CI 2.9~49.1)个月]及OS时间[36.0 (95%CI 2.3~69.7)个月对29.0 (95%CI 23.4~34.6)个月]比较，差异均无统计学意义(P=0.401、0.866)。 结论 PCNSL预后不佳，化放疗联合并不能显著改善患者生存，其最佳治疗方案应需进一步探索。OBJECTIVE To investigate the characteristics, treatment and outcome of patients with primary central nervous system lymphoma （PCNSL）. METHODS A total of 37 patients with PCNSL treated in Peking Union Medical College Hospital from June 1999 to June 2012 were enrolled into this retrospective study. The clinical characteristics, results of treatment and prognostic factors were analyzed. RESULTS The median age of 37 patients with PCNSL at diagnosis was 57 years（range 17 to 78 years） with a male to female ratio of 2.7:1. The symptoms or signs of elevated intracranial pressure and cognitive dysfunction were the most common initial manifestations. The median time period between onset of symptoms and diagnosis was 1.5 months. The majority of lesions were located in the cerebral hemisphere. At a median follow-up of 50 months, the median overall survival for all treated patients was 36.0 months （95% CI 21.7-50.3 months）, with a progression-free survival of 18.0 months（95% CI 9.1-26.9 months）. The 3-year cumulative survival rate was 46.9%. Compared to chemotherapy alone, combined-modality regimens which did not improve outcome were associated with a greater risk of neurotoxicity. CONCLUSION The prognosis of PCNSL was still poor, and the optimal treatment strategy for these patients should be explored in the future clinical trials.