Cai H

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.

Prognostic study for overall survival in patients with newly diagnosed POEMS syndrome.

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) is a multisystem disorder with a good long-term prognosis. In its dozens of clinical features, those with independent prognostic value are still not well characterized. We retrospectively included 362 patients with newly diagnosed POEMS syndrome at our institute from 2000 to 2015. On the basis of a randomized sample splitting, we first identified four baseline clinical variables, including age >50 years (hazards ratio (HR) 4.07, 95% confidence interval (CI) 1.41–11.76, P=0.009), pulmonary hypertension (HR 3.99, 95% CI 1.44–11.04, P=0.008), pleural effusion (HR 3.81, 95% CI 1.23–11.79, P=0.02) and estimated glomerular filtration rate <30 ml/min/1.73 m2 (HR 8.25, 95% CI 2.18–31.25, P=0.002), associated with inferior overall survival in the derivation cohort, with the use of multivariate Cox regression model. These factors were incorporated together to develop a prognostic nomogram. Concordance index calculation (0.727, 95% CI 0.601–0.853, P=0.018) and calibration curve plotting demonstrated its significant predictive and discriminatory capacity in the validation cohort. This nomogram could be a useful and convenient tool in clinical practice to evaluate individualized prognosis in patients with newly diagnosed POEMS syndrome.

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.

A rare e13a3 (b2a3) BCR-ABL1 fusion transcript with normal karyotype in chronic myeloid leukemia: The challenges in diagnosis and monitoring minimal residual disease (MRD).

Patients with chronic myeloid leukemia (CML) have a t (9;22)(q34;q11.2) or variant translocation that results in a BCR-ABL1 fusion gene. For many years, conventional karyotyping has been used as the standard diagnostic tool for t (9;22) (q34;q11.2). However, it has several limitations that may lead to failure for detecting BCR-ABL1 gene rearrangements in around 5% of all CML patients. Although reverse transcription polymerase chain reaction (RT-PCR) has evolved as a sensitive method for detecting BCR-ABL1 translocation, this method fail to detect certain BCR-ABL1 fusion transcript type, such as e13a3 (also known as b2a3), as a result of many commercially available and laboratory-developed primer sets. Fortunately, these two rare situations rarely appear at the same time, therefore, the combination of two methods rarely misdiagnosed the patients with CML. In this study, we report a patient with CML who tested both negative by RT-PCR and cytogenetic analysis at the time of diagnosis. She was diagnosed as atypical CML (aCML) and allogeneic hematopoietic stem cell transplantation was suggested. Further fluorescence in situ hybridization (FISH) showed cryptic insertion of ABL into BCR gene on chromosome 22, and DNA sequencing with alternative primer sets demonstrated the presence of an e13a3 BCR-ABL1 fusion. She was diagnosed as CML and received imatinib 400 mg/day. A follow-up BCR-ABL1 FISH analysis demonstrated a markedly reduced BCR-ABL1 fusion rate of 0 after 6months treatment, indicating a complete cytogenetic response.

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.

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.

Diagnostic performance and clinical correlation of serum vascular endothelial growth factor levels in patients with newly diagnosed POEMS syndrome

OBJECTIVE To evaluate the diagnostic performance and clinical correlation of serum vascular endothelial growth factor (VEGF) in patients with newly diagnosed POEMS syndrome. METHODS We recruited 104 patients with POEMS syndrome who diagnosed at Peking Union Medical College Hospital during October 2010 to April 2014 in the current study. Clinical data and serum samples were collected. Serum VEGF levels were measured, comparing to both disease and healthy controls, and its correlation with clinical features were analyzed. RESULTS Patients with newly diagnosed POEMS syndrome showed markedly elevated levels of serum VEGF (median 3503 ng/L, P<0.01). A cut-off value of 1 200 ng/L had a specificity of 90.2%, with a sensitivity of 83.7%, in support of a POEMS diagnosis. Further analyses indicated that patients with higher serum VEGF level (>2 000 ng/L) had more prevalent osteosclerosis (61.0% vs 37.0%, P=0.031) and papilledema (70.1% vs 44.4%, P=0.017). CONCLUSION Serum VEGF level was useful in differentiating POEMS syndrome from other disorders with overlapping clinical presentations, and its levels correlated with several disease features.

Patients with Fever of Unknown Origin and Splenomegaly: Diagnostic Value of Splenectomy and Preoperative Risk Factors Suggestive of Underlying Lymphomas

Background: We reviewed patients with fever of unknown origin (FUO) and splenomegaly and assessed the diagnostic value of splenectomy and measured risk factors suggestive of an underlying lymphoma. Methods: FUO patients (n = 83) who had splenomegaly and underwent splenectomy were enrolled into this retrospective single-center study. Clinical presentations were documented and risk factors suggestive of an underlying lymphoma were tested. Results: Seventy-four patients (89.2%) had a diagnosis of lymphoma or not after splenectomy and follow-up. Of those (55.4%) diagnosed with lymphoma, 29 had B-cell non-Hodgkin lymphoma and 12 had T-cell non-Hodgkin lymphoma. The remaining 33 (44.6%) had diseases other than lymphoma. Using multivariate logistic analysis, the following 3 independent risk factors were found to be related to a final diagnosis of lymphoma: age (continuous) (HR 1.086; 95% CI 1.033-1.141; p = 0.001), massively enlarged spleen (HR 7.797; 95% CI 1.267-47.959; p = 0.027), and enlarged intra-abdominal lymph nodes (HR 63.925; 95% CI 7.962-513.219; p < 0.001). The calibration of the model was satisfactory (p = 0.248 using the Hosmer-Lemeshow test), and the discrimination power was good (area under the receiver operating characteristic curve 0.925; 95% CI 0.863-0.987). Conclusions: Splenectomy is an effective diagnostic procedure for patients with FUO and splenomegaly and lymphoma is a common cause. Older age, a massively enlarged spleen, and enlarged intra-abdominal lymph nodes are risk factors suggesting an underlying lymphoma, and surgery for high-risk patients should be considered.