Duan Mh

Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome.

POEMS syndrome is a rare clonal plasma cell disorder without standard treatment. Based on the efficacy and low toxicity of a combination of melphalan and dexamethasone (MDex) for light chain amyloidosis, we conducted a prospective study of MDex treatment for patients with newly diagnosed POEMS syndrome. Thirty-one patients (19 men) were enrolled and the median age at the time of diagnosis was 44 years (range, 32-68 years). All patients received 12 cycles of MDex treatment. Twenty-five patients (80.6%) achieved hematologic response including 12 (38.7%) complete remission and 13 (41.9%) partial remission. Of all 31 patients, the neurologic response rate was 100%, assessed by overall neuropathy limitation scale (ONLS). The initial neurologic response was observed in 24 patients (77.4%) at 3 months after treatment and the median time to maximal neurologic response was 12 months (range, 3-15 months). Moreover, MDex substantially improved the level of serum vascular endothelial growth factor and relieved organomegaly, extravascular volume overload, and pulmonary hypertension. Only 6 patients (19.3%) suffered from grade 3 adverse events during treatment. All patients are alive and free of neurologic relapse after the median follow-up time of 21 months. Therefore, MDex is an effective and well-tolerated treatment option for patients with newly diagnosed POEMS syndrome.

Pulmonary hypertension in POEMS syndrome

POEMS syndrome is a rare clonal plasma cell disease. Patients with POEMS syndrome are at risk of developing pulmonary hypertension, but the data on its incidence and impact on outcome are limited. We reviewed records of 154 POEMS syndrome patients with complete duplex echocardiography data for estimation of pulmonary artery systolic pressure (sPAP) at the time of diagnosis. Forty-two (27%) of 154 patients with pulmonary hypertension (estimated sPAP ≥50mmHg) were identified. Median age was 46 years (range 31–71 years). Patients with pulmonary hypertension were more likely to have peripheral edema (P=0.04), ascites (P=0.02), pleural effusion (P=0.005), and have longer time from onset to diagnosis (P=0.004) when compared with those without pulmonary hypertension. Restrictive abnormalities and decreased diffusion capacity of carbon monoxide were observed in 83% and 96% patients with pulmonary hypertension, compared with 50% and 72% in patients without pulmonary hypertension, respectively. Reversibility of pulmonary hypertension was observed after treatment of POEMS syndrome. After median follow of 32 months, survival of patients with pulmonary hypertension was worse than those without (median overall survival 54 months vs. median not reached, P=0.021). In conclusion, pulmonary hypertension is a common feature of POEMS syndrome, and is associated with signs of extravascular volume overload. Although active treatment of POEMS syndrome can reverse pulmonary hypertension, survival of these patients is worse than those without pulmonary hypertension.

Markedly elevated serum total N-terminal propeptide of type I collagen is a novel marker for the diagnosis and follow up of patients with POEMS syndrome

POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) is a rare plasma-cell dyscrasia.[1][1],[2][2] Its diagnosis relies on both clinical and laboratory features, and osteosclerosis is a major diagnostic criterion.[3][3] Although conventional imaging

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.

Renal impairment in patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes syndrome: incidence, treatment and outcome

BACKGROUND Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome is a multisystem disorder arising from underlying plasma cell dyscrasia. Renal impairment and related pathological changes have been reported, but data on its prevalence, response to therapy and impact on survival are still lacking. METHODS We retrospectively reviewed 299 patients diagnosed with POEMS syndrome in a tertiary-care university hospital from 2000 until 2014. The estimated glomerular filtration rate (eGFR) was used to define renal impairment and response, according to International Myeloma Working Group criteria. We examined the impact of renal impairment and response on patient survival. RESULTS Sixty-seven patients (22.4%) had renal impairment (eGFR < 60 mL/min/1.73 m(2)) at baseline. In a multivariate analysis, ascites was independently associated with renal impairment [odds ratio (OR) 12.366, P < 0.001]. Renal impairment was reversible in 66.0% of patients receiving therapy and was associated with a shorter time interval between symptom onset and treatment (OR 0.059, P = 0.043) and a vascular endothelial growth factor remission (OR 15.958, P = 0.050) in a multivariate analysis. In terms of therapy, patients with a renal response more commonly received a novel agent-based regimen (P = 0.037), which also led to a shorter response time (P = 0.001). With a median follow-up of 27.4 months, inferior survival was observed in patients with severe renal impairment (eGFR < 30 mL/min/1.73 m(2)), but not in those with moderate dysfunction (eGFR 30-59 mL/min/1.73 m(2)), compared with patients without renal impairment. A renal response, if achieved, predicted improved survival. CONCLUSIONS Renal impairment is a common complication of POEMS syndrome, but can be reversed with effective therapy in most cases.

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.

14q32 translocations and 13q14 deletions are common cytogenetic abnormalities in POEMS syndrome.

POEMS syndrome is a paraneoplastic syndrome characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell (PC) proliferative disease, and skin changes. Although chromosomal aberrations have been found and extensively described for other PC disorders, whether POEMS syndrome shares similar cytogenetic profiles has been rarely reported. In this study, we aimed to clarify the cytogenetic abnormalities of patients with POEMS syndrome in our center.

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.

Prognostic value of serum heavy/light chain ratios in patients with POEMS syndrome

POEMS syndrome is a rare plasma cell dyscrasia. Serum concentrations of the monoclonal protein in this disorder are typically low, and inapplicable to monitor disease activity in most cases, resulting in limited practical and prognostic values. Novel immunoassays measuring isotype‐specific heavy/light chain (HLC) pairs showed its utility in disease monitoring and outcome prediction in several plasma cell dyscrasias. We report results of HLC measurements in 90 patients with POEMS syndrome. Sixty‐six patients (73%; 95% confidence interval, 63–82%) had an abnormal HLC ratio at baseline. It could stratify the risk of disease relapse and was strongly associated with worse progression‐free survival in a multivariate analysis (P = 0.021; hazard ratio [HR] 6.89, 95% CI 1.34–35.43). After therapy, HLC ratios improved, with 43 patients (48%) remaining abnormal. The post‐therapeutic HLC ratio, if abnormal, also remained as an independent prognostic factor associated with worse progression‐free survival (P = 0.019; HR 4.30, 95% CI 1.27–14.56). These results suggest the prognostic utility of HLC ratios in clinical management of POEMS patients.

Prevalence and risk factors for depression in newly diagnosed patients with POEMS syndrome

Abstract This prospective study delineated the prevalence and risk factors for clinical depression in patients with POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes). Using a PHQ-9 (Patient Health Questionnaire scale-9, which evaluates the severity of depressive symptoms) score cut-off ≥ 10, the prevalence of pretreatment depression was 38.0%. Based on multivariate logistic regression, higher ONLS (Overall Neuropathy Limitation Scale, which assesses the severity of neuropathy) upper limb scores (hazard ratio [HR] 1.75; 95% confidence interval [CI] 1.09–2.81; p = 0.02) and ascites (HR 4.30; 95% CI 1.03–17.9; p = 0.04) were significant and independent predictors for depression. The incidence of post-treatment depression was 1.53% by the end of follow-up, while no patients received antidepressants. A preliminary logistic regression suggested depression to be a risk factor for early death (within 3 months after diagnosis) (HR 9.77; 95% CI, 1.08–88.9; p = 0.04).