Efficacy of lenalidomide plus dexamethasone for POEMS syndrome relapsed after autologous peripheral stem-cell transplantation

POEMS syndrome is a rare paraneoplastic condition associated to an underlying plasmacellular dyscrasia. The pathogenesis of POEMS is poorly understood, but overproduction of VEGF, probably secreted by clonal plasma cells, is thought to be responsible for the signs and symptoms of the syndrome, and it seems to be useful for the monitoring of the response to therapy. At present, an effective therapeutic option for the patients is represented by autologous peripheral blood stem-cell transplantation (aPBSCT), although relapses have been described, and there is an important morbidity associated with this procedure. Before the implementation of aPBSCT, the clinical course of POEMS syndrome was characterized by progressive polyneuropathy potentially leading to death for respiratory failure. Given the high serum and plasma levels of VEGF observed in POEMS patients, the use of anti-angiogenetic drugs such as thalidomide and lenalidomide and other drugs with anti-VEGF and anti-TNF effect such as bortezomib have been considered to treat this syndrome. There are evidences of lenalidomide benefit in both front-line and previously treated patients, but scanty data are available about its use for relapse after aPBSCT. Here, we report the successful use of lenalidomide in a patient who relapsed after aPBSCT.     

Efficacy and safety of low‐dose lenalidomide plus dexamethasone in patients with relapsed or refractory POEMS syndrome

Although autologous stem cell transplantation or melphalan‐based chemotherapy has significantly improved the prognosis of POEMS syndrome, a few patients will relapse or be refractory to primary therapy, and there is a lack of studies regarding these patients. In this study, we used low‐dose lenalidomide (10 mg daily) and dexamethasone (40 mg, once weekly) to treat twelve patients with relapsed (n = 8) or refractory (n = 4) POEMS syndrome. After a median follow‐up time of 20 months, the overall hematologic response rate was 77% with 44% having a complete response. Eight (67%) patients had neurological response, and the median overall neuropathy limitation scale score was reduced from 3 (range, 1–9) to 2 (range, 0–6). Serum vascular endothelial growth factor response rate was 91% and 46% of patients had normal serum VEGF levels. One patient had progression of the disease 3 months after the end of treatment and subsequently died from the disease. Therefore, the estimated 2 year overall survival and progression‐free survival were 92%. The low‐dose lenalidomide and dexamethasone regimen was well tolerated, with no treatment‐related death or any grade 3 or 4 toxicity. In conclusion, low‐dose lenalidomide plus dexamethasone therapy is an effective and safe regimen for patients with relapsed or refractory POEMS syndrome.     

Pulmonary manifestations in patients with POEMS syndrome: a retrospective review of 137 patients

BACKGROUND: POEMS syndrome is a monoclonal plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. Rare reports of pulmonary manifestations of POEMS syndrome such as pulmonary hypertension exist; however, a comprehensive review of the pulmonary manifestations of POEMS syndrome is lacking. METHODS: Retrospective review of patients with a diagnosis of POEMS syndrome at our institution between 1975 and 2003. Demographics, signs and symptoms, test findings (ie, radiographs, pulmonary function tests, and echocardiography), and survival data were extracted. Kaplan-Meier survival analysis was performed. In addition, categoric variables were compared using the Pearson chi(2) test or Fisher exact test, where appropriate. RESULTS: The study comprised 137 patients (66% male) with a mean age of 51.6 years. Respiratory symptoms were common within 2 years of diagnosis (28%). The median overall survival time was 147 months. Pulmonary manifestations of POEMS syndrome included pulmonary hypertension, restrictive lung disease, respiratory muscle weakness, and an isolated diminished diffusing capacity. Significant radiographic findings such as pleural effusions, diaphragm elevation, and increased cardiac silhouette were seen in 23% of patients. When separated by the presence or absence of respiratory muscle weakness, the median survival time was 87 vs 139 months, respectively (p < 0.05). The presence of cough was associated with reduced survival time. CONCLUSIONS: Pulmonary manifestations of POEMS are common, and both symptomatic and asymptomatic respiratory involvements are frequent on presentation in patients with POEMS syndrome. Respiratory muscle weakness and cough portend a poorer prognosis. These results suggest the need for increased awareness of the association between POEMS syndrome and pulmonary disease to guide appropriate screening and supportive therapy.     

Pachymeningeal involvement in POEMS syndrome: dramatic cerebral MRI improvement after lenalidomide therapy

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes) syndrome is a rare multisystemic disease associated with plasma cell dyscrasia and increased serum or plasma vascular endothelial growth factor (VEGF) levels, the latter likely responsible for several POEMS syndrome manifestations. Whereas peripheral neuropathy is the main neurological feature and a mandatory diagnostic criterium, central nervous system involvement is less common except for papilledema and stroke. We recently reported the frequent occurrence at brain MRI of cranial pachymeningeal involvement ina series of POEMS syndrome patients. Meningeal histopathology revealed hyperplasia of meningothelial cells, neovascularization, and obstructive vessel remodeling without inflammatory signs pointing to a role of VEGF in the meningeal manifestations. Here, we report the dramatic pachymeningeal improvement in patients undergoing lenalidomide therapy. These findings support the therapeutic role of lenalidomide and might shed further light on the pathophysiology of the disease     

Antisynthetase syndrome: a retrospective study of 14 patients

Purpose

Antisynthetase syndrome is a rare entity characterized by myositis (dermatomyositis or polymyositis), interstitial lung disease, arthritis, Raynaud's phenomena and mechanic's hands skin manifestation, and the presence of autoantibodies against aminoacyl-transfer RNA synthetase.

Patients and methods

Fourteen patients with antisynthetase syndrome followed-up between 1997 and 2009 were included. We studied retrospectively their clinical, radiological, and pathological findings.

Results

The sex ratio women/men was 2.5. Mean age at disease onset was 46 years. Arthritis (43%) and interstitial lung disease (38%) were the most frequent features at disease onset. Seven patients had myositis. Ten patients had anti-Jo1 autoantibodies, three had anti-PL7 and one anti-PL12. Corticosteroid therapy was given in all cases, immunosuppressive drugs in 12 cases, due to initial severity (n = 8), disease relapse (n = 3) or corticosteroid dependence (n = 1). After a mean follow-up of 64 months, nine patients improved, four stabilized and one patient died after lung transplantation, required for pulmonary hypertension.

Conclusion

The diffusion of immunologic assay will help us in the future to identify the specificity of this syndrome in order to improve care.     

Pneumocystis pneumonia in patients with Cushing's syndrome: A French multicenter retrospective study

ObjectivePneumocystis pneumonia (PcP) is an opportunistic infection occurring in immunocompromised patients. Cushing's syndrome (CS) impairs the immune system, and several authors have reported PcP in patients with CS. The present study aimed to characterize PcP occurring in a CS context and its management in French tertiary centers, in order to highlight the similarities in clinical presentation and treatment according to whether prophylaxis is implemented or not.MethodsThis was a multicenter retrospective study conducted in several French University Hospitals and Cancer Centers. Patients with PcP and confirmed CS regardless of etiology were included. We excluded patients with other known causes of acquired immunodeficiency with increased risk of PcP.ResultsTwenty-five patients were included. CS etiology was neoplastic in 84.0% of cases. CS clinical presentation associated predominant catabolic signs (76.0%), hypokalemia (91.7%) and lymphopenia (89.5%). CS was intense in most patients, with mean plasma cortisol levels at diagnosis of 2.424 ± 1.102 nmol/L and urinary free cortisol > 10× the upper limit of normal in 85.0%. In all patients, PcP onset followed introduction of cortisol blockers, at a median 5.5 days. Patients were treated with 1 to 3 cortisol blockers, mainly metyrapone (88%), which significatively lowered plasma cortisol levels to 667 ± 541 nmol/L at the onset of PcP (P < 0.001). PcP occurred in 7 patients despite prophylaxis. Finally, 60.0% patients were admitted to intensive care, and 20.0% died of PcP.ConclusionHigh mortality in patients with PcP implies that clinicians should be better informed about this rare infectious complication. Prophylaxis remains controversial, requiring comparative studies.     

POEMS syndrome: A multisystem clonal disorder

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is a rare condition defined by monoclonal plasma cell disorder, peripheral neuropathy, and other systemic symptoms. The pathophysiology of POEMS syndrome is unknown, but the overproduction of vascular endothelial growth factor (VEGF) appears to be an important contributory element. The diagnosis of POEMS syndrome requires the presence of both mandatory criteria (ie, polyneuropathy and a monoclonal plasma cell disorder), at least one major criterion (ie, osteosclerotic bone lesions, Castleman disease, or elevated serum or plasma levels of vascular endothelial growth factor), and at least one of the six minor criteria. POEMS syndrome lacks a standard treatment, but patients with limited sclerotic bone lesions are typically treated with radiation therapy. In contrast, those with widespread lesions receive chemotherapy and hematopoietic stem cell transplantation.     

Efficacy and safety of pemafibrate in patients with hypertriglyceridemia in clinical settings: A retrospective study

Background and aimsRecently, pemafibrate, a selective PPARα modulator, has been developed as a treatment for hypertriglyceridemia and has attracted much attention. The aims of this study were to evaluate the efficacy and safety of pemafibrate in hypertriglyceridemia patients under clinical settings.Methods and resultsWe evaluated changes in lipid profiles and various parameters before and after 24-week pemafibrate administration in patients with hypertriglyceridemia who had not previously taken fibrate medications. There were 79 cases included in the analysis. 24 weeks after the treatment with pemafibrate, TG was significantly reduced from 312 ± 226 to 167 ± 94 mg/dL. In addition, lipoprotein fractionation tests using PAGE method showed a significant decrease in the ratio of VLDL and remnant fractionations, which are TG-rich lipoproteins. After pemafibrate administration, body weight, HbA1c, eGFR, and CK levels were not changed, but liver injury indices such as ALT, AST, and γ-GTP were significantly improved.ConclusionIn this study, pemafibrate improved the metabolism of atherosclerosis-induced lipoproteins in hypertriglyceridemia patients. In addition, it showed no off-target effects such as hepatic and renal damage or rhabdomyolysis.     

Efficacy of bed exercise in elderly patients after total hip arthroplasty: A retrospective study of 539 patients

The purpose of this study was to observe the necessity of bed exercise therapy in the rehabilitation of elderly patients after hip replacement and to analyze whether bed exercise therapy has an impact on patients’ psychological scores, hip function and postoperative complications. From January 2018 to January 2021, a total of 539 patients with end-stage femoral head necrosis or hip osteoarthritis were retrospectively analyzed. According to the method of postoperative rehabilitation exercise, patients were divided into 2 groups: Group A (routine gait) and Group B (bed exercise). There was no significant difference in general information between the 2 groups. There was no significant difference in baseline pain scores between patients in Group A and Group B (25.2 ± 9.6 vs 24.8 ± 10.4, P = .429). However, at 5 weeks post-operatively, the pain scores of patients in Group A were significantly higher than those in Group B (38.6 ± 7.7 vs 34.1 ± 8.1, P = .016). At 17 weeks post-operatively, the difference between Group A and Group B remained (40.9 ± 6.9 vs 37.5 ± 7.5, P = .041). Similar to the pain score, the hip function score compared between the 2 groups was significantly different at 5 weeks (39.7 ± 8.4 in Group A, 45.9 ± 9.2 in Group B, P < .001) and 17 weeks post-operatively (41.5 ± 7.6 in Group A, 47.2 ± 8.8 in Group B, P < .001). At 17 weeks post-operatively, between the 2 groups, only the range of motion (ROM) of abduction showed no significant difference. Patients in Group B exhibited a better ROM in any other movement posture. The results showed that compared with Group A, bed exercise rehabilitation training could reduce the incidence of deep venous thrombosis. This study demonstrates that bed exercise can improve the hip function and quality of life of elderly patients with total hip arthroplasty (THA) at an early postoperative stage. It can reduce the incidence of deep venous thrombosis of the lower limbs after surgery. For these patients, systematic bed exercise rehabilitation training is recommended in the early postoperative period.     

78例传染性非典型肺炎病例临床分析

目的　分析传染性非典型肺炎 (世界卫生组织又称严重急性呼吸综合征 ,SARS)患者的临床特点 ,并对其诊断标准和治疗方法进行探讨。方法　对广州呼吸疾病研究所 2 0 0 2年 12月 2 2日至 2 0 0 3年 3月 31日收治的 78例SARS患者的临床、实验室、影像学资料进行回顾性分析。结果78例SARS患者 :男 4 2例 ,女 36例 ;年龄 2 0～ 75岁 ,平均 (37 5± 11 6 )岁 ;医务人员 4 4例 (5 6 % )。临床症状包括 :发热 (10 0 % )、咽痛 (17% )、咳嗽 (88% )、气促 (80 % )、畏寒 (5 9% )、肌肉酸痛 (41% )。血常规 :白细胞 (WBC) <4 0× 10 9/L 12例 (15 % ) ,WBC(4 0～ 10 0 )× 10 9/L 4 9例 (6 3% ) ,WBC >10 0× 10 9/L 17例 (2 2 % ) ,平均为 (7 6± 5 0 )× 10 9/L ;中性粒细胞为 0 75± 0 14 ,淋巴细胞 0 18±0 11。胸部X线和CT显示肺部斑片状阴影 ,短期内病灶增多 ,累计单侧 2 3例 (30 % )、双侧 5 2例(6 7% )。分析医护人员被感染途径 ,提示本病具有较强的飞沫近距离传染特性。出现急性肺损伤(ALI) 37例 (47% ) ,其中发展为急性呼吸窘迫综合征 (ARDS) 2 1例。 7例死亡患者均为ARDS合并有多器官功能衰竭综合征 (MODS)。结论　流行病接触史、发热、X线肺炎征及白细胞计数正常或减少是诊断本病的临床依据。     

Chronic graft-versus-host syndrome in man: A long-term clinicopathologic study of 20 seattle patients

This study of chronic graft-versus-host disease (GVHD) describes the clinical, pathologic and laboratory features, and the causes of morbidity and mortality in 20 patients who received allogeneic marrow transplants from HLA identical sibling donors. Chronic GVHD is a pleiotropic syndrome with variability in the time of onset, organ systems involved and rate of progression. The clinical-pathologic features resemble an overlap of several collagen vascular diseases with frequent involvement of the skin, liver, eyes, mouth, upper respiratory tract, esophagus and less frequent involvement of the serosal surfaces, lower gastrointestinal tract and skeletal muscles. Major causes of morbidity are scleroderma with contractures and ulceration, dry eyes and mouth, pulmonary insufficiency and wasting. Chronic GVHD has features of immune dysregulation with elevated levels of eosinophils, circulating autoantibodies, hypergammaglobulinemia and plasmacytosis of viscera and lymph nodes. In this study, three patients had limited chronic GVHD with relatively favorable prognosis characterized by localized skin involvement and/or hepatic disease without chronic aggressive histology. Most patients, however, had extensive disease with a progressive course. Survival was largely determined by the presence or absence of serious recurrent bacterial infections. The over-all severity of disease was best assessed by using the Karnofsky performance rating.     

The characteristics of ascites in patients with POEMS syndrome

The characteristics of ascites in patients with POEMS syndrome, which comprise polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes, are unknown. We described the frequency of ascites at presentation of POEMS syndrome and further evaluated for the pathogenesis and nature of the ascites. One hundred and six consecutive patients with POEMS syndrome in Chinese PLA General Hospital were evaluated for the presence of ascites, and the cellular and biochemical characteristics of the ascitic fluids were assessed. Serum levels of complement, cytokines, and clinical chemistry parameters were analyzed in peripheral blood samples of the patients with POEMS syndrome. Ascites was observed in 42 of 106 (39.6 %) patients with POEMS syndrome. Patients with ascites had significantly high serum levels of C3 and C4 complement components and TNF-α (all p?<?0.01). In 31 (73.8 %) patients who underwent paracentesis, the ascitic fluids had low serum ascites albumin gradients (SAAG), indicating non-portal hypertension. Spontaneous bacterial peritonitis was not observed. Ascites is a common complication of POEMS syndrome and has characteristics of non-portal hypertension, based on low SAAG. Increased immune activation and inflammatory status could contribute to the pathogenesis of ascites in POEMS syndrome.     

Outcomes of patients with Down syndrome and acute leukemia: A retrospective observational study

Children with Down syndrome (DS) have a higher risk of developing acute leukemia than do those without DS. There are few studies in the literature about outcome, survival, and difficulties of treating patients with DS and acute leukemia in a developing country. This study aimed to analyze the outcome, response to treatment, survival, treatment complications, and causes of death in patients with DS and acute leukemia compared with those in patients with acute leukemia without DS diagnosed in the same period of time.We conducted a retrospective observational analysis including a cohort of 21 patients with DS and acute leukemia diagnosed between 2009 and 2018 in 3 hemato-oncology centers (2 pediatric centers and 1 adult hematology center). A group of patients with DS-acute lymphoblastic leukemia (DS-ALL) was analyzed and compared with a group of 165 patients with acute lymphoblastic leukemia without DS, and a group of patients with DS-acute myeloid leukemia (DS-AML) was analyzed and compared with a group of 50 patients with acute myeloid leukemia without DS, which was diagnosed during the same period of time (2009–2018) and treated under similar conditions in terms of both treatment protocols and economic resources.The overall survival rates in children with DS-ALL and DS-AML were 35.7% and 57.1%, respectively (P = .438). The overall survival rate was significantly worse in children with DS-ALL than in those with acute lymphoblastic leukemia without DS (35.71% vs 75.80%, P = .001). We noted that treatment-related mortality in the patients with DS-ALL was high (50%) (infections and toxicities related to chemotherapy); this result was significantly different from that for patients with leukemia without DS (P < .0001). The relapse rate was higher in patients with DS-ALL but not significantly higher than that in patients without DS (P = .13).In contrast, the overall survival rate was better for patients with DS-AML than for those with acute myeloid leukemia without DS (57.1% vs 45.1%, P = .47).Because of the particularities of the host, we suggest that DS-ALL and DS-AML should be considered as independent diseases and treated according to specific protocols with therapy optimization per the minimal residual disease.     

腹膜后神经鞘瘤误诊20例

目的:探讨腹膜后神经鞘瘤的一般资料、诊断、治疗及预后.方法:收集2004-11/2011-11中国医科大学第一附属医院普通外科收治的腹膜后肿物患者113例的临床资料(其中20例为腹膜后神经鞘瘤),进行回顾性分析,并回顾复习国内外现有相关文献资料.结果:本组患者均行影像学检查并且均行手术治疗,术后进行病理诊断.20例中除1例肿瘤部分切除,1例包膜内切除外,获得随访18例.其中完整切除者17例,随访时间最短11mo,最长83mo,平均随访时间40.5mo,中位随访时间41mo,生活质量均良好,期间经复查均无复发迹象.包膜内切除者1例,随访时间28mo,预后良好,无复发迹象.结论:腹膜后神经鞘瘤是一种罕见的肿瘤,术前诊断困难缺乏特异性,手术完整切除肿瘤是首选的治疗方法,预后良好,少见复发.     

POEMS综合征23例临床分析

POEMS综合征又称Crow-Fukase综合征,是一种临床少见的多器官损害综合征,以进行性多发性周围神经病变(polyneuropathy,P)、器官肿大(organomegaly,O)、内分泌病变(endocrinopathy,E)、M蛋白增高(M protein,M)和皮肤改变(skin changes,S)为主要特征的一类疾病.临床表现复杂多样,易误诊、漏诊.本文总结了本院2000-2008年收治的23例患者临床资料,进行回顾性分析提高对本病的认识,现分析如下.     

A prospective phase II study of low dose lenalidomide plus dexamethasone in patients with newly diagnosed polyneuropathy,organomegaly, endocrinopathy,monoclonal gammopathy,and skin changes (POEMS) syndrome

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare plasma dyscrasia without standard treatment. This phase II prospective trial evaluates the safety and response of 12 cycles of low dose lenalidomide (10 mg) plus dexamethasone (Rdex) in patients with newly diagnosed POEMS syndrome. Forty‐one patients (28 men) were enrolled and the median age at diagnosis was 49 years (range, 21‐70 years). Twenty‐one patients (46%) achieved complete hematologic response and the neurologic response rate was 95%. The median serum vascular endothelial growth factor (VEGF) declined from 5155 pg/mL (range, 534‐14 328 pg/mL) to 832 pg/mL (95‐6254 pg/mL) after therapy. The overall VEGF response rate was 83%, and the median time to response was 2 months, with a mean VEGF reduction of 43% at the first month. In terms of clinical response, Rdex substantially relieved extravascular volume overload, organomegaly, and pulmonary hypertension. No treatment‐related deaths occurred and no patients suffered from lenalidomide‐related grade 3 or above adverse events. After a median follow‐up of 34 months, median overall survival (OS) and progression‐free survival (PFS) were not reached, with an estimated 3‐year OS and PFS of 90% and 75%, respectively. In conclusion, Rdex was active with high hematologic, VEGF and organ response rate and well tolerated for patients with newly diagnosed POEMS syndrome. This trial was registered at www.clinicaltrials.gov as #NCT01816620.