High-dose therapy and autologous stem cell transplantation in patients with POEMS syndrome: a retrospective study of the Plasma Cell Disorder sub-committee of the Chronic Malignancy Working Party of the European Society for Blood & Marrow Transplantation.
ABSTRACT: POEMS syndrome is a rare para-neoplastic syndrome secondary to a plasma cell dyscrasia. Effective treatment can control the disease-related symptom complex. We describe the clinical outcome of autologous stem cell transplantation for patients with POEMS syndrome, determining the impact of patient- and disease-specific factors on prognosis. One hundred and twenty-seven patients underwent an autologous stem cell transplantation between 1997-2010 with a median age of 50 years (range 26-69 years). Median time from diagnosis to autologous stem cell transplantation was 7.5 months with 32% of patients receiving an autologous stem cell transplantation more than 12 months from diagnosis. Engraftment was seen in 97% patients and engraftment syndrome was documented in 23% of autologous stem cell transplantation recipients. Hematologic response was characterized as complete response in 48.5%, partial response in 20.8%, less than partial repsonse in 30.7%. With a median follow up of 48 months (95%CI: 38.3, 58.6), 90% of patients are alive and 16.5% of patients have progressed. The 1-year non-relapse mortality was 3.3%. The 3-year probabilities of progression-free survival and overall survival are 84% and 94%, respectively, with 5-year probabilities of progression-free survival and overall survival of 74% and 89%. In a cohort of graft recipients, detailed organ-specific symptom response demonstrated clear symptom benefit after autologous stem cell transplantation especially in relation to neurological symptom control. The data analyzed in this study demonstrate the clinical utility of autologous stem cell transplantation for patients with POEMS syndrome.
Project description:To study the evolution of the neuropathy and long-term disability in a large cohort of patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome following autologous stem cell transplantation (ASCT).Retrospective chart review documenting the clinical, electrophysiologic, and laboratory characteristics of patients with POEMS syndrome undergoing ASCT at Mayo Clinic, Rochester.Sixty patients with a median follow-up time of 61 months were studied. All patients had peripheral polyneuropathy and demonstrated neurologic improvement after ASCT (apart from one patient who died early). Before ASCT, 27 patients (45%) required a wheelchair and 17 (29%) required a walker or foot brace. At the end of the follow-up period, no patient was using a wheelchair and 23 patients (38%) were using a foot brace. The median Neuropathy Impairment Score improved from 66 to 48 points at 12 months and to 30 points at most recent follow-up (p < 0.0001). Median Rankin Scale score improved from 3 to 1.5 (p < 0.0001). Vascular endothelial growth factor levels decreased from a median of 452 to 63.5 pg/mL (p < 0.0001). The ulnar compound motor action potential amplitude (median) improved from 4.3 to 7.6 mV (p < 0.0001) and ulnar compound motor action potential conduction velocity (median) improved from 34 to 51 m/s (p < 0.0001). Predicted forced vital capacity improved from 81% to 88% (p < 0.0001). Periengraftment syndrome occurred in 24 patients. Fourteen patients required additional chemotherapy and/or radiation following ASCT, but there was no clinical deterioration in the neuropathy in any of these patients. Six patients died: 1 due to POEMS, 1 due to failed engraftment, and 4 due to other malignancies (2 myelodysplastic syndrome, 1 lymphoma, 1 metastatic lung cancer).Patients with POEMS syndrome who undergo ASCT have a significant and meaningful improvement of their neuropathy by multiple measurements during both short and long-term follow-up, which corresponds to reduction in morbidity and disability (none are in wheelchair long-term). Periengraftment syndrome was common but manageable. Fatal complications, although rare, did occur, usually in association with other malignancies.This study provides Class IV evidence that for patients with POEMS syndrome, ASCT improves neuropathy-related function.
Project description:POEMS syndrome is a rare plasma cell dyscrasia. This study compared the responses to and survival of 347 POEMS syndrome patients given three first-line treatment regimens: autologous stem cell transplantation (ASCT, N = 165) and melphalan + dexamethasone (MDex, N = 79), or lenalidomide + dexamethasone (LDex, N = 103). After a median 45-month follow-up, overall hematologic complete remission (CRH) was 46.4%, vascular endothelial growth factor complete remission (CRV) was 55.1%, and neurological remission (RN) was 93.8%. CRH was better with ASCT (49.7%) than with MDex (37.7%, p = 0.001). CRV was better with ASCT (66.2%) than with MDex (38.5%, p = 0.001) or LDex (47.7%, p = 0.008). Differences in RN achieved by three regimens (91.5% vs. 100% vs. 93.8%, p = 0.234) were not significant. Overall 3-year progression-free survival (PFS) was 80.5% and overall 3-year overall survival (OS) was 90.8%. PFS was 87.6% with ASCT and 64.9% with LDex (p = 0.003). OS in the three regimens did not differ (p = 0.079). In medium-high risk patients, ASCT had better CRH and CRV than MDex, and better PFS than LDex. Therefore, although all three treatments had reasonable responses and survivals, patients with higher risk may benefit more from ASCT treatment.
Project description:Autologous hematopoietic stem cell transplantation (ASCT) for multiple myeloma (MM) is associated with high symptom burden, particularly for older patients and those with amyloid light-chain (AL) amyloidosis. Symptom burden peaks during leukopenia. We hypothesized that higher doses of CD34(+) stem cells would be associated with an improved symptom outcome. Patients undergoing ASCT for MM who were ?60 years old or had AL amyloidosis were randomized to receive either a standard (4 to 6 × 10(6) cells/kg) or high dose (10 to 15 × 10(6) cells/kg) of CD34(+) cells after melphalan 200 mg/m(2). Symptom burden was assessed via the MD Anderson Symptom Inventory MM module. Eighty patients were enrolled. Median CD34(+) cell doses were 5.1 × 10(6) cells/kg (standard dose) and 10.5 × 10(6) cells/kg (high dose). The most severe symptoms during the first week were fatigue, lack of appetite, drowsiness, disturbed sleep, and pain. The area under the curve for the mean composite severity score of these symptoms was similar between treatment arms (P = .819). Median times to neutrophil, lymphocyte, and platelet engraftment were also similar between groups. IL-6 increased similarly for both groups throughout the ASCT course. Infusion of higher autologous stem cell dose after high-dose chemotherapy does not yield a difference in symptom burden or engraftment time in the first few weeks after ASCT.
Project description:Arterial and venous thromboses occur in patients with POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein level, and skin changes) syndrome at a previously reported rate of 20%. We reviewed the University College London Hospitals (UCLH) POEMS Registry to determine the rate of venous thromboembolism (VTE), arterial events, and risk factors. This registry, established in 1999 and comprising 103 patients at the time of this study, is the largest single-center cohort in Europe. Of the 83 assessable patients, median age at presentation was 52 years (range, 31-84). Twenty-five patients experienced clinically apparent arterial or venous events, and 2 had concurrent arterial and venous thromboses. Eleven patients had VTEs, including deep vein thrombosis (DVT; 3 of 11), pulmonary embolism (4 of 11), and peripherally inserted central catheter-associated DVT, which occurred during autologous stem cell transplantation (3 of 11). Sixteen patients experienced arterial events: stroke (7 of 16), peripheral arterial occlusion (5 of 16), myocardial infarction (3 of 16), and microvascular disease (1 of 16), with no discernible relationship with thrombocytosis or polycythemia. Thirty percent of POEMS patients have arterial and venous thromboses, higher than previously reported. There were more arterial than venous events, and most occurred during active disease, before the start of chemotherapy, indicating the need for a preemptive approach to thromboprophylaxis.
Project description:BACKGROUND AND OBJECTIVES:Our study evaluated the efficiency and safety of autologous hematopoietic stem cell transplantation treatment for patients with refractory lupus nephritis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS:From July 2011 to January 2015, a total of 22 patients with refractory lupus nephritis were enrolled in this study. Peripheral blood stem cells were mobilized with cyclophosphamide and granulocyte colony stimulating factor and reinfused after treatment with cyclophosphamide and antithymocyte globulin. The primary end point was the rate of remission, and secondary end points included the survival and relapse rates, changes in proteinuria, kidney function, and serology immunologic test. All complications were recorded for safety assessment. RESULTS:Twenty-two patients were enrolled and underwent stem cell mobilization. There were nine men and 13 women, with a median lupus nephritis duration of 46 (33-71) months. The mean number of CD34+ cells was (7.3±3.8)×106/kg. All patients had successful engraftment, and the median times of granulocyte and platelet engraftment were 8 (7-9) and 9 (6-10) days, respectively. The major complications of stem cell transplantation were fever and gastrointestinal tract symptoms. The treatment-related mortality was 5% (one of 22). After a median follow-up of 72 (60-80) months, 18 (82%) patients achieved completed remission, one (5%) patient achieved partial remission, and one patient had no response and received peritoneal dialysis at 12 months after transplantation. The 5-year overall survival and disease-free survival rates were 91% and 53%, respectively. Six patients experienced relapse during the follow-up, and the relapse rate was 27%. CONCLUSIONS:Autologous hematopoietic stem cell transplant could be used as a treatment option for refractory lupus nephritis, because it was relatively safe and associated with good outcomes.
Project description:Aim. To evaluate whether patients with multiple myeloma at various risks can still benefit the same from autologous stem cell transplantation consolidation in the era of novel agents. We retrospectively analyzed 67 consecutive myeloma patients receiving autologous stem cell transplantation after bortezomib and/or thalidomide based inductions. Totally 17 high-risk, 24 intermediate-risk, and 26 low-risk patients were enrolled, based on fluorescence in situ hybridization and ISS stage. Meanwhile, another 67 risk-, response depth-, and age-matched patients not proceeding to autologous stem cell transplantation were chosen as controls. Our preliminary data indicated that, in the high-risk subgroup, progression-free survival and overall survival were both significantly prolonged after autologous stem cell transplantation (P < 0.001 and P = 0.015) while, in the intermediate-risk subgroup, neither progression-free survival nor overall survival was prolonged significantly after autologous stem cell transplantation (P > 0.05), and in the low-risk subgroup, only progression-free survival was extended significantly (P = 0.012) after autologous stem cell transplantation. Multiple variables analysis further indicated that autologous stem cell transplantation and risk stratification were two independent prognostic factors for overall survival. Our results indicated that myeloma patients at different risks all benefit from autologous stem cell transplantation consolidation even in the era of novel agents.
Project description:The shortage of liver organ donors is increasing and the need for viable alternatives is urgent. Liver cell (hepatocyte) transplantation may be a less invasive treatment compared with liver transplantation. Unfortunately, hepatocytes cannot be expanded in vitro, and allogenic cell transplantation requires long-term immunosuppression. Organoid-derived adult liver stem cells can be cultured indefinitely to create sufficient cell numbers for transplantation, and they are amenable to gene correction. This study provides preclinical proof of concept of the potential of cell transplantation in a large animal model of inherited copper toxicosis, such as Wilson's disease, a Mendelian disorder that causes toxic copper accumulation in the liver. Hepatic progenitors from five COMMD1-deficient dogs were isolated and cultured using the 3D organoid culture system. After genetic restoration of COMMD1 expression, the organoid-derived hepatocyte-like cells were safely delivered as repeated autologous transplantations via the portal vein. Although engraftment and repopulation percentages were low, the cells survived in the liver for up to two years post-transplantation. The low engraftment was in line with a lack of functional recovery regarding copper excretion. This preclinical study confirms the survival of genetically corrected autologous organoid-derived hepatocyte-like cells in vivo and warrants further optimization of organoid engraftment and functional recovery in a large animal model of human liver disease.
Project description:High-dose chemotherapy followed by autologous stem cell transplantation can be a rescue for patients with severe refractory systemic lupus erythematosus (SLE). However, the procedure might have fatal complications including infections and bleeding. We report on a young female patient with SLE whose disease started in her early childhood. After many years, severe renal, neurological, and bone marrow involvement developed that did not respond to conventional therapy. She was selected for autologous stem cell transplantation. A successful peripheral stem cell apheresis was performed in March 2006. The nonselected graft was reinfused in August 2006 after a conditioning chemotherapy containing high-dose cyclophosphamide and antithymocyte globulin. Engraftment was detected within 11 days. On the 38th posttransplant day, severe cytomegalovirus (CMV) infection developed that included pneumonitis, hepatitis, and pancytopenia. The patient died in a week due to multiorgan failure. With her case, we want to call the attention to this rare, but lethal complication of the autologous transplantation.
Project description:Autologous transplantation of patient-specific induced pluripotent stem cell (iPSC)-derived neurons is a potential clinical approach for treatment of neurological disease. Preclinical demonstration of long-term efficacy, feasibility, and safety of iPSC-derived dopamine neurons in non-human primate models will be an important step in clinical development of cell therapy. Here, we analyzed cynomolgus monkey (CM) iPSC-derived midbrain dopamine neurons for up to 2 years following autologous transplantation in a Parkinson's disease (PD) model. In one animal, with the most successful protocol, we found that unilateral engraftment of CM-iPSCs could provide a gradual onset of functional motor improvement contralateral to the side of dopamine neuron transplantation, and increased motor activity, without a need for immunosuppression. Postmortem analyses demonstrated robust survival of midbrain-like dopaminergic neurons and extensive outgrowth into the transplanted putamen. Our proof of concept findings support further development of autologous iPSC-derived cell transplantation for treatment of PD.
Project description: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 ?50 mmHg) 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.