for the Multiple Sclerosis-Autologous Hematopoietic Stem Cell Transplantation (MS-AHSCT) Long-term Outcomes Study Group IMPORTANCE Autologous hematopoietic stem cell transplantation (AHSCT) may be effective in aggressive forms of multiple sclerosis (MS) that fail to respond to standard therapies. OBJECTIVE To evaluate the long-term outcomes in patients who underwent AHSCT for the treatment of MS in a large multicenter cohort.DESIGN, SETTING, AND PARTICIPANTS Data were obtained in a multicenter, observational, retrospective cohort study. Eligibility criteria were receipt of AHSCT for the treatment of MS between January 1995 and December 2006 and the availability of a prespecified minimum data set comprising the disease subtype at baseline; the Expanded Disability Status Scale (EDSS) score at baseline; information on the administered conditioning regimen and graft manipulation; and at least 1 follow-up visit or report after transplant. The last patient visit was on July 1, 2012. To avoid bias, all eligible patients were included in the analysis regardless of their duration of follow-up. Data analysis was conducted from September 1, 2014 to April 27, 2015.EXPOSURES Demographic, disease-related, and treatment-related exposures were considered variables of interest, including age, disease subtype, baseline EDSS score, number of previous disease-modifying treatments, and intensity of the conditioning regimen. MAIN OUTCOMES AND MEASURESThe primary outcomes were MS progression-free survival and overall survival. The probabilities of progression-free survival and overall survival were calculated using Kaplan-Meier survival curves and multivariable Cox proportional hazards regression analysis models. RESULTSValid data were obtained from 25 centers in 13 countries for 281 evaluable patients, with median follow-up of 6.6 years (range, 0.2-16 years). Seventy-eight percent (218 of 281) of patients had progressive forms of MS. The median EDSS score before mobilization of peripheral blood stem cells was 6.5 (range, 1.5-9). Eight deaths (2.8%; 95% CI, 1.0%-4.9%) were reported within 100 days of transplant and were considered transplant-related mortality. The 5-year probability of progression-free survival as assessed by the EDSS score was 46% (95% CI, 42%-54%), and overall survival was 93% (95% CI, 89%-96%) at 5 years. Factors associated with neurological progression after transplant were older age (hazard ratio [HR], 1.03; 95% CI, 1.00-1.05), progressive vs relapsing form of MS (HR, 2.33; 95% CI, 1.27-4.28), and more than 2 previous disease-modifying therapies (HR, 1.65; 95% CI, 1.10-2.47). Higher baseline EDSS score was associated with worse overall survival (HR, 2.03; 95% CI, 1.40-2.95). CONCLUSIONS AND RELEVANCEIn this observational study of patients with MS treated with AHSCT, almost half of them remained free from neurological progression for 5 years after transplant. Younger age, relapsing form of MS, fewer prior immunotherapies, and lower baseline EDSS score were factors associated with better outcomes. The results suppor...

Neither prednisone nor allopurinol showed a beneficial influence on the incidence and severity of post-ERCP pancreatitis.

There are multiple sclerosis patients who suffer from an aggressive course of the disease with severe relapses and rapid accumulation of disability despite adequate treatment. In such cases high-dose immunoablation with autologous haematopoietic stem cell transplantation (ASCT) may be considered. Our objective was to report our experience with 26 multiple sclerosis patients treated with ASCT within the years 1998-2008. Twenty-six patients (Expanded Disability Status Scale 2.5-7.5 (median 6.0), multiple sclerosis duration 2-19 years (median 7)) with aggressive multiple sclerosis underwent autologous haematopoietic stem cell transplantation. Stem cells were mobilized by high-dose cyclophosphamide and granulocyte colony-stimulating factor, BEAM (carmustine, etoposide, cytarabine, melphalan) was used for immunoablation. Patients were evaluated at baseline and every six months post ASCT for adverse events and clinical outcome. Follow-up period was 11-132 months (median 66). Progression-free survival was calculated using the Kaplan- Meier method. At 3 and 6 years of follow-up 70.8% and 29.2% of patients respectively were free of progression. Patients with relapsing multiple sclerosis course, disease duration <5 years and age <35 years had a more favourable outcome. There was no death within 100 days after ASCT. We conclude that ASCT represents a viable and effective treatment option for aggressive multiple sclerosis.

The phase II CAVALLI (NCT02055820) study assessed efficacy and safety of venetoclax, a selective, B-cell lymphoma-2 (Bcl-2) inhibitor, with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in first-line (1L) diffuse large B-cell lymphoma (DLBCL), including patients demonstrating Bcl-2 protein overexpression by immunohistochemistry (Bcl-2 IHC-positive). Eligible patients ≥18 years with previously untreated DLBCL, Eastern Cooperative Oncology Group performance status ≤2, and International Prognostic Index 2-5. Venetoclax 800 mg (days 4-10, cycle 1 and days 1-10, cycles 2-8) was administered with rituximab (8 cycles) and CHOP (6-8 cycles); 21-day cycles. Primary endpoints: safety, tolerability, and complete response (CR) at end of treatment (EOT). Secondary endpoints: progression-free survival (PFS) and overall survival. Comparative analyses used covariate-adjusted R-CHOP controls from the GOYA/BO21005 study, an appropriate contemporary benchmark for safety and efficacy. Safety and efficacy analyses included 206 patients. CR rate at EOT was 69% in the overall population and was maintained across Bcl-2 IHC-positive subgroups. With median follow-up of 32.2 months, trends were observed for improved investigator-assessed PFS for venetoclax plus R-CHOP in the overall population (Hazard ratio [HR] = 0.61, 95% confidence interval [CI], 0.43-0.87) and Bcl-2 IHC-positive subgroups (HR = 0.55, 95% CI, 0.34-0.89), versus R-CHOP. Despite a higher incidence of grade 3/4 hematologic adverse events (86%), related mortality was not increased (2%). Chemotherapy dose intensity was similar in CAVALLI versus GOYA. The addition of venetoclax to R-CHOP in 1L DLBCL demonstrates increased but manageable myelosuppression and the potential of improved efficacy particularly in high-risk, Bcl-2 IHC-positive patient subgroups.

No abstract