melphalan and Multiple-Sclerosis--Chronic-Progressive

Autologous haematopoietic stem cell transplantation (AHSCT) has been explored as a therapeutic intervention in multiple sclerosis (MS) over the last two decades; however, prospective clinical trials of the most common myeloablative conditioning regimen, BEAM, are limited. Furthermore, patient selection, optimal chemotherapeutic regimen and immunological changes associated with disease response require ongoing exploration. We present the outcomes, safety and immune reconstitution (IR) of patients with active, treatment refractory MS.. This study was a single-centre, phase II clinical trial of AHSCT for patients with active relapsing remitting (RRMS) and secondary progressive MS (SPMS). Patients underwent AHSCT using BEAM (carmustine, etoposide, cytarabine, melphalan)+antithymocyte globulin chemotherapeutic regimen.. The primary outcome was event-free survival (EFS); defined as no clinical or radiological relapses and no disability progression. Multiparameter flow cytometry was performed for evaluation of post-transplant IR in both MS and lymphoma patients receiving the same chemotherapy regimen.. Thirty-five patients (20 RRMS, 15 SPMS) completed AHSCT, with a median follow-up of 36 months (range 12-66). The median Expanded Disability Status Scores (EDSS) was 6 (2-7) and patients had failed a median of 4 (2-7) disease modifying therapies. 66% failed treatment with natalizumab. EFS at 3 years was 60%, (70% RRMS). Sustained improvement in EDSS was seen in 15 (44%) of patients. There was no treatment-related mortality. A sustained rise in CD39. The EFS in our MS cohort is significantly greater than other high-efficacy immunosuppressive therapies and similar to other AHSCT studies despite a more heavily pretreated cohort.. ACTRN12613000339752.

Topics: Adult; Antilymphocyte Serum; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Etoposide; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Melphalan; Middle Aged; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Progression-Free Survival; Prospective Studies; Transplantation, Autologous; Treatment Outcome; Young Adult

To evaluate clinical outcomes of autologous peripheral blood stem cell transplantation (APBCST) between opticospinal multiple sclerosis (OSMS) and conventional multiple sclerosis (CMS) during disease progressive stage in a Chinese population. Thirty-six secondary progressive MS patients, among whom 21 were with OSMS and 15 with CMS, underwent APBSCT and were followed up for an average of 48.92 months (range, 10-91 months). Peripheral blood stem cells were obtained by leukapheresis after mobilization with granulocyte colony-stimulating factor. Modified BEAM conditioning regimen (Tiniposide, melphalan, carmustin, and cytosine arabinoside) were administered. Outcomes were evaluated using the expanded disability status scale (EDSS). No maintenance treatment was administered if there was no disease progression. No treatment-related mortality occurred. Among the 36 patients, one OSMS patient dropped during the follow-up. Among the 22 relapse-free patients, 20 were with continuous neurological improvement without any relapse events, and two remained in neurologically stable states. Among the 13 relapse patients, seven had experienced of neurological relapse, but with no progression during the follow-up period; and six experienced neurological deterioration after transplantation and needed further immunosuppressant treatment. The confirmed relapse-free survival rate was 62.9% and progression-free survival rate was 83.3% after 91 months according to Kaplan and Meier survival curves. Eleven of the 20 OSMS patients (55%) and two of the 15 CMS patients (13.3%) stayed in disease active group (P = 0.014). For the 20 OSMS patients, the overall EDSS score decreased significantly after transplantation (P = 0.016), while visual functions had no significant improvement (P = 0.716). Progressive OSMS has a higher relapse rate than CMS following APBSCT.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; China; Cytarabine; Disease-Free Survival; Etoposide; Female; Hematopoietic Stem Cell Mobilization; Humans; Male; Melphalan; Middle Aged; Multiple Sclerosis, Chronic Progressive; Neuromyelitis Optica; Peripheral Blood Stem Cell Transplantation; Recurrence; Remission Induction; Spinal Cord; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Young Adult

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Female; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Middle Aged; Multiple Sclerosis, Chronic Progressive; Myeloablative Agonists; Podophyllotoxin; Remission Induction; Transplantation Conditioning; Transplantation, Autologous; Vidarabine

Autologous hematopoietic stem cell transplantation (ASCT) has been recently utilized with encouraging results in patients with poorly controlled MS.. To determine in severe cases of MS the effect of ASCT on gadolinium (Gd)-enhanced MRI and to obtain information on clinical course and safety.. In a cooperative study, 10 patients with rapidly evolving secondary progressive MS were transplanted, after BEAM conditioning regimen (carmustine, etoposide, cytosine-arabinoside, and melphalan), with unmanipulated autologous peripheral blood SC mobilized with high-dose cyclophosphamide (CY; 4 g/m2) and granulocyte-colony-stimulating factor. Triple-dose Gd-enhanced scans were performed monthly for a pretreatment period of 3 months and compared with serial monthly Gd-enhanced MRI for the following 6 months and then once every 3 months.. The median follow-up is now 15 months (range 4 to 30 months). The number of Gd-enhancing lesions decreased immediately after mobilization with CY and finally dropped to zero in all cases after the conditioning regimen. The number of new T2-weighted positive lesions paralleled data obtained for Gd-enhanced MRI. Clinically, patients improved slightly or remained stable.. These results demonstrate that the therapeutic sequence CY-BEAM-ASCT has the capacity to completely suppress MR-enhancing activity, an effect that is sustained with time. The final impact of this procedure on disease course remains to be established.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cyclophosphamide; Cytarabine; Etoposide; Female; Gadolinium; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; Image Enhancement; Magnetic Resonance Imaging; Male; Melphalan; Middle Aged; Multiple Sclerosis, Chronic Progressive; Preoperative Care; Transplantation, Autologous; Treatment Outcome