melphalan and Nervous-System-Diseases

We report the incidence, characteristics and outcome of neurological complications occurring following reduced-intensity conditioning (RIC) in 85 patients who received a related/unrelated donor stem cell transplantation following therapy with alemtuzumab, fludarabine and melphalan. Six patients (probability 8.9%) developed severe neurological complications at a median of 151 days (24-334 days). Five of them presented with progressive peripheral sensori-motor radiculo-neuropathy and/or myelitis, preceded by one or more viral reactivation/infection. Despite treatment with immunoglobulins/plasmapheresis/steroids, four died of respiratory failure due to progressive peripheral neurophathy. Viral infection was identified as the only risk factor for the development of neurological complications. Patients who are treated with alemtuzumab-based RIC may have a lower risk of developing regimen-related neurological complications, but are more susceptible to develop peripheral radiculo-neuropathy or myelitis. This phenomenon may be possibly related to viral infection associated with delayed immunological recovery or immunological dysregulation caused by alemtuzumab-induced T-cell depletion.

Topics: Adolescent; Adult; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Antineoplastic Combined Chemotherapy Protocols; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Male; Melphalan; Middle Aged; Nervous System Diseases; Risk Factors; Transplantation Conditioning; Transplantation, Homologous; Vidarabine; Virus Diseases

We treated 5 patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and multifocal bone lesions or diffuse bone marrow plasmacytic infiltration with high-dose therapy (HDT) and autologous blood stem cell transplantation. In all cases, the treatment produced remission of plasma cell proliferation associated with marked improvement in the patients' performance status, neurologic symptoms, and other manifestations of the syndrome. HDT with stem cell support should be investigated further as a therapeutic option in patients with POEMS syndrome and disseminated plasma cell dyscrasia.

Topics: Adult; Antineoplastic Agents, Alkylating; Clone Cells; Combined Modality Therapy; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulins; Male; Melphalan; Middle Aged; Nervous System Diseases; Plasma Cells; POEMS Syndrome; Remission Induction; Transplantation, Autologous; Treatment Outcome

A single high-dose cycle of chemotherapy with stem cell support can produce disease-free survival of 15-20% for at least 3 years in women with responding stage IV breast cancer. North American Autologous Bone Marrow Transplant Registry data suggest that a complete response (CR) is the single most important prognostic factor associated with prolonged disease-free survival. Therefore, if sequential high-dose chemotherapy can increase the CR rate, then perhaps an increased proportion of patients will remain disease free. Women with at least a partial response (PR) to induction chemotherapy received three separate high-dose cycles of chemotherapy with peripheral blood progenitor support and granulocyte colony-stimulating factor. The first intensification was a dose escalation of paclitaxel (400-825 mg/ m2), the second intensification was melphalan (180 mg/m2), and the third intensification consisted of 6000 mg/m2 cyclophosphamide (1500 mg/m2/day), 500 mg/m2 thiotepa (125 mg/m2/day), and 800 mg/m2 carboplatin (200 mg/m2/day; CTCb). Thirty-six women were enrolled and 31 completed all three cycles. After the paclitaxel infusion most patients developed reversible predominantly sensory neuropathy. Of the 19 patients with measurable disease, 6 converted to CR, 7 converted to a PR* (the complete resolution of all soft tissue or visceral disease with sclerosis of prior lytic bone lesions), and 2 had a further PR for an overall response rate of 79%. Two patients had no further response and disease in two patients progressed, and thus they were taken off the study before CTCb. Seventy-eight percent are progression-free at a median follow-up of 14 months (range, 3-24+). Three sequential cycles of high-dose chemotherapy are feasible and were administered in this study with no mortality. Single agent paclitaxel at doses up to 825 mg/m2 were well tolerated with moderate reversible toxicity.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carboplatin; Cyclophosphamide; Female; Hematopoietic Stem Cell Mobilization; Humans; Melphalan; Middle Aged; Neoplasm Staging; Nervous System Diseases; Neutropenia; Paclitaxel; Thiotepa; Treatment Outcome

Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six elderly (>65 years) newly diagnosed MM patients from six European randomized trials were retrospectively analyzed and matched for age, albumin, and beta2-microglobulin at diagnosis, 296 patients were selected from the VMP groups, and 294 from MPT. Complete response rate was 21% in the VMP patients and 13% in the MPT patients (P = 0.007). After a median follow-up of 34 months (range, 1-92), VMP significantly prolonged both PFS (median 32.5 vs. 22.9 months, HR 0.65; 95% CI 0.52-0.82; P < 0.001) and OS (median 79.7 vs. 45.1 months, HR 0.44; 95% CI 0.32-0.59; P < 0.001) in comparison with MPT. The benefit in terms of OS of the VMP group was quite similar among patients with different risk factors defined by sex, ISS, ECOG performance status, or serum creatinine but not among patients ≥ 75 years. Multivariate analysis confirmed that VMP was an independent predictor of longer PFS and OS. In a control-case matched analysis, PFS and OS were prolonged in patients who received VMP in comparison with those treated with MPT.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Case-Control Studies; Disease-Free Survival; Drug Evaluation; Female; Hematologic Diseases; Humans; Kaplan-Meier Estimate; Male; Melphalan; Multiple Myeloma; Nervous System Diseases; Prednisone; Prognosis; Proportional Hazards Models; Pyrazines; Randomized Controlled Trials as Topic; Retrospective Studies; Thalidomide; Treatment Outcome

Topics: Adult; Follow-Up Studies; Humans; Immunoglobulins, Intravenous; Male; Melphalan; Nervous System Diseases; Scleromyxedema; Stem Cell Transplantation; Syndrome; Thalidomide; Time Factors; Treatment Outcome

Between April 2006 and June 2009, 34 newly diagnosed patients with multiple myeloma received one to three courses of bortezomib 1.3 mg/m(2) i.v. four times, lenalidomide 25 mg p.o. daily for 21 days and dexamethasone 20 mg/m(2) p.o. for 4 days beginning on days 1, 9 and 17 (BLD). There was rapid onset of remission in 30 patients (88%) similar to the frequency of 87% induced by a previous combination of bortezomib-thalidomide-dexamethasone (BTD). After a median of 3.6 months, 28 patients received intensive therapy with high-dose melphalan supported by autologous blood stem cells, so that the overall frequency of complete remission (CR) was 44%, similar to the frequency of 37% observed previously. Side effects due to thalidomide with previous BTD were less frequent and severe with BLD. The combination of BLD given for one or two courses was an effective primary treatment for newly diagnosed patients with multiple myeloma.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Combined Modality Therapy; Dexamethasone; Drug Evaluation; Female; Hematologic Diseases; Humans; Lenalidomide; Male; Melphalan; Middle Aged; Multiple Myeloma; Nervous System Diseases; Peripheral Blood Stem Cell Transplantation; Pyrazines; Remission Induction; Retrospective Studies; Thalidomide; Time Factors; Transplantation, Autologous