melphalan and Scleroderma--Systemic

Haematopoietic stem cell transplantation (HSCT) has been proposed for refractory autoimmune diseases, including systemic sclerosis (SSc). A sequential Bayesian phase I-II clinical trial was conducted in SSc patients to assess the feasibility, the tolerance and the efficacy of autologous HSCT. Peripheral blood stem cells (PBSC) were collected using cyclophosphamide (4 g/m2) and recombinant human granulocyte colony-stimulating factor (5 micro g/kg/d) and reinfused after positive CD34+ selection. Conditioning used cyclophosphamide (200 mg/kg) or melphalan (140 mg/m2) according to cardiac function. The main end-point was the failure of the procedure, defined by failure of either PBSC mobilization, CD34+ selection or intensification procedure, or by procedure-related death. Among the 12 enrolled patients, three failures occurred: one PBSC mobilization, one CD34+ selection and one CD34+ intensification. Probability of graft failure was estimated at 0.286 (95% confidence interval: 0.095-0.54). Autologous PBSC (n = 10) or bone marrow (n = 1) transplantation was actually performed in 11 patients with one procedure-related death. Median time to neutrophil (> 0.5 x 10(9)/l) and platelet (> 25 x 10(9)/l) haematopoietic reconstitution was 12 and 10 d respectively. After 18 months (range 1-26), eight out of 11 patients have shown major or partial response. Non-myeloablative conditioning, followed by a T cell-depleted autologous PBSC or bone marrow transplantation, appears feasible with low toxicity in severe SSc with short-term clinical benefits.

Topics: Adolescent; Adult; Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; CD4-Positive T-Lymphocytes; Cyclophosphamide; Feasibility Studies; Female; Follow-Up Studies; Graft Survival; Granulocyte Colony-Stimulating Factor; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Immunomagnetic Separation; Immunosuppressive Agents; Lymphocyte Depletion; Male; Melphalan; Middle Aged; Recurrence; Scleroderma, Systemic; Survival Analysis; Transplantation, Autologous; Treatment Failure

A 66-year-old patient presented in our clinic with increasing painful swelling of his hands, whole body stiffness, weight loss and dyspnoea upon exercise.. The physical examination revealed a marked skin sclerosis of hands, extremities and the face. Fist closure was impossible. Pulmonary CT scan showed lung fibrosis and ground glass opacities. Antinuclear antibodies and antibodies against Scl70 were positive. CRP, LDH, NT-Pro-BNP were elevated.. A diffuse cutaneous systemic sclerosis with an active interstitial pneumonia and lung fibrosis was diagnosed. Three pulses of cyclophosphamide 1.4 g every three weeks were ineffective to halt the progression of skin sclerosis, joint contractures and decline of pulmonary function. Mobilisation chemotherapy was initialized and blood stem cells were harvested. Blood stem cells were reinfused after myeloablative chemotherapy with melphalan. A maintainance therapy with mycophenolic acid was initiated after recovery of hematopoiesis. Six months after blood stem cell transplantation a decrease of skin sclerosis and an increasing recovery of joint mobility and physical strength was observed.. Patients with a progressive systemic sclerosis and further risk factors should be treated with high-dose chemotherapy with blood stem cell transplantation before organ function is severely compromised. In cases with contraindications against cyclophosphamide or anti-thymocyte-globulin melphalan can be discussed as an alternative.

Topics: Aged; Hematopoietic Stem Cell Mobilization; Hematopoietic Stem Cell Transplantation; Humans; Male; Melphalan; Myeloablative Agonists; Premedication; Scleroderma, Systemic; Treatment Outcome

Scleromyxedema, the most severe manifestation of the spectrum of lichen myxedematosus, is characterized by cutaneous mucinosis, extracutaneous manifestations, and a monoclonal gammopathy. Seven of 8 patients evaluated at our center were treated with high-dose melphalan (180 mg/m(2) intravenously) and autologous peripheral blood stem cell transplantation, with marked improvement of gastrointestinal, central nervous system, pulmonary manifestations, and Karnofsky performance status. Five patients obtained a cutaneous complete remission and 2 patients had partial remissions. Three patients with slight progression in the skin at 12, 8, and 4 months after treatment received a second cycle of high-dose melphalan and had further symptomatic improvement. The lichen myxedematosus-scleromyxedema spectrum appears to be a continuum that requires the presence of a serum paraprotein and differs in severity of skin lesions, extracutaneous manifestations, and performance status. High-dose melphalan followed by autologous transplantation appears effective for improving the symptoms and systemic manifestations of scleromyxedema.

Topics: Adult; Aged; Antineoplastic Agents, Alkylating; Dose-Response Relationship, Drug; Female; Hematopoietic Stem Cell Transplantation; Humans; Male; Maximum Tolerated Dose; Melphalan; Middle Aged; Myxedema; Palliative Care; Remission Induction; Scleroderma, Limited; Scleroderma, Systemic; Transplantation, Autologous; Treatment Outcome

Topics: Aged; Biopsy, Needle; Drug Therapy, Combination; Female; Follow-Up Studies; Humans; Immunoglobulin A; Melphalan; Multiple Myeloma; Prednisone; Scleroderma, Systemic; Treatment Outcome

We report the case of a patient with scleromyxedema with abnormal monoclonal gamma globulin of the kappa type who was treated with melphalan (Alkeran), an alkylating agent. After nine and one-half years of therapy, the patient showed myelomonocytic leukemia. The risk of secondary malignancies must be considered when weighting the benefits and risks of melphalan treatment.

Topics: Adult; Diabetes Mellitus, Type 1; Humans; Leukemia, Myeloid; Male; Melphalan; Paraproteinemias; Scleroderma, Systemic

Topics: Antineoplastic Agents; Azathioprine; Chlorambucil; Cyclophosphamide; Hair; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Melphalan; Mercaptopurine; Methotrexate; Neoplasms; Scleroderma, Systemic; Skin Diseases; Vinblastine

Topics: Adult; Aged; Blood Protein Disorders; Diagnosis, Differential; Female; Humans; Immunoglobulin G; Immunoglobulins; Immunosuppressive Agents; Male; Melphalan; Methotrexate; Middle Aged; Multiple Myeloma; Myxedema; Scleroderma, Systemic; Serum Globulins; Skin Diseases