melphalan and Arthritis--Rheumatoid

Autologous hematopoietic stem cell transplantation (HSCT) is becoming more widely accepted as an investigational therapeutic modality for selected patients with severe autoimmune diseases such as rheumatoid arthritis. However, many aspects of the procedure remain controversial--not the least of these is the choice of conditioning regimen. This article briefly reviews the potential advantages and disadvantages of the conditioning regimens commonly employed for the treatment of severe autoimmune diseases in order to facilitate the development of future clinical trials of HSCT for rheumatoid

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Arthritis, Rheumatoid; Busulfan; Carmustine; Cyclophosphamide; Cytarabine; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Melphalan; Podophyllotoxin; Radiotherapy, Adjuvant; Transplantation Conditioning; Transplantation, Autologous; Vidarabine

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Arthritis, Rheumatoid; Cyclophosphamide; Dexamethasone; Doxorubicin; Humans; Male; Melphalan; Multiple Myeloma; Paraproteins; Prednisolone; Prednisone; Risk Factors; Vincristine

Previous reports have stressed the association between autoimmune disease and lympho-proliferative neoplasm. Here we report a patient in whom multiple myeloma developed about 30 years after the onset of rheumatoid arthritis. A 79 year-old woman with an about 30-year history of rheumatoid arthritis was admitted because of lumbago in December, 1993. Laboratory findings revealed M-proteinemia (IgA 2,380 mg/dl, IgG 728 mg/dl, IgM 51 mg/dl) and serum immunoelectrophoresis showed monoclonal IgA with lambda type light chain. Bone marrow aspirate contained 66.0% plasma cells. Serological tests of rheumatoid factor were positive. X-ray findings revealed radiolucent myelomatous foci in the skull and typical destructive changes of rheumatoid arthritis in multiple joint. From these findings, IgA lambda-type multiple myeloma with rheumatoid arthritis was diagnosed. Although the pathogenesis of the association between rheumatoid arthritis and multiple myeloma is unknown, prolonged antigenic stimulation manifested by rheumatoid arthritis is considered to be a possible pathogenetic factor in the development of multiple myeloma.

Topics: Aged; Anti-Inflammatory Agents; Antineoplastic Agents, Alkylating; Arthritis, Rheumatoid; Female; Humans; Melphalan; Multiple Myeloma; Prednisolone

To determine the possible boundaries of high-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HDIT-autoHSCT) for autoimmune diseases (AUDs), such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS).. A long-term trial was conducted at one center to evaluate the efficiency and safety of HDIT-autoHSCT in patients with AUDs. The previous standard therapy was noted to be resistant or lowly effective. The age of 10 patients with systemic connective tissue diseases was 27.6±2.8 years; the pre-HDIT-autoHSCT disease duration was 5.9±1.3 years; the median posttransplantation follow-up was 39.3 months. The age of 49 patients with MS reached 34.9±1.33 years; the pretransplantation disease duration was 8.4±0.69 years; the median post-HDIT-autoHSCT follow-up was 42 months. The efficiency of transplantation was evaluated on the basis of clinical findings, by using scales, laboratory tests, and magnetic resonance imaging. Pretransplantation conditioning was carried out according to the protocols: a) BEAM + antilymphocyte globulin (ALG); b) fludarabine + melphalan + ALG. No fatal outcomes due to a transplant procedure were observed.. Overall 5-year survival after transplantation was 80% for systemic connective tissue diseases and 95% for MS; 5-year progression-free survival rates were 30% in the RA and SLE groups and 45% in the MS group. HDIT-autoHSCT turned out safe and reduced the activity of the process and further disease progression for a long period of time, as confirmed by regression of clinical symptoms and/or status stabilization in 9 patients with SLE or RA and in all patients with MS.. The favorable factors associated with the results of transplantation are age younger than 35 years in collagenoses with their short-term duration and moderate signs; age younger than 40 years in MS with a disease duration of less than 10 years and expanded disability status scale scores of not more than 6.5. Of importance are functional system scores, duration of first remission, and an index of disease progression in different types of MS.. Цель исследования. Определение возможных границ применения высокодозной иммуносупрессивной терапии с аутотрансплантацией стволовых кроветворных клеток (ВИСТ-аутоТСКК) при аутоиммунных заболеваниях (АИЗ): системной красной волчанке (СКВ), ревматоидном артрите (РА), рассеянном склерозе (РС). Материалы и методы. Проведено многолетнее одноцентровое исследование по оценке эффективности и безопасности применения ВИСТ-аутоТСКК у больных с АИЗ. Отмечена резистентность или низкая эффективность предшествующей стандартной терапии. Возраст 10 больных с системными заболеваниями соединительной ткани составил 27,6±2,8 года, длительность заболевания до ВИСТ-аутоТСКК - 5,9±1,3 года, медиана наблюдения после трансплантации - 39,3 мес. Возраст 49 больных РС достигал 34,9±1,33 года, длительность заболевания до трансплантации - 8,4±0,69 года, медиана наблюдения после ВИСТ-аутоТСКК 42 мес. Оценку эффективности трансплантации осуществляли на основании клинических данных с применением шкал, лабораторных методов, магнитно-резонансной томографии. Предтрансплантационное кондиционирование проводили по протоколам: а) ВЕАМ + антилимфоцитарный глобулин (АЛГ); б) флударабин + мелфалан + АЛГ. Летальных исходов, связанных с процедурой трансплантации, не отмечено. Результаты. Общая 5-летняя выживаемость от даты трансплантации при системных заболеваниях соединительной ткани составила в среднем 80%, при РС - 95%; 5-летняя выживаемость без прогрессирования в группе РА и СКВ - 30%, в группе РС - 45%. ВИСТ-аутоТСКК безопасна, снижала активность процесса и дальнейшее прогрессирование заболевания на длительный срок, что подтверждено регрессом клинических симптомов и/или стабилизацией состояния у 9 пациентов с СКВ, РА и у всех больных РС. Заключение. Благоприятными факторами, связанными с результатами трансплантации, являются при коллагенозах возраст моложе 35 лет с небольшой длительностью заболевания и умеренными признаками активности болезни; при РС возраст моложе 40 лет с длительностью заболевания менее 10 лет при показателе по расширенной шкале инвалидизации (EDSS) не более 6,5 балла. Имеют значение данные шкалы функциональных систем (FS), длительность первой ремиссии, индекс прогрессирования болезни при различных типах течения РС.

Topics: Adult; Age Factors; Antilymphocyte Serum; Arthritis, Rheumatoid; Cyclophosphamide; Female; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Melphalan; Multiple Sclerosis; Patient Acuity; Retrospective Studies; Transplantation, Autologous; Treatment Outcome; Vidarabine

A 57-year-old Japanese woman with a 5-year history of rheumatoid arthritis (RA) was admitted to our hospital for an evaluation of nephrotic range proteinuria (4.8 g/day). A renal biopsy led to the diagnosis of amyloidosis according to strong positivity for Congo red staining and the detection of microfibrillar structures on electron microscopy that were negative for AA and positive for kappa light chain. Combination therapy with high-dose melphalan and autologous stem cell transplantation was performed according to the regimen for AL amyloidosis. Her proteinuria and RA subsided, but relapsed after 3 years. This is the first report regarding kappa light chain amyloidosis in an RA patient.

Topics: Amyloidosis; Antineoplastic Agents, Alkylating; Arthritis, Rheumatoid; Combined Modality Therapy; Female; Hematopoietic Stem Cell Transplantation; Humans; Melphalan; Middle Aged; Proteinuria

There have been a number of reports on the improvement of concomitant autoimmune disease (AID) after autologous hematopoietic stem cell transplantation (SCT) performed for hematologic malignancy. However, in some cases of hematologic malignancy with AID, exacerbation of AID after autologous SCT has been reported. We have treated 27 adults with multiple myeloma with single or tandem autologous SCT. After peripheral blood stem cells were collected and stored without CD34+ cell selection or T-cell depletion, all patients received melphalan (200 mg/m2) as a conditioning regimen. In 2 patients with a history of AID (one with rheumatoid arthritis [RA] and the other with bullous pemphigoid [BP]) and in 1 patient with Sjögren syndrome, AID recurred 7 to 12 months after autologous SCT. The RA and BP were in durable remission before SCT, and no Sjögren syndrome-related disease activity was clinically documented at the time of SCT. No progression of the myeloma was observed when the AIDs recurred. The patients required systemic steroid therapy for their AID, and successful control of the disease was achieved. Our experience suggests that autologous SCT with unmanipulated stem cells for myeloma is unlikely to cure preexisting AID; rather, the AID may worsen. Transplantation physicians should be aware of this possible complication.

Topics: Aged; Antigens, CD34; Arthritis, Rheumatoid; Autoimmune Diseases; Female; Humans; Lymphocyte Depletion; Male; Melphalan; Middle Aged; Multiple Myeloma; Pemphigoid, Bullous; Peripheral Blood Stem Cell Transplantation; Recurrence; Sjogren's Syndrome; Steroids; Transplantation Conditioning; Transplantation, Autologous

Allogeneic blood stem cell transplantation with reduced conditioning has been proposed as a new, potentially curative treatment option for patients with rheumatoid arthritis (RA). We report a 60-year-old woman with RA and coexisting multiple myeloma who was treated with high-dose melphalan and autologous blood stem cell transplantation (BSCT) followed by a nonmyeloablative allogeneic BSCT from her healthy dizygotic twin brother. She achieved a complete remission of her RA after autologous BSCT, but relapsed early despite complete donor chimerism following successful allogeneic transplantation with reduced intensity conditioning. This case illustrates that allogeneic BSCT following nonmyeloablative conditioning may be an uncertain option for curing patients with RA.

Topics: Arthritis, Rheumatoid; Female; Humans; Melphalan; Middle Aged; Multiple Myeloma; Peripheral Blood Stem Cell Transplantation; Recurrence; Transplantation Conditioning; Transplantation, Autologous; Transplantation, Homologous; Treatment Failure

Although studies of patients with rheumatoid arthritis have found no increases in overall cancer rates, significant elevations in rates of lymphoma and myeloma have been reported, suggesting a causal relationship between autoimmune disorders and lymphoid malignancies. Nevertheless, only 22 cases of concomitant rheumatoid arthritis and multiple myeloma were identified during a retrospective national multicenter study carried out in France. Neither disease exhibited unusual features. In every case, rheumatoid arthritis preceded multiple myeloma. Monoclonal gammopathy preceded multiple myeloma in two patients, by 3 and 7 years respectively. No patient had amyloid arthritis. Analysis of data from the cancer registry of the Somme district in northern France did not suggest a significantly increased risk of multiple myeloma in rheumatoid arthritis patients (relative risk 2.3). Use of interferon alpha to treat myeloma has been reported to exacerbate concomitant autoimmune disorders.

Topics: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Female; France; Health Surveys; Humans; Interferon-alpha; Male; Melphalan; Middle Aged; Multiple Myeloma; Retrospective Studies; Risk

Topics: Adrenal Cortex Hormones; Aged; Arthritis, Rheumatoid; Female; Humans; Melphalan; Multiple Myeloma

Two cases of the development of acute myeloid leukemia (AML) after treatment with alkylating agents are reported. In Case 1, melphalan and then cyclophosphamide had been given for multiple myeloma. 46 months after onset of cytostatic treatment AML occurred, as confirmed cytochemically and by qualitative determination of urinary lysozyme. In Case 2, cyclophosphamide had been given for rheumatoid arthritis. After a latency of 34 months 'smouldering leukaemia' developed with an atypical monocytic leukaemic cell population. In a third case, multiple myeloma and monocytic leukaemia developed synchronously. The causative role of melphalan and cyclophosphamide in the development of AML seems securely established. Despite the risk of alkylating agents in the treatment of multiple myeloma or Hodgkin's disease causing AML, they should not be replaced, as other drugs have been shown to be less beneficial. On the other hand, alkylating agents should be used with great caution in the treatment of non-malignant diseases.

Topics: Aged; Alkylating Agents; Arthritis, Rheumatoid; Cyclophosphamide; Female; Humans; Immunoglobulin G; Leukemia, Monocytic, Acute; Male; Melphalan; Middle Aged; Muramidase; Plasmacytoma; Time Factors

Topics: Adult; Amino Acid Sequence; Amyloid; Amyloidosis; Arthritis, Rheumatoid; Bence Jones Protein; Child; Female; Humans; Immunoglobulins; Melphalan; Microscopy, Electron; Multiple Myeloma; Staining and Labeling; Thyroid Neoplasms; X-Ray Diffraction

Topics: Aged; Animals; Antibodies, Anti-Idiotypic; Arthritis, Rheumatoid; Bence Jones Protein; Cell Division; Chromatography, DEAE-Cellulose; Chromatography, Ion Exchange; Horses; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulin G; Immunoglobulin M; Immunoglobulins; Male; Melphalan; Methylcellulose; Multiple Myeloma; Plasma Cells; Rheumatoid Factor