melphalan and Lupus-Erythematosus--Systemic

The association of systemic lupus erythematosus (SLE) and multiple myeloma (MM) is an uncommon event. We report the relapse of SLE in a patient with a previous history of MM, treated with chemotherapy and, subsequently, with alpha-2b interferon (alpha-2b IFN) as a maintenance therapy. The case is discussed in light of past relevant literature.. The history and clinical, laboratory and radiographic findings of the patient, as well as the subsequent therapeutic approach are discussed. In our review of the literature, journal articles are identified by Medline search.. We describe the case of a woman who developed a multiple myeloma 14 years after a diagnosis of SLE. A careful literature review confirms that the association of these two diseases has been reported only in a few cases. When the plasma cell neoplasia occurred, SLE had been quiescent for several years; the patient was treated with prednisone-melphalan and, subsequently, with alpha-2b IFN as a maintenance therapy. On admission to our department, SLE was in a relapse phase, probably because of IFN treatment. The disease was poorly responsive to steroid therapy and required the use of cytotoxic drugs.. The coexistence of SLE and MM is very rare and the possible pathogenetic mechanisms underlying this association remain unclear. The use of interferon in a patient with an autoimmune disease always invites caution.

Topics: Antineoplastic Agents; Cyclophosphamide; Female; Humans; Interferon alpha-2; Interferon-alpha; Lupus Erythematosus, Systemic; Melphalan; Methylprednisolone; Middle Aged; Multiple Myeloma; Recombinant Proteins; Recurrence

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

To investigate the presence of a host-encoded superantigen as possible etiologic factor in pediatric rheumatic disease. We measured the expression and the ability of interferon-alpha (IFN-alpha) to induce the human endogenous retrovirus HERV-K18 superantigen in juvenile rheumatoid arthritis (JRA) and pediatric systemic lupus erythematosus (SLE).. Expression levels of HERV-K18 were measured in peripheral blood or synovial fluid mononuclear cells (SFMC) from 13 patients with JRA, 11 pediatric SLE patients, and 24 healthy controls, by semiquantitative reverse transcription-polymerase chain reaction, comparing 18S ribosomal transcripts as endogenous standard. IFN-alpha induction was tested by pretreatment of samples with 2000 U/ml.. HERV-K18 expression was significantly elevated in peripheral blood from patients with JRA (mean ratio of HERV-K18 to 18S ribosomal transcripts 2.456, SD 2.122; p = 0.014), but not patients with SLE (mean 0.997, SD 0.579; p = 0.258), compared to controls (mean 0.749, SD 0.598). HERV-K18 transcripts were detected in SFMC of 7/7 JRA patients. IFN-alpha induced HERV-K18 strongly in JRA (mean fold induction = 8.934, SD 15.556) and controls (mean 8.270, SD 6.609), but weakly in SLE (mean 2.432, SD 2.219; p = 0.009). HERV-K18 levels were found to be independent of previously determined modifiers of expression, including Epstein-Barr virus infection, IFN-alpha levels, or the percentage of B cells in peripheral blood.. HERV-K18 superantigen levels were elevated in JRA patients, but not pediatric patients with SLE, suggesting a possible mechanism for autoimmunity in the former group by superantigen stimulation of autoreactive T cells.

Topics: Adolescent; Arthritis, Juvenile; Biomarkers; Case-Control Studies; Child; Child, Preschool; Cohort Studies; DNA, Viral; Endogenous Retroviruses; Enzyme-Linked Immunosorbent Assay; Female; Flow Cytometry; gamma-Globulins; Humans; Immunotoxins; Lupus Erythematosus, Systemic; Male; Melphalan; Probability; Prognosis; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Sensitivity and Specificity; Severity of Illness Index; Superantigens

A case of systemic lupus erythematosus (SLE) complicated by multiple myeloma is presented. The lupus diagnosis was established together with the diagnosis of myeloma but the symptoms had commenced a few years before. The putative mechanisms underlying this unusual combination are discussed.

Topics: Aged; Chloroquine; Female; Humans; Lupus Erythematosus, Systemic; Melphalan; Multiple Myeloma; Paraproteinemias; Prednisone

Topics: Adult; Chlorambucil; Female; Humans; Lupus Erythematosus, Systemic; Lymphoma; Melphalan

A patient with a 20-year history of clinical systemic lupus erythematosus (SLE) who later developed multiple myeloma is described. SLE was diagnosed on the basis of a butterfly rash, photosensitivity, nondeforming arthritis, pleuropericarditis, and alopecia. However, the patient has never had LE cells, antinuclear antibody, or depressed complement. The patient was treated with intermittent courses of corticosteroids over a 20-year period with good results. Multiple myeloma, diagnosed by bone marrow biopsy, has responded favorably to therapy with L-phenylalanine mustard and prednisone.

Topics: Adrenal Cortex Hormones; Adult; Bone Marrow; Drug Therapy, Combination; Female; Humans; Lupus Erythematosus, Systemic; Melphalan; Middle Aged; Multiple Myeloma; Prednisone; Skin

Topics: Adolescent; Adult; Antibody Formation; Azathioprine; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Lupus Erythematosus, Systemic; Male; Melphalan; Methotrexate; Middle Aged; Prednisone

Topics: Adenoma; Adolescent; Adult; Aged; Anemia, Hypochromic; Anemia, Macrocytic; Anemia, Sideroblastic; Blood Protein Disorders; Chlorambucil; Female; Hemoglobinometry; Humans; Immunosuppressive Agents; Kidney Neoplasms; Leukemia; Lupus Erythematosus, Systemic; Male; Melphalan; Multiple Myeloma; Polycythemia; Pyridoxine; Waldenstrom Macroglobulinemia

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: Adolescent; Antibodies, Antinuclear; Autoantibodies; Betamethasone; Female; Hepatitis; Humans; Immune Tolerance; Immunosuppressive Agents; Kidney Diseases; Lupus Erythematosus, Systemic; Melphalan; Methotrexate; Neutrophils; Prednisone; Splenectomy

Topics: Antimitotic Agents; Humans; Lupus Erythematosus, Systemic; Melphalan