Antithymocyte globulin in the treatment of gold induced severe aplastic anemia

Severe aplastic anemia is the most serious complication of chrysotherapy. No treatment for this condition has been demonstrated effective. We report 3 patients with gold induced severe aplastic anemia treated with antithymocyte globulin. Complete marrow recovery was obtained in 1 case and a partial but satisfactory response in the other. All the patients remain alive without requiring blood transfusion after followup of longer than 16 months.     

Gold- induced aplastic anemia

Summary Three patients receiving gold salt treatment for rheumatoid arthritis devel oped severe aplastic anemia. All three patients experienced remission of their disease at the time of the occurrence of marrow aplasia. Reviewing data on these patients and recen literature indicate that fatal marrow aplasia seems to occur more frequently in sero-negative women who respond well to therapy with gold salts. Frequent blood monitoring in search for any pronounced or sustained drop in red, white or platelet count, even within normal range could serve as a warning sign for myelotoxicity. Despite intensive supportive measure and specific therapeutic attempts, all three patients eventually died of septic shock.     

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再生障碍性贫血(aplastic anemia,AA)是一组不同病因引起的机体造血功能衰竭综合征,以骨髓造血红髓容量减少和外周血全血细胞减少为特征.患者临床表现为贫血、出血和感染,但发病缓急、病情轻重又不全相同.临床上,全血细胞减少的患者应考虑AA的可能,进一步行骨髓穿刺和骨髓活检常可确诊.     

Danazol as first-line therapy for aplastic anemia

Immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG) plus cyclosporine A (CsA) is the standard treatment for aplastic anemia (AA) patients not eligible for allogeneic hematopoietic stem cell transplantation (HSCT). In the absence of ATG + CsA, androgens continue to be a treatment option. We documented the clinical evolution of AA patients treated with danazol instead of ATG + CsA. AA patients lacking both, human leukocyte antigen-matched donor and access to IST, were treated with danazol and modern support therapy and compared with those receiving a HSCT. Overall survival (OS), response rates, and death risk odds were calculated. Fifty AA patients were studied. Thirteen received a HSCT and 37 danazol and support therapy. Median daily dose of danazol was 400 mg (300 to 600 mg), administered during a median of 12 months. Five-year OS was higher for patients receiving HSCT (92%) compared to the danazol group (41%) (P = 0.001). Overall response rate was 46% (17/37) in the danazol-treated group and the median time to initial response was 3 months (1–27). Tendency to achieve remission was similar among severity groups (P = 0.094). The only adverse side effect recorded on the danazol group was an episode of gastrointestinal bleeding. No patient treated with danazol suffered clonal evolution of his/her disease. Although ATG plus CsA is the therapy of choice for AA patients without a donor when neither HSCT nor IST is available, danazol remains an acceptable therapeutic option for AA patients.     

Marrow transplantation for treatment of pregnancy-associated aplastic anemia

This report describes the results of marrow transplantation in four patients with aplastic anemia during the last trimester of their pregnancies. All patients were treated with supportive care until delivery. Because of persistent severe aplasia, marrow transplantation was then performed 1.6-11.0 months postpartum. Marrow donors were HLA-identical siblings. Although all were at increased risk for graft rejection because of their pregnancies as well as their long transfusion histories, two patients were successfully engrafted and now survive 12 and 95 months after transplant. The other two patients rejected their grafts despite attempts at second or third marrow infusions. Both died of infectious complications, 42 and 111 days after transplant.     

Further studies on experimental benzene induced aplastic anemia

Summary Autoradiographic studies on bone marrow cells of rabbits with benzene induced oancytopenia revealed a severely disturbed DNA and RNA synthesis. Also a high incidence of chromosome aberrations were demonstrated. It is concluded this type of pancytopenia is primarly due to interference of benzene with DNA and RNA synthesis and not to a failure of the hemopoietic stem cell.

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Zusammenfassung Autoradiographische Untersuchungen an Knochenmarkzellen von Kaninchen mit benzolinduzierter Panzytopenie zeigten eine schwer gestörte DNS- und RNS-Synthese. Ebenfalls wurde eine hohe Inzidenz von Chromosomenaberrationen gefunden. Es wird der Schluß gezogen, daß diese Art von Panzytopenie, verursacht durch Benzol, primär eine Störung der DNS- und RNS-Synthese und nicht ein Versagen der hämopoietischen Stammzellen ist.

     

High-dose cyclophosphamide as salvage therapy for severe aplastic anemia

OBJECTIVE: The treatment options for patients with aplastic anemia who do not respond to conventional immunosuppression are limited. The aim of this study was to evaluate high-dose cyclophosphamide in patients with refractory severe aplastic anemia (SAA). MATERIALS AND METHODS: We treated 17 SAA patients with high-dose cyclophosphamide (50 mg/kg/day for 4 consecutive days) who previously did not respond to one or more courses of immunosuppressive therapy. Median age was 31 years (range 6-58); median disease duration was 14 months (range 6-58), and 8 patients met criteria for very severe aplastic anemia (absolute neutrophil count <0.2 x 10(9)/L) at the time of treatment. RESULTS: At median follow-up of 29 months, 10 patients (59%) are alive. Nine patients (53%) achieved a drug-free remission after high-dose cyclophosphamide; 4 patients achieved a complete remission and 5 patients currently meet criteria for a partial remission but continue to improve. One nonresponder to high-dose cyclophosphamide developed paroxysmal nocturnal hemoglobinuria; another nonresponder developed a myelodysplastic syndrome. In responding patients, median time to 500 neutrophils was 54 days (range 35-119), median time to the last platelet transfusion was 99 days (range 51-751), and median time to the last red cell transfusion was 125 days (range 63-796). CONCLUSION: High-dose cyclophosphamide shows promise for salvaging patients with refractory SAA.     

Intensive immunosuppression with antithymocyte globulin and cyclosporine as treatment for severe acquired aplastic anemia

Immunosuppressive therapy can produce hematologic improvement in a large proportion of patients with severe aplastic anemia. Antithymocyte globulin (ATG) is the current treatment of choice for patients who do not have histocompatible sibling donors or who are otherwise inegligible for allogeneic bone marrow transplantation. About 50% of patients respond to an initial course of ATG, and many nonresponders can be salvaged by subsequent treatment with cyclosporine (CsA). To determine whether simultaneous administration of these agents could further improve response rates, we enrolled 55 patients in a therapeutic trial of 4 days of ATG and 6 months of CsA. Among the 51 patients who had not received previous courses of ATG or CsA, 67% had responded by 3 months, and 78% had responded by 1 year (response was defined as an increase in peripheral blood counts sufficient that a patient no longer met the criteria for severe disease). There was a high incidence of relapse (36% actuarial risk at 2 years), but most relapsed patients responded to additional courses of immunosuppression, and relapse was not associated with a significant survival disadvantage. Evolution to myelodysplastic syndromes and acute leukemia was rare (1 of 51 patients), but the later appearance of paroxysmal nocturnal hemoglobinuria was more common (5 of 51 patients). Actuarial survival was 86% at 1 year and 72% at 2 years. These data support the use of a combination immunosuppressive regimen containing both ATG and CsA as first-line therapy for severe aplastic anemia.