Objective: To evaluate the treatment efficacy and tolerance of anti-human T lymphocyte porcine immunoglobulin (p-ALG) plus cyclosporine A (CsA) in acquired severe aplastic anemia (SAA). Method: Forty-eight SAA patients [31 males and 17 females; 17 with very SAA (VSAA)] were treated with p-ALG plus CsA and were analyzed retrospectively according to early mortality, response rate and quality, survival rate, toxicity, and complications. They were stratified further by gender, age, disease severity, interval from diagnosis to treatment, and preexisting infections. Result: The median age was 28 years (range 13–64). The interval from diagnosis to treatment was 45 days. The median neutrophil count was 0.178 × 10⁹/l. The overall response was 83.3% (54.2% complete and 29.2% partial) with a 90-day median time (range 23–380), and 10.4% died of infection within 30 days. The 1.5-year survival was 87.5%. vSAA patients had less response, a higher early mortality, and less survival (64.7, 29.4, 51.8%) compared to SAA patients (93.5, 0, and 100%, respectively; p < 0.05). Groups with different age, gender, intervals between diagnosis and treatment, and preexisting infections had the same response. Mild toxicities were observed. Conclusion: p-ALG plus CsA is a reliable and well-tolerated treatment for SAA, and it has the great advantage of a much lower cost compared to horse/rabbit ATG. VSAA was a poor predictive factor for the response rate.

Immunosuppressive therapy with antithymocyte immunoglobulin (ATG) and cyclosporine A is the first treatment option for severe aplastic anemia (SAA) patients without transplantation. Horse ATG is not marketed in China. Because the price of porcine ATG (pATG) is only about one-third of the price of rabbit ATG (rATG), long-term follow-up studies of pATG's efficacy will help provide valuable insights into the treatment of SAA. Retrospective studies were performed to analyze the clinical information of 102 SAA patients treated with pATG and cyclosporine A from 1999 to 2014 in Peking Union Medical College Hospital. The median age was 29 years old (range 12-72). Median follow-up time was 59.6 months (0.2-176.8). The overall response rate was 74.5% (CR 42.1%, PR 32.4%). The recurrence rate was 9.9%. The mortality rate was 16.7%. The median survival time has not been reached, and the 5-year survival rate was 81.8%. Other hematologic abnormalities were observed in 7.8% of patients, including symptomatic PNH, MDS, and AML. Multivariate analysis revealed there was no significant effect on survival by factors such as gender, age, severity of disease, treatment time, and PNH clone (P > 0.05). These data have indicated pATG therapy combined with cyclosporine A has significant long-term efficacy and high overall survival in SAA.

Thrombopoietin (TPO) is the key regulator of megakaryocytepoiesis and platelet production. TPO binds to its specific receptor, c-Mpl, on the surfaces of megakaryocytes, and may promote the proliferation, differentiation and maturation of megakaryocytes, and finally increase the circulating platelet count. The role of TPO in the pathogenesis of idiopathic thrombocytopenic purpura (ITP) is not certain. Plasma concentrations of TPO in ITP patients were similar to or little lower than that in healthy subjects. Therefore it is possible that supplemental TPO could significantly promote platelet production and increase platelet counts in ITP patients. Here, we report the result of multiple cycles of recombinant human thrombopoietin (rhTPO) therapy in a patient with refractory ITP. The patient, a 42-year-old woman, was admitted to our department on December 30, 2003. She had suffered from chronic ITP for more than 4 years. The patient had been treated with glucocorticosteroids, immunosuppressive agents and splenectomy. No sustained response could be achieved. The diagnosis of chronic refractory ITP was made. There were petechiae and gingival bleeding on admission. Liver and spleen were not palpable. Hemoglobin was 142g/L, white blood cell count 7.6×10 9/L, platelet count 15×10 9/L. Bone marrow aspiration revealed that erythroid and myeloid development were normal, megakaryocytes were increased in number and no dysplastic features. After an informed consent was obtained from the patient, rhTPO (Sunshine Pharmaceutical Corporation, China) was administrated subcutaneously at dosage of 1.0 μg/kg, daily for 14 days or until platelet count sustained more than 50×109/L. Anti-rhTPO antibodies were determined weekly by ELISA. Three cycles of rhTPO therapy was given with 6, 13 and 8 dosing for each cycle. The platelet counts before each cycle were all less than10×109/L and increased above 50×109/L on day 5, 11 and 8 of rhTPO administration, respectively. The peak platelet counts of 456, 130 and 82×109/L were reached on day 9, 15 and 13 for each cycle. Then platelet count decreased gradually. The durations of platelet count more than 50×109/L in 3 cycles were 13, 7 and 10 days respectively. No increase of WBC count and Hb level occurred. No liver and kidney function damage, abnormal coagulation functions or thrombosis developed during the treatment. rhTPO antibodies were not detectable. The result indicated that rhTPO could transiently increase peripheral platelet counts of the patient with chronic refractory ITP. It was uncertain why peak platelet counts declined and durations of platelet count more than 50×109/L shortened when multiple cycles of rhTPO were given.