Long-term follow-up study of porcine anti-human thymocyte immunoglobulin therapy combined with cyclosporine for severe aplastic anemia.

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.

[Prevalence and features of pathogenic bacteria in the department of hematology without bone marrow transplantation in Peking Union Medical College Hospital from 2010 to 2012].

OBJECTIVE: To investigate the incidence, pathogens, and clinical features of infection in consecutive cases from 2010 to 2012 in Peking Union Medical College Hospital. METHOD: The incidence, pathogen, treatment, and outcomes of patients with hematological diseases who had positive findings of bacterium in their samples from 2010 to 2012 were retrospectively analyzed. RESULTS: There were 449 positive samples (5.8%) from 4 890 patients during this period, among which 388 were proved to be with pathogenic bacteria. Samples separated from patients with community-aquired infections accounted for 8.4% of all positive samples. Most community-aquired infections were caused by Gram-negative bacteria (75%), although no multidrug-resistant bacteria was observed. Samples separated from patients with nosocomial infections accounted for 91.6% of all positive samples. Respiratory tract (49.4%) and peripheral blood (32.6%) were the most common samples with positive results. Skin soft tissues (10.4%), and urine (3.7%) were less common samples. Most of the pathogenic bacteria of the nosocomial infections were Gram-negative (66.9%). The most common Gram-negative bacteria included Escherichia coli (13.8%), Pseudomonas aeruginosa (12.1%), and Klebsiella pneumonia (12.1%), while Staphylococcus aureus (10.4%), Enterococcus faecium (7.0%), and Staphylococcus epidermidis (5.1%) were the most common Gram-positive bacteria. Gram-negative bacteria consisted of most of sputum samples and peripheral blood samples. Samples from the surface of skin wound and anal swab were composed largely by Gram-positive bacteria (63.8%). The detection rates of extended-spectrum beta-lactamase-producing Klebsiella pneumonia/Klebsiella oxytoca, Escherichia coli, and Proteus mirabilis were 24.0%, 87.9% and 38.4%, respectively. The resistance to Acinetobacter baumannii was serious. Multidrug-resistant, extensive drug resistant and pan drug resistant A. baumannii acountted for 74% of all A. Baumannii infections. Stenotrophomonas maltophilia showed low resistance to sulfamethoxazole/trimethoprim, levofloxacin and minocycline. Also, 22 methicillin-resistant Staphylococcus aureus and 9 methicillin-resistant Staphylococcus Epidermidis were detected, which were only sensitive to vancomycin, teicoplanin, and linezolid. All patients were treated in the haematology wards and most of them were under agranulocytosis or immunosuppression. Finally, 22 patients reached clinical recovery through anti-infective therapy, whereas 49 patients died. Among those deaths, 42 patients attributed to severe infections and infection-associated complications. Fourteen of all the deaths might be infected with drug-resistance bacteria. There were 61 samples proved to be bacteria colonization. Nonfermenters such as Acinetobacter baumannii and Stenotrophomonas maltophilia made up for a large amount of bacteria colonization. CONCLUSIONS: The pathogens of nosocomial infections in the hematology ward are mainly Gram-negative bacteria. The incidences and pathogens vary from different infection sites. Nosocomial infection still has a higher mortality rate. Once nonfermenters are detected positive, the pathogenic or colonial bacteria should be distinguished.

[Efficacy and safety of rituximab therapy for refractory/relapsing thrombotic thrombocytopenic purpura].

OBJECTIVE: To evaluate the efficacy and safety of rituximab in treating patients with refractory and/or relapsing thrombotic thrombocytopenic purpura (TTP). METHODS: Totally three patients received rituximab as salvage therapy in our hospital. Rituximab was administered at a weekly dose of 375 mg/m(2) for 2 or 4 consecutive weeks. After clinical remission, patients were followed up every 3 months. RESULTS: All three patients achieved complete remission. The median time to platelet count recovery was 7 days (4-12 days) after the first rituximab infusion. During the follow-up (median: 12 months; range: 9-18 months), no patients experienced relapse. No side effect was noted during treatment and follow-up period. CONCLUSION: Therapy with rituximab is effective and well tolerated for patients with refractory or relapsing TTP.

[Comparison of efficacy and adverse effects between arsenic trioxide and all-trans retinoic acid in patients with acute promyelocytic leukemia].

OBJECTIVE: To compare the efficacy and adverse effects between arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) in patients with acute promyelocytic leukemia (APL). METHODS: The clinical data of 71 patients with newly diagnosed APL were retrospectively analyzed. Two groups were classified according to the induction regimens, namely ATO group (n = 41) and ATRA group (n = 30). The complete remission (CR) rate and the time to CR were compared between these two groups. RESULTS: The CR rate was 97.5% in ATO group and 93.3% in ATRA group (P > 0.05). The median time to CR was 29 days (21-45 days) in ATO group, which was significantly shorter than 38.5 days (24-63 days) in ATRA group (P < 0.001). Retinoic acid syndrome occurred in 52.9% of patients treated with ATRA, which affected the further use of ATRA. CONCLUSIONS: Both ATO and ATRA have high response rates for newly diagnosed patients with APL. Compared with ATRA, ATO induction therapy has shorter time to achieve CR and less adverse effects, and therefore may be the first-line therapy for APL.

[Clinical features of invasive pulmonary fungal infection secondary to malignant blood diseases].

OBJECTIVE: To summarize the clinical features of invasive pulmonary fungal infection (IPFI) secondary to malignant blood diseases (MBD). METHODS: We retrospectively analyzed the clinical data of 52 patients with IPFI secondary to MBD admitted to Peking Union Medical College Hospital from January 1995 to December 2008. RESULTS: The incidences of IPFI secondary to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma (NHL), and aplastic anemia (AA) were 4.6%, 3.2%, 2.8%, and 2.5%, respectively. In patients with IPFI secondary to AML, 88.5% (23/26) of the patients suffered from the infections during the non-remission (NR) period (including relapse), and 11.5% (3/26) in the complete-remission (CR) period. In all the patients with IPFI secondary to malignant blood diseases, 86.5% (45/52) of MBD were neutropenic or agranulocytic, and 67.3% (35/52) had been treated with broad-spectrum antibiotics for more than 96 hours before anti-fungal therapy. The total mortality after anti-fungal therapy was 13.7% (7/51). More than half of patients with fluconazole or itraconazole as the first-line therapy had to switch to other medicines because of poor infection control. CONCLUSIONS: IPFI secondary to MBD is most common in AML patients. Patients with NR of AML, neutropenia or agranulocytosis, and long-term broad-spectrum antibiotics usage are susceptible to IPFI. Fluconazole and itraconazole have low efficacy, and other more potent anti-fungal medicines should be considered.

[Infection pathogen analysis of 2388 patients in an open hematology ward from 1993 to 2004].

OBJECTIVE: To investigate the incidence of infection and pathogens in hematology ward. METHODS: The data of incidence, pathogen, and outcome of infection of 2388 hospitalized patients in an open hematology ward of Peking Union Medical College Hospital from 1993 to 2004 were analyzed retrospectively. RESULTS: The overall incidence of infection was 34.3% according to the person-times of hospitalization, 24.4% for nosocomial infection and 9.9% for community-acquired infection. Most of the pathogenic bacteria of the nosocomial infection were Gram negative. The most common bacteria in the sputum samples included Enterobacter (27%), Pseudomonas aeruginosa (16%) and coagulase negative Staphylococcus (MRSCoN, 12%), the most common bacteria in the blood samples included Escherichia coli (43%), Enterobacter cloacae (11%), and Klebsiella (11%). Whereas in the community-acquired infection the most common bacteria in the sputum samples were Haemophilus parainfluenzae (15%), MRSCoN (28%), and Staphylococcus epidermidis (10%), and the most common bacteria in the blood samples were MRSCoN (28%), E. coli (28%), and Klebsiella (9.4%). Fungi were more often found in nosocomial infection, especially in the sputum samples. 12-year follow up showed that in nosocomial infection Pseudomonas aeruginosa remained the most common bacteria in the sputum samples, whereas E. coli and Enterobacter cloacae became the major bacteria in the blood samples. In community-acquired infection, the proportion of Staphylococcus aureus, that of Klebsiella in blood samples, and that of E. coli in throat swab samples increased in recent years. The incidence of fungi infection had increased in both nosocomial infection and community acquired infection. The mortality of nosocomial infection was 6.1%, higher than that of the community-acquired infection, however, not statistically significant (P = 0.17). There was a trend of decrease in the mortality of community-acquired infection but did not in the nosocomial infection. CONCLUSION: The patients in hematology ward are susceptible to infection, especially nosocomial infection that has a higher mortality rate in comparison with the community-acquired infection, however, not statistically significant. The pathogens of nosocomial infection are most likely G- bacteria, fungi and other bacteria resistant to most antibiotics. The mortality rate of nosocomial infection remains almost unchanged in the 12-year follow up.

Multiple cycles of recombinant human thrombopoietin therapy in a patient with chronic refractory idiopathic thrombocytopenic purpura.

We describe a 41-year-old woman with chronic idiopathic thrombocytopenic purpura who received recombinant human thrombopoietin (rhTPO) therapy. rhTPO was administrated subcutaneously at a dosage of 1.0 mug/kg daily for a maximum of 14 days until the platelet count was more than 50 x 10/l. The patient received three cycles (six, 13, and eight doses each) of rhTPO, each initiated when the platelet counts was less than 10 x 10/l. The platelet count increased to above 50 x 10/l on days 5, 11 and 8, and peaked at 456 x 10/l, 130 x 10/l and 82 x 10/l on days 9, 15 and 13 in the three respective cycles, each followed by a gradual decline. The durations of platelet counts at more than 50 x 10/l in the three cycles were 13, 7 and 10 days, respectively. rhTPO was well tolerated with no adverse event observed. Antibodies to rhTPO by enzyme-linked immunosorbent assay were not detected. Our observations suggested that rhTPO could transiently increase the peripheral platelet count in patients with chronic refractory idiopathic thrombocytopenic purpura. The reasons why the peak platelet counts decreased and the duration of response shortened after successive cycles of treatment were unclear.

[Clinical features of 76 Chinese patients with paroxysmal nocturnal haemoglobinuria].

OBJECTIVE: To further analyse the relationship between the new technology and clinical characteristics in paroxysmal nocturnal haemoglobinuria (PNH) patients, and summarize the data of PNH during the past 15 years in China. METHODS: 76 consecutive patients with PNH diagnosed in Peking Union Medical Colleague Hospital from 1997 - 2011 retrospectively. RESULTS: Most of the patients were diagnosed based on flow cytometric data. There were 46 male and 30 female patients. The median age at diagnosis was 40 (10 - 74). 46 (60.5%) patients presented with classical PNH, 16 (21.1%) pancytopenia, and 14 (18.4%) thrombosis. Anatomic locations of first thrombosis were intra abdominal in 7 patients, lower extremities in 3 patients, intracerebral in 2 patients, and pulmonary thrombosis in 2 patients. The size of PNH clone at first determination (shown by CD55 and CD59 negative percentage) was (61.23 ± 27.47)% and (60.24 ± 25.59)% on neutrophils; (34.24 ± 25.50)% and (32.22 ± 23.12)% on erythrocytes, respectively. The mean LDH level was (1199.2 ± 893.5) U/L. In our cohort, 13(17.0%) patients suffered from renal deficiency, 12 (15.8%) patients cholecystolithiasis, 10 (13.2%) patients hemorrhage and 9 (11.8%) patients infections. In a median of 7-year (range 0.5 - 20 years) follow-up (68 patients), 2 (2.9%) patients developed into myelodysplastic syndromes/ acute myeloid leukemia, 1(1.5%) patient ovary cancer, 11(14.5%) patients died. Patients with thrombosis had higher percentage of CD59 negative neutrophils \[(73.45 ± 22.32)%\] compared with those without thrombosis \[(58.3 ± 20.2)%\] (P < 0.05). CONCLUSIONS: The cohort had higher percentage of classical hemolysis, thrombosis and renal dysfunction compared with previous reports in China. Patients with thrombotic events had higher percentages of CD55 and CD59 negative neutrophils.

[Porcine anti-human lymphocyte globulin plus cyclosporine A therapy for severe aplastic anemia].

OBJECTIVE: To evaluate the efficacy of porcine anti-human lymphocyte globulin (P-ALG) plus cyclosporine A (CsA) therapy for severe aplastic anemia (SAA). METHODS: Forty-eight SAA patients (31 males, 17 females) including 17 very severe aplastic anemias (vSAA) were treated with ALG plus CsA between 1999 to 2009 in our hospital and the outcomes were analyzed retrospectively for early mortality, response rate and quality, survival rate, toxicity and complications. RESULTS: The median age was 28 (13 - 64) years. The interval from diagnosis to treatment was 45 days. The median neutrophil count at diagnosis was 0.178 × 10(9)/L. Overall response was 83.3% (54.2% complete, 29.2% partial) with a median time of 90 (23 - 380) days. 10.4% died of infection within 30 days mainly of fungi infection. Only 1 patient relapsed 2 years after treatment. No clonal disease was found. The 1.5-year survival rate was 87.5%. vSAAs had less response, higher early mortality and less survival (64.7%, 29.4% and 51.8%, respectively) compared to that of SAA (93.5%, 0, 100%, respectively, P < 0.05). Grouped patients with different age, gender, intervals between diagnosis and treatment and pre-existing infections had similar response. The main side effects were fever and skin rash (52.1%), serum sickness (16.7%), impaired liver function (60.4%) and hemorrhage (2.1%). No treatment-related mortality was found. CONCLUSION: P-ALG plus CsA is an ideal and well tolerated treatment for SAA but not for vSAA.