Once-weekly prophylactic treatment vs. on-demand treatment with nonacog alfa in patients with moderately severe to severe haemophilia B.

INTRODUCTION: Limited data are available on optimal prophylaxis regimens of factor IX (FIX) replacements for patients with haemophilia B. AIM: This multicentre, open-label study evaluated the efficacy and safety of once-weekly prophylaxis with nonacog alfa compared with on-demand treatment in adolescent and adult patients. METHODS: Males aged 12-65 years with moderately severe to severe haemophilia B (FIX:C ≤ 2%) were eligible for enrolment. Patients received on-demand treatment for 26 weeks, followed by once-weekly prophylaxis of 100 IU kg(-1) for 52 weeks. The primary efficacy end point was the annualized bleeding rate (ABR). Secondary end points included response to on-demand treatment, the number of infusions used to treat bleeding events, and the incidence of less-than-expected therapeutic effect (LETE). FIX:C was measured on day 1 and at weeks 26 and 78. RESULTS: Mean (±SD) ABR was lower during prophylaxis vs. on-demand treatment [3.6 (±4.6) vs. 32.9 (±17.4) events, respectively; P < 0.0001]. The majority (88.4%) of bleeding events had excellent or good responses upon the first infusion; 82.1% of events responded to the first infusion. No incident of LETE occurred. No thrombotic events or FIX inhibitors were reported. Eight of 17 FIX:C approximately 1 week after dosing were >2 IU dL(-1) (min-max of 2.13-10.39 IU dL(-1) ). CONCLUSIONS: Once-weekly prophylaxis of 100 IU kg(-1) was associated with lower ABR compared with on-demand treatment in adolescents and adults with moderately severe to severe haemophilia B. Once-weekly prophylaxis was well tolerated, with a similar safety profile as that reported during the on-demand treatment period. Residual FIX:C may be supportive of effectiveness.

New quantitative aPTT waveform analysis and its application in laboratory management of haemophilia A patients.

Diagnosis of haemophilia A is usually made by the measurement of factor VIII (FVIII) activity that allows categorization of the disease severity. However, tests that assess global haemostasis may better reflect clinical features and give additional clinically relevant information. The aim of this study was to develop a new quantitative activated partial thromboplastin time (aPTT) waveform analysis and compare it with FVIII activities to find out whether waveform parameters are superior determinants of clinical phenotype. A total of 81 haemophilia A patients divided into two groups (37 severe, 44 non-severe) were included in the study. The control group comprised 101 healthy male volunteers. Quantitative aPTT waveform analysis was performed with Actin FS on BCS (Siemens Healthcare Diagnostics, Marburg, Germany) using three parameters (DELTA, RATIO-1, RATIO-2) obtained from a single aPTT measurement with two evaluation modes. FVIII activities were measured by one-stage clotting and two-stage chromogenic assay. Statistically significant difference (P < 0.001) between control group and all haemophilia A patients, as well as between severe and non-severe haemophilia A patients was obtained for all quantitative waveform parameters. Our study revealed parameter DELTA as the best waveform parameter, showing significant correlation with FVIII activities and clinical parameters, and excellent performance for distinguishing between severe and non-severe haemophilia A patients (ROC analysis: sensitivity 97.3%, specificity 93.2%). The results obtained by new quantitative aPTT waveform analysis were superior to those obtained by standard laboratory methods. The simplicity and cost-benefit of the method make this approach a reasonable and promising tool for assessing coagulation in haemophilia A patients.

Long-term results of conventional-dose salvage chemotherapy in patients with refractory and relapsed Hodgkin's disease (Croatian experience).

BACKGROUND: The aim of this study was to analyze outcome of patients with Hodgkin's disease (HD) in whom first-line chemotherapy with mustine/vincristine/procarbazine/prednisone (MOPP) had failed. PATIENTS AND METHODS: From January 1982 to December 1989 among 210 patients treated with MOPP and radiotherapy to initial bulky sites, 65 patients were primary refractory to or relapsed after initial treatment. RESULTS: Twenty-nine of 65 patients (44%) were primary refractory to initial chemotherapy, 20 relapsed within 12 months after complete remission (CR) and 16 relapsed after CR that lasted more than 12 months. Patients with primary refractory HD and early relapse (<12 months after CR) were treated with doxorubicin/bleomycin/vinblastine/darcarbazine. In patients with late relapse (>12 months after CR) MOPP was repeated. The median follow-up for all patients was 115 months. The overall response rate was 63%. Thirty-three patients (51%) achieved a second CR and eight patients (12%) partial response. Remission rate was greatest in patients with late relapse (CR >12 months) (75 versus 55% for early relapse versus 35% for primary refractory HD) (P <0.01). At 10 years, overall and failure-free survival rates were 21 and 16%, respectively. Patients who were in first remission longer than 12 months had a superior overall survival (37 versus 18% for early relapse) and failure-free survival (24 versus 10% for early relapse). No patient with primary refractory HD was alive beyond 52 months after initial treatment failure (P <0.01). Main prognostic factors were duration of the first remission and tumor bulk at relapse. CONCLUSIONS: Our results confirm previous observations that a significant proportion of patients with HD who experience induction treatment failure cannot be cured with conventional treatment and probably need more aggressive therapy.

Decreasing risk of viral transfusion-transmitted diseases in Croatia.

AIM: To assess the risk of viral transfusion-transmitted infections in Croatia. METHODS: The following parameters were analyzed: frequency of blood donations repeatedly reactive for HBsAg and anti-HCV (1993-1999); blood donations confirmed positive for HBsAg and anti-HCV (1997-1999), anti-HIV1/2, and syphilis reactivity (1993-1999); number of registered patients with hepatitis B and C; transfusion-associated hepatitis B and hepatitis C; and frequency of HBV, HCV and HIV markers in patients with congenital bleeding disorders (1993-1998). RESULTS: The frequency of repeatedly reactive HBsAg and anti HCV markers and confirmed positive HBsAg, anti-HCV, and syphilis markers in donors blood decreased during the study, whereas the frequency of anti-HIV1/2 positivity did not change. The frequency of confirmed positive donors in 1999 was 0.068% for HBsAg, 0.035% for anti HCV, 0.002% for anti HIV1/2, and 0.0056% for syphilis. The number of patients with hepatitis B, hepatitis C, and transfusion-associated hepatitis B and C steadily decreased during the 1993-1998 period. The number of transfusion-associated hepatitis patients leveled off in 1997. From the beginning of the follow-up of AIDS patients in 1987, only 7 (2%) of hemophiliacs have been HIV-infected, all before 1990 and due to non-inactivated coagulation factor concentrates. There were no cases of transfusion-associated HIV2 infection in patients with congenital bleeding disorders or transfusion-associated HIV1 infection through transfusion of labile blood components. CONCLUSION: The safety of transfusion therapy in Croatia has improved, and the present risks of viral transfusion transmitted diseases are very low.

Donor buffy-coat infusion and chemotherapy for leukemia in relapse after marrow transplantation.

A patient relapsing with blastic lymphoid transformation of chronic myeloid leukemia after bone marrow transplantation received donor buffy-coat infusion. Low-dose chemotherapy was added because of a rapid WBC increase. Complete hematologic and cytogenetic remission was obtained. The patient remained in complete hematologic and cytogenetic remission for four months until he died in an accident. Two patients with acute leukemia failed to respond to a similar treatment.

[The combined immunoenzyme test: anti-HIV-1 and -2 and anti-HTLV-1 in the detection of donors with retrovirus infections]. / Ispitivanje kombiniranog enzimskog imunoloskog testa: anti-HIV 1/2 i anti HTLV-1 u otkrivanju davatelja zarazenih retrovirusima.

Serums of whole blood donors, plasma donors, hemophiliacs, persons with risks behavior and normal population simultaneously were tested for markers of infectious diseases, anti-HIV-1 with Plivazim and anti-HIV-1/2 and anti-HTLV-1/2 with Roche Retrovirus EIA. The positive results were confirmed by immunofluorescence assay and Western blot. Nonspecific reactive serums were detected by Roche Retrovirus EIA and by Plivazim EIA, but there was no significant difference in the frequence of reactive results. Roche Retrovirus EIA test had specificity of 99.16% and sensibility of 97.56% as compared to Plivazim. Simultaneous testing of donors with a combined test for anti-HIV-1/2 and anti-HTLV-1 is equally reliable as testing with only anti-HIV-1.

Antilymphocyte globulin for treatment of pure red cell aplasia after major ABO incompatible marrow transplant.

A patient developed pure red cell aplasia after ABO incompatible BMT for leukemia. He did not respond to plasma exchange. Antilymphocyte globulin therapy was followed by complete and permanent erythroid recovery with disappearance of recipient-derived isoagglutinins.