Clinical experience with moroctocog alfa (AF-CC) in younger paediatric patients with severe haemophilia A: Two open-label studies.

INTRODUCTION: The pharmacokinetics (PK), efficacy and safety of moroctocog alfa (AF-CC) have been demonstrated in haemophilia A patients aged ≥6 years. AIM: These studies aimed to further describe moroctocog alfa (AF-CC) experience in paediatric patients (<12 years) with severe haemophilia A (FVIII:C < 1%). METHODS: Two prospective, open-label studies enrolled patients aged <12 years: one study with 37 previously treated patients (PTPs) and another with 23 previously untreated patients (PUPs). All patients initially received 50 IU/kg of moroctocog alfa (AF-CC) to evaluate either recovery alone, or with other PK parameters (6 to <12 years) before continuing treatment for 100 exposure days (EDs) or 24 months. RESULTS: At baseline, mean (±SD) recovery ranged between 1.32 ± 0.65 (PUPs aged <2 years) and 2.13 ± 0.82 (PTPs aged 6 to <12 years). The mean (±SD) half-life was 9.12 ± 1.94 hours in PTPs aged 6 to <12 years. No new safety signals were detected in either study, 2 transient lower titre inhibitors occurred in PTPs while 8 inhibitors (3 low and 5 high titre) were detected in PUPs. Most bleeding episodes resolved with one infusion (94% [893/954]). The annualised bleeding rate (ABR) in the PTP study was 27.5 and 4.2 for patients reporting an on-demand and routine prophylaxis regimen at baseline, respectively. In the PUP study, the overall ABR was 5.9. CONCLUSION: Moroctocog alfa (AF-CC) had expected PK findings (lower recovery in young children compared with older children) along with being safe and efficacious in a population of young severe haemophilia A patients.

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.

Lack of seasonal variation in bleeding and patient-assessed pain patterns in patients with haemophilia B receiving on-demand therapy.

Spontaneous haemorrhage in patients with haemophilia is generally considered to occur randomly and without a predictable temporal or seasonal pattern; however, there is a lack of evidence in the literature on the effects of weather, temperature and atmosphere on bleeding episodes. This post hoc analysis of a multicentre, open-label crossover study examined the influence of seasonality on bleeding frequency and patient-assessed pain in patients with moderately severe and severe (FIX C ≤ 2%) haemophilia B. Fifty patients were enrolled and treated on-demand for 16 weeks; 47 were subsequently randomized to one of two prophylactic regimens (nonacog alfa 100 IU kg(-1) once weekly or 50 IU kg(-1) twice weekly) for 16 weeks. Patients then underwent an 8-week washout period of on-demand therapy before being crossed over to the other prophylactic regimen for 16 weeks. Bleeding episodes during the on-demand treatment periods were analysed. To assess for temporal trends, data were graphed as scatter plots. The primary end point was the annualized bleeding rate (ABR). Additional measures included raw and median pain scores during every joint bleeding event (spontaneous or traumatic), with pain scored using the Brief Pain Inventory (0 = 'no pain' to 10 = 'pain as bad as you can imagine'). The observed ABRs during the on-demand periods showed no distinguishable trend over time. Analysis of pain associated with joint bleeding episodes also did not demonstrate any discernible temporal trend. No apparent seasonal variation in bleeding pattern or patient-reported pain was observed in this analysis of patients with haemophilia B.

Multicentre, randomized, open-label study of on-demand treatment with two prophylaxis regimens of recombinant coagulation factor IX in haemophilia B subjects.

Few randomized studies have reported on the use of factor IX (FIX) for secondary prophylaxis in haemophilia B patients. This study aimed to evaluate the efficacy and safety of two secondary prophylaxis regimens of recombinant coagulation FIX, nonacog alfa, compared with on-demand therapy. Male subjects aged 6-65 years with severe or moderately severe haemophilia B (FIX:C ≤ 2, n = 50) and ≥12 bleeding episodes (including ≥6 haemarthroses episodes) within 12 months of study participation were enrolled in this multicentre, randomized, open-label, four-period crossover trial. The primary measure was the annualized bleeding rate (ABR) of two prophylactic regimens vs. on-demand therapy. In the intent-to-treat group, mean ABR values were 35.1, 2.6 and 4.6 for the first on-demand period, the 50 IU kg(-1) twice-weekly period, and the 100 IU kg(-1) once-weekly period respectively. Differences in ABR between the first on-demand period and both prophylaxis regimens were significant (P < 0.0001); no significant differences were observed between prophylaxis regimens (P = 0.22). Seven serious adverse events occurred in five subjects, none related to study drug. Results demonstrated that secondary prophylaxis therapy with nonacog alfa 50 IU kg(-1) twice weekly or 100 IU kg(-1) once weekly reduced ABR by 89.4% relative to on-demand treatment. Both prophylaxis regimens demonstrated favourable safety profiles in subjects with haemophilia B.

A prospective registry of European haemophilia B patients receiving nonacog alfa, recombinant human factor IX, for usual use.

Nonacog alfa, a recombinant factor IX (FIX) used for the treatment of haemophilia B, was approved in Europe in 1998. In accordance with European Medicines Agency requirements, a registry study was conducted from 2002 to 2009. A reformulated iso-osmotic version was approved for European use in 2007. This study was conducted to evaluate the safety of nonacog alfa in a usual care setting, and provide clinical trial and postmarketing surveillance data support. This open-label, non-interventional, prospective observational cohort study (registry) comprised 52 sites in nine European countries. Patients with haemophilia B receiving nonacog alfa in either formulation for prevention or treatment were followed on a usual care schedule. A total of 218 patients were enrolled, of whom 66 (30.3%) were <18 years of age. Haemophilia severity was evenly distributed, with baseline FIX activity of <1%, 1-5% and >5% in 33.3%, 36.6% and 30.1% of patients, respectively. One hundred thirty-eight patients received the original formulation alone; 80 switched to or received only the new formulation. There was a low incidence of events of special interest (ESIs), with less-than-expected therapeutic effect in five patients (2.2%), inhibitor development in two (0.9%), thrombosis in one (0.5%) and allergic events in eight (3.7%). These accounted for the majority of the 15 serious AEs reported in six patients. Six patients discontinued because of AEs, primarily related to hypersensitivity. Nonacog alfa was shown to be safe for the treatment of haemophilia B, with a low incidence of serious AEs and ESIs.

Interferon DNA polymorphism in chronic leukemia.

The interferon (IFN) system (alpha, beta and gamma IFNs) is closely related to the first line of defenses against viral and tumoral diseases. Chronic leukemic and chronic lymphoproliferative patients respond in variable degrees to therapy with exogenous IFN. Remission after treatment with IFN-alpha in hairy cell leukemia (HCL) and in chronic myelogenous leukemia (CML) have been reported by other authors. In order to determine whether there are differences in IFN-alpha and beta genes between healthy and chronic leukemic individuals and among the different chronic leukemic patients, restriction fragment length polymorphism (RFLP) analyses was performed in a panel of patients with HCL, CML and chronic lymphocytic leukemia (CLL), and in a sample of healthy individuals. A significant difference in the allelic frequencies for the IFN-beta and Sst I enzyme in Chronic leukemias, mainly of myeloid origin, compared with the healthy individuals, was found.

Phase II trial of recombinant interferon-alpha2b in patients with advanced intractable multidrug-resistant pulmonary tuberculosis: long-term follow-up.

SETTING: Multidrug-resistant tuberculosis patients without human immunodeficiency virus (HIV) infection, with Mycobacterium tuberculosis resistant to almost all of the available drugs. OBJECTIVE: Limited phase II trial with recombinant interferon-alpha2b in five chronic multidrug-resistant tuberculosis patients. METHODS: Three million units of r-IFN-alpha2b were administered subcutaneously every week for 12 weeks. Before and after treatment, and during a 30-month follow-up period, the patients underwent clinical and radiological examination, together with bacteriological, immunological and routine laboratory testing. RESULTS: Two of the five patients became long-term sputum smear and culture negative after r-IFN-alpha2b therapy; one of the patients showed clinical improvement and negative smear after therapy, but remained culture positive. The other two patients showed no response. CONCLUSION: The results of this trial suggest that r-IFN-alpha2b should be evaluated further in multidrug-resistant tuberculosis in prospective controlled trials.

Decline of high hepatitis C virus prevalence in a hemodialysis unit with no isolation measures during a 6-year follow-up.

AIMS: It has been recently suggested that isolation measures may be necessary to avoid hepatitis C virus (HCV) spread in hemodialysis units with a high HCV prevalence. To assess the variation in prevalence and long-term incidence of HCV infection, we studied our hemodialysis patients during a 6-year follow-up period. MATERIAL AND METHODS: We compared anti-HCV prevalence in 1994, 1996, 1998 and 2000 according to the anti-HCV status, and we analyzed the seroconversion of anti-HCV. Strict adherence to universal precautions has been fulfilled since 1993 and systematic anti-HCV testing in blood donors has been performed since 1994. No isolation measures were adopted. RESULTS: In 1994,22 of 53 (41.5%) patients tested positive for anti-HCV; in 1996, 18 of 67 (26.9%); in 1998,9 of 75 (12.0%); and in 2000, 7 of 82 (8.5%) (p < 0.001). In 2000, 7 of 14 (50.0%) patients who had been attending the unit since 1994 and 0 of 68 (0%) who had entered after 1994 were anti-HCV-positive (p = 0.000). Eight of 1 71 (4.7%) patients who entered the unit and 24 of 142 (16.9%) who left it were anti-HCV-positive (p < 0.001). Two patients became anti-HCV-negative. Seroconversion of anti-HCV was observed in 3 patients. The yearly seroconversion rate was 0.5% during the period 1994-1996 (1 of 98 patients at risk), 0.5% during the period 1996-1998 (1 of 91 patients at risk), and 0.4% during the period 1998-2000 (1 of 120 patients at risk). CONCLUSIONS: It was possible to reduce a high HCV prevalence in a hemodialysis unit when a low incidence was achieved without taking isolation measures. All anti-HCV-positive patients in 2000 had been undergoing hemodialysis since 1994.

Plasma erythropoietin levels in the oldest old.

UNLABELLED: Erythropoietin (EPO) regulates erythrocytes production and is synthesized mainly by the kidney. Its production is reduced during chronic renal failure but is not altered by the senescence process in spite of the morphological changes that occur in the kidney. However, there is no information regarding what happens to erythropoietin synthesis during advanced ageing. Thus, we carried out an investigation to determine whether there was any significant difference in plasma erythropoietin between adults, old and very old people. MATERIAL AND METHODS: We studied 74 healthy volunteers: 22 adults, 30 old, and 22 very old. None of them were smokers or were suffering from any disease that may intefere with hemoglobin (Hb) levels or with EPO production. Hematocrit, Hb, plasma creatinine and plasma erythropoietin were measured, and creatinine clearance was calculated from serum creatinine using two different formulae. Statistical analysis was performed using ANOVA and Bonferroni tests. RESULTS AND CONCLUSION: Among the three groups we found a significant difference in creatinine clearance (p < 0.001), but not in plasma erythropoietin levels; we conclude that normal senescence does not alter plasma erythropoietin levels, even during advanced ageing.

[Treatment of anemia in children undergoing chronic hemodialysis with recombinant human erythropoietin]. / Tratamiento de la anemia en niños sometidos a hemodiálisis crónica con eritropoyetina humana recombinante.

Anemia associated to chronic renal failure (CRF) is a very frequent disorder. Twenty five per cent of adult patients under hemodialysis require periodical transfusions to maintain acceptable quality of life. This anemia is due mainly to a relative deficit of erythropoietin (EPO). Thanks to recombinant DNA techniques, EPO availability has made it possible to treat this population with the hormone. Most of the reported experience has been obtained from adult patients and literature on children is scarce. For this reason, a controlled prospective trial on 18 patients (9 males and 9 females) with a mean age of 12.4 years (range 7-17) was conducted, evaluating hematimetric response, safety of treatment and effect on quality of life after one year of treatment. Seventeen patients could be evaluated; mean follow-up was of 365 days (180-323). Treatment started with an administration scheme of 25 U/kg/dose, i.v. route, three times weekly, and dose was corrected according to the hematimetric response. Target hemoglobin was set in 10 g%. Mean dose required to reach target was 101.5 +/- 37.7 U/kg/dose (50-200) three times weekly and time elapsed was of 223.3 days (175-355). Only one patient did not achieve target hemoglobin value with the maximal dose planned (200 U/kg/dose). Bone marrow biopsy in this patient showed alpha widespread fibrosis secondary to hyperparathyroidism caused by CRF. Direct correlation was found between the required rHuEPO dose and basal levels of serum alkaline phosphatase (Table 2). Results obtained in status performance on six patients showed significant increase in all the variables under analysis (Table 4).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of hemodialysis procedure on HCV RNA detection in serum and peripheral blood mononuclear cells.

AIM: To assess whether hemodialysis procedure induces qualitative or quantitative changes in hepatitis C virus (HCV) RNA. METHODS: We obtained blood samples in the 10 HCV RNA-positive patients of our hemodialysis unit before (sample I) and 5 min after a dialysis session (sample II), and before the next dialysis session (sample III). HCV RNA was tested by PCR in serum and peripheral blood mononuclear cells (PBMC). Serum viral load was measured by branched-DNA assay. RESULTS: Serum HCV RNA was positive in samples I, II and III of the 10 patients. PBMC HCV RNA was detected in samples I, II and III of seven patients. Mean viral load was 1.43+/-0.99 Meq genome/mL in sample I, 0.86+/-0.40 Meq genome/mL in sample II and 1.27+/-0.56 Meq genome/mL in sample III. CONCLUSIONS: HCV load was low in most HCV RNA-positive patients. It had a downward trend during dialysis procedure but HCV RNA remained detectable in all serum samples and in most PBMC samples. Therefore, qualitative HCV RNA seems to be better than viral load to assess HCV infection in hemodialysis patients.

Massive plasmocytosis due to methimazole-induced bone marrow toxicity.

Pancytopenia is a rare complication of the thionamide therapy reported secondary to aplastic anemia, the bone marrow being invariably hypocellular. We present a case of a 16-year-old female with Graves' disease who presented with massive bone marrow plasmocytosis mimicking multiple myeloma. The patient had already been on methimazole for a month when she was admitted to the Pediatric Unit with the diagnosis of sepsis. CBC revealed pancytopenia. Bone marrow aspirations showed hypocellular-normocellular bone marrow, 98% of plasma cells. At that time, MMI was discontinued and the patient was started on broad-spectrum antibiotics, dexamethasone, and G-CSF. Bone marrow aspiration day +4 still showed hypo-normocellular marrow, with remaining 6% plasma cells. Myeloma screen was negative; ANC >1,000 at day +7, platelets >50,000 at day +24. Twenty-four months after patient's discharge, her clinical condition, CBC, and bone marrow remained normal. To our knowledge this is the first report of pancytopenia due to MMI, where the usual hypoplasia found is replaced by massive plasmocytosis.

A double-blind controlled trial of recombinant interferon-alpha 2b in haemodialysis patients with chronic hepatitis C virus infection and abnormal aminotransferase levels. Nephrologists' Group for the Study of HCV infection.

The efficacy and safety of recombinant interferon-alpha 2b (rIFN-alpha 2b) was evaluated in a double-blind controlled trial comprising 23 haemodialysis patients with antibodies to hepatitis C virus (anti-HCV), detectable serum HCV RNA by polymerase chain reaction and chronic alanine aminotransferase elevation. The patients were randomly assigned to receive rIFN-alpha 2b at a dose of 1.5 MU (increasing to 3 MU if no response was observed) (Group I: n = 14) or identical placebo (Group II: n = 9), for 6 months. A biochemical response (normal alanine aminotransferase) was observed in 10 patients (71.4%) from Group I and in one patient (11.1%) from Group II (P < 0.01) at the end of therapy, and in four patients from Group I (28.6%) and in none from Group II (NS) 12 months after therapy. Virological response (HCV RNA negative) was observed in four patients (28.6%) from Group I and in none from Group II (NS) at the end of therapy, and in two patients (14.2%) from Group I and in none from Group II (NS) 12 months after therapy. Interferon doses were 1.5 MU in 12 patients and 3 MU in two patients. Therapy interruption owing to severe side-effects was necessary in three patients (21.4%) from Group I and in two patients (22.2%) from Group II. Although long-term statistical differences were not observed, these results suggest that rIFN-alpha 2b at a low dose is a reasonable and well tolerated therapeutic approach for haemodialysis patients with chronic hepatitis C.

Hepatitis G virus infection in hemodialysis patients and its relationship with hepatitis C virus infection.

Our aim was to study the characteristics of hepatitis G virus (HGV) infection in hemodialysis (HD) patients. We evaluated 108 patients from two different units (A: 67 patients; B: 41 patients). HGV RNA and HCV RNA were detected by PCR. Nineteen patients (17.6%) were HGV RNA positive (20.9% in unit A and 12.2% in unit B (NS)). HCV RNA was positive in 19 patients (17.6%) (28.4% in unit A and 0 in unit B (p < 0.01)). Eight patients were HGV RNA and HCV RNA positive (group I), 11 HGV RNA positive (group II), 11 HCV RNA positive (group III), and 78 negative for both viruses (group IV). Time on HD was 51.3 +/- 37.0 months for group I, 36.0 +/- 27.9 months for group II, 63.5 +/- 40.2 months for group III, and 26.4 +/- 27.1 months for group IV (p < 0.01 for I and III). Seven patients (87.5%) from group I, 9 (81.8%) from group II, 10 (90.9%) from group III, and 44 (56.4%) from group IV had a history of transfusion (p < 0.03 for I, II and III). Two patients (25%) from group I, none from group II, 5 (45.4%) from group III, and 6 (7.7%) from group IV had chronic ALAT elevation (p < 0.01 for I and III). We conclude that HGV infection was frequent in our HD patients, related to transfusions and independent of HCV prevalence, and that HGV infection itself was not a cause of ALAT elevation suggesting chronic hepatitis.

Hepatitis C virus RNA and long-term response to recombinant interferon-alpha 2b in patients with chronic hepatitis C.

The effectiveness of recombinant interferon-alpha 2b (rIFN-alpha 2b) in eradicating hepatitis C virus (HCV) RNA from serum has not been completely assessed. We studied 39 patients with compensated chronic hepatitis C diagnosed by liver biopsy and positive HCV RNA measured by polymerase chain reaction (PCR). Group I consisted of 26 patients treated with 3 MU of rIFN-alpha 2b for 6 months; group II, 13 control patients observed for six months; and group III, 12 out of 13 patients from group II who subsequently received 5 MU of rIFN-alpha 2b for 6 months. In group I, 11 out of 23 (47.8%) patients who completed treatment had an immediate response and five (21.7%) had a sustained response to therapy six months after treatment. No response was observed in patients from group II. In group III, 7 out of 12 (58.3%) patients who completed treatment had an immediate response and none had a sustained response. Considering all patients who completed rIFN-alpha 2b treatment, HCV RNA remained positive at the end of therapy in three of five sustained responders (60%), six of 13 patients who relapsed (46.1%), and in all nonresponders (100%). HCV RNA was positive 6 months after therapy in four (80%), 13 (100%), and 17 (100%) patients respectively. All patients with a sustained response had normal aminotransferase levels 18 months after therapy. We conclude that in chronic hepatitis C rIFN-alpha 2b causes a significant immediate response but this is not sustained, only 2.8% of treated patients had a sustained loss of HCV RNA. Normal aminotransferase persist in the long term, despite persistence of HCV RNA.

Evidence of hepatitis C virus passage across dialysis membrane.

The passage of hepatitis C virus (HCV) across the dialysis membrane is a controversial issue. We performed a study applying extreme conditions of permeability to the dialysis membrane and avoiding the use of heparin and dialysis bath that might interfere with polymerase chain reaction (PCR) results. We obtained samples from the ultrafiltrate at the beginning of 18 hemodialysis sessions carried out in 6 HCV RNA-positive patients. HCV RNA was detected by PCR in 3 (16.7%) ultrafiltrate samples belonging to 1 of the patients. HCV genotype was the same as that found in positive ultrafiltrate samples and in the serum corresponding to this patient. The viral load of this patient was under the levels detectable by the assay employed. Therefore, contamination of the ultrafiltrate may constitute a potential risk for HCV transmission in hemodialysis units.

Low levels of serum erythropoietin in children with endemic hemolytic uremic syndrome.

Serum erythropoietin (EPO) levels were measured in ten previously non-transfused children with hemolytic uremic syndrome (HUS). Complete blood cell count, serum EPO, and renal function tests were carried out upon admission and weekly thereafter. Blood samples were obtained: (1) prior to the first transfusion; (2) after the first transfusion but before recovery from renal failure; (3) during the recovery stage. All patients required transfusions (mean 1.8+/-0.8 per child). Absolute values of EPO correlated positively with the hematocrit during the three stages (r = 0.53, 0.36, and 0.12, respectively) which is opposite to expected results. The observed EPO logarithm/predicted EPO logarithm upon admission was low (0.70+/-0.08), falling further during stage 2 (0.57+/-0.03), but increasing thereafter (0.78+/-0.07) without reaching normal values. The reticulocyte production rate followed a parallel course (0.74+/-0.14, 0.54+/-0.11, and 0.60+/-0.10, respectively). On comparing the observed serum EPO levels with those expected, 9 of 11 pre-transfusion samples showed low values; in stage 2, all samples were below normal; in the recovery phase most (77.8%) were still low. Our results show an inadequate EPO synthesis in children with HUS, which could play an important pathogenic role, since it aggravates the severity of the existing hemolytic anemia; the secondary inhibitory effect of repeated transfusions exacerbates this inadequate synthesis.

Alpha-interferon therapy induces improvement of platelet counts in children with chronic idiopathic thrombocytopenic purpura.

PURPOSE: To investigate alpha-interferon (IFN) therapy for children with chronic idiopathic thrombocytopenic purpura (ITP). PATIENTS AND METHODS: Patients with refractory ITP lasting more than 12 months from diagnosis were included if they had platelet counts <50 x 10(9)/L and had received no treatment during the past month. Patients received IFN (3 x 10(6) U/m2 per dose), three times per week for 4 weeks; if partial (<150 x 10(9)/L) or no response was obtained, the same dose was continued for another 8 weeks. In patients with favorable response and subsequent decrease to pre-treatment values, an additional 4 weeks of treatment could be administered. RESULTS: Fourteen patients (ages 4-20 y) receiving 17 IFN courses were included. Mean initial platelet count was 29 +/- 15 x 10(9)/L. A significant increase was achieved during 14 of 17 courses (82.4%). All but two responses were transitory, and platelets returned to initial values after IFN discontinuation (mean 44 +/- 26 days). Considering the best response achieved by each patient, we observed: 1) 10 patients who achieved a sustained improvement of platelet count throughout the treatment period, decreasing to initial values after therapy was stopped; 2) one patient who achieved platelet count >150 x 10(9)/L, remaining with normal platelets at 18 months; 3) one patient who achieved platelet count >150 x 10(9)/L, remaining with platelets between 100 and 140 x 10(9)/L at 48 months; 4) one patient who had no response; and 5) one patient in whom therapy worsened the thrombocytopenia. A mild to moderate flu-like syndrome and a moderate decrease of the absolute neutrophil count were the only side effects observed. CONCLUSION: Interferon therapy induces a significant increase of platelet count and seems to be a valid alternative therapy to attempt the achievement of prolonged remission in refractory ITP, to defer splenectomy in younger children, or to improve platelet count before planned splenectomy.