Prognostic Significance of IL-10 in Childhood Chronic Immune Thrombocytopenic Purpura / 임상소아혈액종양

BACKGROUND: The proposal of the present study was to assess the cytokine imbalances such as serum levels of IL-2, IL-10 and TGF-β1 in childhood chronic ITP during the thrombocytopenic and spontaneous remission phases. The findings of this study are anticipated to offer new insights into the pathogenesis of childhood chronic ITP and the prognostic factors involved in spontaneous remission.METHODS: Ten children with chronic ITP, 6 thrombocytopenic and 4 recovered cases, were enrolled. Five healthy children and eight healthy adults were included in this study as controls. The serum levels of IL-2, IL-10 and TGF-β1 were measured by ELISA technique.RESULTS: During this study, four patients achieved spontaneous remission. The serum level of IL-10 was higher in the patients that recovered spontaneously compared to the patients with persistent chronic thrombocytopenia. The serum level of IL-2 was not able to be detected as the levels were too low for analysis. TGF-β1 showed no significant differences among the groups in this study.CONCLUSION: These data suggest that increased serum level of IL-10 could have prognostic significance in the natural course and long-term outcome of childhood chronic ITP.

Prognostic Significance of IL-10 in Childhood Chronic Immune Thrombocytopenic Purpura / 임상소아혈액종양

BACKGROUND: The proposal of the present study was to assess the cytokine imbalances such as serum levels of IL-2, IL-10 and TGF-β1 in childhood chronic ITP during the thrombocytopenic and spontaneous remission phases. The findings of this study are anticipated to offer new insights into the pathogenesis of childhood chronic ITP and the prognostic factors involved in spontaneous remission. METHODS: Ten children with chronic ITP, 6 thrombocytopenic and 4 recovered cases, were enrolled. Five healthy children and eight healthy adults were included in this study as controls. The serum levels of IL-2, IL-10 and TGF-β1 were measured by ELISA technique. RESULTS: During this study, four patients achieved spontaneous remission. The serum level of IL-10 was higher in the patients that recovered spontaneously compared to the patients with persistent chronic thrombocytopenia. The serum level of IL-2 was not able to be detected as the levels were too low for analysis. TGF-β1 showed no significant differences among the groups in this study. CONCLUSION: These data suggest that increased serum level of IL-10 could have prognostic significance in the natural course and long-term outcome of childhood chronic ITP.

Roles of CD5+, CD19+, CD41a+, CD55+ and CD59+ in Chronic Immune Thrombocytopenic Purpura (ITP).

Aims: The aim of this study was to investigate of the roles of CD5+ and CD19+ on lymphocytes, CD5+ on B lymphocytes, CD41a+ on platelets and CD55+ and CD59+ on erythrocytes in platelet destruction; and evaluate them according to the patient response status to steroid therapy and platelet counts in chronic immune thrombocytopenic purpura (ITP). Study Design: This study included 20 chronic ITP patients and 20 healthy controls. We investigated the roles of CD5+ and CD19+ expression on lymphocytes, CD5+ expression on B lymphocytes, CD41a+ expression on platelets, and CD55+ and CD59+ expression on erythrocytes, as well as the platelet counts in healthy and chronic ITP patients. Additionally, these markers were evaluated according to the patient response status to steroid therapy and platelet counts. Place and Duration of Study: This study took place at the Department of Internal Medicine and Haematology, Meram Medical Faculty at Selçuk University in Turkey, between November, 2008 and July, 2009. Methodology: A total of 40 patients (26 women, 14 men, age range: 19-79 years) were studied. The study group included 20 chronic ITP patients (12 women and 8 men, age range: 19-78 years) and the control group included 20 healthy volunteers (14 women and 6 men, age range: 22-79 years). The platelet counts and expressions of CD5+ and CD19+ on lymphocytes, CD5+ on B lymphocytes, CD41a+ on platelets, and CD55+ and CD59+ on erythrocytes were analysed in the patients and control subjects. The chronic ITP patients were evaluated according to their requirements of treatment. Five patients whose platelet counts were above 50,000 mm–3 were observed without treatment. The other 15 patients whose platelet counts were under 50.000 mm–3 and had bleeding, or whose platelet counts were under 20,000 mm–3, were given methylprednisolone treatments (1 mg/kg/day orally). Three of the 15 patients discontinued treatment for various reasons. The twelve patients who continued the methylprednisolone treatment were divided into two subgroups according to their responder status of steroid treatment. The patients whose platelet counts slowly increased above 30,000 mm–3 within three months included the steroid treatment responder subgroups. The chronic ITP patients were also divided into two subgroups according to the severity of their thrombocytopenia. The limit of the platelet count was 30,000 mm–3 for severe thrombocytopenia. These parameters were analysed according to the response status of the steroid treatment and platelet counts. The platelet counts, and the expressions of these markers, were compared between the subgroups. Results: The level of CD5+ on B lymphocyte expression (2.19 ± 1.65) in peripheral blood lymphocytes was significantly higher in the immune thrombocytopenic purpura patients than in the controls (P = .05). The CD55+ + CD59+ expression on erythrocytes (98.03 ± 1.77) was significantly higher in the ITP patients than in the controls (P = .05). There was no significant relationship between the expression of CD5+, CD19+ or CD5+ on B lymphocytes, CD41a+ expression on platelets or CD55+ and CD59+ expression on erythrocytes, according to the response status to steroid therapy in the patient group (P > 0.05). Additionally, the patients were evaluated according to platelet counts, and there was a significantly positive correlation between the level of CD41a+ expression on the platelets and the platelet count (P = .05). Conclusion: The level of CD5+ on B lymphocytes was significantly higher in the ITP patients than in the controls. A relationship between CD55+ plus CD59+ expression on erythrocytes and immune destruction of platelets was not observed in the chronic ITP patients.

Treatment of chronic immune thrombocytopenic purpura with rituximab.

Objective. To evaluate the rituximab treatment in children with chronic immune thrombocytopenic purpura Methods. This study included ten children with chronic immune thrombocytopenic purpura, which were nonresponsive to Steroid (S), IVIG and anti-D treatments. Rituximab was given with a dosage of 375 mg/m2 weekly for 4-6 weeks. Initial platelet count was less than 30x109/L and responses were assessed in follow-up. The patients’ groups were categorized as complete remission (CR);a platelet count ≥150x109/L,partial remission (PR);a platelet count ranging from 50x109/L to 150x109/L, minimal remission (MR); a platelet count ranging from 30x109/L to 50x109/L and no response (NR); a platelet count less than 30x109/L. Results. Of our patients, four female and six male, their ages ranged from 39 mth to 13 yr and the mean age was 83.4±44.58 mo. None of the patients was splenectomized. The follow-up period after rituximab treatment ranged between 12 to 42 mo and the mean follow-up period was 25.10±13.03 months. While on this treatment, we had a CR in two patients, a PR in one, a MR in three, but no response in four. The patients in CR/PR are still being followed as in remission and they have 40 mo of mean follow-up period. The three patients in MR had a decrease in values of platelets earliest in one mo and the latest in four mo. Adverse effects of rituximab, such as itching and scraps that were not clinically significant were observed in three patients during rituximab infusion. There were no increase in infections after rituximab in any patient. Conclusion. CR was found in 20% of our patients, PR in 10% and MR in 30% with rituximab. On this treatment, while some series had good outcomes with this treatment (72%-100%, remission ratios), but many series, such as ours, had a poor response rate contrast to many reported case series in the literature. This condition may be associated with the age of our most patients who were young at the time of commenced rituximab. However, we believe that more studies are required to elucidate the reasons for different results in different case series reported in literature.

Treatment of Chronic Idiopathic Thrombocytopenic Purpura in Children with Cepharanthin (R) / 대한소아혈액종양학회지

PURPOSE: Cepharanthin (R) has been reported to improve the symptoms of intractable or steroid-resistant chronic idiopathic thrombocytopenic purpura (ITP). We report the clinical efficacy of oral high dose Cepharanthin (R) in refractory chronic ITP. METHODS: We analyzed eleven patients who were diagnosed as chronic ITP at the Department of Pediatrics, Seoul National University Hospital from January, 2002 to February, 2004. After informed consent patients with platelet count below 20, 000/mm3 were treated with Cepharanthin (R) at the initial dose of 5 gm/day. The doses were increased up to 15 gm/day if there was no response. For the purposes of this study, complete remission was defined as an elevation of the platelet count > or =50, 000/mm3 from the baseline after 4 weeks of treatment. Partial remission was defined as an elevation of the platelet count 20, 000/mm3 and < = or50, 000/mm3 from the baseline. RESULTS: Seven boys and four girls with a median age of 10 were enrolled. Two to four weeks after the initiation of this therapy, 4 patients showed their platelet counts over 50, 000/mm3 1 patients reached partial remission state, 6 patients had no response. Side effects of Cepharanthin (R) were not observed in all patients. CONCLUSION: We suggest that the oral administration of Cepharanthin (R) could be a beneficial and a safe treatment strategy for the refractory chronic ITP patients. Further studies should be performed to elucidate the mechanism of responses.

Clinical Study of Idiopathic Thrombocytopenic Purpura: Focused on Reticulated Platelet / 대한소아혈액종양학회지

PURPOSE: Immune thrombocytopenic purpura (ITP) is divided into acute and chronic forms. Unfortunately, there have been no known specific laboratory or clinical predictors for the diagnosis of chronic ITP. This study was performed to elucidate the prognostic significance of various clinical and laboratory parameters, including reticulated platelet percentage. METHODS: We retrospectively analyzed 60 patients who were diagnosed as ITP at the Department of Pediatrics, Wonju Christian Hospital from January, 1989 to January, 2001. Various kind of clinical parameters such as age, sex, symptom duration, prior URI history, response to treatment, and laboratory parameters like platelet count at initial presentation, lowest platelet count, duration of thrombocytopenia, initial reticulated platelet percentage, antiplatelet antibody IgG and IgM, antinuclear antibody (ANA), direct and indirect Coombs' test were compared between acute and chronic ITP. RESULTS: Fifteen % of patients (9/60) was chronic ITP. The peak age incidence was from 1 to 3 year of age in both acute (29.4%) and chronic ITP (22.2%). The acute ITP was prevalent in spring season, May and June. There was no difference in the incidence of prior URI history between acute and chronic ITP. Higher proportion of chronic ITP patients (5/9; 55.5%) than acute ITP patients (7/51; 13%) had symptom duration longer than 1 month (P or =1 months duration of presenting symptoms and relapse after 2 months from initial presentation have the propensity of developing chronic ITP. Reticulated platelet percentage could not discriminate acute and chronic ITP. A more accurate detection method should be developed for reticulated platelets.

Partial Splenic Embolization Therapy of Chronic Idiopathic Thrombocytopenic Purpura / 대한혈액학회지

BACKGROUND: Initial treatment of chronic idiopathic thrombocytopenic purpura (ITP) is generally done with corticosteroid. In case of refractory to corticosteroid or dependency, splenectomy seems to be the most effective and definitive treatment. Partial splenic embolization is an easier procedure with minimal morbidity. We evaluated the efficacy and complications of partial splenic embolization as treatment of chronic ITP refractory to corticosteroid or corticosteroid dependency. METHODS: Eight patients with chronic ITP and two systemic lupus erythematosus (SLE) patients with immunothrombocytopenia underwent partial splenic embolization. Embolization of 70~80% of the splenic volume was performed with endocoils or gelform particles without anesthesia by selective arterial catheterization and followed up for 4~50 months. The therapeutic effect of partial splenic embolzation was defined on the basis of the platelet count at the last follow-up after partial splenic embolzation : complete response, >100,000/nL,partial response, 100,000~50,000/nL and no response, <50,000/nL without medication. RESULTS: Partial splenic embolization brought a complete response in six of ten patients, a partial response in three, and no response in one. With a follow-up of 4~50 months, these responses were maintained in all except three patients. One patient was treated by splenectomy and one by partial splenic embolization again. Tolerance was good in all patients. Abdominal pain and fever was observed in 8 and 4 patients, respectively. One patient had a left pleural effusion with spontaneous resolution. No serious infection occurred. All patients were discharged within 6 days after partial splenic embolization. CONCLUSION: We conclude that partial splenic embolization may be useful and safe procedure and a good alternative to splenectomy in chronic ITP refractory to medical treatment.

Long-term Observation of 87 Cases with Chronic Idiopathic Thrombocytopenic Purpura in Adult / 대한혈액학회지

BACKGROUND: Information about the natural history of chronic idiopathic thrombocytopenic purpura (ITP) is still vague and far from complete due to a lack of studies. The purpose of the present study is to define ultimate outcome of adults with chronic ITP by long-term observation of patients. Method : We retrospectively analyzed eighyty-seven ITP patients diagnosed at the Department of Internal Medicine, Kyungpook National University Hospital and Taegu-Hyosung Catholic University Hospital and Taegu-Fatima Hospital between March 1986 and March 1998. RESULTS: Median age was 36 years (range 15 to 74) at the time of diagnosis and median follow-up duration was 46 months (7 to 133). Female to male ratio was 4 : 1. Twenty-four patients who were asymptomatic with stable disease or a platelet count over 50,000/microliter were managed on a wait and see basis. A total of 63 patients received an initial treatment with prednisone (1 mg/kg/day for 1 month). Refractory or relapsed cases underwent splenectomy and/or other therapeutic modalities. An initial complete or partial response to prednisone was observed in 79%. A sustained complete remis- sion (CR) lasting more than 6 months was attained in 11%. Thirty-two refractory or relapsed patients underwent splenectomy. Twenty-two patients (69%) had a CR, with twenty-one (66%) achieving a sustained CR. 5 other cases obtained a partial remission (PR). Long-lasting responses were observed in 3 other case (12 %) following alternative treatment. Five deaths were recorded, but only one was due to thrombocytopenia and the remaining four deaths were unrelated to ITP. Two patients had laboratory features and a clinical history consistent with an autoimmune disease. CONCLUSION: The majority of patients who undergo splenectomy can have a CR for many years. The therapeutic modalities tried as supplements or alternatives to splenectomy all produced some transient remissions but few prolonged recoveries. But the long-term prognosis of chronic ITP is benign even in refractory cases and the development of overt autoimmune diseases is relatively uncommon.

Long-term Outcome of Chronic Childhood Idiopathic Thrombocytopenic Purpura according to Therapeutic Methods / 대한소아혈액종양학회지

PURPOSE: Idiopathic thrombocytopenic purpura (ITP) was the most common disease of thrombocytopenic purpura in children, chronic course was shown in 10%. Splenectomy had been used in chronic thrombocytopenic purpura as classic therapy, and many therapeutic method had been tried. We define response to therapy and long-term outcome of chronic childhood idiopathic thrombocytopenic purpura. METHODS: We retrospectively analyzed 41 patients that treated and diagnosed as chronic thrombocytopenic purpura at the Department of Pediatrics, Severance Hospital between Aug. 1981 and Aug. 1999 and followed for mean 8.2 years. The mean age was 6.2 years (range from 1month to 12.3 years) and sex-ratio of male to female was 1:2. According to therapeutic methods, they were divided into splenectomy group, spleen irradiation group, azathioprine group, interferon group, high-dose oral dexamethasone group, vincristine group, intravenous gammaglobulin group, low-dose prednisone group, and low-dose prednisone with intermittent intravenous gammaglobulin group. The results were classified into complete response (CR: platelets> 100,000/mm3), partial response (PR: platelets> 50,000/mm3), no response (NR: platelets <50,000/mm3). RESULTS: The treatment response and number of patients according to therapeutic methods were as follows; splenectomy group, 12 cases (CR-9 cases, PR-1 case, NR-2 cases), spleen irradiation group, 1 case (CR), azathioprine group, 6 cases (CR-1 case, NR-5 cases), interferon group, 3 cases (CR-1 case, PR-1 case, NR-1 case), high-dose oral dexamethasone group, 4 cases (CR-2 cases, PR-1 case, NR-1 case), vincristine group, 2 cases (NR), intravenous gammaglobulin group, 35 cases (CR-5 cases, PR-5 cases, NR-25 cases), low-dose prednisone group, 5 cases (NR), and low-dose prednisone with intermittent intravenous gammaglobulin group, 30 cases (CR-7 cases, PR-3 cases, NR-20 cases). CONCLUSION: The results of therapeutic method in splenectomy group were the most highest score (12 cases: CR-9 cases, PR-1 case, NR-2 cases), high-dose oral dexamethasone group, interferon group, and low-dose prednisone with intermittent intravenous gammaglobulin group in high incidence order. Spleen irradiation was supposed to trial method of treatment before splenectomy, because the risk was lower than splenectomy, although they had 1 case.

Platelet transfusion support for splenectomy in patients with chronic immune thrombocytopenic purpura / 대한수혈학회지

BACKGROUND: Splenectomy is often performed for the patients with refractory chronic immune thrombocytopenic purpura (ITP). Still, there are no generally accepted guidelines for the minimum level of platelet count and the average requirement of platelet transfusion so that the patients can safely undergo splenectomy. We evaluated the changes of platelet count and transfusion requirements around the splenectomy in patients with chronic ITP. METHODS: We reviewed the medical records of 25 patients with chronic ITP. We compared the platelet counts at admission, immediately pre-op and several post-op days. We also investigated the number of platelet concentrates transfused around splenectomy. We determined the effect of splenectomy according to Difino's classification. RESULTS: The median platelet counts of the patients was 18x109/L (7-238x109/L) on admission and recovered to 108x109/L (22-460x109/L) on preoperation day by platelet transfusion and immunosuppressive treatment. The platelet counts were rapidly recovered after splenectomy from the day of operation. Only 3 patients needed platelet transfusion after splenectomy. Thirteen among twenty five patients (52%) underwent operation without platelet transfusion support. Most transfusions were done before the surgery and 80% (12/15) of the patients required transfusion of more than 10 units of random donor platelet concentrate. Twenty one patients (84%) showed the complete remission after splenectomy. CONCLUSION: Splenectomy can lead to rapid remission even in most cases of refractory chronic ITP. Many cases can undergo the operation only with treatment modalities other than transfusion such as immunosuppressive agents and/or immunoglobulin. The minimum level of platelet counts for splenectomy may be safe over 50x109/L and about 10 units of platelet concentrate may be enough for preparation of splenectomy.

Chronic Childhood Idiopathic Thrombocytopenic Purpura: Long-term Follow-up / 대한소아혈액종양학회지

PURPOSE: The purpose of this study was to evaluate the spontaneous remission rate in children with chronic ITP. METHODS: The medical records of 21 patients diagnosed with chronic ITP and followed for at least 6 months at Hanyang University Hospital between Mar. 1985 and Feb. 1997 were reviewed. Complete remission(CR) was defined as a recovery of platelet count of more than 100x109/L and partial remission(PR) was defined as a recovery of platelet count of 50-100x109/L, maintained for at least 6 months. RESULTS: Of 21 patients, 9 boys and 12 girls, the mean age at diagnosis was 5.5 years (0.4~15.5 years). The mean platelet count at diagnosis was 26.5x109/L(2-86x109/L). Of 21 patients, 5 with persistent thrombocytopenia and severe bleeding tendency underwent splenectomy. With a median follow up of 39.5 months after splenectomy, 4 achieved CR. The time to CR of the 4 patients were 2 weeks, 13.6, 18.6, 31.0 months, respectively. Of 16 patients, excluding 5 splenectomized children, 6 achieved CR and 4 PR. With a median follow-up of 21 months, the predicted spontaneous CR and PR rate at 5 years were 37.5%, and 68.7%, respectively(The percentage of PR includes that for CR). No serious complications including ICH or death were observed. CONCLUSION: Our study indicates that many cases of chronic ITP in childhood may remit without therapy even several years from onset. Splenectomy should be delayed as long as possible and reserved for the symptomatic and severely thrombocytopenic patient.

The Therapeutic Effect of Splenectomy in Childhood Chronic Thrombocytopenic Purpura / 대한소아혈액종양학회지

BACKGROUND: The aim of this study is to evaluate the therapeutic effect of splenectomy in children with chronic idiopathic thrombocytopenic purpura(ITP) who do not respond to corticosteroids and intravenous immunoglobulin(IVIG). METHODS: Fifteen patients(7 boys and 8 girls) who were admitted to St. Mary's Hospital under the diagnosis of ITP from December 1990 to February 1997 were enrolled In this study. All had chronic forms(more than 6 months after diagnosis) and were refractory to corticosteroids(prednisolone 1~2mg/kg) and IVIG(400mg/kg for 5 days or 1 g/kg for 2 days). We you-finely employ pneumococcal vaccine in 13 patients before splenectomy slnce 1992. Antiplatelet antibody was examed in 10 patients. We measured platelet count at preoperative time, postoperative 1 day, 1 month, and 3 months or more. Hematologic results were analyzed according to Berchtold and McMillan's criteria (1) complete response(CR) >120 x 10(9)/l; (2) partial response(PR) >50 x 10(9)/l (3) no response(NR) < 50 x 10(9)/l. RESULTS: The median age at operation was 10 yr(6~16). The median time interval between diagnosis and splenectomy was 2 yr 2 mo(6 mo~5 yr 5 mo). Antiplatelet antibody was positive in 2 cases of 10 cases(20%). Of 15 cases, 12 cases were corticosteroid resistant and 3 cases were corticosteroid dependent. The postsplenectomy platelet count(median 407 x 10(9)/l of 1 day; 254 x 10(9)/l of 1 month; 227 x 10(9)/l of 3 months or more) was significantly higher than presplenectomy platelet count(median 9 x 10(9)/l)(P<0.05). All patients showed complete or parial response throughout the follow up period. Accessory spleen was found in 1 case and removed during operation. There were no serious complications following splenectomy except mild fever in 2 cases(14%). CONCLUSION: Splenectomy appears to be an effective and relatively safe treatment for patients with chronic ITP who have had inadequate response to conventional therapies.

Predictors of Chronicity in Childhood Idiopathic Thrombocytopenic Purpura / 대한소아혈액종양학회지

BACKGROUND: Acute idiopathic thrombocytopenic purpura(ITP) in children has a low morbidity and mortality, and most of cases are self limited illness. But some of them are not responsive to treatment and finally progress to chronic disease. The purpose of this study is to evaluate the factors which influence the outcome in childhood idiopathic thrombocytopenic purpura. METHOD: From January 1990 to December 1995, patients with ITP who were admitted to the Pediatric department of Pusan National University Hospital were divided into acute and chronic form depending on whether the platelet count had returned to normal(150 x 10(9)/1) by six months after diagnosis. Between two groups, the clinical and laboratory characteristics, response to treatment were compared. RESULT: 1) Out of 55 patients with ITP, 36 cases(65.5%) were acute and 19 cases(34.5%) were chronic ITP. 2) Sex, previous viral infection history, clinical manifestations were not significantly different between two groups, but the chronic ITP was rare in less than 1 year of age. 3) The duration of symptoms over >2 weeks at presentation was strongly predictive of chronic ITP. 4) Most of chronic disease (87.5%) showed platelet counts below 150 x 10(9)/1 at 28 days after diagnosis as compared with acute disease(25.0%). 5) Among 19 cases of chronic disease, 6 cases responded completely to treatment, but 11 cases(57.9%) did not respond to any treatments, 2 cases improved spontaneously. CONCLUSION: A history of symptoms over 2 weeks at presentation and platelet counts below 150 x 10(9)/1 at 28 days after diagnosis were strong predictors of chronic ITP in children.