Patcharee Komvilaisak

Eltrombopag for children with chronic immune thrombocytopenia (PETIT2): a randomised, multicentre, placebo-controlled trial.

BACKGROUND The thrombopoietin receptor agonist eltrombopag has been shown to be safe, tolerable, and effective for adults with chronic immune thrombocytopenia. We aimed to investigate the safety and efficacy of eltrombopag for children with chronic immune thrombocytopenia. METHODS PETIT2 was a two part, randomised, multicentre, placebo-controlled study done at 38 centres in 12 countries (Argentina, Czech Republic, Germany, Hong Kong, Israel, Italy, Russia, Spain, Taiwan, Thailand, UK, and USA). Paediatric patients aged 1-17 years who had chronic immune thrombocytopenia and platelet counts less than 30 × 10(9) per L were randomly assigned (2:1) to receive eltrombopag or placebo. We stratified patients by age into three cohorts (patients aged 12-17 years, 6-11 years, and 1-5 years) before randomly entering them into a 13 week, double-blind period. Randomisation was done by the GlaxoSmithKline Registration and Medication Ordering System and both patients and study personnel were masked to treatment assignments. Patients who were allocated eltrombopag received tablets (except for those aged 1-5 years who received an oral suspension formulation) once per day for 13 weeks. Starting doses for patients aged 6-17 were based on bodyweight, and ethnic origin and ranged between 50 mg/day and 25 mg/day (starting dose for patients aged 1-5 years was 1·2 mg/kg/day or 0·8 mg/kg/day for east Asian patients). Patients who completed the double-blind period entered a 24 week open-label treatment period in which all patients received eltrombopag at either the starting dose (if they were formerly on placebo) or their established dose. The primary outcome was the proportion of patients achieving platelet counts of at least 50 × 10(9) per L in the absence of rescue therapy for 6 or more weeks from weeks 5 to 12 of the double-blind period. The intention-to-treat population included in the efficacy assessment consisted of all patients who were randomly assigned to one of the treatment groups, and the safety population included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT01520909. FINDINGS Beginning in March 15, 2012, 92 patients were enrolled, and the trial was completed on Jan 2, 2014. 63 patients were assigned to receive eltrombopag and 29 were assigned to receive placebo. In the double-blind period, three patients discontinued treatment because of adverse events: two patients in the eltrombopag group withdrew because of increased liver aminotransferases and one in the placebo group withdrew because of abdominal haemorrhage. 25 (40%) patients who received eltrombopag compared with one (3%) patient who received placebo achieved the primary outcome of platelet counts of at least 50 × 10(9) per L for 6 of the last 8 weeks of the double-blind period (odds ratio 18·0, 95% CI, 2·3-140·9; p=0·0004). Responses were similar in all cohorts (eltrombopag vs placebo: 39% vs 10% for patients aged 12-17 years, 42% vs 0% for patients aged 6-11 years, and 36% vs 0% for patients aged 1-5 years). Proportionately fewer patients who received eltrombopag (23 [37%] of 63 patients) had WHO grades 1-4 bleeding at the end of the double-blind period than did those who received placebo (16 [55%] of 29 patients); grades 2-4 bleeding were similar (three [5%] patients who received eltrombopag vs two [7%] patients who received placebo). During the 24-week open-label treatment period, 70 [80%] of 87 patients achieved platelet counts of 50 × 10(9) per L or more at least once. Adverse events that occurred more frequently with eltrombopag than with placebo included nasopharyngitis (11 [17%] patients), rhinitis (10 [16%] patients), upper respiratory tract infection (7 [11%] patients), and cough (7 [11%] patients). Serious adverse events occurred in five (8%) patients who received eltrombopag and four (14%) who received placebo. Safety was consistent between the open-label and double-blind periods. No deaths, malignancies, or thromboses occurred during the trial. INTERPRETATION Eltrombopag, which produced a sustained platelet response in 40% of patients with chronic immune thrombocytopenia, is a suitable therapeutic option for children with chronic symptomatic immune thrombocytopenia. We identified no new safety concerns and few patients discontinued treatment because of adverse events. FUNDING GlaxoSmithKline.

Retrospective study on the combination of desferrioxamine and deferasirox for treatment of iron-overloaded thalassemic patients: first evidence of more than 2 years.

Some iron-overloaded patients have problems being treated with iron chelators. We therefore retrospectively studied 7 iron-overloaded thalassemic patients. Within the same week, patients received 20 to 30 mg/kg/d of oral deferasirox for 4 consecutive days, then a subcutaneous infusion of 20 to 40 mg/kg/d of desferrioxamine for 8 to 12 hours on the next 3 consecutive days. The median treatment duration was 25 months (range, 8 to 32). All of the patients showed a decrease in serum ferritin without any side effects. The protocol, combining deferasirox and desferrioxamine in sequence, was effective and safe: more cases should be studied.

Incidence and survival rates among pediatric osteogenic sarcoma cases in Khon Kaen, Thailand, 1985-2010.

BACKGROUND Osteosarcoma is the most common bone cancer in children, responsible for a high rate of amputation and death. This is the first long-term, population-based, epidemiologic and survival study in Thailand. OBJECTIVE To study the incidence and survival rates of pediatric osteosarcoma in Khon Kaen. METHOD Childhood osteosarcoma cases (0-19 years) diagnosed between 1985-2010 were reviewed. The data were retrieved from the population-based data set of the Khon Kaen Cancer Registry and medical records from Srinagarind Hospital, Faculty of Medicine, Khon Kaen University. All cases were censored until the end of April 2012. The age-standardized incidence rate (ASR) was calculated using the standard method. Survival experience was analyzed using the standard survival function (STATA 9.0) and presented with a Kaplan-Meier curve. RESULTS 58 cases were enrolled. The overall ASR was 14.1 per million. Males and females were equally affected. The peak incidence was for 15-19 year-olds in both sexes (ASR=10.4 per million in males and 8.5 in females). The 5-year overall survival rate was 27.6% (95% CI: 15.8-40.8%). The median survival time was 1.6 years (95% CI: 1.2-2.1). In a subgroup analysis, the patients who received only chemotherapy survived longer (5-year survival 45.7%, median survival time 4.1 years, p=0.12). CONCLUSION The incidence rate for childhood osteosarcoma was slightly less than those reported for Western countries. The survival rate was also lower than reports from developed countries. Further evaluation of the treatment protocol and risk factor stratification is needed.

Childhood Cancer Incidence and Survival 1985-2009, Khon Kaen, Thailand

BACKGROUND The Khon Kaen Cancer Registry (KKCR) was established in 1984. Previous population-based incidences and survivals of childhood cancer in Thailand were determined using a short cancer registration period. MATERIALS AND METHODS Data were retrieved of all children residing in Khon Kaen, between 0-15 years, diagnosed as having cancer and registered in the KKCR (1985-2009). The follow-up censored date was December 31, 2012. The childhood cancers were classified into 12 diagnostic groups, according to the International Classification of Childhood Cancer. The incidence was calculated by the standard method. Survival of childhood cancer was investigated using the KKCR population-based registration data and overall survival calculated using the Kaplan Meier method. RESULTS In the study period, 912 newly diagnosed cases of childhood cancer were registered. The respective mean and median age was 6.4 (SD=4.6) and 6 (0-14) years. The age-peak for incidence was 0-4 years. The age-standardized rate (ASR) was 83 per million. Leukemia was the most common cancer (N=360, ASR 33.8) followed by neoplasms of the central nervous system (CNS, N=150, ASR 12.8) and lymphoma (N=79, ASR 7.0). The follow-up duration totaled 101,250 months. The death rate was 1.11 per 100 person-months (95%CI: 1.02 -1.20). The 5-year overall survival was 52% (95%CI: 53-56.9) for all cancers. The respective 5-year overall survival for (1) acute lymphoblastic leukemia (ALL), (2) acute non-lymphoblastic leukemia (ANLL), (3) lymphoma, (4) germ cell tumors, (5) renal tumors, (6) retinoblastoma, (7) soft tissue tumors, (8) CNS tumors, (9) bone tumors, (10) liver tumors, and (11) neuroblastoma was (1) 51%, (2) 37%, (3) 63%, (4) 74%, (5) 67%, (6) 55%, (7) 46%, (8) 44%, (9) 36%, (10) 34%, and (11) 25%. CONCLUSIONS The incidence of childhood cancer is lower than those of western countries. Respective overall survival for ALL, lymphoma, renal tumors, liver tumors, retinoblastoma, soft tissue tumors is lower than that reported in developed countries while survival for CNS tumors, neuroblastoma and germ cell tumors is comparable.

Lupus Anticoagulant-hypoprothrombinemia Syndrome (LAC-HPS) in Children With Systemic Lupus Erythematosus: Report of 3 Cases

Lupus anticoagulant, also known as lupus antibody, is generally associated with thrombosis rather than bleeding events. Lupus anticoagulant-hypoprothrombinemia syndrome in children is rather rare but can lead to mild to life-threatening bleeding. Here, we report 3 cases of lupus anticoagulant-hypoprothrombinemia syndrome associated with systemic lupus erythematosus. They initially presented with mucocutaneous bleedings, and subsequently developed other symptoms fulfilling the laboratory criteria for systemic lupus erythematosus. Case 2 and 3 had significant epistaxis and intracerebral hemorrhage responded to systemic corticosteroid along with fresh frozen plasma. Three cases demonstrated acquired hypoprothrombinemia with no correction of mixing studies. Case 1 had low factor X level, which has never been reported previously. In all 3 cases, their coagulogram returned to normal level after corticosteroid treatment.

Incidences, Trends and Long Term Outcomes of Retinoblastoma in Three Cancer Registries, Thailand.

BACKGROUND Retinoblastoma (RB) is rare, albeit the most common primary intraocular malignancy among children. To elucidate the true incidence, trend and survival, we studied incidences and trends of retinoblastoma in a large population with long-term follow-up using data from 3 population-based cancer registries. OBJECTIVE To describe the incidence, trends and survival of RB between 1990 and 2009 in Khon Kaen, Songkhla and Chiang Mai, Thailand. MATERIALS AND METHODS We sourced the data from the cancer registries in Khon Kaen, Songkhla and Chiang Mai on children with retinoblastoma, diagnosed between 1990 and 2009. Retinoblastoma was defined as per the International Classification of Disease for Oncology version 3 using the code 9510/3. Incidence was analyzed using the standard method with the criteria of the International Association of Cancer Registries. The Kaplan-Meier method was applied to calculate cumulative survival. Trends were calculated using the log rank test. RESULTS We identified 75 cases of children between 0 and 15 years of age diagnosed with RB (Khon Kaen 31, Chiang Mai 20, Songkhla 24). Males and females were equally affected. The most common age group was 0-4 years. The morphological verification of the disease was 90.7%. The respective ASR in Khon Kaen, Chiang Mai and Songkhla was 4.4, 4.0 and 4.6 per million; for which the overall ASR for all 3 areas was 4.3 per million. The respective trend in incidence was 4, 2.8, 5.8 and 5.4 during 1990-4, 1995-9, 2000-4 and 2005-9. Overall, incidence trended gradually upward by 2% annually. The respective survival rate in Khon Kaen, Chiang Mai and Songkhla was 50, 40 and 75% (differences not significantly different at p=0.14) and the overall survival for all centers was 60%. CONCLUSIONS Over the last two decades, the incidence and overall survival of retinoblastoma has increased. The ASRs and survival in Thailand were less than those in resource-rich countries.