Treatment outcomes of pediatric acute myeloid leukemia: a retrospective analysis from 1996 to 2019 in Taiwan.

Improvement in outcomes of children with acute myeloid leukemia (AML) is attributed to several refinements in clinical management. We evaluated treatment outcomes of Taiwanese pediatric AML patients in the past 20 years. Overall, 860 de novo AML patients aged 0-18 years and registered in the Childhood Cancer Foundation of R.O.C during January 1996-December 2019 were included. Survival analysis was performed to identify factors that improved treatment outcomes. Regardless of treatment modalities used, patients during 2008-2019 had better 5-year event-free survival (EFS) and overall survival (OS) rates than patients during 1996-2007. For patients received the TPOG-AML-97A treatment, only 5-year OS rates were significantly different between patients diagnosed before and after 2008. Patients with RUNX1-RUNX1T1 had similar relapse-free survival rates, but 5-year OS rates were better during 2008-2019. However, the survival of patients who received hematopoietic stem-cell transplantations (HSCT) did not differ significantly before and after 2008. For patients without relapse, the 5-year OS improved during 2008-2019. Non-relapse mortality decreased annually, and cumulative relapse rates were similar. In conclusion, 5-year EFS and OS rates improved during 2008-2019, though intensities of chemotherapy treatments were similar before and after 2008. Non-relapse mortality decreased gradually. Further treatment strategies including more intensive chemotherapy, novel agents' use, identification of high-risk patients using genotyping and minimal residual disease, early intervention of HSCT, and antibiotic prophylaxis can be considered for future clinical protocol designs in Taiwan.

Pediatric acute lymphoblastic leukemia with t(1;19)/TCF3-PBX1 in Taiwan.

BACKGROUND: In childhood acute lymphoblastic leukemia (ALL), t(1;19)(q23;p13.3) with TCF3-PBX1 fusion is one of the most frequent translocations. Historically, it has been associated with poor prognosis. Intensive treatment, however, has improved its outcome. We determined the outcome of children with this genotype treated with contemporary intensive chemotherapy in Taiwan. PROCEDURE: In Taiwan Pediatric Oncology Group 2002 ALL studies, genotypes were determined by cytogenetic analysis and/or reverse transcriptase polymerase chain reaction assay. Based on presenting features, immunophenotype and genotype, patients were assigned to one of the three risk groups: standard risk (SR), high risk (HR), or very high risk (VHR). The patients with t(1;19)/TCF3-PBX1 were treated in the HR arm receiving more intensive chemotherapy. The outcomes of patients with t(1;19)/TCF3-PBX1 were compared to that of patients with other subtypes of B-precursor ALL (B-ALL). RESULTS: Of the 1,129 patients with B-ALL, 64 (5.7%) had t(1;19)/TCF3-PBX1; 51 of whom were treated in the HR arm, but 11 were treated in the VHR and 2 in the SR arm because of physician's preference. As a group, 64 patients with t(1;19)/TCF3-PBX1 had similar 5-year event-free survival (83.3 ± 4.8%) as those with TEL-AML1 (85.2 ± 3.4%, P = 0.984) or those with hyperdiploidy >50 (84.0 ± 3.1%, P = 0.748). The cumulative risk of any (isolated plus combined) central nervous system relapse among patients with t(1;19)/TCF3-PBX1 (8.7 ± 3.8%) tended to be higher than that of patients with TEL-AML1 (5.8 ± 2.3%, P = 0.749) or those with hyperdiploidy (4.1 ± 1.8%, P = 0.135), albeit the differences did not reach statistical significance. CONCLUSIONS: With contemporary intensive chemotherapy, children with t(1;19)/TCF3-PBX1 fared as well as those with favorable genotypes (TEL-AML1 or hyperdiploidy).

Treatment for childhood acute lymphoblastic leukemia in Taiwan: Taiwan Pediatric Oncology Group ALL-2002 study emphasizing optimal reinduction therapy and central nervous system preventive therapy without cranial radiation.

BACKGROUND: Reinduction therapy has improved the outcomes in children with acute lymphoblastic leukemia (ALL). We sought to determine the optimal course(s) of reinduction therapy for standard-risk (SR, or "low-risk" in other groups) patients. Also, we evaluated outcomes using triple intrathecal therapy without cranial radiation (CrRT) for central nervous system (CNS) preventive therapy. PROCEDURE: From 2002 to 2012, all newly diagnosed children with ALL in Taiwan were enrolled in Taiwan Pediatric Oncology Group ALL-2002 protocol. SR patients were randomized to receive single or double reinduction courses. The patients enrolled before 2009 received CrRT, while those enrolled later did not. The Kaplan-Meier method was used to estimate survival rates and the difference between two groups was compared by the two-sided log-rank test. RESULTS: In 1,366 eligible patients, the 5-year overall survival (OS) was 81.6 ± 1.1% (standard error) and 5-year event-free survival (EFS) was 74.3 ± 1.2%. In SR patients, the 5-year OS for one and two reinduction courses was 91.6 ± 2.1% and 93.7 ± 1.8%, respectively, and the 5-year EFS was 85.2 ± 2.7% and 89.8 ± 2.3%, respectively. There were no significant differences in survival between these two groups. Patients with MLL or BCR-ABL1 had the worst outcomes: 5-year EFS was 23.4 and 31.8% and 5-year OS was 28.6 and 44.7%, respectively. There was no significant difference in CNS relapse or survival between the era with or without CrRT. CONCLUSIONS: For SR patients, one-course reinduction was adequate. Triple intrathecal therapy alone successfully prevented CNS relapse.

Thrombocytopenic purpura following vaccination in early childhood: experience of a medical center in the past 2 decades.

BACKGROUND: The etiology of thrombocytopenia during infancy and early childhood may be different from that of older children, because young children frequently receive vaccines. The following study was performed to understand whether there was a causal relationship between vaccinations and thrombocytopenia. METHODS: We retrospectively studied, through chart review, the relationship between vaccination and thrombocytopenic purpura in 20 children with thrombocytopenia (platelet count < 150 x 10³/mm³) under the age of 3 years who were hospitalized between 1989 and 2010. Cases with a history of infectious symptoms/signs between vaccination and the occurrence of thrombocytopenia were excluded. Thrombocytopenia cases not diagnosed as idiopathic thrombocytopenic purpura but as post-vaccination thrombocytopenic purpura should have a similar vaccination-to-thrombocytopenia interval as reported in Western journals, but which should not be more than 9 weeks after vaccination. RESULTS: Of the 20 cases of thrombocytopenic purpura, 12 followed vaccination and 8 were considered idiopathic. Of the 12 post-vaccination cases, 5 occurred after the second dose of hepatitis B virus vaccine at 1 month of age, 4 occurred after the first dose of diphtheria-tetanus-acellular pertussis-containing vaccine at 2-3 months of age, 2 occurred after the first dose of measles-mumps-rubella vaccine at 16 months of age, and 1 occurred after the first dose of varicella vaccine at 14 months of age. One of these 12 cases, who also had a marked decrease in hemoglobin level without bleeding, was suspected to have Evans syndrome. CONCLUSION: Vaccination may be a risk factor for infant thrombocytopenic purpura.

Progression from an immature teratoma with miliary gliomatosis peritonei to growing teratoma syndrome with nodular gliomatosis peritonei.

A 4 1/2-year-old girl presented with an incompletely resected, huge, immature abdominal teratoma, elevated serum alpha-fetoprotein (AFP), and numerous miuiary gliomatosis peritonei (GP). Two courses of chemotherapy resulted in normalization of her AFP level and marked tumor shrinkage. Further chemotherapy was interrupted by complications. During treatment for these complications, ascites increased and the tumor enlarged, but serum AFP remained within the normal range. Second-took surgery revealed that the tumor had changed histologically to a mature teratoma, and GP had enlarged to nodular size, causing massive ascites. The still incompletely resected, growing mature teratoma was reduced with interferon. Nodular GP and ascites slowly regressed with interferon use, and finally disappeared after several months. One residual mass thought to be GP was reduced by gamma-knife surgery 3 years later.

Retinoblastoma with spinal recurrence presenting as spinal cord compression.

Central nervous system (CNS) involvement is not rare in extraocular retinoblastoma, and it is not surprising to find it in view of its route of spread. However, although spinal recurrence presenting as spinal cord compression (SCC) is a form of CNS involvement, it is extremely rare. This report describes two patients with unilateral retinoblastoma with spinal recurrence presenting as SCC. The first patient developed erythematous swelling of the right foot and weakness of the bilateral lower limbs at 7 months after left enucleation. Examination revealed pitting edema of bilateral feet and muscle power of 2+ to 3+, with intact sensory function. The second patient developed weakness of the bilateral lower limbs, and defecative and urinary difficulty for 2 days at 8 months after left enucleation. Examination revealed pitting edema of bilateral feet and muscle power of 2+, with defective sensory function. Both patients received surgery and local irradiation after SCC. The first patient refused chemotherapy and survived only 4 months due to disease progression. The second patient received systemic and intrathecal chemotherapy, and survived 19.5 months without disease progression. Spinal recurrence with SCC should be suspected when leg weakness or bowel or bladder disturbance occurs in patients with retinoblastoma.

Retinoblastoma in Taiwan: survival rate and prognostic factors.

PURPOSE: The mortality rate of patients with retinoblastoma still varies in developing countries, and data for Asia and Taiwan are relatively scarce. In this retrospective study, we aimed to describe the survival characteristics and prognostic factors of 54 retinoblastoma cases diagnosed at the Taipei Veterans General Hospital between 1982 and 2004. METHODS: From medical records, we retrospectively analyzed the data of 54 consecutive children diagnosed in our hospital between 1982 and 2004 as having retinoblastoma. Data on sex, laterality, age at diagnosis, presenting signs, family history, duration of symptoms, lag time for treatment, spread of tumor, treatment mode, and survival time were collected. RESULTS: Seventy-five percent of the cases were unilateral and 25% of the cases were bilateral. The mean patient age at the time of diagnosis was 26.3 months. The mean duration of symptoms was 2.96 months. After diagnosis, the mean lag time before treatment was 2.59 months. The most common presenting signs were leukocoria (71.4%), red, painful, or tearing eye (18.4%), strabismus (14.3%), and blurred vision (14.3%). Only 3 of 52 cases (5.8%) were familial. The most common sites of extraocular invasion included the central nervous system (seven cases) and the orbit (seven cases). In 13.7% of the cases, parents had refused the treatment suggested by the doctors. None of the patients developed a secondary neoplasm. The 5-year overall survival rate was 80.9% (unilateral, 88.1%; bilateral, 64.3%). The survival rate of patients with an interval between onset and treatment of <5 months was 90.9%, and that for an interval of >5 months was 60.9%. The survival rate of those with a lag time of <2.5 months was 90.0%, and that of those with one of >2.5 months was 31.3%. The survival rate of patients with intraocular and extraocular disease was 96.9% and 39.2%, respectively. Extraocular disease was an independent factor indicating a poor prognosis, determined by multivariate analysis. CONCLUSIONS: The mortality rate of patients with retinoblastoma is higher in Taiwan than in developed countries. The proportion of patients' parents refusing or delaying treatment in Taiwan is high. The factors for a poor prognosis were an interval between onset and treatment of >5 months, a lag time before treatment of >2.5 months, and extraocular disease. The duration of symptoms was not a prognostic factor. The only independent factor indicating a poor prognosis was extraocular disease.

Orbital metastatic osteosarcoma.

A 15-year-old girl with right tibial osteosarcoma, diagnosed 22 months previously, developed right orbital and skull base metastases, with symptoms including painful protrusion of the right eyeball and severe visual impairment. She underwent embolization of the metastatic tumor, local irradiation, and chemotherapy followed by intralesional resection of the mass because extensive involvement of the skull base precluded complete surgical resection. The best corrected visual acuity in her right eye initially decreased to 20/200, then dropped to no light perception after embolization, and then improved to counting fingers at 50 cm after radiotherapy. The symptoms of pain and proptosis subsided completely. After 24 months of follow-up from the presentation of orbital metastasis, the patient's right-eye vision remained unchanged. The surgical specimen revealed a necrotic tumor similar to osteosarcoma. In conclusion, orbital metastasis of osteosarcoma is rare, but may lead to severe visual impairment. Combined radiotherapy, chemotherapy and surgery can partially relieve symptoms, but cannot completely eradicate the tumors.

Deep sedation with methohexital or thiamylal with midazolam for invasive procedures in children with acute lymphoblastic leukemia.

Pediatric oncology/hematology patients, especially those with acute lymphoblastic leukemia (ALL), often undergo repeated painful invasive procedures. Deep sedation, mandatory for these procedures in young children, can reduce patient anxiety and get their compliance during procedures. This study assessed clinical experience of employing methohexital or thiamylal with midazolam as sedative for elective invasive procedures in children with ALL. Between November 1997 and March 2004, 20 out of 33 ALL children received deep sedation after evaluation, mainly because of relatively young age (mean age 4.60 +/- 2.03 years). A total of 176 procedures were done, with 139 being intrathecal therapy. There were 98 and 78 procedures for the methohexital and thiamylal groups, respectively. The average dosages to complete the procedures were 2.2 +/- 1.2 mg/kg for methohexital and 3.4 +/- 2.1 mg/kg for thiamylal. One out of the 176 procedures was failed due to bradycardia, hypotension and cyanosis, in the methohexital group. Otherwise, no significant adverse events were found. Increased heart rate (HR) during stable blood pressure (BP) was observed in both groups. In conclusion, under careful monitoring and performed by experienced practitioners, the application of methohexital or thiamylal combined with midazolam to achieve deep sedation for invasive procedures in young children with ALL is safe.

Epidemiology, clinical features and treatment outcome of Wilms' tumor in Taiwan: a report from Taiwan Pediatric Oncology Group.

BACKGROUND AND PURPOSE: Taiwan Pediatric Oncology Group (TPOG)-W-91 is the first multi-institutional Wilms' tumor study for children in Taiwan. This clinical trial used a multidisciplinary approach, based on and similar to the National Wilms' Tumor Study 4. The study was conducted to evaluate the epidemiological characteristics and analyze the outcome of Wilms' tumor patients treated with this protocol. METHODS: Ninety eight children with Wilms' tumor (WT) were analyzed for distributions of age, gender, associated congenital anomalies, tumor sites, histology, tumor weights, and clinical stages. Patients received individualized multimodality treatment based upon the histology of the tumor and clinicopathologic stage. The treatment included surgery, radiotherapy and 2-, 3-, and 4-agent active chemotherapeutic agents. Seventy patients were eligible for analysis of treatment outcome. The endpoints were progression-free and overall survival (PFS, OS). Patients were divided into various subgroups according to the chemotherapy regimen used, tumor stage, age at diagnosis, gender, and tumor weight. The prognostic factors were evaluated and the survival rates of various clinical subgroups were compared using log-rank test. RESULTS: The average annual incidence rate of WT was 2.9 per million children under 15 years of age. The M/F ratio was 1.04. The mean age at diagnosis was 3.7 years. All bilateral tumors occurred in females. Congenital anomalies were present in 17.3% of patients. Anaplastic histology was found in 6 of 98 cases (6.1%). The stage distribution was: I, 43.2%; II, 19.3%; III, 23.9%; IV, 6.8%; and V, 6.8%. The median follow-up time was 89.1 months (range, 1.8 to 128.1 months). The 5-year PFS rate was 0.7841 (SE, 0.0494; 53 of 70 patients) and the 5-year OS rate was 0.886 (SE, 0.038; 63 of 70 patients). Gender was found to be the only significant prognostic variable. CONCLUSIONS: This study evaluated the epidemiological characteristics, clinical features, multimodality therapy regimens, and treatment outcome of WT in Taiwan. Data obtained from this study may lead to further improvement in the prognosis of pediatric malignant solid tumor.

Leukemic infiltration of the urinary bladder presenting as uncontrollable gross hematuria in a child with acute lymphoblastic leukemia.

Acute leukemia can result in leukemic infiltration of many organs, but leukemic infiltration of the bladder is rare. The authors describe an 8-year-old girl with acute lymphoblastic leukemia who, during marrow relapse, had uncontrollable gross hematuria secondary to leukemic infiltration of the bladder. Cystoscopic biopsy confirmed the diagnosis. Literature review revealed 13 cases of acute leukemia with bladder involvement. Although leukemic infiltration of the bladder is rare, it should be considered in patients with acute leukemia and hematuria. Urine cytology might help detect bladder involvement.

Ganglioneuroma presenting as an asymptomatic huge posterior mediastinal and retroperitoneal tumor.

Ganglioneuroma is a rare, differentiated, benign and slow-growing tumor that commonly arises from sympathetic ganglion cells. Most of them are asymptomatic and found incidentally. We here report a quite rare case of silent huge ganglioneuroma growing in both posterior mediastinum and retroperitoneum occurring in a 3.5-year-old girl. The patient was relatively well before and incidentally found to have a huge chest mass by chest X-ray film at an episode of respiratory tract infection. Computed tomography showed a huge tumor extending from bilateral posterior mediastinum to the level of the adrenal gland in the retroperitoneum. Initially, neuroblastoma was highly suspected and 24-hour urine vanillyl mandelic acid was slightly elevated. Cytology by bone marrow aspiration revealed no tumor nests or clumps. Biopsy and pathology proved it as ganglioneuroma (GN). Due to too extensive involvement of the tumor and compression of the vital vessels, surgical removal became difficult. The family of the patient refused surgery due to there being no significant symptoms. Because of the potential for growth of unresectable GN and because the component of neuroblasts could not be completely excluded, the patient was still in dangerous status. The only thing we can do is to keep the family alert and continue regular follow-up.

Childhood Langerhans cell histiocytosis increased during El Niño 1997-98: a report from the Taiwan Pediatric Oncology Group.

From 1995-1999, a nation-wide study of Langerhans cell histiocytosis (LCH) in children less than 15 years old was conducted by the Taiwan Pediatric Oncology Group. The demographic and clinical data of 55 cases were analyzed. Thirty-two cases presented from the beginning of 1997 to the end of 1998, when the most severe El Niño in the century occurred. The incidence was higher than expected during this El Niño period (32 cases versus 22 cases, p = 0.003). During 1997-98, most LCH was diagnosed in summer (n = 15), autumn (n = 8), and winter (n = 8) but rarely in spring (n = 1); coincidentally, rainfall was least in winter but peaked in summer. During 1997-98, the most significant increase occurred in the polyostotic LCH subcategory (p = 0.017), with younger ages at diagnosis (p = 0.039). The incidence of LCH cytopenia, fever, and diseases of the skin, liver, spleen or other organs did not differ significantly. Local treatment modality, disseminated diseases and diagnosis during the El Niño of 1997-98 were independent risk factors predicting the recurrence or progression of LCH. Our findings suggest that particular infections or other environmental factors associated with El Niño might be related to the etiology of childhood LCH.