Characteristics and outcomes of second cancers in patients with childhood cancer: A report from the Taiwan Pediatric Oncology Group.

BACKGROUND: Patients with childhood cancer are at increased risk for the development of second cancers. METHODS: A national multicenter survey of second cancers conducted by the Taiwan Pediatric Oncology Group retrieved retrospective data from the database at the Children Cancer Foundation in Taiwan beginning in 1995. The characteristics of second cancers and associations of patient demographic and clinical characteristics with time to death due to a second cancer were analyzed. RESULTS: We examined the records of 8782 patients with a primary cancer diagnosed between January 1, 1995 and December 31, 2013, and a total of 99 patients with a second cancer were identified. The most common type of second cancer was acute myeloid leukemia (n = 35), followed by acute lymphoblastic leukemia (n = 15), central nervous system (CNS) tumors (n = 15), and sarcomas (n = 10). Secondary hematological malignancies occurred earlier than other secondary cancers. The frequencies of second CNS tumors and second bone cancers and sarcomas were notably increased when prior radiation doses increased from zero, low dose to high dose. The overall 5-year survival of patients with a second cancer was poor (33.7%). Multivariate survival analysis revealed that the year of primary diagnosis ≤2002, secondary hematological malignancies, and age at second cancer diagnosis ≤9.3 years or >26.8 years increased the risk of death following second cancer. CONCLUSION: Children who develop a second cancer have an unfavorable outcome. Early detection and improved treatment for second cancers are needed.

Treatment of childhood acute lymphoblastic leukemia with delayed first intrathecal therapy and omission of prophylactic cranial irradiation: Results of the TPOG-ALL-2002 study.

BACKGROUND: To eliminate cranial irradiation (CrRT)-related sequelae and to minimize the adverse impact of traumatic lumbar puncture (TLP) with blasts, the Taiwan Pediatric Oncology Group (TPOG) introduced a modified central nervous system (CNS)-directed regimen characterized by delayed triple intrathecal therapy (TIT) and the omission of CrRT for all children with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: This study compared the treatment outcomes of patients overall and patients with a non-CNS-1 status (CNS-2, CNS-3, or TLP with blasts) in 2 treatment eras, one before and another after the revision of the TPOG-ALL-2002 protocol by the introduction of the modification (era 1 [2002-2008] with CrRT and era 2 [2009-2012] with delayed first TIT and no CrRT). RESULTS: There were no statistically significant differences in major outcomes between the 903 patients treated in era 1 and the 444 patients treated in era 2: the 5-year event-free survival (EFS) rates were 75.7% ± 1.4% and 72.1% ± 2.4%, respectively (P = .260), and the cumulative risks of isolated CNS relapse were 4.0% ± 0.7% and 4.1% ± 1.0%, respectively (P = .960). There were also no differences between non-CNS-1 patients treated in era 1 (n = 76) and era 2 (n =28): the 5-year EFS rates were 52.3% ± 5.8% and 62.9% ± 9.4%, respectively (P = .199), and the cumulative risks of isolated CNS relapse were 6.3% ± 3.1% and 3.6% ± 3.5%, respectively (P = .639). Notably, TLP with blasts was completely eliminated after the first TIT was delayed in era 2. CONCLUSIONS: The delay of the first TIT until the clearance of circulating blasts and the total omission of CrRT did not compromise survival or CNS control in patients with childhood ALL, including those with a non-CNS-1 status.

Mutational status of NRAS, KRAS, and PTPN11 genes is associated with genetic/cytogenetic features in children with B-precursor acute lymphoblastic leukemia.

BACKGROUND: We aimed to investigate the frequencies and the association with genetic/cytogenetic abnormalities as well as prognostic relevance of RAS pathway mutations in Taiwanese children with B-precursor acute lymphoblastic leukemia (ALL), the largest cohort in Asians. PROCEDURE: Between 1995 and 2012, marrow samples at diagnosis from 535 children were studied for NRAS, KRAS, and PTPN11 mutations. The mutational status of each gene was correlated with the clinico-hematological features, recurrent genetic abnormalities, and outcomes for those treated with TPOG-ALL-2002 protocol (n = 346). RESULTS: The frequencies of NRAS, KRAS, and PTPN11 mutations were 10.8% (57/530), 10.2% (54/530), and 3.0% (16/526), respectively. NRAS mutations were associated with a higher frequency of hyperdiploidy (P = 0.01) and lower frequency of ETV6-RUNX1 (P < 0.01), whereas KRAS mutations were associated with younger age (P < 0.01), a higher frequency of KMT2A rearranged (P < 0.01) but no significant difference if infants with ALL were excluded, and inferior event-free survival (66.6% vs. 80.5%, P = 0.04). None of patients with TCF3-PBX1 had KRAS mutation (P = 0.02). CONCLUSIONS: Our study showed that the frequency of KRAS mutations in Taiwan was significantly higher than that reported in Caucasians. The occurrence of RAS pathway mutations was associated with recurrent genetic/cytogenetic abnormalities in pediatric B-precursor ALL.

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.

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).

Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A.

Gene mutations involving epigenetic regulators recently have been described in adult acute myeloid leukemia (AML). Similar studies are limited in children. We analyzed gene mutations and cooperation in pediatric AML with special reference on mutated epigenetic regulators. Nineteen gene mutations, including 8 class I genes, 4 class II genes, WT1 and TP53 (class III), and 5 epigenetic regulator genes (class IV), were analyzed in 206 children with de novo AML. Mutational analysis was performed with polymerase chain reaction-based assay followed by direct sequencing. One hundred seventeen of 206 patients (56.8%) had at least one mutation: 51% class I, 13% class II, 6.8% class III, and 5.6% class IV. FLT3-internal tandem duplication was most frequent, and 29% of patients had more than one gene mutation. Two patients carried ASXL1 mutations, both with t(8;21), 2 had DNMT3A mutations, 2 had IDH1 mutations, 1 had IDH2 mutation, and 3 had TET2 mutations. Both patients with IDH1 mutations had AML-M0 subtype and MLL-partial tandem duplication. Cooperating mutations with mutated epigenetic regulators were observed in 8 of 10 patients. We conclude that mutated epigenetic regulators were much less than those in adult AML but with frequent cooperating mutations. ASXL1, TET2, and IDH1 mutations were associated with specific genetic subtypes.

Single-institution Experience of Unrelated Cord Blood Transplantation for Primary Immunodeficiency.

Pediatric patients with primary immunodeficiencies (PID) constitute life-threatening medical emergencies. In the absence of an HLA-identical hematopoietic stem cell donor, unrelated donor cord blood transplantation (CBT) is another treatment option. There are little data regarding the outcome of unrelated CBT for PID in Taiwan. We report the results of CBT performed in 8 patients with PID between 2004 and 2013 at Chang Gung Memorial Hospital. The cases included severe combined immunodeficiency (n=4), chronic granulomatous disease (n=2), Wiskott-Aldrich syndrome (n=1), and T-cell immunodeficiency (n=1). Median follow-up time was 73 months. Most UCB recipients received a myeloablative conditioning regimen. There were 7 boys and 1 girl with a median age of 2.5 months at diagnosis (range, antenatal to 17 mo). Median age at transplant was 5.5 months (range, 2 to 74 mo). All but 1 patients engrafted at a median time of 14 days. One developed significant grade III graft-versus-host disease after transplant. Our data show that unrelated CBT in PID is possible. However, no definite conclusions can be drawn from this small number of patients, and more studies are needed to further investigate and confirm these findings.

Successful hematopoietic reconstitution by unrelated donor cord blood transplantation in children with Fanconi anemia: report of 3 cases.

To potentially reduce late effects of malignancy and chronic graft-versus-host disease in patients with Fanconi anemia, 3 patients received unmanipulated umbilical cord blood grafts with 0 or 1 HLA antigen mismatch. The conditioning regimen consisted of fludarabine (30 mg/m/d) for 6 days, cyclophosphamide (60 mg/kg/d) for 2 days, and rabbit antithymocyte globulin (ATG) (2.5 mg/kg/d) for 3 days. Radiation was not used in the preparative regimen. None of the patients had significant conditioning-related toxicity. All were engrafted within 10 to 19 days. All patients are well with stable or full donor chimerism after a median follow-up of 64 months (range, 13 to 69 mo).

Phyllodes tumor in survivors of childhood osteosarcoma: a single institution's experience.

We evaluate the incidence of second neoplasms in 86 patients with osteosarcoma (OS) of the extremities treated with different protocols of adjuvant chemotherapy. Three patients developed phyllodes tumors as the second neoplasm. One of these patients simultaneously developed a third cancer with therapy-related acute myeloid leukemia. The sites of primary OS were the tibia (2) and humerus (1). None had received prior radiotherapy before excision of phyllodes tumor. All the patients were female with a median age of 21.7 years at the time of presentation. As yet, that precise causation is unclear, but it can increase our understanding of carcinogenic processes, in general.

Outcome of Tocilizumab Treatment in Febrile Neutropenic Children with Severe Sepsis/Septic Shock in a Single-Center Retrospective Case Series.

PURPOSE: To assess the efficacy of an IL-6 blockade with tocilizumab on treatment outcome of severe sepsis/septic shock in children with febrile neutropenia. METHODS: We performed a retrospective study of febrile neutropenic patients younger than 18 years old who developed severe sepsis/septic shock at a single medical center between November 2022 and October 2023. RESULTS: Seven patients with febrile neutropenia complicated with severe sepsis/septic shock were identified. Four of seven patients received tocilizumab in addition to standard of care. The median IL-6 level before administration of tocilizumab was 14,147 pg/mL (range: 672-30,509 pg/mL). All four patients successfully recovered from severe sepsis/septic shock. Three of seven patients received standard of care without tocilizumab. IL-6 levels were checked intwo2 patients, with a median of 1514.5 (range: 838-2191). Only one of three (33%) patients without tocilizumab therapy made a full recovery from severe sepsis/septic shock. The mortality rate was higher in patients without tocilizumab therapy compared to patients with tocilizumab therapy (67% vs. 0%). CONCLUSIONS: Administration of tocilizumab reduced mortality of severe sepsis/septic shock in children with febrile neutropenia. However, it warrants confirmation with a larger number of patients and a longer follow-up.

Psychosocial and emotional adjustment for children with pediatric cancer and their primary caregivers and the impact on their health-related quality of life during the first 6 months.

PURPOSE: To evaluate caregiver-reported psychosocial adjustment and health-related quality of life (HrQoL) of Taiwanese children with newly diagnosed cancer and their caregivers during the first 6 months of treatment. METHODS: Caregivers of 89 newly diagnosed children completed the child behavior checklist, the pediatric quality of life inventory (PedsQL(™) 4.0), the Parenting Stress Index, and the SF-36 questionnaire at diagnosis, and again 3 and 6 months into treatment. They were compared with a group of age- and sex-matched controls from general community. RESULTS: Significantly worse HrQoL in both children and their caregivers and greater parenting stress were noted in the cancer group than the controls during the first 6 months. Children with cancer were found to have significantly more internalizing behavioral problems and somatic complaints, especially those younger than 12 years old. After starting chemotherapy, significant decrease in parenting stress and improvements of both caregivers and children's HrQoL were noted within the first 6 months, although not to the level comparable with normal controls. CONCLUSIONS: Although children and their caregivers can adjust themselves gradually during the first 6 months after diagnosis of cancer, intervention and efforts aimed at reducing their distress and promoting adjustments are still required during this period.

Catheter-related bloodstream infection with removal of catheter in pediatric oncology patients: a 10-year experience in Taiwan.

BACKGROUND: Long-term central venous catheter (CVC) implantation has become more affordable in Taiwan since 1995. Surgical removal of the catheter may be the essential treatment for catheter-related bloodstream infections (CRBSI). The aim of this study was to evaluate the clinical features and microbial isolates in pediatric cancer patients with removal of CVC for CRBSI. PROCEDURE: The records of positive blood culture from hospitalized pediatric oncology patients between 1995 and 2004 were reviewed. One hundred and forty-three patients implanted with a long-term CVC were further identified. RESULTS: Seventeen catheters in 16 patients developed catheter-related bacteremia that needed catheter removal. The rate of catheter removal was 11.9%. The median device life was 7.7 months. Six catheters were removed within 3 months of insertion. Nine of the 17 catheters were removed from patient younger than 2 years. Eight infections occurred during severe neutropenia, and 6 patients had refractory or relapsed underlying disease. The cultural isolates were Gram-negative bacilli in 7, Gram-positive in 5, fungi in 5, and atypical mycobacterium in 1. The frequency of catheter removal for infection control was significantly higher in the first 5 years (1994-1999) compared to the last 5 years (2000-2004) (30.9 vs. 4.0%, p = 2.3 × 10(-4)). CONCLUSIONS: Factors such as microbiological isolates, age of infection, the status of malignancy, and neutropenia are related to catheter outcome. The reduction in patients with positive cultures needing removal of the catheters can be related to improved nursing care and more aggressive antibiotic therapy.

Cord blood transplantation in children with relapsed or refractory severe aplastic anemia.

Early results of cord blood transplantation (CBT) for severe aplastic anemia were poor with a high rate of engraftment failure. We carried out CBT in 5 children with relapsed or refractory severe aplastic anemia, using immunosuppressive preparative regimens. The median time from the diagnosis to the CBT was 16 months (15 to 47 mo), with all the children having failed at least 1 course of immunosuppressive therapy. The conditioning regimens consisted of fludarabine, cyclophosphamide, and antithymocyte globulin. One patient had an HLA-identical sibling donor, and 4 had unrelated donors selected from an NMDP-affiliated cord blood bank. Two patients received double-unit grafts to attain a target TNC dose of at least 3.0×10/kg. Donor/recipient HLA matching was 6 of 6 (n=2) and 5 of 6 (n=5). The median nucleated cell dose infused was 5.6 (range, 3.6 to 6.1) ×10 cells/kg. The median infused CD34 dose was 2.9 (range, 1.8 to 7.5) ×10 cells/kg. All the patients achieved neutrophil engraftment at a median of 13 days (range, 11 to 25 d). The median time to platelet engraftment was 48 days (range, 34 to 56 d). After CBT, acute GVHD developed in 4 cases, CMV reactivation in 1, pneumonia in 1, and sepsis in 1. Four patients successfully engrafted, but 1 failed to engraft and had delayed autologous recovery. However, all patients were now transfusion-independent at the time of reporting. This result suggests that CBT using optimal conditioning regimens can be a salvage treatment for patients without a suitable bone marrow donor and warrants further prospective studies.

Treatment outcomes for hepatoblastoma: experience of 35 cases at a single institution.

BACKGROUND/PURPOSE: Hepatoblastoma is the most common malignant liver tumor in children. Comparative studies have elucidated the optimal pre- or postoperative chemotherapeutic regimens. The aim of this study was to investigate the prognostic significance of baseline tumor characteristics for overall survival and disease-free survival in children with hepatoblastoma. METHODS: There were 19 male and 16 female children with a median age of 19 months at diagnosis (range: 1-169 months) in our institution between February 1990 and June 2009. We reviewed the clinical presentation, serum α-fetoprotein level at diagnosis, histological subtype, treatment, and outcomes. RESULTS: Twenty-seven patients (78%) underwent neoadjuvant chemotherapy. The majority of patients subsequently underwent either hemihepatectomy (56%) or bisegmentectomy (16%). Only six patients underwent extended hepatic resection, and one of them required rescue liver transplantation. During follow-up, six patients died of progressive disease and two of perioperative mortality. Four of the six who died had pulmonary metastases at the time of diagnosis or follow-up. The median survival time was 28 months (range: 1-181 months). Five-year overall survival was 67.7% (95% confidence interval: 52.0-87.8%) and disease-free survival was 60.2% (95% confidence interval: 41.9-86.5%). CONCLUSION: The potential down-staging effect of neoadjuvant chemotherapy on hepatoblastoma might facilitate remission and convert unresectable tumors into operable ones.

Cytogenetic aberration in mixed-phenotype acute leukemia in children: A single-center retrospective review.

BACKGROUND: Mixed-phenotype acute leukemia (MPAL) poses a diagnostic and therapeutic dilemma. No consensus exists on the strategy to assign patients with MPAL to either lymphoid- or myeloid-directed treatment. Thus, a better understanding of the characteristics of MPAL is a crucial unmet need. This study aims to provide information on a population-based cohort of children who received treatment based on standard, simple immunophenotypic criteria. METHODS: Single-center, retrospective clinical and laboratory reviews of patients with MPAL were provided by morphology, immunophenotyping, cytogenetics, and molecular methods. We identified 242 flow cytometry samples. Of all consecutive pediatric patients with acute leukemia, we identified 8 (3.3%) patients with MPAL fulfilling WHO 2016 criteria; these were classified as follows: B-lymphoid + myeloid (n = 4), T-lymphoid + myeloid (n = 2), and B + T-lymphoid (n = 2). RESULTS: Of 8 MPAL cases, 4 were boys and 4 girls [median age at diagnosis: 10.8 (range 1.1-17) years]. The b3a2 (p210) and e1a2 (p190) BCR/ABL fusion transcripts were detected in 1 patient with B/myeloid MPAL. Regarding the morphology, all patients were initially diagnosed as acute lymphoblastic leukemia, but no morphological characteristics or cytogenetic aberration was particularly predictive of an MPAL. Furthermore, 4 of 8 patients (50%) with MPAL were associated with chromosome 21 monosomy or partial trisomy. CONCLUSION: Despite no single recurrent chromosomal abnormality that could serve as a hallmark lesion in MPAL, cytogenetic alterations are frequent and predominantly associated with complex karyotype involving chromosome 21 abnormalities.

Malignant sacrococcygeal germ cell tumors in children in Taiwan: A retrospective single-center case series.

ABSTRACT: Although the incidence of malignant sacrococcygeal germ cell tumors (MSGCTs) is high in the East Asian countries, information about MSGCTs from this region is limited. This report aimed to analyze the data of children with MSGCTs in a single medical center in Taiwan.Patients aged 18 years or younger with primary MSGCTs or malignant recurrence of a sacrococcygeal teratoma who underwent surgery during the neonatal period between January 1999 and December 2016 were identified from the Linkou Chang Gung Cancer Center registry. The clinical features, laboratory data, and treatment outcomes were reviewed.Fifteen children (1 man and 15 women) with MSGCTs were identified. Sacrococcygeal tumors were present at birth in 7 patients. All patients presented with a bulging mass at the buttock region and they had normal alpha-fetoprotein levels at the time of diagnosis. They underwent primary excision of the tumor. Immature teratoma was histologically diagnosed in 5 neonates, and mature teratoma in 2. Only 1 patient with grade 3 immature teratoma received adjuvant chemotherapy. Two patients with mature teratoma developed malignant recurrence 1.6 and 2.1 years later, respectively. Eight patients were diagnosed with MSGCTs after the neonatal period. The common presenting symptoms included buttock asymmetry (37.5%), abdominal distension (25%), and constipation (12.5%). Seven patients had elevated alpha-fetoprotein levels for their age. They were administered neoadjuvant chemotherapy followed by tumor excision if a residual tumor was present. The histology of the excised tumor included mature teratoma (66.7%) and necrosis (33.3%). One patient with a normal alpha-fetoprotein level underwent primary tumor excision followed by adjuvant chemotherapy. Grade 2 immature teratoma with embryonal carcinoma was diagnosed histologically. Among the 15 patients with MSGCTs, 3 had a recurrence (at age of 2.1, 0.5, and 2.4 years, respectively) and 1 died (at age of 6.1 years) of disease progression. The 5-year overall and event-free survival rates were 90% and 80%, respectively.Children with MSGCTs had good overall prognoses in this case series. For those with sacrococcygeal mature teratoma or low-grade immature teratoma in the neonatal period, we recommend close follow-up for at least 3 years after surgery to detect malignant recurrence.

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.

Transplantation of unrelated donor umbilical cord blood for nonmalignant diseases: a single institution's experience with 45 patients.

The potential benefits of unrelated donor bone marrow transplantation are offset by the immunologic complications of graft-versus-host disease (GVHD) and infection. We used cryopreserved umbilical cord blood (UCB) as a strategy to reduce the risks of GVHD and treatment-related mortality (TRM) and improved survival. Data on 45 patients with median age of 4.5 years who received transplants between October 2003 and February 2009 for the treatment of nonmalignant diseases were evaluated. As of May 15, 2009, the median follow-up was 25 months (range: 3-66). The majority (82%) of patients received an HLA-mismatched graft. The median infused total nucleated cell dose was 7.6 x 10(7)/kg and CD34(+) count 4.0 x 10(5)/kg. Primary graft failure was encountered after 4 transplantations (8%). Log-rank tests and Cox regression analyses were used to determine the effects of various demographic, graft-related, and treatment factors on engraftment, GVHD, TRM, graft failure, and survival. Incidences of neutrophil and platelet engraftment were 88% and 82%, respectively. The incidence of severe grade III-IV acute GVHD (aGVHD) was 42%. Five-year overall survival (OS) and disease-free survival (DFS) were 88.1% and 77.1%, respectively. The cumulative incidence of TRM at 2 years was 12.0%. When cell dose and other factors are optimal, unrelated CBT is a promising approach for curative therapy of nonmalignant diseases.

Clinical features, molecular diagnosis, and treatment outcome of infants with leukemia in Taiwan.

BACKGROUND: Infant leukemia is rare and quite distinct from other childhood leukemias. Differentiating between leukemia and transient myeloproliferative disorder (TMD) in phenotypically normal infants is sometimes difficult. The clinical features and molecular analyses for the fusion transcripts of mixed lineage leukemia (MLL) gene rearrangement in infant leukemia have not been well documented in the Chinese population. PROCEDURE: Forty-five consecutive infants diagnosed with leukemia between 1995 and 2007 in a tertiary medical center in Taiwan were studied. Acute lymphoblastic leukemia (ALL) was diagnosed in 23 infants, acute myeloid leukemia (AML) in 21 (including TMD in 4), and juvenile myelomonocytic leukemia (JMML) in 1. RESULTS: The median white count at diagnosis was higher in ALL than in AML (154.4 × 10(9)/l vs. 58.3 × 10(9)/l, P = 0.05). Chromosome 11q23/MLL abnormalities were present in 77% of ALL and 31% of AML. The 5-year event-free survival (EFS) in infant ALL and AML showed no difference (18% vs. 12%, respectively). The only independent predictor of an adverse prognosis among infants diagnosed with ALL was high presenting white count ≥ 100 × 10(9)/l (P = 0.05). However, no factor was associated with an adverse outcome for infants with AML. CONCLUSIONS: The molecular assessments and prognostic factors of infant leukemia in Taiwan mirror those in developed Western countries. Continued molecular investigations and development of more effective therapies are needed.

Frequencies of ETV6-RUNX1 fusion and hyperdiploidy in pediatric acute lymphoblastic leukemia are lower in far east than west.

BACKGROUND: Both ETV6-RUNX1 (TEL-AML1) fusion and hyperdiploidy (>50 chromosomes) in transformed lymphoblasts are favorable genetic features in childhood acute lymphoblastic leukemia (ALL). PROCEDURE: Among 433 Taiwanese children with ALL diagnosed at our hospitals between 1997 and 2007, the ETV6-RUNX1 fusion was found in 15.8%, and hyperdiploidy (>50 chromosomes) in 14.1% of the patients. These frequencies were lower than those reported in the West, leading us to conduct a meta-analysis of ETV6-RUNX1 fusion and hyperdiploidy frequencies in childhood ALL based on published reports. RESULTS: The frequency of ETV6-RUNX1 fusion in the Far East (Japan, Korea, China, Hong Kong, Chinese in Singapore, and Taiwan) was 13.4% (177/1,321, range: 9-23%, median 13%), significantly lower than the 22.8% (1,664/7,291, range: 19-26%, median 23%) in the West (West Europe and the United States) (P < 0.001, odds ratio = 2.0, 95% CI: 1.7-2.4). Similarly, the frequency of hyperdiploidy in Japan and Taiwan was 14.3% (333/2,334, range: 12-20%, median 16%), significantly lower than the 25.2% in the West (5,173/20,510, range: 18-34%, median 23.5%; P < 0.001, odds ratio = 2.0, 95% CI: 1.8-2.3). CONCLUSIONS: This meta-analysis demonstrates lower frequencies of ETV6-RUNX1 fusion and hyperdiploidy among leukemia patients in the Far East compared with the West. The integral relationship of these genetic features with a favorable outcome in childhood ALL warrants further study of potentially important epidemiologic factors, including placental exposure to leukemogenic agents, and host pharmacogenetics.