Telomere Length in Adolescent and Young Adult Survivors of Childhood Cancer.

We examined the leukocyte relative telomere length (RTL) in Korean adolescent and young adult (AYA) survivors of childhood cancer and evaluated the association of leukocyte RTL with multiple factors, including malignancy type, cancer treatment, age, and chronic health conditions (CHCs). Eighty-eight AYA survivors of childhood cancer with a median follow-up period of 73 months were recruited. RTL in pediatric cancer survivors was not significantly shorter than the predicted value for age-matched references. Neither age at diagnosis nor duration of therapy influenced the RTL. Among the 43 patients with hematologic malignancies, those who underwent allogeneic hematopoietic stem cell transplantation (HSCT) showed a significant shortening of the RTL compared with those who did not (p = 0.039). Among the 15 patients who underwent allogeneic HSCT, those who developed acute graft-versus-host disease (GVHD) of grade II or higher had significantly shorter RTL than those who did not (p = 0.012). Patients with grade II CHCs had significantly shorter RTL than those without CHCs or with grade I CHCs (p = 0.001). Survivors with ≥2 CHCs also exhibited shorter RTL (p = 0.027). Overall, pediatric cancer survivors had similar telomere lengths compared to age-matched references. HSCT recipients and patients with severe or multiple CHCs had shorter telomeres. GVHD augmented telomere attrition in HSCT recipients.

Excellent Outcomes in Children, Adolescents, and Young Adults with Ovarian Germ Cell Tumors Treated by Either Reduced- or Standard-Dose Bleomycin.

To investigate the outcomes of children, adolescents, and young adults (AYAs) with malignant ovarian germ cell tumors (MOGCTs), we analyzed the data of 61 patients aged ≤39 years diagnosed with MOGCT between 2006 and 2022. Among 59 patients who received chemotherapy after initial diagnosis, 57 received BEP (standard dose of bleomycin with 30 units per week, n = 13) or bEP (reduced dose of bleomycin with 15 units/m2 on day 1, n = 44). The 5-year overall survival (OS) and event-free survival (EFS) rates were 98.3% and 84.9%, respectively. Reduced bleomycin dose did not adversely affect survival. Normalization of tumor markers within 3 months after surgery was significantly associated with better EFS (p < 0.01). Of the 59 surviving patients, 8 experienced surgery-related menopause, while 49 demonstrated menstrual recovery. After completion of chemotherapy, there was no significant difference in pulmonary function regarding bleomycin dose, and no overt nephrotoxicity. Approximately 60% and 25% of survivors experienced peripheral neuropathy at the end of chemotherapy and after 1 year, respectively (p < 0.01). Children and AYAs with MOGCT have favorable survival rates with minimal long-term toxicity, which are not influenced by a reduced bleomycin dose. Rapid normalization of tumor markers is associated with improved outcomes.

High-dose chemotherapy followed by autologous stem cell transplantation in pediatric patients with relapsed osteosarcoma.

BACKGROUND: Patients with relapsed osteosarcoma have poor treatment outcomes. High-dose chemotherapy with autologous stem cell transplantation (HDCT/ASCT) has been used in several high-risk malignant solid tumors; however, few studies have evaluated their role in treating osteosarcoma. We evaluated the effectiveness of HDCT/ASCT in relapsed pediatric osteosarcoma cases. PROCEDURE: We retrospectively reviewed the medical records of 40 patients diagnosed with and treated for relapsed osteosarcoma at Asan Medical Center and Samsung Medical Center from January 1996 to July 2019. RESULTS: The median age of this cohort was 13.4 years (range: 6.1-18.2). The cohort's 5-year overall survival (OS) was 51.0% ± 0.1% during a median follow-up period of 67.5 months. Twenty-five patients (62.5%) achieved complete remission (CR) with salvage treatment, and the 5-year OS was 82.4% ± 0.1%, whereas none of the remaining 15 patients who did not achieve CR survived (p < .0001). Of the 25 CR cases, 15 underwent subsequent HDCT/ASCT. We compared the effect of HDCT/ASCT among patients who achieved CR. There were no significant differences in the 5-year OS outcomes between patients who did and did not receive HDCT/ASCT (83.9% ± 0.1%, 13/15 vs. 80.0% ± 0.1%, 8/10, respectively; p = .923). CONCLUSION: To our knowledge, we report the first comparative cohort study that proved HDCT/ASCT does not significantly improve survival outcomes in relapsed osteosarcoma. Achievement of CR remains the most crucial factor for good survival outcomes.

Favorable outcomes with durable chimerism after hematopoietic cell transplantation using busulfan and fludarabine-based reduced-intensity conditioning for pediatric patients with hemophagocytic lymphohistiocytosis.

Background: The incorporation of a reduced-intensity conditioning (RIC) regimen in hematopoietic cell transplantation (HCT) for patients with hemophagocytic lymphohistiocytosis (HLH) has decreased early mortality but is associated with a high rate of mixed chimerism and graft failure. Here, we present a successful single-center experience using busulfan and a fludarabine-based RIC regimen for the treatment of HLH. Methods: The medical records of pediatric patients with HLH who underwent HCT using a busulfan/ fludarabine-based RIC regimen between January 2008 and December 2017 were reviewed retrospectively. Results: Nine patients received HCT with a busulfan/fludarabine-based RIC regimen. Three patients had primary HLH, and the other six patients had secondary HLH with multiple reactivations. All three patients with primary HLH had UNC13D mutations. All patients achieved neutrophil and platelet engraftment at a median of 11 days (range, 10‒21) and 19 days (range, 13‒32), and all eight evaluable patients had sustained complete donor chimerism at the last follow-up. Two patients (22%) experienced grade 2 acute graft-versus- host disease (GVHD). Two patients (22%) developed chronic GVHD, and one died from chronic GVHD. One patient (11%) experienced reactivation 4 months after HCT from a syngeneic donor and died of the disease. The 8-year overall survival and event-free survival rates were 78%. No early treatment-related mortality within 100 days after HCT was observed. Conclusion: Our experience suggests that a busulfan/fludarabine-based RIC regimen is a viable option for pediatric patients with HLH who require HCT.

Hematopoietic Stem Cell Transplantation-Associated Neurological Complications and Their Brain MR Imaging Findings in a Pediatric Population.

PURPOSE: To determine the prognostic indicators for hematopoietic stem cell transplantation (HSCT)-associated neurological complications, the clinical characteristics and brain magnetic resonance imaging (MRI) lesions in pediatric HSCT recipients were reviewed. METHODS: This retrospective study included 51 patients who had underwent a brain MRI due to newly developed neurological symptoms or infection signs during chemotherapy or HSCT. We reviewed the demographics, received treatments, treatment-related morbidities, laboratory findings and brain MRI findings, which were compared between good and poor neurologic outcome groups. RESULTS: Thirty-seven patients (72.5%) fully recovered from the neurologic deficits and fourteen (27.5%) persisted or aggravated. The children with an underlying malignant disease had significantly poorer neurological outcomes (p = 0.015). The neurologic complications associated with infection were more frequent in the poor outcome group (p = 0.038). In the neuroimaging findings, the extent of the white matter lesions was significantly higher in the poor outcome group, as was that of abnormal enhancement, ventriculomegaly, cortical change, deep gray matter abnormalities and cerebellar abnormalities. CONCLUSION: Most children with neurologic complications and neuroimaging abnormalities during HSCT had recovered. However, children with neurologic complications associated with infectious causes, malignant disease or severe brain MRI abnormalities should be more carefully monitored during HSCT.

Genetic Confirmation and Identification of Novel Variants for Glanzmann Thrombasthenia and Other Inherited Platelet Function Disorders: A Study by the Korean Pediatric Hematology Oncology Group (KPHOG).

The diagnosis of inherited platelet function disorders (IPFDs) is challenging owing to the unavailability of essential testing methods, including light transmission aggregometry and flow cytometry, in several medical centers in Korea. This study, conducted by the Korean Pediatric Hematology Oncology Group from March 2017 to December 2020, aimed to identify the causative genetic variants of IPFDs in Korean patients using next-generation sequencing (NGS). Targeted exome sequencing, followed by whole-genome sequencing, was performed for diagnosing IPFDs. Of the 11 unrelated patients with suspected IPFDs enrolled in this study, 10 patients and 2 of their family members were diagnosed with Glanzmann thrombasthenia (GT). The variant c.1913+5G>T of ITGB3 was the most common, followed by c.2333A>C (p.Gln778Pro) of ITGB2B. Known variants of GT, including c.917A>C (p.His306Pro) of ITGB3 and c.2975del (p.Glu992Glyfs*), c.257T>C (p.Leu86Pro), and c.1750C>T (p.Arg584*) of ITGA2B, were identified. Four novel variants of GT, c.1451G>T (p.Gly484Val) and c.1595G>T (p.Cys532Phe) of ITGB3 and c.1184G>T (p.Gly395Val) and c.2390del (p.Gly797Valfs*29) of ITGA2B, were revealed. The remaining patient was diagnosed with platelet type bleeding disorder 18 and harbored two novel RASGRP2 variants, c.1479dup (p.Arg494Alafs*54) and c.813+1G>A. We demonstrated the successful application of NGS for the accurate and differential diagnosis of heterogeneous IPFDs.

Recent advances in the understanding of the molecular pathogenesis and targeted therapy options in Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder caused by the clonal expansion of myeloid precursors that differentiate into CD1a+/CD207+ cells in the lesion. Advances in genomic sequencing techniques have improved our understanding of the pathophysiology of LCH. Activation of the mitogen-activated protein kinase (MAPK) pathway is a key molecular mechanism involved in the development of LCH. Recurrent BRAF mutations and MAP2K1 mutations are the major molecular alterations involved in the activation of the MAPK pathway. Recent studies have supported the "misguided myeloid differentiation model" of LCH, where the extent of disease is defined by the differentiation stage of the cell in which the activating somatic MAPK mutation occurs, suggesting LCH. Several studies have advocated the efficacy of targeted therapy using BRAF inhibitors with a high response rate, especially in patients with high-risk or refractory LCH. However, the optimal treatment scheme for children remains unclear. This review outlines recent advances in LCH, focusing on understanding the molecular pathophysiology, emerging targeted therapy options, and their clinical implications.

Recent improvement in survival outcomes and reappraisal of prognostic factors in hepatoblastoma.

BACKGROUND: Prognostic factors in hepatoblastoma need to be reevaluated considering the advances in treatment modalities. The study aimed to evaluate current outcomes of hepatoblastoma and reappraise the association of prognostic factors, including pre-treatment extent of tumor (PRETEXT) stage with annotation factors and Children's Hepatic tumors International Collaboration-Hepatoblastoma Stratification (CHIC-HS) system, with survival outcomes. METHODS: We evaluated 103 consecutive patients with hepatoblastoma retrospectively according to the treatment period based on the introduction of a liver transplantation program. RESULTS: The 5-year overall survival (OS), event-free survival (EFS), and transplant-free survival rates were 80.2%, 74.2%, and 61.8%, respectively. EFS and OS were improved significantly from 58.6% to 81.6% (P = 0.024) and from 58.6% to 90.8% (P < 0.001), respectively, in the late period (N = 74) compared with the early period (N = 29). The PRETEXT stage was significant or marginally significant for EFS and OS in the early period but not in the late period. The P, F, R, and C factors were significant for OS and EFS in the early period. However, in the late period, only the P factor was significant for OS, and the F and M factors were significant for EFS. The CHIC-HS system was significant or marginally significant for EFS in both the early and late periods; however, it was significant for OS only in the early period. CONCLUSION: Survival rates were significantly improved in children with hepatoblastoma, especially in those with advanced PRETEXT stages with positive annotation factors and in a high-risk CHIC-HS group. Prognostic factors had different clinical implications with evolved treatment modalities.

Erratum: Correction of Affiliations in the Article "Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study".

This corrects the article on p. e393 in vol. 35, PMID: 33258329.

Clinical Characteristics and Treatment Outcomes in Children, Adolescents, and Young-adults with Hodgkin's Lymphoma: a KPHOG Lymphoma Working-party, Multicenter, Retrospective Study.

BACKGROUND: Hodgkin's lymphoma (HL) constitutes 10%-20% of all malignant lymphomas and has a high cure rate (5-year survival, around 90%). Recently, interest has increased concerning preventing secondary complications (secondary cancer, endocrine disorders) in long-term survivors. We aimed to study the epidemiologic features and therapeutic outcomes of HL in children, adolescents, and young adults in Korea. METHODS: We performed a multicenter, retrospective study of 224 patients aged < 25 years diagnosed with HL at 22 participating institutes in Korea from January 2007 to August 2016. RESULTS: A higher percentage of males was diagnosed at a younger age. Nodular sclerosis histopathological HL subtype was most common, followed by mixed cellularity subtype. Eighty-one (36.2%), 101 (45.1%), and 42 (18.8%) patients were classified into low, intermediate, and high-risk groups, respectively. Doxorubicin, bleomycin, vinblastine, dacarbazine was the most common protocol (n = 102, 45.5%). Event-free survival rate was 86.0% ± 2.4%, while five-year overall survival (OS) rate was 96.1% ± 1.4%: 98.7% ± 1.3%, 97.7% ± 1.6%, and 86.5% ± 5.6% in the low, intermediate, and high-risk groups, respectively (P = 0.021). Five-year OS was worse in patients with B-symptoms, stage IV disease, high-risk, splenic involvement, extra-nodal lymphoma, and elevated lactate dehydrogenase level. In multivariate analysis, B-symptoms and extra-nodal involvement were prognostic factors for poor OS. Late complications of endocrine disorders and secondary malignancy were observed in 17 and 6 patients, respectively. CONCLUSION: This is the first study on the epidemiology and treatment outcomes of HL in children, adolescents, and young adults in Korea. Future prospective studies are indicated to develop therapies that minimize treatment toxicity while maximizing cure rates in children, adolescents, and young adults with HL.

Long-term treatment outcomes of children and adolescents with lymphoblastic lymphoma treated with various regimens: a single-center analysis.

BACKGROUND: Lymphoblastic lymphoma (LBL) is the second most common subtype of pediatric non-Hodgkin lymphoma. Modified treatments derived from the LSA2-L2 regimen resulted in encouraging survival, but toxicities and long-term sequelae have been problematic. At present, the acute lymphoblastic leukemia (ALL)-type protocol has demonstrated efficacy in LBL. We analyzed the outcomes of children and adolescents with LBL treated with various regimens. METHODS: From 1991‒2018, this study enrolled 63 patients diagnosed with LBL at Asan Medical Center. Medical records were retrospectively analyzed. RESULTS: Among 63 patients, most patients (38.1%) presented with stage IV at diagnosis, and two had central nervous system (CNS) involvement. At a median follow-up of 160 months, the 5-year event free survival (EFS), overall survival (OS), and relapse free survival (RFS) were 68.8%, 79.3%, and 71.3%, respectively. Among 61 patients who received chemotherapy, 27 patients (44.3%) received the NY protocol, and 14 (23.0%) received the ALL-type protocol. There was no significant difference in 5-yr OS (85.2%/78.6%), EFS (73.5%/78.6%), and RFS (73.5%/78.6%) between the NY and ALL protocol groups, regardless of immunophenotype. Thirteen patients (21.3%) received prophylactic cranial radiotherapy with no difference in the incidence of CNS relapse based on irradiation. CONCLUSION: This study showed no difference in outcome between the NY and ALL-type protocols, regardless of stage or immunophenotype. In addition to improving the effectiveness of treatment, it is necessary to continuously appraise the appropriate chemotherapy regimen, considering toxicities and long-term prognosis, for pediatric LBL.

Genetic Alterations Detected by Targeted Next-generation Sequencing and Their Clinical Implications in Neuroblastoma.

BACKGROUND/AIM: This study was conducted to evaluate the clinical usefulness of panel next-generation sequencing (NGS) and to investigate the spectrum of genetic alterations and their clinical implications in neuroblastoma. PATIENTS AND METHODS: Formalin-fixed, paraffin-embedded archival samples from 41 cases of neuroblastoma were used for targeted sequencing. RESULTS: A total of 145 somatic mutations were identified, including 51 synonymous, 86 missense, 3 nonsense, 2 frameshift deletion, 2 splice-site, and 1 in-frame deletion mutations. The most frequently mutated gene was ALK (9 missense mutations). The common copy number variations (CNVs) were amplification at 2p24.2 and deletion at 11q22.3 and 1p36.21. ALK mutations were more frequent in patients with stage 4 or 4S (0% vs. 33.3%, p=0.017). Among 27 patients with high-risk disease, the 5-year overall survival was inferior in patients with ALK mutations to those without (25.0% vs. 67.0%, p=0.009). CONCLUSION: Genetic analysis using targeted NGS was feasible and helpful in detecting point mutations and CNVs in neuroblastoma. Targeted NGS could predict prognosis and be used to find molecular target-based therapies for neuroblastoma.

Feasibility and effectiveness of treatment strategy of tandem high-dose chemotherapy and autologous stem cell transplantation in combination with 131 I-MIBG therapy for high-risk neuroblastoma.

This study was performed to evaluate the safety and effectiveness of tandem HDCT/ASCT combined with targeted radiotherapy using 131 I-MIBG for high-risk neuroblastoma. Patients with high-risk neuroblastoma were treated with 8 to 10 cycles of induction chemotherapy before tandem HDCT/ASCT. Patients received 131 I-MIBG treatment before the second HDCT/ASCT. Local radiotherapy and maintenance therapy were performed after tandem HDCT/ASCT. Between 2012 and 2016, 19 patients were diagnosed with high-risk neuroblastoma in our institution and 18 of them received tandem HDCT/ASCT combined with 131 I-MIBG therapy. For the first HDCT/ASCT regimen, 12 patients received busulfan/melphalan and six patients received melphalan/etoposide/carboplatin. The second HDCT included ThioCy. The median dose of 131 I-MIBG was 17.2 mCi/kg for the first eight patients, while 12 patients in the latter period of the study received reduced dose of 10.7 mCi/kg. The 5-year OS and EFS rates were 79% and 61%, respectively, for all 19 patients with high-risk neuroblastoma, and 83% and 64%, respectively, for 18 patients who completed tandem HDCT/ASCT combined with 131 I-MIBG therapy. Six patients experienced disease relapse and five patients died. Treatment-related mortality was not observed. Among 15 evaluable patients, 11 patients (73%) developed hypothyroidism, six patients (40%) had CKD, and six patients (40%) had growth failure. Hypothyroidism and growth failure were less frequent in patients who received reduced doses of 131 I-MIBG therapy. Tandem HDCT/ASCT combined with HD 131 I-MIBG therapy could be feasible for patients with high-risk neuroblastoma with acceptable toxicity profiles and favorable outcomes.

Clinical Characteristics and Treatment Outcomes of Pediatric Patients with Non-Hodgkin Lymphoma in East Asia.

PURPOSE: The presentations and geographic incidence of pediatric non-Hodgkin lymphoma (NHL) differ from those of adults. This study delineated the characteristics and outcomes of pediatric NHL in East Asia. MATERIALS AND METHODS: Medical records of 749 pediatric patients with NHL treated at participating institutions in mainland China, Japan, Korea, and Taiwan from January 2008 to December 2013 were reviewed. Demographic and clinical features, survival outcomes, and putative prognostic factors were analyzed. RESULTS: Five hundred thirty patients (71%) were male. The most common pathologic subtypes were Burkitt lymphoma (BL) (36%). Six hundred seven patients (81%) had advanced diseases at diagnosis. The 5-year overall survival and event-free survival (EFS) rates were 89% and 84%. The 5-year EFS rates of BL, lymphoblastic lymphoma, and diffuse large B-cell lymphoma were 88%, 88%, and 89%, and those of anaplastic large cell lymphoma (ALCL) and peripheral T-cell lymphoma (PTCL) were 71% and 56% (p < 0.001). Central nervous system involvement, high lactate dehydrogenase level (> 250 IU/mL), and advanced disease at diagnosis (≥ stage III) were associated with poor outcomes (p < 0.05). ALCL and PTCL relapsed more frequently than other pathologic subtypes (p < 0.001). CONCLUSION: In East Asia, PTCL was more frequent than in Western countries, and bone marrow involvement did not affect treatment outcome. This international study should motivate future collaborative study on NHL in East Asia.

Central nervous system vasculitis from Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorder in children: A case report.

BACKGROUND: Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disorders (EBV-T/NK-LPD) is a group of rare disorders resulting from EBV-infected T/NK-cells. It manifests as a broad spectrum of clinical symptoms according to immunologic status and viral load of an infected patient. Here, we report a boy who developed central nervous system (CNS) vasculitis and myelopathy as possible neurologic manifestations of EBV-T/NK-LPD. CASE REPORT: A 16-year-old boy came to our hospital with a necrotic skin lesion on his right shoulder. He suffered from local skin reactions with high fevers after mosquito bites since he was 10 years old. During the evaluation of his skin lesion, he suddenly developed left facial palsy. Brain magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) showed acute infarctions of the pons and middle cerebellar peduncle and irregularities of both anterior inferior cerebellar arteries. Serologic testing showed an elevation of total Ig E levels, anti-VCA IgG levels, and anti-EA IgG titers. EBV DNA copy numbers of the whole blood and cerebrospinal fluid (CSF) were elevated. Biopsy of the right shoulder skin showed extranodal NK/T-cell lymphoma. According to clinical features and laboratory findings, he was diagnosed with EBV-T/NK-LPD. He was treated with chemotherapy and hematopoietic stem cell transplantation but developed recurrent infarctions during treatment. CONCLUSION: This case showed the diagnostic challenge of neurologic manifestations of EBV-T/NK-LPD. EBV-T/NK-LPD-associated CNS vasculitis needs to be considered as a differential diagnosis of CNS vasculitis, when it is accompanied by the typical clinical spectrum of EBV-T/NK-LPD such as severe mosquito bite allergy, extranodal NK/T-cell lymphoma.

Clinical characteristics and treatment courses for cytomegalovirus-associated thrombocytopenia in immunocompetent children after neonatal period.

BACKGROUND: Cytomegalovirus (CMV) causes severe diseases in premature infants and immunocompromised hosts, and antiviral therapy is often required for disease control. However, the clinical manifestations and treatment courses for CMV-associated thrombocytopenia in immunocompetent children are unclear. METHODS: Medical records of the children who suffered from thrombocytopenia, and showed positive CMV polymerase chain reaction and CMV-like symptoms were retrospectively analyzed at three university hospitals in Daegu from January 2000 to March 2017. Patients suffering from leukemia, immunodeficiency, and other infections were excluded. RESULTS: Among 1,065 children with thrombocytopenia, 29 (2.7%) displayed CMV-associated thrombocytopenia. The median age at diagnosis was 15 months and the median platelet count was 26,000/µL. They were classified into the CMV-induced thrombocytopenia (23/29) and CMV-related secondary immune thrombocytopenia (ITP, 6/29) groups. Fourteen subjects had hepatic dysfunction, four had Evans syndrome, two had pneumonitis, and one had gastritis. IVIG was used for 21 patients, and six patients among them showed recurrence, for whom IVIG or antiviral therapy was used. All, except one, recurrent or chronic cases belonged to the CMV-induced thrombocytopenia group. Antiviral therapy was used more frequently for the CMV-induced thrombocytopenia group (8/23, 34.8%) than for the CMV-related secondary ITP group (0/6); however, the results were not statistically significant (P=0.148). CONCLUSION: CMV is a rare but unique etiology of thrombocytopenia, and observed even in healthy children after the neonatal period. About one-third patients need antiviral therapy for disease control. Further, CMV-induced thrombocytopenia is more complex than CMV-related secondary ITP.

Treatment outcome of pediatric acute lymphoblastic leukemia in Yeungnam region: Multicenter retrospective study of Study Alliance of Yeungnam Pediatric Hematology-Oncology (SAYPH).

OBJECTIVES: We aimed to evaluate treatment outcomes of pediatric acute lymphoblastic leukemia (ALL) subgroups by risk-stratification, in the Yeungnam region of Korea. METHODS: We reviewed the courses of 409 newly diagnosed ALL patients from January 2004 to December 2013 in the Yeungnam region. RESULTS: All patients were classified into three risk groups: standard risk (SR, n=212), high risk (HR, n=153) and very high risk (VHR, n=44). The mean follow-up time was 73.6 ± 39.4 months. The 7-year event-free survival (EFS) and overall survival (OS) rates were 78.7 ± 2.1% and 86.8 ± 1.8%, respectively. Significant 7-year EFS and OS rates for SR (84.0 ± 2.7%, 93.7 ± 1.8%), HR (76.5 ± 3.5%, 82.1 ± 3.3%), and VHR (60.6 ± 7.5%, 69.9 ± 7.5%) were observed (P<0.001), respectively. Relapse occurred in 52 patients, and the cumulative 7-year incidence of relapse differed according to risk groups (SR vs. HR vs. VHR=12.6% vs. 14.0% vs. 29.6%, P=0.003).For the 46 relapsed patients who were treated, the 3-year EFS and OS were 42.3 ± 8.3%and 46.4± 8.4%. Among the 44 VHR patients, EFS was not significantly different between the chemotherapy-treated patients and those received hematopoietic stem cell transplantation (P=0.533). The 7-year EFS of the hyperleukocytosis subgroup (24 cases, 14 under 10 years of age)showed a tendency for better prognosis than that of the other VHR subgroups (P=0.178). CONCLUSION: Our results revealed improved outcomes in pediatric ALL patients with risk-stratified therapy. The hyperleukocytosis subgroup without any combined chromosomal abnormalities may respond favorably to chemotherapy alone after first complete remission.

Hematopoietic stem cell transplantation in pediatric patients with acute myeloid leukemia without favorable cytogenetics.

Intensified chemotherapy, HSCT, and supportive care improve the survival of pediatric patients with AML. However, no consensus has been reached regarding the role of HSCT in patients without favorable cytogenetics. We evaluated OS and EFS according to prognostic factors that affect clinical outcomes, including cytogenetics risk group, conditioning regimen, donor type, disease status at the time of HSCT, and number of chemotherapy cycles prior to HSCT in 65 pediatric patients with AML without favorable cytogenetics who underwent HSCT. Fifteen of the 65 patients died: three of TRM and 12 of disease-related mortality. The 5-year OS and EFS were 78.0% and 72.0%, respectively, and the 5-year cumulative relapse and TRM rates were 26.9% and 5.1%, respectively. Survival rates were not influenced by cytogenetic group (intermediated vs. poor), donor type (related vs. unrelated), transplant type (myeloablative vs. reduced-intensity conditioning), or number of pretransplant chemotherapy cycles (≤3 vs. >3 cycles). The low TRM rate and encouraging outcomes suggest that HSCT may be a feasible treatment for pediatric patients with AML without favorable cytogenetics.