Congenital anemia reveals distinct targeting mechanisms for master transcription factor GATA1.

Master regulators, such as the hematopoietic transcription factor (TF) GATA1, play an essential role in orchestrating lineage commitment and differentiation. However, the precise mechanisms by which such TFs regulate transcription through interactions with specific cis-regulatory elements remain incompletely understood. Here, we describe a form of congenital hemolytic anemia caused by missense mutations in an intrinsically disordered region of GATA1, with a poorly understood role in transcriptional regulation. Through integrative functional approaches, we demonstrate that these mutations perturb GATA1 transcriptional activity by partially impairing nuclear localization and selectively altering precise chromatin occupancy by GATA1. These alterations in chromatin occupancy and concordant chromatin accessibility changes alter faithful gene expression, with failure to both effectively silence and activate select genes necessary for effective terminal red cell production. We demonstrate how disease-causing mutations can reveal regulatory mechanisms that enable the faithful genomic targeting of master TFs during cellular differentiation.

Impacts of physical late effects on presenteeism in childhood cancer survivors.

BACKGROUND: Many childhood cancer survivors (CCSs) experience physical late effects related to their cancer types and treatment modalities. Physical late effects are an important factor in various occupational outcomes among CCSs. However, the relationship between physical late effects and presenteeism has remained unclear. This study aimed to estimate the impacts of physical late effects on presenteeism among employed CCSs. METHODS: Childhood cancer survivors replied to a questionnaire regarding presenteeism, and their attending physicians assessed their physical late effects between September 2014 and December 2015. The Work Limitations Questionnaire was used to measure presenteeism. Propensity score analysis and a generalized linear model were used to adjust covariates related to physical late effects and / or presenteeism. RESULTS: Of the 125 questionnaires distributed, 114 were returned. The data from 61 employed CCSs were analyzed. After controlling for covariates by propensity score analysis and generalized linear model, there were no significant differences in presenteeism between employed CCSs with either no or single physical late effects. However, employed CCSs with multiple physical late effects reported higher scores in Output (Estimate = 9.3, P = 0.041), Physical Demands (Estimate = 12.2, P = 0.020), and Productivity Loss scores (Estimate = 2.4, P = 0.045) on the Work Limitations Questionnaire than employed CCSs with no physical late effects. CONCLUSIONS: Employed CCSs with multiple physical late effects were at an increased risk for presenteeism. Healthcare and social welfare systems should be established to provide vocational assistance for CCSs after being employed to alleviate presenteeism.

Secondary cancer after a childhood cancer diagnosis: viewpoints considering primary cancer.

BACKGROUNDS: Multidisciplinary therapy has increased the risk of subsequent late effects, but detailed analyses on secondary cancers in childhood cancer survivors (CCSs) are limited in Asian countries. METHODS: This was a retrospective cohort study comprising 10,069 CCSs who were diagnosed between 1980 and 2009 across 15 Japanese hospitals. We conducted secondary analyses to estimate the incidence of secondary cancer according to each primary malignancy and to elucidate the association between primary and secondary cancers. We also explored the risk factors for the development of secondary cancer in each independent primary malignancy. RESULTS: The cumulative incidence of secondary cancer at 20 years varied among primary cancers: hematological malignancy, 3.1% (95% CI 2.2-4.3); retinoblastoma, 6.6% (95% CI 1.5-16.8); pediatric solid tumor, 2.5% (95% CI 1.3-4.2); brain tumors, 5.2% (95% CI 1.7-11.8) bone/soft tissue sarcoma, 5.2% (95% CI 2.3-10.1); and others, 3.3% (95% CI 1.6-6.0) (p = 0.015). The cumulative incidence of secondary cancers is highest in those with osteosarcoma (13.1%) followed by those with hepatoblastoma (8.4%) and retinoblastoma (6.6%). Close association between the primary and secondary cancer diagnoses was found. The risk factors for secondary cancer development depended on the primary cancer, but autologous/allogeneic stem cell transplantation was a relatively common risk factor. CONCLUSION: The cumulative incidence of secondary cancer varied among primary cancers. The primary cancer was closely associated with the secondary cancer but stem cell transplantation was a common risk factor for secondary cancers among CCSs.

Neuroblastoma.

Neuroblastoma is one of the most common solid tumors in children and has a diverse clinical behavior that largely depends on the tumor biology. Neuroblastoma exhibits unique features, such as early age of onset, high frequency of metastatic disease at diagnosis in patients over 1 year of age and the tendency for spontaneous regression of tumors in infants. The high-risk tumors frequently have amplification of the MYCN oncogene as well as segmental chromosome alterations with poor survival. Recent advanced genomic sequencing technology has revealed that mutation of ALK, which is present in ~10% of primary tumors, often causes familial neuroblastoma with germline mutation. However, the frequency of gene mutations is relatively small and other aberrations, such as epigenetic abnormalities, have also been proposed. The risk-stratified therapy was introduced by the Japan Neuroblastoma Study Group (JNBSG), which is now moving to the Neuroblastoma Committee of Japan Children's Cancer Group (JCCG). Several clinical studies have facilitated the reduction of therapy for children with low-risk neuroblastoma disease and the significant improvement of cure rates for patients with intermediate-risk as well as high-risk disease. Therapy for patients with high-risk disease includes intensive induction chemotherapy and myeloablative chemotherapy, followed by the treatment of minimal residual disease using differentiation therapy and immunotherapy. The JCCG aims for better cures and long-term quality of life for children with cancer by facilitating new approaches targeting novel driver proteins, genetic pathways and the tumor microenvironment.

Critical Diamond-Blackfan anemia due to ribosomal protein S19 missense mutation.

Diamond-Blackfan anemia (DBA) is a rare congenital disorder characterized by pure erythrocyte aplasia, and approximately 70% of patients carry mutations in the genes encoding ribosomal proteins (RP). Here, we report the case of a male infant with DBA who presented with anemic crisis (hemoglobin [Hb] concentration 1.5 g/dL) at 58 days after birth. On admission, the infant was pale and had tachypnea, but recovered with intensive care, including red blood cell transfusions, and prednisolone. Based on the clinical diagnosis of DBA, the father of the infant had cyclosporine-A-dependent anemia. On analysis of RP genes when the infant was 6 months old, both the infant and the father, but not the mother, were found to harbor a mutation of RPS19 (c.167G > C, p. R56P). Therefore, genetic background search and early neonatal health check-ups are recommended for families with a history of inherited bone marrow failure syndromes.

Secondary cancers after a childhood cancer diagnosis: a nationwide hospital-based retrospective cohort study in Japan.

BACKGROUND: The epidemiology of secondary cancers in childhood cancer survivors has been unknown in Asian countries. Our aim is to assess the incidence and risk factors for secondary cancers through a nationwide survey in Japan. METHODS: A retrospective cohort study comprising 10,069 children who were diagnosed with cancer between 1980 and 2009 was conducted in 15 Japanese hospitals. The cumulative incidence rate was calculated using death as the competing risk and compared by the Gray method. The standardized incidence ratio (SIR) was defined as the ratio of the number of observed cancers divided by the number of expected cancers. The risk factors were analyzed using Cox regression analysis. RESULTS: One hundred and twenty-eight patients (1.3 %) developed secondary cancers within a median follow-up of 8.4 years. The cumulative incidence rate was 1.1 % (95 % confidence interval [CI] 0.9-1.4) at 10 years and 2.6 % (95 % CI 2.1-3.3) at 20 years after primary cancer diagnosis. Sensitivity analysis, limited to 5-year survivors (n = 5,387), confirmed these low incidence rates. The SIR of secondary cancers was 12.1 (95 % CI 10.1-14.4). In the Cox analysis, the hazard ratios for secondary cancers were 3.81 (95 % CI 1.53-9.47) for retinoblastoma, 2.78 (95 % CI 1.44-5.38) for bone/soft tissue sarcomas, and 1.81 (95 % CI 1.16-2.83) for allogeneic stem cell transplantation. CONCLUSIONS: The cumulative incidence of secondary cancers in children in Japan was not high; however, the SIR was relatively high. Retinoblastoma or sarcoma in addition to allogeneic stem cell transplantation were significant risk factors for secondary cancers.

Randomized study of granulocyte colony stimulating factor for childhood B-cell non-Hodgkin lymphoma: a report from the Japanese pediatric leukemia/lymphoma study group B-NHL03 study.

The objective of this study was to assess the impact of the primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) in the management of childhood B-cell non-Hodgkin lymphoma (B-NHL). Patients with advanced-stage mature B-NHL were randomized to receive prophylactic G-CSF (G-CSF+) or not receive G-CSF (G-CSF-) based on protocols of the B-NHL03 study. The G-CSF group received 5 µg/kg/d Lenograstim from day 2 after each course of six chemotherapy courses. Fifty-eight patients were assessable, 29 G-CSF + and 29 G-CSF-. G-CSF + patients showed a positive impact on the meantime to neutrophil recovery and hospital stay. On the other hand, they had no impact in the incidences of febrile neutropenia, serious infections, stomatitis and total cost. Our study showed that administration of prophylactic G-CSF through all six chemotherapy courses for childhood B-NHL showed no clinical and economic benefits for the management of childhood B-NHL treatment.

Predictors of Posttraumatic Stress Symptoms Among Adolescent and Young Adult Survivors of Childhood Cancer: Importance of Monitoring Survivors' Experiences of Family Functioning.

The purpose of this study was to identify factors associated with posttraumatic stress symptoms (PTSS) among Japanese long-term childhood cancer survivors (CCSs). Subjects comprised 185 adolescent and young adult (AYA) CCSs who completed anonymous self-report questionnaires. Attending physicians also completed an anonymous disease/treatment data sheet. Mean age of survivors was approximately 8 years at diagnosis and 23 years at participation. Multiple regression analysis showed that family functioning, satisfaction with social support, being female, and interactions between family functioning and gender and age at the time of diagnosis were associated with PTSS among survivors. This study revealed family functioning as the most predictive factor of PTSS among AYA CCSs in Japan. Even when the survivor may have unchangeable risk factors, family functioning can potentially moderate the effects on PTSS. Thus, it is crucial for health professionals to carefully monitor and attend to survivors' experiences of family functioning to mitigate PTSS.

Prognostic impact of cytogenetic abnormalities in children and adolescents with mature B-cell non-Hodgkin lymphoma: A report from the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG).

Little information is available on cytogenetic abnormalities and their prognostic importance in childhood mature B-cell non-Hodgkin lymphoma (B-NHL). We performed a review of 79 abnormal karyotypes in childhood B-NHL treated by a uniform protocol. Del(17p) was independently associated with significantly inferior event-free survival in Burkitt or Burkitt-like lymphoma. The adverse prognosis of MYC/8q24 rearrangement, +7q or del(13q), was not observed, which had been suggested as risk factors in FAB/LMB96. Our results imply the possible existence of a biological difference among ethnicities and should be useful to narrow down the gene causing poor prognosis in childhood B-NHL.

Statistical analysis of relation between plasma methotrexate concentration and toxicity in high-dose methotrexate therapy of childhood nonHodgkin lymphoma.

BACKGROUND: Plasma monitoring of Methotrexate (MTX) levels is a standard approach to predict MTX-related toxicities in a high-dose (HD) MTX monotherapy for childhood acute lymphoblastic leukemia. However, it is uncertain whether plasma MTX levels can predict MTX-related toxicity in the HDMTX plus additional chemotherapy for childhood B-cell nonHodgkin lymphoma (B-NHL). PROCEDURES: To statistically analyze the relationship between MTX pharmacokinetic parameters and MTX-related toxicities, we collected data from patients with delayed MTX elimination (≥1 µM at 48 hr and/or ≥0.5 µM at 72 hr) in the Japanese Pediatric Leukemia/Lymphoma Study Group (JPLSG) BNHL 03 study. Blood MTX levels were measured at 24, 48, and 72 hr after 3 or 5 g/m2 HD-MTX administration for 24 hr. RESULTS: Three hundred and four patients received 2-4 courses of the HDMTX plus additional chemotherapy, and delayed MTX elimination was observed in 165 courses of 127 patients. In those, nephrotoxicity was significantly correlated with plasma MTX levels for each patient (P = 0.03), and also for each course (P = 0.009), but no other toxicities were correlated. Another analysis according to HDMTX courses showed no significant correlation between the first high plasma MTX levels and subsequent MTX levels in later course. It also showed that incidence of liver and gastrointestinal toxicities was most frequent in the first HDMTX course, and then sharply decreased in later courses (P < 0.001). CONCLUSIONS: Our results suggest that plasma MTX level is not a reliable predictor for adverse events except for nephrotoxicity in multiple HDMTX therapy courses in childhood B-NHL. Pediatr Blood Cancer 2015;62:279-284. © 2014 Wiley Periodicals, Inc.

General health status and late effects among adolescent and young adult survivors of childhood cancer in Japan.

OBJECTIVE: We sought to investigate general health status and late effects among adolescent and young adult survivors of childhood cancer. METHODS: We conducted a cross-sectional survey, using self-rated questionnaires on current and past health problems. Questionnaires were provided to childhood cancer survivors, a comparison group of siblings and a general population control group that was recruited online. χ(2) tests were used to compare responses to the 72 survey items. RESULTS: The final sample included 185 childhood cancer survivors (72% response rate), 72 siblings and 1000 general population controls. In the childhood cancer survivors group, the median age of diagnosis was 8 years and the median age at survey was 23 years. According to the physicians' reports, 56% of the childhood cancer survivors experienced at least one late effect. In descending order of prevalence, the current symptoms in the childhood cancer survivors group were (i) impaired visual acuity (45%), (ii) dizziness (36%) and (iii) any allergy (34%). The three most common symptoms had similar prevalence rates in each of the groups. As compared with the control group, the following physical symptoms were significantly more common in the childhood cancer survivors group: mental retardation (odds ratio: 48.6, P < 0.01); cataract (odds ratio: 29.7); suspected infertility (odds ratio: 25.1); delayed puberty (odds ratio 24.9); growth hormone deficiency (odds ratio: 23.0); and other audiovisual, urinary, endocrine, infertility, cardiovascular, respiratory, gastrointestinal, spinal, extremity and neuromuscular problems. CONCLUSIONS: Many adolescent/young adult childhood cancer survivors could be suffering from ongoing late effects that stem from cancer and its treatment. Overall health monitoring for childhood cancer survivors can provide indispensable benefits.

Clinical characteristics and genetic analysis of childhood acute lymphoblastic leukemia with hemophagocytic lymphohistiocytosis: a Japanese retrospective study by the Kyushu-Yamaguchi Children's Cancer Study Group.

This present study sought to analyze acute lymphoblastic leukemia (ALL) patients with hemophagocytic lymphohistiocytosis (HLH) registered in Kyushu-Yamaguchi Children's Cancer Study Group studies conducted between 1996 and 2007. Four of 357 patients, including two of 318 patients with B cell precursor acute lymphoblastic leukemia (BCP-ALL) and two of 39 of those with T cell acute lymphoblastic leukemia (T-ALL), were identified. HLH was observed more frequently in the T-ALL patients than in the BCP-ALL patients (P = 0.061). The mean age of 13.0 years at the diagnosis of leukemia in the HLH + ALL group was significantly higher than the 6.05 years observed in the remaining ALL groups (P = 0.001). A female predisposition was noted, as all four patients were female (P = 0.043). In two of four patients, the leukemic cells exhibited deletions on the long arm of chromosome 6 (P = 0.003). Three patients suffered from HLH during maintenance therapy. Parvovirus B19 infection and cytomegalovirus reactivation were identified as causes of HLH in one and two patients, respectively. All four patients are currently in complete remission, although one developed relapse of leukemia after receiving maintenance therapy. Based on the genetic analyses, non-synonymous single nucleotide polymorphisms (SNPs) in UNC13D, syntaxin 11, and STXBP2 were identified in all patients. Clinicians should therefore be aware of the risk of HLH during maintenance therapy, especially in older T-ALL patients with SNPs in familial HLH causative genes.

The prognostic significance of blastemal predominant histology in initially resected Wilms' tumors: a report from the Study Group for Pediatric Solid Tumors in the Kyushu Area, Japan.

BACKGROUND AND PURPOSE: The strategy used to treat pediatric renal tumors in Japan is based on the Japanese Wilms' Tumor Study (JWiTS) protocol, which was based on the National Wilms' Tumor Study (NWTS)-5 regimen. The regimen is characterized by an initial radical operation, followed by adjuvant chemotherapy and radiotherapy. Concerning the histological classification, a new classification based on the International Society of Pediatric Oncology (SIOP) classification was used beginning in 2008. The main points of revision are that the "blastemal predominant type" was classified as an independent category in the Wilms' tumor subtypes. The purpose of this study was to analyze the biological characteristics from the standpoint of the newly established histological classification. MATERIALS AND METHODS: From 1971 to 2005, 174 cases of Wilms' tumors treated with an initial operation followed by adjuvant therapy were re-evaluated by the new histological classification. Histologically, all these materials showed no secondary changes associated with adjuvant therapy. RESULTS: According to the new classification, Wilms' tumors were classified into four subtypes, including the mixed type (n=112), epithelial type (n=17), mesenchymal type (n=15), and blastemal predominant type (n=26). The 5 year overall survival rates were as follows; mixed type (90.1%), epithelial type (100%), mesenchymal type (93.3%), and blastemal predominant type (65.4%). CONCLUSION: The patients with blastemal predominant tumors demonstrated a significantly worse prognosis compared with those of other subtypes. The treatment strategy of blastemal predominant category should be distinguished from the other favorable subtypes.

[Treatment outcome of non-Hodgkin lymphoma in childhood: KYCCSG NHL-89, 96].

Two consecutive treatment protocols, NHL-89 and NHL-96, for pediatric diffuse large cell lymphoma (DLC) and lymphoblastic lymphoma (LBL) were conducted between March 1989 and December 2004 by Kyushu-Yamaguchi Children's Cancer Study Group. Forty-two patients (DLC: 15, LBL: 27) and 34 patients (DLC: 8, LBL: 26) were enrolled in NHL-89 and NHL-96, respectively. DLC patients received induction therapy of high-dose methotrexate (MTX) followed by repeated administration of intermediate MTX. LBL patients received a 4-drug induction followed by intensification, consolidation with cranial radiotherapy (15 to 24Gy), and maintenance. The maintenance phase consisted of multiple drug treatment; including prednisolone, vincristine, cyclophosphamide, and 6-mercaptopurine. With a median follow-up of 150 months for NHL-89 and 90.5 months for NHL-96, the estimated event-free survival at 5 years are 76.2±6.6% and 67.7±8.0%, respectively. Both studies improved the prognosis of DLC and LBL over our previous study of NHL-858.

[Retrospective analysis of 157 patients with pediatric Hodgkin lymphoma in Japan: investigation by four pediatric cancer study groups].

Hodgkin lymphoma is an easily curable malignancy in the pediatric age group and is less frequently observed in Japan. No study with a large sample size of Japanese patients has been conducted. From 1985 to 2000, 157 Japanese patients with Hodgkin lymphoma were retrospectively analyzed based on their clinical characteristics, treatment regimen, and treatment outcome by 4 pediatiric cancer study groups. There were 107 male and 50 female patients with a median age of 10 years 1 month (range: 1 year 8 months to 17 years 8 months). Clinical stage I lymphoma was observed in 37 patients, stage II in 62, stage III in 40, and stage IV in 18. Fifty patients presented with B symptoms (32%). Most patients (n=125, 82%) received more than 6 courses of combination chemotherapy mainly comprising cyclophosphamide, vincristine, procarbazine, prednisolone (COPP), doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). The 5-year overall and event-free survival rates were 81.5% and 94.8%, respectively. High-risk disease and age (>10 years) were considered to be poor prognostic factors.

Social outcomes and quality of life of childhood cancer survivors in Japan: a cross-sectional study on marriage, education, employment and health-related QOL (SF-36).

Social outcomes and quality of life (QOL) of childhood cancer survivors (CCSs) remain unknown in Japan. We investigated these outcomes in young adult CCSs compared to those of their siblings in Japan, and analyzed the association between social outcome and SF-36 health survey subscale scores. Between 2007 and 2009, we performed a cross-sectional survey using self-rating questionnaires. We estimated social outcomes and health-related QOL by performing the SF-36 in each group: CCSs with or without stem cell transplantation (SCT)/radiotherapy (RT) and their siblings. Adjusted odds ratios for outcomes of interest were estimated using logistic regression analysis. Questionnaires from 185 CCSs and 72 CCS's siblings were analyzed. There were no differences in educational attainment or annual income. The SF-36 subscale scores of CCSs with SCT and RT were significantly lower than those of siblings in physical functioning (PF) (p < 0.001 and 0.003, respectively) and general health (GH) (both p = 0.001). Lower PF scores correlated with recurrence (p = 0.041) and late effects (p = 0.010), and poor GH scores with late effects (p = 0.006). The CCSs had made efforts to attain educational/vocational goals; however, a significant proportion of CCSs who had experienced late effects remain at increased risk of experiencing diminished QOL.

Juvenile myelomonocytic leukemia characterized by cutaneous lesion containing Langerhans cell histiocytosis-like cells.

We present a 1-year-old boy who developed a cutaneous lesion on the trunk and hepatosplenomegaly. Laboratory examination showed leukocytosis with peripheral blasts, atypical monocytosis, anemia, hyper IgG, and a mild elevation of C-reactive protein. Clinical features and skin biopsy findings matched the diagnostic criteria of both juvenile myelomonocytic leukemia (JMML) and Langerhans cell histiocytosis (LCH). Histopathology revealed atypical mononuclear cells that had infiltrated around vessels throughout the dermis in a skin biopsy specimen. These cells were CD1a (+), S-100 (+), CD68 (+), CD207 (-), lysozyme (+), and myeloperoxidase (-). The diagnosis of JMML was confirmed by detection of spontaneous colony formation and granulocyte-macrophage colony-stimulating factor hypersensitivity in vitro, and a somatic NRAS point mutation. Transplantation of bone marrow from an HLA-matched unrelated donor was performed, and the marrow was successfully engrafted. The cutaneous lesion and hepatosplenomegaly were improved at the time of discharge. It is often difficult to distinguish between JMML and LCH-like infiltrates by assessing clinical and light microscopic features of various cutaneous lesions. In the current case, molecular biological analysis enabled us to develop a precise diagnosis.

Late effects and quality of life of childhood cancer survivors: Part 2. Impact of radiotherapy.

To examine the late effects and health-related quality of life of childhood cancer survivors (CCS) after radiotherapy (RT), we performed a cross-sectional survey using self-rating questionnaires. The subjects were divided into 3 groups: CCS treated with or without RT, and a general population matched for age, gender, residential area, and work status. The numbers in each group were 113, 72, and 1,000, respectively. The median ages of CCS at diagnosis and the time of the survey were 8 and 22 years, respectively. The mean final heights of males and females were significantly lower in CCS with RT than in the other 2 groups. Risk factors for a short stature were total body irradiation (TBI) [odds ratio (OR) 17.8, p < 0.001], spinal irradiation (OR 8.31, p = 0.033), and an age younger than 10 years at diagnosis. Late effects were observed in 68% of CCS with RT compared with 36% of CCS without RT. Multivariate analysis revealed that TBI was significantly associated with endocrine dysfunction (OR 12.3), skull and spinal irradiation with cognitive dysfunction (OR 16.1 and 11.5, respectively), and spinal irradiation with a short stature (OR 14.1), respectively. Physical dysfunction, psychological stress, and problems of social adaptation were observed in >50% of CCS with RT.

Randomized trial to compare LSA2L2-type maintenance therapy to daily 6-mercaptopurine and weekly methotrexate with vincristine and dexamethasone pulse for children with acute lymphoblastic leukemia.

BACKGROUND: A total of 201 pediatric cases of acute lymphoblastic leukemia were treated with the ALL-96 protocol by the Kyushu-Yamaguchi Children's Cancer Study Group. PROCEDURE: Risk stratification was based on white cell counts, immunophenotype, the presence of central nervous system disease at diagnosis, organomegaly, and early treatment response (day 14 bone marrow status). All of the patients were classified into standard-risk (SR) or high-risk (HR) groups and were randomly assigned to receive maintenance therapy with either LSA2L2-type or 6-mercaptopurine (6-MP)/methotrexate (MTX) with vincristine (VCR) and dexamethasone (DEX) pulse in both risk groups. RESULTS: The 7-year event-free survival (EFS) and overall survival (OS) rates in the entire study population were 72.1% (95% CI: 68.0-76.2%) and 84.8% (95% CI: 79.7-89.9%), respectively, and the EFS of the SR patients (85.3% [95% CI: 78.2-92.4%]) was significantly better than HR patients (62.4% [95% CI: 52.2-72.6%]) (P = 0.0007). CONCLUSIONS: There were no differences in the EFS between the different maintenance therapies in each risk group; however, grade IV liver toxicity occurred more often in the patients receiving 6-MP/MTX with VCR and DEX therapy than in patients receiving LSA2L2.

Late effects and quality of life of childhood cancer survivors: part 1. Impact of stem cell transplantation.

To examine the late effects and health-related quality of life among childhood cancer survivors (CCS) after stem cell transplantation (SCT), we performed a cross-sectional survey using self-rating questionnaires. The subjects were divided into 3 groups: SCT-treated CCS, CCS treated without SCT, and the general population who matched for age, gender, residential area, and work status with the CCS. We analyzed the questionnaires of 185 CCS and 1,000 control participants. The median ages of CCS at diagnosis and survey were 8 and 22 years, respectively. The mean final heights of male and female participants were significantly lower for SCT-treated CCS than for CCS treated without SCT and the controls. Among the SCT-treated CCS, >40% were underweight (BMI < 18.5). Late effects were observed in 78% of SCT-treated CCS versus 45% of CCS treated without SCT. Multivariate analysis revealed that >15 years' duration after therapy completion (OR 2.95; p = 0.014), solid tumors (4.31; p = 0.040), radiotherapy (2.82; p = 0.009), recurrence (4.22; p = 0.017), and SCT (3.39; p = 0.014) were significant risk factors for late effects. Subjective symptoms were significantly frequent in SCT-treated CCS. Physical dysfunction, psychological stress, and social adaptation problems were observed in >70% of SCT-treated CCS.