Increasing and Worsening Late Effects in Childhood Cancer Survivors during Follow-up

Recent advances in childhood cancer treatment have increased survival rates to 80%. Two out of three survivors experience late effects (LEs). From a group of 241 survivors previously described, 193 were followed at the long-term follow-up clinic (LTFC) of Severance Hospital in Korea; the presence of LEs was confirmed by oncologists. We reported the change in LEs during 3 yr of follow-up. The median follow-up from diagnosis was 10.4 yr (5.1-26.2 yr). Among 193 survivors, the percentage of patients with at least one LE increased from 63.2% at the initial visit to 75.1% at the most recent visit (P = 0.011). The proportion of patients having multiple LEs and grade 2 or higher LEs increased from the initial visit (P = 0.001 respectively). Forty-eight non-responders to the LTFC were older and had less frequent and severe LEs than responders at initial visit (all P < 0.05). In multivariate analysis, younger age at diagnosis, older age at initial visit, a diagnosis of a brain tumor or lymphoma, and use of radiotherapy were significant risk factors for LEs (all P < 0.05). Adverse changes in LEs were seen among the survivors, regardless of most clinical risk factors. They need to receive comprehensive, long-term follow up.

Combined chemotherapy and intra-arterial chemotherapy of retinoblastoma / 소아과

PURPOSE: Retinoblastoma (RB) is the most common primary malignant intraocular tumor in children. Although systemic chemotherapy has been the primary treatment, intra-arterial chemotherapy (IAC) represents a new treatment option. Here, we performed alternate systemic chemotherapy and IAC and retrospectively reviewed the efficacy and safety of this approach. METHODS: Patients diagnosed with intraocular RB between January 2000 and December 2011 at Severance Children's Hospital, Yonsei University, were reviewed. Before February 2010, the primary treatment for RB was chemotherapy (non-IAC/CTX). Since February 2010, the primary treatment for RB has been IAC (IAC/CTX). External beam radiotherapy or high-dose chemotherapy were used as "last resort" treatments just prior to enucleation at the time of progression or recurrence during primary treatment. Enucleation-free survival (EFS) and progression-free survival were assessed. RESULTS: We examined 19 patients (median age, 11.9 months; range, 1.4 to 75.6 months) with a sum of 25 eyes, of which, 60.0% were at advanced Reese Ellsworth (RE) stages. The enucleation rate was 33.3% at early RE stages and 81.8% at advanced RE stages (P=0.028). At 36 months, EFS was significantly higher in the IAC/CTX group than in the non-IAC/CTX group (100% vs. 40.0%, P=0.016). All 5 patients treated with IAC achieved eye preservation, although most patients were at advanced RE stages (IV-V). CONCLUSION: Despite the limitation of a small sample size, our work shows that an alternative combined approach using IAC and CTX may be safe and effective for eye preservation in advanced RB.

Survival Benefit of Hematopoietic Stem Cell Transplantation in Infant Acute Lymphoblastic Leukemia, According to Classification of High Risk Group / 임상소아혈액종양

BACKGROUND: In comparison to older children, acute leukemia in infants has a dismal outcome, despite introduction of intensive multi-agent chemotherapy. Patients with age under 1 year and mixed-lineage leukemia (MLL) gene rearrangements are the most high risk group. In this study, we investigate the outcome of more intensive chemotherapy and the role of hematopoietic stem cell transplantation (HSCT) in high risk group of infant leukemia. METHODS: This study analyzed on 9 infants with acute lymphoblastic leukemia (ALL) who were diagnosed and treated between 1998 and 2008 at Severance hospital. We classified high risk group with age at diagnosis is under 6 months or white blood cell at diagnosis are over 50,000/microL or presence of MLL gene rearrangements. Patients in high risk group were treated on a protocol of intensive chemotherapy followed by HSCT. RESULTS: In this study, the 3-years EFS rate for 9 infant ALL patients was 66.7+/-15.7%. Both of 2 patients younger than 6 months of age at diagnosis did not survive. 3yr-EFS rate for the 7 patients categorized in high risk group out of 9 infant ALL patients was 57.1+/-18.7%, and 3 yr EFS of the 6 patients in the high risk group who received HSCT was 60+/-21.9%. We did not experience relapse in 6 patients treated with HSCT. CONCLUSION: This study showed promising results and lesser risks in high risk group infant ALL treated with intensive chemotherapy and HSCT. We suggest early HSCT with intensive chemotherapy for infant leukemia patients in high risk group.

Survival Benefit of Hematopoietic Stem Cell Transplantation in Infant Acute Lymphoblastic Leukemia, According to Classification of High Risk Group / 임상소아혈액종양

BACKGROUND: In comparison to older children, acute leukemia in infants has a dismal outcome, despite introduction of intensive multi-agent chemotherapy. Patients with age under 1 year and mixed-lineage leukemia (MLL) gene rearrangements are the most high risk group. In this study, we investigate the outcome of more intensive chemotherapy and the role of hematopoietic stem cell transplantation (HSCT) in high risk group of infant leukemia.METHODS: This study analyzed on 9 infants with acute lymphoblastic leukemia (ALL) who were diagnosed and treated between 1998 and 2008 at Severance hospital. We classified high risk group with age at diagnosis is under 6 months or white blood cell at diagnosis are over 50,000/microL or presence of MLL gene rearrangements. Patients in high risk group were treated on a protocol of intensive chemotherapy followed by HSCT.RESULTS: In this study, the 3-years EFS rate for 9 infant ALL patients was 66.7+/-15.7%. Both of 2 patients younger than 6 months of age at diagnosis did not survive. 3yr-EFS rate for the 7 patients categorized in high risk group out of 9 infant ALL patients was 57.1+/-18.7%, and 3 yr EFS of the 6 patients in the high risk group who received HSCT was 60+/-21.9%. We did not experience relapse in 6 patients treated with HSCT.CONCLUSION: This study showed promising results and lesser risks in high risk group infant ALL treated with intensive chemotherapy and HSCT. We suggest early HSCT with intensive chemotherapy for infant leukemia patients in high risk group.

Expression Profiles of Immune-related Genes in Fluoxetine-treated Human Mononuclear Cells by cDNA Microarray

To investigate the effect of fluoxetine, one of selective serotonin reuptake inhibitors (SSRIs), on the immune system, human peripheral blood mononuclear cells (PBMC) were treated with fluoxetine (10 7 M) for 24 h, and immune-related genes were analyzed by cDNA microarray. Expression of the immune- related genes such as CD107b (LAMP-2), CD47 receptor (thrombospondin receptor), CD5 antigen-like (scavenger receptor cysteine rich family), copine III (CPNE3), interleukin (IL) -18 (interferon-gamma- inducing factor), integrin alpha 4 (CD49d), integrin alpha L subunit (CD11a), IL-3 receptor alpha subunit, L apoferritin, and small inducible cytokine subfamily A (Cys-Cys) member 13 (SCYA13) was induced by fluoxetine. This result suggests that fluoxetine may affect the immune system, and provides fundamental data for the involvement of SSRIs on immunoregulation.