Introduction. Resection of pulmonary metastases has previously been reported to improve Outcome in high-grade osteosarcoma (OS) patients. Factors influencing Survival in OS patients with pulmonary... Show moreIntroduction. Resection of pulmonary metastases has previously been reported to improve Outcome in high-grade osteosarcoma (OS) patients. Factors influencing Survival in OS patients with pulmonary metastases are important for clinical decision making. Methods. All 88 OS patients with pulmonary metastases either at diagnosis or during follow-up treated at the Leiden University Medical Center between January 1, 1990 and January 1, 2008 under the age of 40 were included in this Study, including 79 cases of conventional, 8 cases of telangiectatic and 1 case of small cell OS. Results. In total, 56 of 88 patients with pulmonary metastases were treated by metastasectomy. Resectability Of pulmonary metastases was the main prognostic factor. In patients with primary non-metastatic OS, a longer relapse free interval to Pulmonary metastases was significantly associated with better survival (P=0.02). Independent risk factors determining worse survival after metastasectomy in multivariate analysis were male sex (P=0.05), higher number of pulmonary nodules (P=0.03), and non-necrotic metastases (P=0.04). Whether Surgery for recurrent pulmonary metastases was performed did not influence Survival. Histological Subtype of the primary tumor, histological response in the primary tumor after neoadjuvant chemotherapy, occurrence of local relapse, local resection or amputation of the primary tumor and age at diagnosis did not influence Outcome. Conclusion. This cohort of patients with detailed follow-up data enabled US to identify important risk factors determining Survival in OS patients with pulmonary metastases. We demonstrate that after repeated metastasectomies, a subset of patients can be cured. Pediatr Blood Cancer 2010;54:216-221. (C) 2009 Wiley-Liss, Inc. Show less
INTRODUCTION: Resection of pulmonary metastases has previously been reported to improve outcome in high-grade osteosarcoma (OS) patients. Factors influencing survival in OS patients with pulmonary... Show moreINTRODUCTION: Resection of pulmonary metastases has previously been reported to improve outcome in high-grade osteosarcoma (OS) patients. Factors influencing survival in OS patients with pulmonary metastases are important for clinical decision making. METHODS: All 88 OS patients with pulmonary metastases either at diagnosis or during follow-up treated at the Leiden University Medical Center between January 1, 1990 and January 1, 2008 under the age of 40 were included in this study, including 79 cases of conventional, 8 cases of telangiectatic and 1 case of small cell OS. RESULTS: In total, 56 of 88 patients with pulmonary metastases were treated by metastasectomy. Resectability of pulmonary metastases was the main prognostic factor. In patients with primary non-metastatic OS, a longer relapse free interval to pulmonary metastases was significantly associated with better survival (P = 0.02). Independent risk factors determining worse survival after metastasectomy in multivariate analysis were male sex (P = 0.05), higher number of pulmonary nodules (P = 0.03), and non-necrotic metastases (P = 0.04). Whether surgery for recurrent pulmonary metastases was performed did not influence survival. Histological subtype of the primary tumor, histological response in the primary tumor after neo-adjuvant chemotherapy, occurrence of local relapse, local resection or amputation of the primary tumor and age at diagnosis did not influence outcome. CONCLUSION: This cohort of patients with detailed follow-up data enabled us to identify important risk factors determining survival in OS patients with pulmonary metastases. We demonstrate that after repeated metastasectomies, a subset of patients can be cured. Show less
Leukemia represents the most common pediatric malignancy, accounting for approximately 30% of all cancers in children less than 20 years of age. Most children diagnosed with leukemia are cured... Show moreLeukemia represents the most common pediatric malignancy, accounting for approximately 30% of all cancers in children less than 20 years of age. Most children diagnosed with leukemia are cured without hematopoietic stem cell transplantation (HSCT), but for some high-risk subgroups, allogeneic HSCT plays an important role in their therapeutic approach. The characteristics of these high-risk subgroups and the role of HSCT in childhood leukemias are discussed. Show less
The transplant policy for unrelated donor (UD) BMT at Leiden Paediatrics' SCT-Centre consisted of the use of (1) fully HLA-matched donors or, if not available, HLA-class I matched and/or cytotoxic... Show moreThe transplant policy for unrelated donor (UD) BMT at Leiden Paediatrics' SCT-Centre consisted of the use of (1) fully HLA-matched donors or, if not available, HLA-class I matched and/or cytotoxic T-lymphocyte precursor (CTLp)-negative donors and (2) protective isolation of the recipient and antimicrobial suppression of his/her gut microflora to prevent infections and acute GVHD. Engraftment, GVHD, relapse in the case of malignancy and survival were studied retrospectively in 126 evaluable children, transplanted between 1988 and 2005. In addition to the effect of HLA-matching, that of other transplant-relevant variables on the outcome was also studied. Actuarial OS was 65% and the EFS was 59%, 13% graft failures occurred and 7.5% >= grade II acute GVHD. HLA-class II mismatches combined with HLA-class I matches resulted in a superior OS of 92%, as did a negative vs positive CTLp test, that is, 65 vs 33%. Analysis of other variables showed a poorer OS in patients >= 10 yrs vs <10 yrs, that is, 54 vs 73%, and in male recipients of a female donor graft, that is, 53 vs 69% for other combinations. UD-BMT can be optimized by permitting HLA-class I-matched and/or CTLp-negative donors, and probably by choosing male donors for male recipients. Bone Marrow Transplantation (2010) 45, 87-95; doi: 10.1038/bmt.2009.104; published online 18 May 2009 Show less
The transplant policy for unrelated donor (UD) BMT at Leiden Paediatrics' SCT-Centre consisted of the use of (1) fully HLA-matched donors or, if not available, HLA-class I matched and/or cytotoxic... Show moreThe transplant policy for unrelated donor (UD) BMT at Leiden Paediatrics' SCT-Centre consisted of the use of (1) fully HLA-matched donors or, if not available, HLA-class I matched and/or cytotoxic T-lymphocyte precursor (CTLp)-negative donors and (2) protective isolation of the recipient and antimicrobial suppression of his/her gut microflora to prevent infections and acute GVHD. Engraftment, GVHD, relapse in the case of malignancy and survival were studied retrospectively in 126 evaluable children, transplanted between 1988 and 2005. In addition to the effect of HLA-matching, that of other transplant-relevant variables on the outcome was also studied. Actuarial OS was 65% and the EFS was 59%, 13% graft failures occurred and 7.5% > or =grade II acute GVHD. HLA-class II mismatches combined with HLA-class I matches resulted in a superior OS of 92%, as did a negative vs positive CTLp test, that is, 65 vs 33%. Analysis of other variables showed a poorer OS in patients > or =10 yrs vs <10 yrs, that is, 54 vs 73%, and in male recipients of a female donor graft, that is, 53 vs 69% for other combinations. UD-BMT can be optimized by permitting HLA-class I-matched and/or CTLp-negative donors, and probably by choosing male donors for male recipients. Show less
The aim of our study was to assess the cumulative incidence and severity ('burden') of late effects in a single-centre cohort of childhood haematopoietic stem cell transplantation (HSCT) survivors,... Show moreThe aim of our study was to assess the cumulative incidence and severity ('burden') of late effects in a single-centre cohort of childhood haematopoietic stem cell transplantation (HSCT) survivors, at least 2 years after transplantation. The presence and severity of late effects in each survivor was documented according to the Common Terminology Criteria for Adverse Events (version 3.0). The burden of late effects was graded from mild to disabling/life-threatening. Risk factors for a high burden of late effects were assessed by univariate and multivariate logistic regression analyses. Among 162 survivors of HSCT seen in our late effects outpatient clinic, cumulative incidence of late effects was 93.2% after a median follow-up time of 7.2 years (range 2.0-21.0 years) after HSCT. The burden of late effects was mild, moderate, severe and disabling in 28, 41, 24 and 1% of survivors respectively. Risk factors for a severe or disabling burden of late effects were older age at HSCT (P for trend <0.001) and a conditioning regimen including irradiation OR 2.2, 95% CI 1.1-4.7, P = 0.03). In conclusion, a high burden of late effects is found in childhood HSCT survivors after a median follow-up of only 7 years. Bone Marrow Transplantation (2010) 45, 79-85; doi: 10.1038/bmt.2009.92; published online 4 May 2009 Show less
The aim of our study was to assess the cumulative incidence and severity ('burden') of late effects in a single-centre cohort of childhood haematopoietic stem cell transplantation (HSCT) survivors,... Show moreThe aim of our study was to assess the cumulative incidence and severity ('burden') of late effects in a single-centre cohort of childhood haematopoietic stem cell transplantation (HSCT) survivors, at least 2 years after transplantation. The presence and severity of late effects in each survivor was documented according to the Common Terminology Criteria for Adverse Events (version 3.0). The burden of late effects was graded from mild to disabling/life-threatening. Risk factors for a high burden of late effects were assessed by univariate and multivariate logistic regression analyses. Among 162 survivors of HSCT seen in our late effects outpatient clinic, cumulative incidence of late effects was 93.2% after a median follow-up time of 7.2 years (range 2.0-21.0 years) after HSCT. The burden of late effects was mild, moderate, severe and disabling in 28, 41, 24 and 1% of survivors respectively. Risk factors for a severe or disabling burden of late effects were older age at HSCT (P for trend <0.001) and a conditioning regimen including irradiation OR 2.2, 95% CI 1.1-4.7, P=0.03). In conclusion, a high burden of late effects is found in childhood HSCT survivors after a median follow-up of only 7 years. Show less
