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1.
J Pediatr Hematol Oncol ; 44(1): e5-e13, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33885033

RESUMO

Refractory stage M neuroblastoma (NB) is associated with a poor prognosis and a progressive course of disease. Here, we describe a unique group of patients with a discrepant clinical course. Seven histologically confirmed ganglioneuroblastoma (GNB) (n=6) and differentiating NB (n=1) patients were identified who were diagnosed with stage M disease based on iodine-123-metaiodobenzylguanidine avid bone metastases. Six patients started on high-risk treatment, without tumor response (stable disease). Treatment was discontinued before the start of consolidation treatment because of refractory response in all patients. Unexpectedly, after cessation of treatment no progression of disease occurred. In 2 patients, the primary tumors expanded (>25%) very slowly during 1.5 and 3 years, and remained stable thereafter. Metabolically, a slow decrease of urinary homovanillic acid and vanillylmandelic acid levels and iodine-123-metaiodobenzylguanidine avidity was observed. All patients are alive with presence of metastatic disease after a median follow-up of 17 years (range: 6.7 to 27 y). Interestingly, at diagnosis, 6 patients were asymptomatic, 6 patients had GNB morphology, and 5 patients had meningeal metastases. These are all features seen in only a small minority of stage M patients. This GNB entity illustrates the clinical heterogeneity of neuroblastic tumors and can be used to further study the developmental origin of different NB subtypes.


Assuntos
Neoplasias Ósseas , Quimioterapia de Consolidação , Ganglioneuroblastoma , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias Ósseas/urina , Pré-Escolar , Doença Crônica , Feminino , Ganglioneuroblastoma/tratamento farmacológico , Ganglioneuroblastoma/urina , Humanos , Lactente , Masculino , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos
2.
Pediatr Blood Cancer ; 59(7): 1239-44, 2012 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-22378688

RESUMO

BACKGROUND: The outcome of the treatment of pediatric acute myeloid leukemia (AML) is still disappointing, due to relatively high treatment-related mortality and relapse rates (30-40%). Past treatment protocols have called for routine screening via bone marrow aspiration (BMA) after achievement of first complete remission (CR1) to detect relapse at an early stage. However, supporting evidence for this policy is lacking for non-FAB type-M3 patients. PROCEDURE: We therefore retrospectively studied the clinical relevance of routine BMA in an unselected cohort of all pediatric AML patients in the Netherlands. RESULTS: Of 440 patients, data for 349 patients, of whom 148 suffered bone marrow relapse (BM-relapse), could be analyzed. A total of 1,790 BMAs had been performed, 1,648 (92%) routinely, and 142 (8%) on indication when a relapse was suspected. Forty routine BMAs showed BM-relapse (2% of all routine BMAs), while as many as 108 (76%) hematological relapses were confirmed by BMA on indication (P < 0.001). Therefore, 1 in 41 routine BMAs, as opposed to 1 in 1.3 BMAs performed on indication, detected a BM-relapse. CONCLUSIONS: Routine BMA after CR1 did not significantly contribute to early detection of relapsed AML. These results suggest that BMA after achievement of CR1 should only be performed on indication or within a clinical research setting. Pediatr Blood Cancer 2012; 59: 1239-1244. © 2012 Wiley Periodicals, Inc.


Assuntos
Exame de Medula Óssea , Leucemia Mieloide Aguda/diagnóstico , Medula Óssea/patologia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Valor Preditivo dos Testes , Recidiva , Sensibilidade e Especificidade
3.
Cancers (Basel) ; 14(4)2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35205701

RESUMO

Survival rates are excellent for children with Wilms tumor (WT), yet tumor and treatment-related complications may require pediatric intensive care unit (PICU) admission. We assessed the frequency, clinical characteristics, and outcome of children with WT requiring PICU admissions in a multicenter, retrospective study in the Netherlands. Admission reasons of unplanned PICU admissions were described in relation to treatment phase. Unplanned PICU admissions were compared to a control group of no or planned PICU admissions, with regard to patient characteristics and short and long term outcomes. In a multicenter cohort of 175 children with an underlying WT, 50 unplanned PICU admissions were registered in 33 patients. Reasons for admission were diverse and varied per treatment phase. Younger age at diagnosis, intensive chemotherapy regimens, and bilateral tumor surgery were observed in children with unplanned PICU admission versus the other WT patients. Three children required renal replacement therapy, two of which continued dialysis after PICU discharge (both with bilateral disease). Two children died during their PICU stay. During follow-up, hypertension and chronic kidney disease (18.2 vs. 4.2% and 15.2 vs. 0.7%) were more frequently observed in unplanned PICU admitted patients compared to the other patients. No significant differences in cardiac morbidity, relapse, or progression were observed. Almost 20% of children with WT required unplanned PICU admission, with young age and treatment intensity as potential risk factors. Hypertension and renal impairment were frequently observed in these patients, warranting special attention at presentation and during treatment and follow-up.

4.
Cancers (Basel) ; 13(19)2021 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-34638426

RESUMO

BACKGROUND: Anti-GD2 based immunotherapy has improved overall (OS) and event free survival (EFS) for high-risk neuroblastoma (HR-NBL) patients. Here, we evaluate the long-term efficacy of anti-GD2 immunotherapy in combination with isotretinoin, GM-CSF, and IL-2. METHODS: Dutch HR-NBL patients treated with immunotherapy according to the COG-ANBL0032 protocol (n = 47) were included and compared to historical controls (n = 37) treated with single-agent isotretinoin maintenance therapy. Survival time was calculated from start of the maintenance therapy. RESULTS: The study and control group were similar concerning baseline characteristics. In the complete cohort, 5 year OS was 64 ± 7% and 49 ± 8% for the immunotherapy group and the control group, respectively (p = 0.16). Five year EFS was 57 ± 7% and 41 ± 8%, respectively (p = 0.16). In the subgroup of patients ≥ 18 months, 5-yr OS was 63 ± 8% and 39 ± 9, respectively (p = 0.04) and EFS 54 ± 8% and 29 ± 8%, respectively (p = 0.05). Landmark analysis for EFS with landmark point at 6 months after start of maintenance suggests a larger effect on the prevention of late than early events. CONCLUSIONS: This study is the first to confirm the results of the COG-ANBL0032 study in a cohort treated with a different induction regimen. Anti-GD2 immunotherapy prevents late events, most significantly in patients older than 18 months of age at diagnosis.

5.
Clin Cancer Res ; 25(3): 1012-1021, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30314967

RESUMO

PURPOSE: Targeted radiotherapy with 131iodine-meta-iodobenzylguanidine (131I-MIBG) is effective for neuroblastoma (NBL), although optimal scheduling during high-risk (HR) treatment is being investigated. We aimed to evaluate the feasibility of stem cell apheresis and study hematologic reconstitution after autologous stem cell transplantation (ASCT) in patients with HR-NBL treated with upfront 131I-MIBG-therapy. EXPERIMENTAL DESIGN: In two prospective multicenter cohort studies, newly diagnosed patients with HR-NBL were treated with two courses of 131I-MIBG-therapy, followed by an HR-induction protocol. Hematopoietic stem and progenitor cell (e.g., CD34+ cell) harvest yield, required number of apheresis sessions, and time to neutrophil (>0.5 × 109/L) and platelet (>20 × 109/L) reconstitution after ASCT were analyzed and compared with "chemotherapy-only"-treated patients. Moreover, harvested CD34+ cells were functionally (viability and clonogenic capacity) and phenotypically (CD33, CD41, and CD62L) tested before cryopreservation (n = 44) and/or after thawing (n = 19). RESULTS: Thirty-eight patients (47%) were treated with 131I-MIBG-therapy, 43 (53%) only with chemotherapy. Median cumulative 131I-MIBG dose/kg was 0.81 GBq (22.1 mCi). Median CD34+ cell harvest yield and apheresis days were comparable in both groups. Post ASCT, neutrophil recovery was similar (11 days vs. 10 days), whereas platelet recovery was delayed in 131I-MIBG- compared with chemotherapy-only-treated patients (29 days vs. 15 days, P = 0.037). Testing of harvested CD34+ cells revealed a reduced post-thaw viability in the 131I-MIBG-group. Moreover, the viable CD34+ population contained fewer cells expressing CD62L (L-selectin), a marker associated with rapid platelet recovery. CONCLUSIONS: Harvesting of CD34+ cells is feasible after 131I-MIBG. Platelet recovery after ASCT was delayed in 131I-MIBG-treated patients, possibly due to reinfusion of less viable and CD62L-expressing CD34+ cells, but without clinical complications. We provide evidence that peripheral stem cell apheresis is feasible after upfront 131I-MIBG-therapy in newly diagnosed patients with NBL. However, as the harvest of 131I-MIBG-treated patients contained lower viable CD34+ cell counts after thawing and platelet recovery after reinfusion was delayed, administration of 131I-MIBG after apheresis is preferred.


Assuntos
3-Iodobenzilguanidina/uso terapêutico , Remoção de Componentes Sanguíneos/métodos , Neuroblastoma/terapia , Células-Tronco de Sangue Periférico/citologia , Transplante de Células-Tronco/métodos , Adolescente , Antígenos CD34/sangue , Quimiorradioterapia/métodos , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Células-Tronco de Sangue Periférico/metabolismo , Estudos Prospectivos , Fatores de Risco , Transplante Autólogo , Resultado do Tratamento
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