Outcome of children less than three years old at diagnosis with non‐metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols

Dhall, Girish; Grodman, H.; Ji, Lingyun; Sands, Stephen A.; Gardner, Sharon; Dunkel, Ira J.; McCowage, Geoffrey; Diez, Blanca; Allen, Jeffrey C.; Gopalan, Anjali; Cornelius, Albert; Termuhlen, Amanda; Abromowitch, Minnie; Sposto, Richard; Finlay, Jonathan L.

doi:10.1002/pbc.21525

Cited by 205 publications

(168 citation statements)

References 22 publications

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“…[13][14][15][16][17][18][19][20][21][22] The basic treatment schema consisted of five 21-to 28-day cycles of induction chemotherapy: cisplatin (3.5 mg/kg) on day 0, vincristine (0.05 mg/kg) on days 0, 8 and 15, cyclophosphamide (65 mg/kg) on days 1 and 2 and etoposide (4 mg/kg) on days 1 and 2 (Regimen A, HS I) with the addition of high-dose methotrexate (400 mg/kg) on day 3 for metastatic patients (HS II Regimen A2), or with two cycles replacing cisplatin and methotrexate by oral etoposide (1.67 mg/kg/day) on days 1-10 and oral temozolomide (6.5 mg/kg/day) on days 1-5 (HS III Regimen D or D2). During HS III, Regimen D was modified due to toxicities by reduction of cyclophosphamide to 55 mg/kg/day and methotrexate to 320 mg/kg.…”

Section: Methodsmentioning

confidence: 99%

“…These trials sought to improve patients' cure rate and quality of survival through avoidance or reduction of CNS irradiation by utilizing a single cycle of marrow-ablative chemotherapy with autologous hematopoietic rescue as consolidation following initial induction chemotherapy. [13][14][15][16][17][18][19][20][21][22] The goal of this present study was to examine changes in the rate of serious toxicities (grades III-V) associated with AuHCR in the first 100 days following transplant over the course of the 'Head Start' trials from 1991 to 2009.…”

Section: Introductionmentioning

confidence: 99%

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Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009

Altshuler

Haley

Dhall

et al. 2016

Bone Marrow Transplant

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Since 1991, three sequential prospective clinical trials have been conducted by the 'Head Start' (HS) Consortium in which young children with newly-diagnosed malignant central nervous system (CNS) tumors were treated with induction chemotherapy followed by single-cycle marrow-ablative chemotherapy and autologous hematopoietic rescue as a means of improving disease cure rate and quality of survival through avoidance (o 6 years old at diagnosis) or reduction (6-10 years old) of brain irradiation. Bone Marrow (HS I) or filgrastim-mobilized peripheral hematopoietic cells (HS II and III) were obtained following recovery from the first and/or second induction cycles. Radiotherapy was administered following all chemotherapy only for patients with residual tumor following completion of induction or with age greater than 6 years at diagnosis. Two hundred and twenty-six children were enrolled on three consecutive HS trials with primary malignant CNS tumors and underwent marrow-ablative chemotherapy. The 100-day treatment-related mortality (TRM) steadily declined as did grade IV transplant-related oropharyngeal mucositis. Factors most likely associated with the decrease in TRM and morbidity are increasing experience with the marrow-ablative chemotherapy regimen combined with improved leukapheresis and post-reinfusion supportive care techniques, contributing toward improved overall survival.Bone Marrow Transplantation (2016) 51, 945-948;

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009

Altshuler

Haley

Dhall

et al. 2016

Bone Marrow Transplant

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“…His postoperative course was uneventful and he exhibited no signs of cerebral ALD. He was treated with five cycles of cisplatin, cytoxan, etoposide, and vincristine ("Head Start" II, Dhall et al 2008) and then received conformal radiation therapy (2,340 Gy to the posterior fossa with 3,660 Gy boost to the tumor bed). MRI after completion was unremarkable without evidence of residual or recurrent tumor.…”

Section: Case Reportmentioning

confidence: 99%

Onset of Adreno-Leukodystrophy After Medulloblastoma Therapy: Causal Connection or Coincidence?

et al. 2011

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X-linked adreno-leukodystrophy (ALD) is a peroxisomal disorder affecting the white matter of the central nervous system and the adrenal cortex. It is caused by mutations in the ABCD1 gene encoding for a peroxisomal membrane protein. The absent genotype-phenotype correlation implies a contribution by environmental factors to explain the phenotypical heterogeneity. We report on a 4-year-old boy with a biochemically confirmed diagnosis of ALD after birth. At the age of 32 months, the additional diagnosis of a medulloblastoma was made. After treatment of the medulloblastoma, he developed active areas of demyelination representing the characteristic neuroimaging features of ALD. The clinical history of our patient supports the hypothesis that external factors, like neurosurgical intervention as part of medulloblastoma treatment, may accelerate or initiate cerebral ALD-related demyelination. A postsurgical inflammatory reaction may facilitate the inclusion of abnormal fatty acids in myelin. The opening of the blood-brain barrier following neurosurgery may enhance the recognition of previously sequestered antigens considered to play a role in ALD onset. Consequently, neurosurgical disruption of the BBB can precipitate the immune-mediated inflammatory process, which progressively destroys myelin in ALD patients. Tumor-related chemotherapy and/or radiotherapy may also play a contributing role. We suggest that X-ALD patients who undergo neurosurgical intervention need close followup imaging to identify active demyelination early.

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“…Radiation therapy was reserved for recurrent disease. In these studies, the 5-year OS rate for all patients Ͻ3 years of age with MB was 52% (Ϯ11%), and 71% of the survivors of nonmetastatic disease were not irradiated [45]. A limitation to this approach was the high toxic mortality rate of 19%.…”

Section: Mbmentioning

confidence: 99%

Current Treatment Approaches for Infants with Malignant Central Nervous System Tumors

Lafay‐Cousin

Strother

2009

The Oncologist

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DisclosuresLucie Lafay-Cousin: None; Douglas Strother: None.Section editors Susan M. Blaney and Ross Pinkerton have disclosed no financial relationships relevant to the content of this article.The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias. LEARNING OBJECTIVES1. Evaluate the challenges of identifying very young children with brain tumors so that they can be enrolled in clinical trials.2. Identify prognostic factors for children with certain brain tumors and assess the influence of these factors on current therapeutic strategies.3. Outline factors affecting survival and neurocognitive outcome of children with malignant brain tumors.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME ABSTRACT

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Outcome of children less than three years old at diagnosis with non‐metastatic medulloblastoma treated with chemotherapy on the “Head Start” I and II protocols

Cited by 205 publications

References 22 publications

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009

Decreased morbidity and mortality of autologous hematopoietic transplants for children with malignant central nervous system tumors: the ‘Head Start’ trials, 1991–2009

Onset of Adreno-Leukodystrophy After Medulloblastoma Therapy: Causal Connection or Coincidence?

Current Treatment Approaches for Infants with Malignant Central Nervous System Tumors

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