Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.

Mason, Warren P.; Grovas, Alfred; Halpern, Steven; Dunkel, Ira J.; Garvin, James H.; Heller, Glenn; Rosenblum, Marc K.; Gardner, Sharon; Lyden, David; Sands, Stephen A.; Puccetti, Diane; Lindsley, Karen; Merchant, Thomas E.; O’Malley, Bernard; Bayer, Lisa A.; Petriccione, Mary Mc Elwain; Allen, Jeffrey C.; Finlay, Jonathan L.

doi:10.1200/jco.1998.16.1.210

Cited by 223 publications

(143 citation statements)

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“…[22][23][24][25][26][27] In the current study, we treated 27 patients with recurrent or newly diagnosed brain tumors. This group, which was heterogeneous with respect to histologic diagnosis and disease stage at study entry, had a 23% response rate to HDCT (Table 2).…”

Section: Discussionmentioning

confidence: 99%

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

Biasin¹,

Mastrodicasa²,

Sandri³

et al. 2004

Cancer

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BACKGROUNDOutcome data were analyzed for 27 patients who were affected with recurrent or newly diagnosed high‐risk brain tumors and who underwent high‐dose chemotherapy with triethylenethiophosphoramide (thiotepa) and etoposide in addition to autologous stem cell transplantation between May 1992 and September 2002.METHODSFifteen males and 12 females (median age, 11 years) were included in the study. Twelve patients had newly diagnosed high‐risk brain tumors, and 15 patients had recurrent brain tumors. The conditioning regimen consisted of thiotepa 900 mg/m2 and etoposide 1500 mg/m2 over 3 days starting on Day −5. Stem cell rescue was performed using bone marrow (BM) in 8 patients, peripheral blood stem cells (PBSCs) in 18 patients, and BM and PBSCs in 1 patient.RESULTSFor the BM group, neutrophil (PMN) engraftment was achieved on Day +14 (median value), whereas platelet (PLT) engraftment was achieved on Day +68 (median value). One patient did not achieve PLT engraftment. For the PBSC group, the PMN engraftment was achieved on Day +10.0 (median value), and the PLT engraftment was achieved on Day +15.5 (median value). Transplantation‐related toxicity (evaluated using the Bearman score) included Grade 2–3 mucositis in 16 patients, Grade 1 kidney toxicity in 6 patients, Grade 1 liver toxicity in 6 patients, and Grade 2 liver toxicity in 1 patient. Transplantation‐related mortality was observed in 1 patient (3.6%), who died of Candida pneumonia. The 3‐year overall survival (OS) rate was 44.6%, and the 3‐year event‐free survival (EFS) rate was 31%. There was a statistically significant difference in OS and EFS rates for patients who underwent ASCT and achieved complete remission compared with patients who had measurable disease.CONCLUSIONSThe results of the current study suggest that high‐dose chemotherapy followed by ASCT may be beneficial for patients who achieve complete remission before ASCT, whereas for other patients, new strategies are required. Cancer 2004. © 2004 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

Biasin¹,

Mastrodicasa²,

Sandri³

et al. 2004

Cancer

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“…In view of the toxicities, complications and overall mortality and morbidity of the BCNU/thiotepa/VP-16 combination, a modified regimen without a nitrosourea, and which incorporates carboplatin in addition to thiotepa and VP-16 has been developed. 21,23,30,31 Toxicity outcome has been improved and progression-free survival appears promising.…”

Section: Discussionmentioning

confidence: 99%

High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors

Papadakis

Dunkel

Cramer

et al. 2000

Bone Marrow Transplant

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Summary:Forty-two patients (29 newly diagnosed) with high grade gliomas (n = 37), medulloblastoma (n = 2) or nonbiopsied tumors (n = 3) with supratentorial (n = 24), brain stem (n = 11), posterior fossa (n = 5) or spinal (n = 2) location were eligible for this study with adequate organ function and no bone marrow tumor infiltration. Median patient age was 12.2 years (range, 0.7-46.8). A total of 600 mg/m 2 BCNU, 900 mg/m 2 thiotepa and 1500 or 750 mg/m 2 etoposide (VP-16) was administered followed by autologous bone marrow reinfusion (ABMR). Twenty-one newly diagnosed patients received local irradiation (RT) post ABMR. Nine early deaths were observed (21%), as well as one secondary graft failure. Half of the patients aged 18 years or older experienced toxic deaths, whereas only 15% of patients younger than 18 years experienced toxic death (P = 0.05). Of 25 evaluable newly diagnosed patients, 20% achieved complete remission (CR) and 4% partial remission (PR), while 28% remained in continuing complete remission (CCR) and 44% remained with stable disease prior to RT. Of eight evaluable patients with recurrent disease, one achieved CR and two PR, while one remained in CCR and four with stable disease for 1 to 110.2 months. Overall survival was 36%, 24% and 17% at 1, 2 and 3 years following ABMR, with three newly diagnosed patients and one patient treated for recurrent disease being alive, without disease progression 64.4, 67.0, 86.3 and 110.2 months after ABMR, respectively. The combination of high-dose BCNU/ thiotepa/VP-16 has substantial toxicity but definite activity for high risk CNS tumors. Similar protocols with lower toxicity merit further evaluation in both

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“…In the Head Start I and II studies, patients received RT only if residual tumor remained at the time of HDCT/auto-SCT or if the tumor had relapsed after HDCT/auto-SCT. [11][12][13] In the present study, the use of RT was determined by the tumor status after initial surgery but not the tumor status after chemotherapy, including HDCT/auto-SCT. Therefore, 9 of 13 patients who were in CR after tandem HDCT/ auto-SCT received RT after 3 years of age according to the tumor status at the time of diagnosis (L-RT alone in 2, CSRT alone in 3, and both L-RT and CSRT in 4 patients).…”

Section: Discussionmentioning

confidence: 99%

“…[8][9][10] Clinical trials using HDCT/auto-SCT for treatment of infants and young children with malignant brain tumors have shown that it is possible to avoid or defer RT until 3 years of age while maintaining or improving survival rates. [11][12][13] Additionally, several recent studies have suggested that dose-escalation using tandem HDCT/auto-SCT might further improve outcomes in the treatment of recurrent or high-risk brain tumors. 14,15 In the present study, we prospectively evaluated the feasibility and effectiveness of tandem HDCT/auto-SCT in children o3 years of age with malignant brain tumors.…”

Section: Introductionmentioning

confidence: 99%

Tandem high-dose chemotherapy and auto-SCT for malignant brain tumors in children under 3 years of age

et al. 2013

Bone Marrow Transplant

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In an effort to improve survival and reduce late adverse effects of radiation therapy (RT), 25 children o3 years of age with malignant brain tumors received tandem high-dose chemotherapy (HDCT) and auto-SCT following six cycles of induction chemotherapy. RT was either not given or deferred until 3 years of age if the patient was in CR after tandem HDCT/auto-SCT. Tumors relapsed or progressed in nine patients (five during induction treatment), and two of these patients survived after receiving salvage treatment, including RT. Two patients died due to toxicities during tandem HDCT/auto-SCT. A total of 16 patients survived to a median follow-up period of 52 months (range 18-96) from the time of diagnosis. Four of these patients did not receive RT, two received local RT (L-RT), three received craniospinal RT (CSRT), and seven received both L-RT and CSRT. The 5-year OS and EFS rates were 67.8 ± 9.4% and 55.5 ± 10.0%, respectively. Neuroendocrine and neurocognitive functions evaluated 3 years after tandem HDCT/auto-SCT were acceptable. Our results indicate that tandem HDCT/auto-SCT may improve survival in young children with malignant brain tumors with an acceptable level of risk of long-term toxicity.

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Intensive chemotherapy and bone marrow rescue for young children with newly diagnosed malignant brain tumors.

Abstract: A significant proportion of children with malignant brain tumors can avoid radiotherapy and prolonged maintenance chemotherapy yet still achieve durable remission with this brief intensive chemotherapy regimen.

Cited by 223 publications

References 38 publications

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

High‐dose thiotepa and etoposide in children with poor‐prognosis brain tumors

High-dose carmustine, thiotepa and etoposide followed by autologous bone marrow rescue for the treatment of high risk central nervous system tumors

Tandem high-dose chemotherapy and auto-SCT for malignant brain tumors in children under 3 years of age

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