title: Toxicity of tandem high-dose chemotherapy and autologous stem cell transplantation using carboplatin-thiotepa-etoposide and cyclophosphamide-melphalan regimens for malignant brain tumors in children and young adults.
abstract: The number of studies examining the use of tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) to treat high-risk or recurrent brain tumors is increasing. However, studies addressing the toxicity associated with tandem HDCT/auto-SCT, particularly during the second HDCT/auto-SCT, are very limited. For this reason, we retrospectively evaluated the toxicity of tandem HDCT/auto-SCT with carboplatin-thiotepa-etoposide (CTE) and cyclophosphamide-melphalan (CM) regimens when used to treat high-risk or recurrent brain tumors. A total of 109 patients who received a first HDCT/auto-SCT and 100 who proceeded to a second HDCT/auto-SCT between May 2005 and December 2013 were included. Hematologic recovery was rapid during both the first and second HDCT/auto-SCT. In the first HDCT/auto-SCT, mucositis-related gastrointestinal toxicity was frequent, and two (1.8 %) patients died from toxicity [one hepatic veno-occlusive disease (VOD) and one sepsis]. In the second HDCT/auto-SCT, mucositis-related toxicity was milder than in the first round. However, hepatic VOD frequency was high (20.0 %), and six (6.0 %) patients died from toxicity (four hepatic VODs, one asphyxia, and one sepsis). Multivariate analysis indicated that age younger than 8 years was the only significant predictor for hepatic VOD. All six patients who died from toxicity during the second HDCT/auto-SCT were younger than 9 years of age. This study demonstrates that tandem HDCT/auto-SCT using CTE/CM regimens was generally feasible. However, dose reduction during the second HDCT/auto-SCT in young children might be needed to decrease the death rate from toxicity.
authors.affiliation: Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-Dong, Gangnam-Gu, Seoul, 135-710, Republic of Korea.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Lee
authors.forename: Meong Hi
authors.initials: MH
authors.lastname: Son
authors.forename: Ki Woong
authors.initials: KW
authors.lastname: Sung
authors.forename: Young Bae
authors.initials: YB
authors.lastname: Choi
authors.forename: Na Hee
authors.initials: NH
authors.lastname: Lee
authors.forename: Keon Hee
authors.initials: KH
authors.lastname: Yoo
authors.forename: Hong Hoe
authors.initials: HH
authors.lastname: Koo
authors.forename: Do Hoon
authors.initials: DH
authors.lastname: Lim
authors.forename: Hyung Jin
authors.initials: HJ
authors.lastname: Shin
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage / Q000633:toxicity*; D001932:Brain Neoplasms / Q000628:therapy*; D016190:Carboplatin / Q000008:administration & dosage / Q000633:toxicity; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000009:adverse effects; D005047:Etoposide / Q000008:administration & dosage / Q000633:toxicity; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000633:toxicity; D012189:Retrospective Studies; D033581:Stem Cell Transplantation / Q000009:adverse effects*; D013852:Thiotepa / Q000008:administration & dosage / Q000633:toxicity; D014182:Transplantation, Autologous / Q000009:adverse effects; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D005047:Etoposide; D013852:Thiotepa; D016190:Carboplatin; D008558:Melphalan
references.citation: J Neurooncol. 2010 Apr;97(2):247-55
references.pmid: 19768658
references.citation: J Clin Oncol. 2002 May 1;20(9):2284-92
references.pmid: 11980999
references.citation: Bone Marrow Transplant. 2007 Jul;40(1):37-45
references.pmid: 17468771
references.citation: J Neurooncol. 2013 Sep;114(3):329-38
references.pmid: 23824533
references.citation: Pediatr Blood Cancer. 2007 Apr;48(4):408-15
references.pmid: 17066462
references.citation: Pediatr Blood Cancer. 2008 Feb;50(2):312-8
references.pmid: 17668858
references.citation: J Clin Oncol. 2006 Jun 20;24(18):2891-6
references.pmid: 16782928
references.citation: Neuro Oncol. 2013 Mar;15(3):352-9
references.pmid: 23258845
references.citation: Pediatr Blood Cancer. 2004 Mar;42(3):261-7
references.pmid: 14752864
references.citation: Cancer. 2007 Jul 1;110(1):156-63
references.pmid: 17541945
references.citation: Bone Marrow Transplant. 2008 Jan;41(2):167-72
references.pmid: 18176620
references.citation: J Clin Oncol. 2004 Dec 15;22(24):4881-7
references.pmid: 15611503
references.citation: Lancet Oncol. 2006 Oct;7(10):813-20
references.pmid: 17012043
references.citation: J Clin Oncol. 1998 Jan;16(1):210-21
references.pmid: 9440745
references.citation: J Clin Oncol. 2009 Mar 1;27(7):1007-13
references.pmid: 19171716
references.citation: Pediatr Blood Cancer. 2008 Aug;51(2):235-40
references.pmid: 18381756
references.citation: J Clin Oncol. 2004 May 15;22(10):1934-43
references.pmid: 15143087
references.citation: J Neurooncol. 2012 Apr;107(2):335-42
references.pmid: 22081297
references.citation: Pediatr Blood Cancer. 2007 Mar;48(3):278-84
references.pmid: 16456857
references.citation: Bone Marrow Transplant. 2013 Jul;48(7):932-8
references.pmid: 23318534
references.citation: Bone Marrow Transplant. 2013 Jan;48(1):68-73
references.pmid: 22635247
references.citation: J Neurooncol. 2005 Jan;71(1):33-8
references.pmid: 15719272
references.citation: J Neurooncol. 2012 Feb;106(3):441-7
references.pmid: 21850536