Tandem high-dose chemotherapy and autologous stem cell transplantation in patients with high-risk neuroblastoma: results of SMC NB-2004 study.
From January 2004 to December 2008, 50 consecutive patients with high-risk neuroblastoma were assigned to receive tandem HDCT (high-dose chemotherapy)/auto-SCT after nine cycles of induction chemotherapy. CEC (carboplatin + etoposide + cyclophosphamide) regimen and TM (thiotepa + melphalan)-TBI regimen (or TM regimen for stage 3 patients) were the first and second HDCT regimens. Local radiotherapy, differentiation therapy with 13-cis-retinoid acid and immunotherapy with interleukin-2 were given after tandem HDCT/auto-SCT. Of the 50 patients, 49 underwent a first HDCT/auto-SCT and 47 underwent a second HDCT/auto-SCT. The tumor relapsed or progressed in 14 patients, secondary malignancy developed in one patient and one patient died from chronic lung disease. Therefore, 34 patients remained event free with a median follow-up of 54.5 months (range, 14-94 months) from diagnosis. The probabilities of 5-year OS and EFS for all 50 patients were 77.0% (95% confidence interval (CI), 63.7-90.3) and 71.4% (95% CI, 58.7-84.1), respectively. However, all patients who remained event free for >3 years after tandem HDCT/auto-SCT experienced late adverse effects. Chemotherapeutic dose-escalation strategy using tandem HDCT/auto-SCT was very encouraging for survival. However, further studies incorporating newer treatment modalities are needed to reduce late adverse effects without jeopardizing the survival rate.
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Republic of Korea. kwsped@skku.edu
K W
KW
Sung
M H
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Son
S H
SH
Lee
K H
KH
Yoo
H H
HH
Koo
J Y
JY
Kim
E J
EJ
Cho
S K
SK
Lee
Y S
YS
Choi
D H
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Lim
J-S
JS
Kim
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Kim
D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000175:diagnosis / Q000473:pathology / Q000556:secondary / Q000628:therapy; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy / Q000009:adverse effects; D056915:DNA Copy Number Variations; D005240:Feasibility Studies; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects; D007223:Infant; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D015474:Isotretinoin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis / Q000473:pathology / Q000556:secondary / Q000628:therapy*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D011379:Prognosis; D011446:Prospective Studies; D011878:Radiotherapy / Q000009:adverse effects / Q000379:methods*; D033581:Stem Cell Transplantation / Q000009:adverse effects; D016019:Survival Analysis; D014182:Transplantation, Autologous; D014916:Whole-Body Irradiation / Q000009:adverse effects
D000970:Antineoplastic Agents; C508594:IL2 protein, human; D007376:Interleukin-2; C459801:MYCN protein, human; D000071447:N-Myc Proto-Oncogene Protein; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D015474:Isotretinoin