ABSTRACT
This corrects the article DOI: 10.1038/leu.2017.290.
ABSTRACT
The optimal autologous stem cell rescue (HDC-SCR) regimen for children with high-risk neuroblastoma (HR-NBL) is not defined. Carboplatin/etoposide/melphalan (CEM) is the current US standard; however, European data suggest busulfan/melphalan (Bu/Mel) may have less toxicity. Published data regarding toxicities associated with CEM and Bu/Mel are limited. We conducted a single-institution retrospective cohort study of children with HR-NBL who received CEM or Bu/Mel preparative regimens. Toxicity data were analyzed using χ(2) or Fisher's exact, Wilcoxon two-sample or log-rank tests. Sinusoidal obstruction syndrome (SOS) was observed in 7/44 CEM (15.9%) and 5/21 (24%) Bu/Mel patients (P=0.50). Median time to SOS was longer following Bu/Mel than CEM (20 versus 9 days, P=0.02). Pulmonary hypertension (PHTN) was observed in ~20% of children after Bu/Mel and none after CEM (P=0.01). CEM patients had more nephrotoxicity (P=0.001), packed red blood cell (P=0.02) and platelet transfusions (P=0.008), and days on maximum pain support (P=0.0007). Time to engraftment, length of stay, documented infection rates and HDC-SCR-related mortality were similar. Nephrotoxicity and resource utilization associated with cytopenias and mucositis were greater after CEM. Pulmonary toxicities were more severe after Bu/Mel, and increased vigilance for PHTN may be warranted, particularly in children with hypoxemia out of proportion to respiratory distress.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/toxicity , Myeloablative Agonists/toxicity , Neuroblastoma/complications , Neuroblastoma/drug therapy , Transplantation Conditioning/adverse effects , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Busulfan/administration & dosage , Carboplatin/administration & dosage , Child , Child, Preschool , Cohort Studies , Etoposide/administration & dosage , Female , Hepatic Veno-Occlusive Disease/chemically induced , Humans , Hypertension, Pulmonary/chemically induced , Infant , Kidney Diseases/chemically induced , Male , Melphalan/administration & dosage , Mucositis/chemically induced , Myeloablative Agonists/administration & dosage , Neuroblastoma/mortality , Neuroblastoma/therapy , Pancytopenia/chemically induced , Retrospective Studies , Stem Cell Transplantation/adverse effects , Stem Cell Transplantation/methods , Stem Cell Transplantation/mortality , Transplantation Conditioning/methods , Transplantation Conditioning/mortality , Young AdultSubject(s)
Gene Expression Regulation, Leukemic , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/metabolism , Precursor Cells, B-Lymphoid/metabolism , Toll-Like Receptors/metabolism , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Core Binding Factor Alpha 2 Subunit/metabolism , Disease Progression , Humans , Immune System , Inflammation , Ligands , Mice , Mice, Transgenic , Neutralization Tests , PAX5 Transcription Factor/metabolism , Phenotype , Pre-B-Cell Leukemia Transcription Factor 1/genetics , Precursor Cells, B-Lymphoid/immunology , Proto-Oncogene Proteins c-ets/metabolism , Repressor Proteins/metabolism , ETS Translocation Variant 6 ProteinABSTRACT
Increasing treatment intensity has improved outcomes for children with neuroblastoma. We performed a pilot study in the Children's Oncology Group to assess the feasibility and toxicity of a tandem myeloablative regimen without TBI supported by autologous CD34-selected peripheral blood stem cells. Forty-one patients with high-risk neuroblastoma were enrolled; eight patients did not receive any myeloablative consolidation procedure and seven received only one. Two patients out of 41 (4.9%) experienced transplant-related mortality. CD34 selection was discontinued after subjects were enrolled due to serious viral illness. From the time of study enrollment, the overall 3-year EFS and OS were 44.8 ± 9.6% and 59.2 ± 9.2% (N=41). These results demonstrate that tandem transplantation in the cooperative group setting is feasible and support a randomized comparison of single vs tandem myeloablative consolidation with PBSC support for high-risk neuroblastoma.
Subject(s)
Neuroblastoma/mortality , Neuroblastoma/therapy , Peripheral Blood Stem Cell Transplantation , Transplantation Conditioning/methods , Autografts , Female , Humans , Infant , Infant, Newborn , Male , Pilot Projects , Transplantation Conditioning/adverse effects , Virus Diseases/etiology , Virus Diseases/mortalityABSTRACT
PURPOSE: The National Cancer Institute-funded cooperative oncology group trials have improved overall survival for children with cancer from 10% to 85% and have set standards of care for adults with malignancies. Despite these successes, cooperative oncology groups currently face substantial challenges. We are working to develop methods to improve the efficiency and effectiveness of these trials. Specifically, we merged data from the Children's Oncology Group (COG) and the Pediatric Health Information Systems (PHIS) to improve toxicity monitoring, to estimate treatment-associated resource utilization and costs, and to address important clinical epidemiology questions. METHODS: COG and PHIS data on patients enrolled on a phase III COG trial for de novo acute myeloid leukemia at 43 PHIS hospitals were merged using a probabilistic algorithm. Resource utilization summary statistics were then tabulated for the first chemotherapy course based on PHIS data. RESULTS: Of 416 patients enrolled on the phase III COG trial at PHIS centers, 392 (94%) were successfully matched. Of these, 378 (96%) had inpatient PHIS data available beginning at the date of study enrollment. For these, daily blood product usage and anti-infective exposures were tabulated and standardized costs were described. CONCLUSIONS: These data demonstrate that patients enrolled in a cooperative group oncology trial can be successfully identified in an administrative data set and that supportive care resource utilization can be described. Further work is required to optimize the merging algorithm, map resource utilization metrics to the National Cancer Institute Common Toxicity Criteria for monitoring toxicity, to perform comparative effectiveness studies, and to estimate the costs associated with protocol therapy.
