Primary tumor control in patients with stage 3/4 unfavorable neuroblastoma treated with tandem double autologous stem cell transplants

• Published in: Journal of pediatric hematology/oncology Vol. 25; no. 12; pp. 934 - 940
• Main Authors: MARCUS, Karen J, SHAMBERGER, Robert, LITMAN, Heather, VON ALLMEN, Daniel, GRUPP, Stephen A, MEDEIROS NANCARROW, Cheryl, GOLDWEIN, Joel, GRIER, Holcombe E, DILLER, Lisa
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott 01-12-2003
• Subjects: Adolescent; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Bone marrow, stem cells transplantation. Graft versus host reaction; Bone Neoplasms - secondary; Child; Child, Preschool; Cohort Studies; Combined treatments (chemotherapy of immunotherapy associated with an other treatment); Female; Humans; Infant; Male; Medical sciences; Myeloablative Agonists - therapeutic use; Neoplasm Staging; Neuroblastoma - pathology; Neuroblastoma - radiotherapy; Neuroblastoma - therapy; Peripheral Blood Stem Cell Transplantation - mortality; Pharmacology. Drug treatments; Radiotherapy, Adjuvant - adverse effects; Radiotherapy, Adjuvant - standards; Recurrence; Remission Induction - methods; Survival Analysis; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation, Autologous; Treatment Outcome; Antineoplastic agent; Human; Nervous system diseases; Relapse; Toxicity; Stem cell; Hematopoietic cell; Malignant tumor; Neuroblastoma; Survival; Autograft; Chemotherapy; Treatment; autologous transplantation; Bone marrow; Graft; Advanced stage; Autonomic neuropathy
• ISSN: 1077-4114; 1536-3678
• DOI: 10.1097/00043426-200312000-00005

To assess the efficacy and toxicity of local radiotherapy in achieving local control in patients with stage 4 or high-risk stage 3 neuroblastoma treated with induction chemotherapy and tandem stem cell transplants.
Fifty-two children with stage 4 or high-risk stage 3 neuroblastoma were treated on a standardized protocol that included five cycles of induction chemotherapy, surgical resection of the primary tumor when feasible, local radiotherapy, and then consolidation with tandem myeloablative cycles with autologous peripheral blood stem cell rescue. Local radiotherapy (10.5-18 Gy) was administered to patients with gross or microscopic residual disease prior to the myeloablative cycles. Thirty-seven patients received local radiotherapy to the primary tumor or primary tumor bed. Two patients with unknown primaries each received radiotherapy to single, unresectable, bulky metastatic sites. The second of the myeloablative regimens included 12 Gy of total body irradiation.
Of the 52 consecutively treated patients analyzed, 44 underwent both transplants, 6 underwent a single transplant, and 2 progressed during induction. Local radiotherapy did not prolong recovery of hematopoiesis following transplants, did not increase peritransplant morbidity, and did not prolong the hospital stay compared with patients who had not received local radiotherapy. Local control was excellent. Of 11 patients with disease recurrence after completion of therapy, 9 failed in bony metastatic sites 3 to 21 months after the completion of therapy, 1 recurred 67 months following therapy in the previously bulky metastatic site that had been irradiated, and 1 had local recurrence concurrent with distant progression 15 months following the second transplant. The three-year event-free survival was 63%, with a median follow-up of 29.5 months. The actuarial probability of local control was 97%.
The use of induction chemotherapy, aggressive multimodality therapy for the primary tumor, followed by tandem myeloablative cycles with stem cell transplant in patients with stage 4 or high risk stage 3 neuroblastoma has resulted in acceptable toxicity, a very low local recurrence risk, and an improvement in survival.