Effect of Tandem Autologous Stem Cell Transplant vs Single Transplant on Event-Free Survival in Patients With High-Risk Neuroblastoma

Abstract

chemotherapy followed by high-dose therapy with autologous stem cell transplant and subsequent antidisialoganglioside antibody immunotherapy is standard of care for patients with high-risk neuroblastoma, but survival rate among these patients remains low. OBJECTIVE To determine if tandem autologous transplant improves event-free survival (EFS) compared with single transplant. DESIGN, SETTING, AND PARTICIPANTS Patients were enrolled in this randomized clinical trial from November 2007 to February 2012 at 142 Children's Oncology Group centers in the United States, Canada, Switzerland, Australia, and New Zealand. A total of 652 eligible patients aged 30 years or younger with protocol-defined high-risk neuroblastoma were enrolled and 355 were randomized. The final date of follow-up was June 29, 2017, and the data analyses cutoff date was June 30, 2017. INTERVENTIONS Patients were randomized to receive tandem transplant with thiotepa/cyclophosphamide followed by dose-reduced carboplatin/etoposide/melphalan (n = 176) or single transplant with carboplatin/etoposide/melphalan (n = 179). MAIN OUTCOMES AND MEASURES The primary outcome was EFS from randomization to the occurrence of the first event (relapse, progression, secondary malignancy, or death from any cause). The study was designed to test the 1-sided hypothesis of superiority of tandem transplant compared with single transplant. RESULTS Among the 652 eligible patients enrolled, 297 did not undergo randomization because they were nonrandomly assigned (n = 27), ineligible for randomization (n = 62), had no therapy (n = 1), or because of physician/parent preference (n = 207). Among 355 patients randomized (median diagnosis age, 36.1 months; 152 [42.8%] female), 297 patients (83.7%) completed the study and 21 (5.9%) were lost to follow-up after completing protocol therapy. Three-year EFS from the time of randomization was 61.6% (95% CI, 54.3%-68.9%) in the tandem transplant group and 48.4% (95% CI, 41.0%-55.7%) in the single transplant group (1-sided log-rank P=.006). The median (range) duration of follow-up after randomization for 181 patients without an event was 5.6 (0.6-8.9) years. The most common significant toxicities following tandem vs single transplant were mucosal (11.7% vs 15.4%) and infectious (17.9% vs 18.3%). CONCLUSIONS AND RELEVANCE Among patients aged 30 years or younger with high-risk neuroblastoma, tandem transplant resulted in a significantly better EFS than single transplant. However, because of the low randomization rate, the findings may not be representative of all patients with high-risk neuroblastoma.

Nervous system: Embryonal tumors: Neuroblastoma

“…The first block, induction, includes high-dose chemotherapy and resection of the primary tumor. The second block is consolidation, which consists of tandem courses of myeloablative dose chemotherapy with autologous stem-cell rescue and external-beam radiotherapy (Park et al, 2019). Lastly, post-consolidation therapy includes anti-ganglioside 2 (GD2) immunotherapy with cytokines and cis-retinoic acid (Yu et al, 2010).…”

Pleuroparenchymal fibroelastosis in an 8‐year old treated for neuroblastoma

“…Median reported age of presentation in the literature is between 46 and 60 years, 4 however, there are case reports of younger individuals, with the youngest being 14‐years old, who developed features similar to PPFE after exposure to cyclophosphamide 5 and a 16‐year old with idiopathic PPFE 6 . While more patients with high‐risk neuroblastoma are surviving, thanks to intensive multimodal chemotherapy, 1 long‐term follow‐up studies have revealed that survivors are at a higher risk of treatment‐related complications including dysfunction of musculoskeletal, neurologic, endocrinal, sensory, cardiovascular, renal, and pulmonary function in addition to increased rates of secondary malignancies 7 . Specific pulmonary complications described include chronic respiratory symptoms, abnormal PFT, and bronchiectasis 7 …”

“…The patient was diagnosed at age 3 with stage four, high‐risk neuroblastoma. Her treatment consisted of six cycles of induction chemotherapy including cisplatin, etoposide, vincristine, cyclophosphamide, doxorubicin, and topotecan per Children's Oncology Group (COG) protocol ANBL0532 1 . She achieved a complete response and proceeded with conditioning chemotherapy with carboplatin, etoposide, and melphalan followed by autologous stem cell rescue and radiation to her resected adrenal tumor bed.…”

Emerging Role of the Macrophage Migration Inhibitory Factor Family of Cytokines in Neuroblastoma. Pathogenic Effectors and Novel Therapeutic Targets?

“…In particular, the antidisialoganglioside (anti-GD2) immunotherapy has recently been successfully incorporated into the standard of care treatment for high-risk NB patients [8]. Moreover, a recent randomized clinical trial (NCT00567567) has demonstrated that tandem autologous stem cell transplant with thiotepa/cyclophosphamide followed by carboplatin/etoposide/melphalan resulted in a significantly better EFS than single transplantation with carboplatin/etoposide/melphalan in high-risk NB patients under 30 years of age [9]. Several innovative strategies aimed at targeting the tumor microenvironment, the noradrenaline transporter, and the genetic pathways are being developed with promising effects in NB diagnosis and treatment [7].…”