Late effects in survivors of high‐risk neuroblastoma following stem cell transplant with and without total body irradiation

Abstract

Background: Neuroblastoma is the most common extracranial solid tumor in children.Those with high-risk disease are treated with multimodal therapy, including high-dose chemotherapy, stem cell transplant, radiation, and immunotherapy that have led to multiple long-term complications in survivors. In the late 1990s, consolidation therapy involved myeloablative conditioning including total body irradiation (TBI) with autologous stem cell rescue. Recognizing the significant long-term toxicities of exposure to TBI, more contemporary treatment protocols have removed this from conditioning regimens. This study examines an expanded cohort of 48 high-risk neuroblastoma patients to identify differences in the late effect profiles for those treated with TBI and those treated without TBI.Procedure: Data on the study cohort were collected from clinic charts, provider documentation in the electronic medical record of visits to survivorship clinic, including all subspecialists, and ancillary reports of laboratory and diagnostic tests done as part of risk-based screening at each visit.

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment

“…The most used North American model, for example, involves the use of a five-cycle strategy consisting in the administration of topotecan/cyclophosphamide for cycles 1 and 2, cisplatin/etoposide for cycles 3 and 5, and vincristine/doxorubicin/cyclophosphamide for cycle 4 [ 51 ], while the well-established COJEC system (cisplatin [C], vincristine [O], carboplatin [J], etoposide [E] and cyclophosphamide [C]) uses another mix of chemotherapy rapidly administered every 21 or 10 days [ 71 , 72 ]. Of course, the use of chemotherapy at a high concentration and frequency inevitably leads to a broad spectrum of side effects, and although the community effort is focused on increasing patient compliance, long-term toxicity still remains a major issue in HR patients [ 73 ]. The most common side effects include growth failure, thyroid dysfunction [ 74 ], hearing loss [ 75 , 76 ], ovarian/testicular failure [ 77 ], diabetes mellitus, pulmonary dysfunction [ 73 , 78 ], cardiac dysfunction [ 79 , 80 ], renal dysfunction, subsequent malignant neoplasm [ 81 , 82 ] and physiologic impairment [ 83 ].…”

“…Of course, the use of chemotherapy at a high concentration and frequency inevitably leads to a broad spectrum of side effects, and although the community effort is focused on increasing patient compliance, long-term toxicity still remains a major issue in HR patients [ 73 ]. The most common side effects include growth failure, thyroid dysfunction [ 74 ], hearing loss [ 75 , 76 ], ovarian/testicular failure [ 77 ], diabetes mellitus, pulmonary dysfunction [ 73 , 78 ], cardiac dysfunction [ 79 , 80 ], renal dysfunction, subsequent malignant neoplasm [ 81 , 82 ] and physiologic impairment [ 83 ]. Interestingly, endocrinopathies are one of the most prevalent complications after the treatment of HR-NB using modern therapies [ 78 , 84 ].…”

High-Risk and Relapsed Neuroblastoma: Toward More Cures and Better Outcomes

“…Until recently, our knowledge regarding the long-term outcomes of survivors of HRNB treated with modern multimodal approaches (high-dose chemotherapy, tandem stem cell transplantation, radiotherapy, and novel biologic agents including retinoids, immunocytokines, and immunotherapy) were limited to small institutional series. [67][68][69][70][71][72] Given the rarity of these patients at individual institutions, a recent multi-institutional effort through the COG (ALTE15N2-LEAHRN Study) assembled a cohort of HRNB survivors treated with contemporary therapy between 2000 and 2016. Within the context of modern therapy that includes novel therapeutics, the goals of LEAHRN are to estimate the prevalence of organ dysfunction, SMNs, growth impairment, abnormal pubertal development, and neurobehavioral dysfunction; identify risk factors for these outcomes; and determine the impact of these late effects on health-related quality of life.…”

To transplant, or not to transplant? That is the question. A patient advocate evaluation of autologous stem cell transplant in neuroblastoma

“…Therein lies an obvious but seldom acknowledged complication of pursuing strategies that repeatedly intensify treatment 2,4,42 . Improvements in short‐term EFS with assessments of acute toxicities establish standard of care, but long‐term effects only become apparent in independent cohort studies many years later 41,43,44 . The resultant paradigm being a greater burden of treatment for all in pursuit of curing more children, but at significant collective cost in terms of severe late effects.…”