Long-Term Safety of Short-Term Administration of Filgrastim (rhG-CSF) and Leukophresis Procedure in Healthy Children: Application of Peripheral Blood Stem Cell Collection in Pediatric Donors.

Administration of filgrastim (recombinant human granulocyte colony-stimulating factor [rhG-CSF]) (Neupogen) in healthy donors to mobilize hematopoietic stem cells (HSCs) is a widespread practice in adults. Application of peripheral blood stem cell (PBSC) collection in normal pediatric donors is scarce due to ethical issues. Hence, there are insufficient data on the long-term impact of PBSC procedure in healthy children. This retrospective study aimed to evaluate the early and late adverse effects of PBSC donation in pediatric donors. Bone marrow and PBSC procedures and known adverse events of each technique were completely explained to parents and when applicable to children and written informed consent was obtained. rhG-CSF was administered for 4 days. HSCs were collected on the fifth day through continuous-flow apheresis and donors were followed for 30 days. Manual chart review was performed to collect short-term complications. Donors' health status was assessed via a questionnaire. A total of 145 healthy pediatric donors with a median age of 10 years at the time of donation (2 to 15 years) were followed for a median of 4.8 years (range, 1.2 to 14.2 years). The most frequent symptoms of rhG-CSF administration were fatigue (5%) and headache (3%). Thirty-five (24%) donors experienced hypocalcaemia during apheresis procedure that quickly responded to treatment. Two pregnancies occurred after rhG-CSF administration that resulted in normal births. We did not encounter any serious adverse events, including neoplastic disorders and death in this study. rhG-CSF and leukophresis procedure were well-tolerated in this study and all children completed the donation process without interruption or reduction of rhG-CSF dosage. Our results suggest that rhG-CSF is a safe drug in healthy children for the purpose of HSC mobilization.

Non-total body irradiation myeloablative conditioning with intravenous busulfan and cyclophosphamide in hematopoietic stem cell transplantation for malignant infantile osteopetrosis.

HSCT is the only curative treatment for MIOP. We prospectively investigated the outcome of HSCT using intravenous busulfan-based conditioning regimen from 2008 to 2013. Nineteen patients (median age = 17 months) underwent transplantation from HLA-matched related donors (n = 14), HLA-haploidentical related donors (n = 2), partially matched cord blood donors (n = 2), and HLA-matched unrelated donor (n = 1). Bone marrow (n = 9), peripheral blood (n = 8), and cord blood (n = 2) were used as stem cell sources. All but one patient demonstrated primary engraftment. Two patients experienced secondary graft failure. During the follow-up period, three patients showed mixed chimerism (45%, 45%, and 70% of donor cells were engrafted in each one of these patients) but are disease free. Two-yr OS and DFS were 84.2% and 73.7%, respectively. Improvement of visual acuity and partial reversal of mild conductive hearing loss occurred in two and four patients, respectively. The causes of death among three patients were infection, GvHD, and disease progression. In conclusion, due to major side effects of MIOP such as visual and hearing loss, early treatment using myeloablative conditioning without irradiation HSCT is suggested. The use of an HLA-matched related donor seems to be highly successful in this regard. Also, according to results of our study, mixed chimerism may be sufficient to resolve symptoms of disease.

The potential role of pretransplant MIBG diagnostic scintigraphy in targeted administration of 131I-MIBG accompanied by ASCT for high-risk and relapsed neuroblastoma: a pilot study.

MIBG is an effective component in treatment of neuroblastoma. Furthermore, MIBG scintigraphy is an imaging modality in primary assessments. None of the previous studies have evaluated the role of pretransplant MIBG scintigraphy in decision making for neuroblastoma treatment. We selected therapeutic regimen based on pretransplant (131) I-MIBG scintigraphy. Twenty high-risk patients were enrolled. On day -30, patients underwent diagnostic MIBG scintigraphy. Patients were then subdivided into two groups (10 cases in each arm). MIBG-avid subgroup received MIBG (12 mCi/kg), etoposide (1200 mg/m2), carboplatin (1500 mg/m2), and melphalan (210 mg/m2). Non-MIBG-avid subgroup received etoposide (600 mg/m2), carboplatin (1200 mg/m2), and melphalan (150 mg/m2). Patients received CRA after ASCT. Mean age at diagnosis was 42.5 months (range, 17-65) in MIBG-avid and 38.9 months (range, 18-65) in non-MIBG-avid patients. Mean age at diagnosis and transplantation did not reveal significant difference between two subgroups. In MIBG-avid patients, the three-yr OS was 66 ± 21%. In MIBG-non-avid subgroup, the three-yr OS was 53 ± 20%. In MIBG-avid and non-MIBG-avid subgroups, the three-yr EFS were 66 ± 21% and 47 ± 19%, respectively. These findings may suggest an effective role in selecting the therapeutic strategy for pre-ASCT MIBG scintigraphy in high-risk neuroblastoma. MIBG-avid subset may benefit from the combination of therapeutic MIBG and high dose of chemotherapy.