RESUMO
Total body irradiation (TBI) in combination with chemotherapy is widely used as a conditioning regimen in pediatric and adult hematopoietic stem cell transplantation (HSCT). The combination of TBI with chemotherapy has demonstrated superior survival outcomes in patients with acute lymphoblastic and myeloid leukemia when compared with conditioning regimens based only on chemotherapy. The clinical application of intensity-modulated radiation therapy (IMRT)-based methods (volumetric modulated arc therapy (VMAT) and TomoTherapy) seems to be promising and has been actively used worldwide. The optimized conformal total body irradiation (OC-TBI) method described in this study provides selected dose reduction for organs at risk with respect to the most significant toxicity (lungs, kidneys, lenses). This study included 220 pediatric patients who received OC-TBI with subsequent chemotherapy and allogenic HSCT with TCRαß/CD19 depletion. A group of 151 patients received OC-TBI using TomoTherapy, and 40 patients received OC-TBI using the Elekta Synergy™ linac with an Agility-MLC (Elekta, Crawley, UK) using volumetric modulated arc therapy (VMAT). Twenty-nine patients received OC-TBI with supplemental simultaneous boost to bone marrow-(SIB to BM) up to 15 Gy: 28 patients (pts)-TomoTherapy; one patient-VMAT. The follow-up duration ranged from 0.3 to 6.4 years (median follow-up, 2.8 years). Overall survival (OS) for all the patients was 63% (95% CI: 56-70), and event-free survival (EFS) was 58% (95% CI: 51-65). The cumulative incidence of transplant-related mortality (TRM) was 10.7% (95% CI: 2.2-16) for all patients. The incidence of early TRM (<100 days) was 5.0% (95% CI: 1.5-8.9), and that of late TRM (>100 days) was 5.7 (95% CI: 1.7-10.2). The main causes of death for all the patients were relapse and infection. The concept of OC-TBI using IMRT VMAT and helical treatment delivery on a TomoTherapy treatment unit provides maximum control of the dose distribution in extended targets with simultaneous dose reduction for organs at risk. This method demonstrated a low incidence of severe side effects after radiation therapy and predictable treatment effectiveness. Our initial experience demonstrates that OC-TBI appears to be a promising technique for the treatment of pediatric patients.
RESUMO
BACKGROUND: Nijmegen breakage syndrome (NBS) is a combined primary immunodeficiency with DNA repair defect, microcephaly, and other phenotypical features. It predominantly occurs in Slavic populations that have a high frequency of carriers with the causative NBN gene c.657_661del5 mutation. Due to the rarity of the disease in the rest of the world, studies of NBS patients are few. Here, we report a prospective study of a cohort of Russian NBS patients. METHODS: 35 Russian NBS patients of ages 1-19 years, referred to our Center between years 2012 and 2016, were prospectively studied. RESULTS: Despite the fact that in 80% of the patients microcephaly was diagnosed at birth or shortly thereafter, the average delay of NBS diagnosis was 6.5 years. Though 80% of the patients had laboratory signs of immunodeficiency, only 51% of the patients experienced significant infections. Autoimmune complications including interstitial lymphocytic lung disease and skin granulomas were noted in 34%, malignancies-in 57% of the patients. T-cell excision circle (TREC)/kappa-deleting recombination excision circle (KREC) levels were low in the majority of patients studied. Lower KREC levels correlated with autoimmune and oncological complications. Fifteen patients underwent hematopoietic stem cell transplantation (HSCT), 10 of them were alive and well, with good graft function. Three patients in the HSCT group and five non-transplanted patients died; tumor progression being the main cause of death. The probability of the overall survival since NBS diagnosis was 0.76 in the HSCT group and 0.3 in the non-transplanted group. CONCLUSION: Based on our findings of low TRECs in most NBS patients, independent of their age, TREC detection can be potentially useful for detection of NBS patients during neonatal screening. KREC concentration can be used as a prognostic marker of disease severity. HSCT is a viable treatment option in NBS and should be especially considered in patients with low KREC numbers early on, before development of life-threatening complications.