Reduced intensity and non-myeloablative allogeneic stem cell transplantation in children and adolescents with malignant and non-malignant diseases.
ABSTRACT Allogeneic hematopoietic stem cell transplant (AlloSCT) from related or unrelated histocompatible donors has been well established as potentially curative therapy for children and adolescents with selected malignant and non-malignant diseases. In the malignant setting non-myeloablative (NMA)/reduced intensity (RI)-AlloSCT eradicates malignant cells through a graft versus malignancy effect provided by alloreactive donor T-lymphocytes and/or natural killer cells. In patients with non-malignant diseases NMA/RI AlloSCT provides enough immunosuppression to promote engraftment and correct underlying genetic defects. In children, myeloablative AlloSCT is not only associated with acute short-term toxicities but also long-term late complications such as growth retardation, infertility, and secondary malignancies. NMA/RI-AlloSCT in children may be associated with reduction in use of blood products, risk of infections, transplant-related mortality, and length of hospitalization. Despite the success of RI-AlloSCT in adults, large prospective and/or randomized multicenter studies are necessary in children and adolescent recipients to define the appropriate patient population, optimal conditioning regimens, cost-benefits, survival and differences in short-term and long-term effects compared to conventional myeloablative conditioning.
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ABSTRACT: Bronchoalveolar lavage (BAL) has been a useful initial diagnostic tool in the evaluation of pulmonary complications following hematopoietic stem cell transplantation (HSCT); however, the diagnostic sensitivity, prevalence, and outcome following BAL versus lung biopsy (LB) in pediatric HSCT patients remains to be determined. We reviewed 193 pediatric HSCT recipients who underwent a total of 235 HSCTs. Sixty-five patients (34%) underwent a total of 101 BALs for fever, respiratory distress, and/or pulmonary infiltrates on chest radiograph and/or CT scan. The 1-year probability of undergoing BAL following allogeneic stem cell transplant (alloSCT) was 43.0% and following autologous stem cell transplant (autoSCT) was 8.5% (p=0.001). Sixteen of the 193 patients (8%) patients underwent 19 LBs. The probability of undergoing LB at 1 year post-HSCT was 9.3%. No grade III or IV adverse events related to either procedure were observed. Of the 101 BALs performed, 40% (n=40) were diagnostic, with a majority revealing a bacterial pathogen. Among the 19 LBs performed, 94% identified an etiology. In multivariate analysis, MAC alloSCT conferred the highest risk of requiring a BAL (HR=8.5, p=0.0002). The probability of 2 year overall survival was 20.2% in patients who underwent BAL, 17.5% for patients who underwent biopsy, and 67.4% for patients who had neither procedure. In multivariate analysis, only the requirement of a BAL was independently associated with an increased risk of mortality (HR=2.960, p <0.0001). In summary, in this cohort of pediatric HSCT recipients BAL and LB were used in approximately 35% and 8% of pediatric HSCTs with diagnostic yields of approximately 40% and 94%, respectively and were both associated with poor long-term outcomes.Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2014; · 3.15 Impact Factor
- The Journal of pediatrics 05/2014; 164(5):952-953.e2. · 4.02 Impact Factor
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ABSTRACT: BU and CY (BU/CY; 200 mg/kg) before HLA-matched sibling allo-SCT in children with sickle cell disease (SCD) is associated with ~85% EFS but is limited by the acute and late effects of BU/CY myeloablative conditioning. Alternatives include reduced toxicity but more immunosuppressive conditioning. We investigated in a prospective single institutional study, the safety and efficacy of a reduced-toxicity conditioning (RTC) regimen of BU 12.8-16 mg/kg, fludarabine 180 mg/m(2), alemtuzumab 54 mg/m(2) (BFA) before HLA-matched sibling donor transplantation in pediatric recipients with symptomatic SCD. Eighteen patients, median age 8.9 years (2.3-20.2), M/F 15/3, 15 sibling BM and 3 sibling cord blood (CB) were transplanted. Mean whole blood and erythroid donor chimerism was 91% and 88%, at days +100 and +365, respectively. Probability of grade II-IV acute GVHD was 17%. Two-year EFS and OS were both 100%. Neurological, pulmonary and cardiovascular function were stable or improved at 2 years. BFA RTC and HLA-matched sibling BM and CB allo-SCT in pediatric recipients result in excellent EFS, long-term donor chimerism, low incidence of GVHD and stable/improved organ function.Bone Marrow Transplantation advance online publication, 5 May 2014; doi:10.1038/bmt.2014.84.Bone marrow transplantation 05/2014; · 3.00 Impact Factor