The objective of this study was to assess the incidence, risk factors, outcome and impact on OS of pericardial effusion (PEF) in a cohort of 156 pediatric SCT recipients. The mean age was 8.15 ± 6.25 years. In all, 74% of the patients had malignant disease and 35% of the patients received autologous stem cell grafts. Twenty-three subjects developed effusion at 2.75 ± 3.54 months after SCT. The overall probability of developing a PEF after SCT was 16.9%. In the multivariate analysis of risk factors associated with time to PEF, increased age, allogeneic risk status and conditioning type, were all significant factors. In a multivariate analysis of time to death, PEF, CMV status and risk status were all independent risk factors. PEF, however, had the highest HR of 3.334. Of the 23 patients with PEF, 19 died (82.6%); however, none died as a direct result of pericardial tamponade. In summary, our results suggest that PEF is a significant risk factor for post transplant mortality. These results suggest a need for more frequent evaluation and monitoring for development of PEF. Studies are needed to determine the etiology of, and new therapeutic strategies for, PEF in the post-SCT population.
Reductions in the duration and nadir of neutropenia have translated into a significant decrease in bacteremia in adult recipients of allogeneic stem cell transplantation (allo-SCT) with reduced-intensity conditioning (RIC) during the first 30 days after transplantation. It remains to be determined whether RIC allo-SCT also will result in a decrease in systemic viral infections (SVIs) and invasive fungal infections (IFIs), which are more dependent on alterations in cellular immunity. We compared the incidence of SVIs and IFIs in children receiving busulfan-based RIC allo-SCT and in children receiving myeloablative conditioning (MAC) allo-SCT for various malignant and nonmalignant diseases. Allo-SCT recipients at risk for cytomegalovirus (CMV) received ganciclovir/foscarnet, and most of the patients received antifungal prophylaxis with liposomal amphotericin B until day +100. Eighty-six patients (median age, 7.5 years; 70% with malignant disease, 30% with nonmalignant disease; 80% average risk, 20% poor risk) were evaluated. The probability of developing grade II-IV acute graft-versus-host disease (aGVHD) was 29.1% (95% confidence interval [CI]=16.7%-41.6%) in RIC allo-SCT versus 40.3% (95% CI=23.9%-56.6%) in MAC allo-SCT (P=.23), and that of chronic GVHD (cGVHD) was 28.9% (95% CI=14.7%-43.0%) in RIC allo-SCT versus 28.4% (95% CI=10.5%-46.3%) in MAC allo-SCT (P=.73). The overall probability of developing an SVI was 58%, and that of developing an IFI was 15%. These probabilities did not differ significantly by conditioning intensity. In a multivariate Cox regression model, the following were identified as independent risk factors for invasive fungal infection: older age (hazard ratio [HR]=1.3; 95% CI=1.1-1.6; P=< .01), poor risk status (HR=6.5; 95% CI =1.1-37.4; P=.03), and CMV-positive recipient (high vs low CMV risk group, HR=26.7; 95% CI=3.4-210.8; P=< .01). Overall infection-related mortality was only 1.1% (1/86) for SVIs and 2.3% (2/86) for IFIs. Our data indicate that RIC allo-SCT does not carry a lower risk of SVIs and IFIs than MAC allo-SCT in pediatric recipients.
G-CSF and GM-CSF both hasten myeloid engraftment post-MA-alloSCT; however, GM-CSF is earlier acting and less expensive. The objective was to evaluate efficacy/safety of sequential administration of GM-CSF followed by G-CSF in children post-MA-alloSCT. From January 2001 to June 2005, 31 children received 32 MA-alloSCT: mean age 6.65 yr; MRD BM or PBSC vs. related or unrelated UCB 11:21; malignant vs. non-malignant disorders 22:10. GM-CSF (250 microg/m(2) IV QD) began on day of stem cell infusion. GM-CSF was switched to G-CSF (10 microg/kg IV QD) when WBC >or= 300/mm(3) x 2 days. G-CSF continued until ANC >or= 2500/mm(3) x 2 days, then tapered to maintain ANC >or= 1000/mm(3). Median time to myeloid engraftment (ANC >or= 500/mm(3) x 3 days) was 17 days [13 days vs. 24 days, MRD BM/PBSC vs. UCB (p < 0.0001)], occurring at a median time of two days after switch to G-CSF. Clinically relevant adverse events were bone pain (n = 8) and large pleural effusion (n = 1). It was estimated that sequential GM-CSF/G-CSF was cost-effective compared with G-CSF alone [cost-savings of $1311/patient ($41,952/study), 2007 Red Book Average Wholesale Price]. In summary, it was demonstrated that sequential administration of GM-CSF/G-CSF post-MA-alloSCT was safe, cost-effective and resulted in prompt myeloid engraftment.
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