Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Dec 2009
Incidence of Viral and fungal infections following busulfan-based reduced-intensity versus myeloablative conditioning in pediatric allogeneic stem cell transplantation recipients.
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. ⋯ 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.
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Biol. Blood Marrow Transplant. · Dec 2009
Impact of conditioning regimen in allogeneic hematopoetic stem cell transplantation for children with acute myelogenous leukemia beyond first complete remission: a pediatric blood and marrow transplant consortium (PBMTC) study.
Total body irradiation (TBI)-based conditioning regimens for pediatric patients with acute myelogenous leukemia (AML) beyond first complete remission (CR1) are controversial. Because the long-term morbidity of busulfan (Bu)-based regimens appears to be lower, determining efficacy is critical. We retrospectively evaluated 151 pediatric patients with AML beyond CR1, comparing outcomes in 90 patients who received a TBI-based conditioning regimen and 61 patients who received a Bu-based conditioning regimen. ⋯ Shorter CR1 and receiving an HLA-mismatched transplant adversely affected EFS and OS in this cohort. Our study provides no evidence of an advantage to using TBI in children with AML beyond CR1. A prospective, randomized study is needed to confirm these results.
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Biol. Blood Marrow Transplant. · Dec 2009
A novel GVHD-prophylaxis with low-dose alemtuzumab in allogeneic sibling or unrelated donor hematopoetic cell transplantation: the feasibility of deescalation.
Prophylaxis of acute graft-versus-host disease (aGVHD), while maintaining the graft-versus-leukemia (GVL)/lymphoma effect and preventing severe infectious diseases, remains the main challenge in allogeneic hematopoetic cell transplantation (allo-HCT). To evaluate this, we examined the feasibility of deescalating the dose of alemtuzumab (MabCampath) in combination with cyclosporine (CsA) as the sole GVHD-prophylaxis in patients after fludarabine (Flu)-based reduced-intensity conditioning (RIC) in an observational cohort study. We included 127 consecutive patients (median age 63 years) with an unrelated (UD; n=69) or related donor (SIB; n=58) after their first transplantation, mostly presenting with advanced disease. ⋯ We observed no statistical differences comparing the 40 mg, 20 mg, or 10 mg dose groups, in terms of cumulative incidences of aGVHD grade III-IV 7% (confidence interval [CI] 95%; 1-51), 12% (1-40), 6% (1-40), extensive chronic GVHD (cGVHD) 24.4% (3.3-55.8), 17% (2.5-42), and 14.2% (1.5-41.5) and of aGVHD grade II-IV 7 % (0-51.5), 29% (11.9-49.1), 21% (15.3-43.1), respectively. The difference between the 20-mg and 40-mg groups was significant for aGVHD grade II-IV(P < .05). In conclusion, we demonstrate the feasibility of reducing the dose of alemtuzumab as GVHD-prophylaxis to 10 mg absolute in combination with CsA only for UD transplantation in particular.
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Biol. Blood Marrow Transplant. · Dec 2009
Tacrolimus/Methotrexate versus cyclosporine/methotrexate as graft-versus-host disease prophylaxis in patients with severe aplastic anemia who received bone marrow transplantation from unrelated donors: results of matched pair analysis.
Tacrolimus (FK) and cyclosporine (CsA) have been shown to be effective in the prophylaxis of graft-versus-host disease (GVHD). However, no comparative studies have yet been conducted to examine the efficacy of FK/methotrexate (MTX) and CsA/MTX in patients with severe aplastic anemia (SAA) given unrelated donor bone marrow transplantation (U-BMT). We used matched-pair analysis to compare FK/MTX with CsA/MTX in patients with SAA who received U-BMT through the Japan Marrow Donor Program. ⋯ The 5-year survival rate was 82.8% in the FK group and 49.5% in the CsA group (P=.012). The study shows the superiority of FK/MTX over CsA/MTX in overall survival because of the lower incidence of transplantation-related deaths. A prospective randomized study comparing FK/MTX and CsA/MTX is warranted.
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Biol. Blood Marrow Transplant. · Dec 2009
Polymorphism of interleukin-23 receptor gene but not of NOD2/CARD15 is associated with graft-versus-host disease after hematopoietic stem cell transplantation in children.
Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). The selection of a suitable donor is the most critical issue in preventing severe GVHD. Recent data suggest that the risk of GVHD does not only depend on human leukocyte antigens (HLA) but also on polymorphisms of genes that influence immune responses. ⋯ We found a significantly reduced incidence of acute GVHD (aGVHD) grade II-IV in patients who were transplanted from a donor with the IL23R polymorphism (5.0% versus 33.3%; P=.009). There was no case of aGVHD grade III-IV if this polymorphism occurred in the donor. These findings could be particularly relevant for children with inborn metabolic or immunologic disorders who do not benefit from a graft-versus-tumor effect, and therefore, selection of a donor with the IL23R polymorphism might be beneficial.