Showing papers by "Todd E. DeFor published in 2014"
TL;DR: The need to optimize the in vivo cytokine milieu where adoptively transferred NK cells compete with other lymphocytes to improve clinical efficacy in patients with refractory AML is supported.
324 citations
TL;DR: In this article, the authors conducted a patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content (LIC) and found that an elevated LIC was not associated with a significant increase in mortality.
58 citations
01 Jan 2014
TL;DR: A patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content suggests that iron overload, as assessed by LIC, is not a strong prognostic factor for OS in a general adult HCT population and ferritin is an inadequate surrogate for iron overload in HCT.
Abstract: An elevated ferritin level before allogeneic hematopoietic cell transplantation (HCT) is an adverse prognostic factor for overall survival (OS) and nonrelapse mortality. Because ferritin is an imperfect surrogate of iron stores, the prognostic role of iron overload remains unclear. We conducted a patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content (LIC). An elevated LIC was not associated with a significant increase in mortality: the hazard ratio (HR) for mortality associated with LIC > 7 mg/g dry weight (primary endpoint) was 1.4 (P ¼ .18). In contrast, ferritin >1000 ng/mL was a significant prognostic factor (HR for mortality, 1.7; P ¼ .036). There was, however, no significant association between ferritin > 2500 and mortality. This meta-analysis suggests that iron overload, as assessed by LIC, is not a strong prognostic factor for OS in a general adult HCT population. Our data also suggest that ferritin is an inadequate surrogate for iron overload in HCT. 2014 American Society for Blood and Marrow Transplantation.
50 citations
TL;DR: It is shown that high throughput neonatal screening for X-linked adrenoleukodystrophy is methodologically feasible and prospectively applied this method to 4689 newborn blood spot samples; no false positives were observed.
45 citations
TL;DR: This study supports the use of HCT in the treatment of FA patients with acute leukaemia or advanced MDS, however, the role of chemotherapy prior to HCT remains unclear for this population.
Abstract: Summary
Acute leukaemia or advanced myelodysplastic syndrome (MDS ≥ 5% blasts) in Fanconi anaemia (FA) patients is associated with a poor prognosis. We report 21 FA patients with acute leukaemia or advanced MDS who underwent haematopoietic cell transplantation (HCT) at the University of Minnesota between 1988 and 2011. Six patients had biallelic BRCA2 mutations. Eight patients received pre-transplant cytoreduction, with 3 achieving complete remission. HCT donor source included human leucocyte antigen-matched sibling (n = 2) or alternative donors (n = 19). Neutrophil engraftment was 95% for the entire cohort, and the incidence of acute graft-versus-host disease was 19%. 5-year overall survival (OS) was 33%, with a relapse rate of 24%, with similar OS in patients with biallelic BRCA2 mutations. Our study supports the use of HCT in the treatment of FA patients with acute leukaemia or advanced MDS, however, the role of chemotherapy prior to HCT remains unclear for this population. FA patients with biallelic BRCA2 are unique and may benefit from higher dose chemotherapy relative to other complementation groups.
45 citations
TL;DR: It is found that higher weighted average CsA trough levels early post transplantation contributed to lower risk of acute GVHD, and lower non-relapse and overall mortality, and these data support close monitoring with active adjustments ofCsA dosing to maintain therapeutic Cs a levels in the first weeks of allo-HCT.
Abstract: Higher therapeutic CsA levels early post transplantation reduce risk of acute GVHD and improves survival
32 citations
TL;DR: While follow‐up is shorter in recipients of UCB and peripheral blood, incidence of DD‐MDS/AL is, thus far, similar between HSC sources.
Abstract: Donor-derived myelodysplastic syndrome/acute leukaemia (DD-MDS/AL) is a rare life-threatening complication of allogeneic haematopoietic stem cell (HSC) transplantation. However, it is unknown whether the risk differs by HSC source. Therefore, we evaluated the incidence of DD-MDS/AL in 2390 engrafted patients. With a median follow-up of 7·1 years (1–20·8), the incidence of DD-MDS/AL was 0·53% (95% confidence interval (CI), 0·01–1·41%], 0·56% (95%CI, 0·01–1·36%) and 0·56% (95%CI, 0·01–1·10%) in recipients of bone marrow (n = 1117), peripheral blood (n = 489) and umbilical cord blood (UCB, n = 784), respectively. While follow-up is shorter in recipients of UCB and peripheral blood, incidence of DD-MDS/AL is, thus far, similar between HSC sources.
29 citations
TL;DR: Administration of ATG to AML patients undergoing RIC had no adverse impact on major clinical outcomes and may be indicated for patients at higher risk of graft failure after allogeneic hematopoietic cell transplantation (allo-HCT).
Abstract: Whether or not the benefits of antithymocyte globulin (ATG) on engraftment and GVHD are offset by increased risk of relapse, delayed T-cell recovery and increased infections remains controversial. We retrospectively studied the effect of ATG in 144 AML patients, 34 of whom received ATG, undergoing reduced intensity conditioning (RIC) umbilical cord blood transplantation (UCB) or HLA-matched sibling PBSC. ATG patients had not received intensive chemotherapy for 3 months before transplantation for UCB, 6 months for PBSC. There were no differences in engraftment between ATG and non-ATG patients. The cumulative incidences of TRM as well as acute and chronic GVHD in ATG-treated patients were not statistically different. ATG patients had significantly more infections between 46 and 180 days post transplantation. Unexpectedly, after adjusting for donor type, relapse was lower among ATG recipients (relative risk (RR) 0.5, 95% confidence interval (CI) 0.3-1.0, P=0.04). In summary, administration of ATG to AML patients undergoing RIC had no adverse impact on major clinical outcomes. ATG may be indicated for patients at higher risk of graft failure after allogeneic hematopoietic cell transplantation (allo-HCT).
10 citations
3 citations
TL;DR: 1-year relapse rates in 674 allogeneic HCT recipients at the University of Minnesota are analyzed to determine whether the preparative regimen also influenced adaptive NK cell differentiation post-transplant, and the percentage of CD56dimCD57+NKG2C+ NK cells.
3 citations
TL;DR: Although FS is critical for tissue regeneration after injury, excess FS may reflect more extensive tissue damage or loss and has recently been linked to delayed healing in a rodent model.