Daniel J Weisdorf

University of Minnesota Duluth, Duluth, Minnesota, United States

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Publications (557)3395.32 Total impact

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    ABSTRACT: The novel bispecific ligand-directed toxin (BLT) DT2219 consists of a recombinant fusion between the catalytic and translocation enhancing domain of diphtheria toxin (DT) and bispecific single-chain variable fragments (scFV) of antibodies targeting human CD19 and CD22. We conducted a phase I dose-escalation study to assess the safety, maximum tolerated dose, and preliminary efficacy of DT2219 in patients with relapsed/refractory B-cell lymphoma or leukemia. DT2219 was administered intravenously over 2 hours every other day for 4 total doses. Dose was escalated from 0.5 μg/kg/day to 80 μg/kg/day in nine dose cohorts until a dose-limiting toxicity (DLT) was observed. Twenty-five patients with mature or precursor B-cell lymphoid malignancies expressing CD19 and/or CD22 enrolled to the study. Patients received median 3 prior lines of chemotherapy and 8 failed hematopoietic transplantation. All patients received a single course of DT2219; one patient was retreated. The most common adverse events, including weight gain, low albumin, transaminitis, and fever were transient grade 1-2 and occurred in patients in higher dose cohorts (≥40 μg/kg/day). Two subjects experienced DLT at dose levels 40 and 60 μg/kg. Durable objective responses occurred in 2 patients; one was complete remission after 2 cycles. Correlative studies showed a surprisingly low incidence of neutralizing antibody (30%). We have determined the safety of a novel immunotoxin DT2219 and established its biologically active dose between 40 and 80 μg/kg/day ×4. A phase II study exploring repetitive courses of DT2219 is planned. Clin Cancer Res; 21(6); 1267-72. ©2015 AACR. ©2015 American Association for Cancer Research.
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    ABSTRACT: Circulating angiogenic factors (AF) reflect tissue healing capacity, although some AF can also contribute to inflammation and are indicative of endothelial dysfunction. The AF milieu in acute graft-versus-host disease (aGVHD) has not been broadly characterized. We hypothesized that patients with abundant AF involved in repair/regeneration vs. those mediating damage/inflammation would have improved outcomes. Circulating AF known predominantly for repair/regeneration (epidermal growth factor [EGF], fibroblast growth factor-1 and -2, heparin binding-EGF-like growth factor, vascular endothelial growth factor-A, -C, and -D) and for damage/inflammation (angiopoietin-2, endothelin-1, soluble endoglin [sEng], follistatin [FS], leptin, placental growth factor [PlGF]) were measured in a discovery set of HCT recipients with grade III/IV aGVHD versus controls, then validated in two aGVHD cohorts enrolled in Blood and Marrow Transplant Clinical Trials Network (BMT CTN) trials 0302 (N=105, serum) and 0802 (N=158, plasma) versus controls without aGVHD (N=53, serum). Levels of EGF and VEGF-A were lower than controls at the onset of aGVHD in both trials and higher with complete response to first-line aGVHD therapy in CTN 0802. FS and PlGF were elevated in aGVHD measured in either serum or plasma. At day 28 after initial aGVHD therapy, elevated FS was an independent negative prognostic factor for survival in both cohorts (hazard ratio 9.3 in CTN 0302, 2.8 in CTN 0802). These data suggest that circulating AF are associated with clinical outcomes after aGVHD and thus may contribute to both pathogenesis and recovery. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2015; DOI:10.1016/j.bbmt.2015.02.018 · 3.15 Impact Factor
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    ABSTRACT: Failure-free survival, defined as absence of relapse, non-relapse mortality or addition of another systemic therapy, has been proposed as a potential endpoint for clinical trials, but it has only been reported for single center studies. We measured failure free survival in a prospective observational cohort of patients with both newly diagnosed and existing chronic graft-versus-host disease (n=575) from nine centers. Failure was observed in 389 (68%) during the observation period. Median follow up of all patients was 30.9 months, and median failure free survival was 9.8 months (63% at 6 months, 45% at one year, and 29% at two years). Of the variables measured at enrollment, ten were associated with shorter failure free survival: higher NIH 0-3 skin score, higher NIH 0-3 GI score, worse range of motion summary score, lower forced vital capacity (%), bronchiolitis obliterans syndrome, worse quality of life, moderate to severe hepatic dysfunction, absence of treatment for gastric acid, female donor into male patient, and prior grade II-IV acute graft-versus-host disease. Addition of a new systemic treatment, the major cause of failure, was associated with an increased risk of subsequent non-relapse mortality (HR=2.06, 95%CI: 1.29-3.32, p<0.003) and decreased survival (HR=1.51, 95%CI: 1.04-2.18, p<0.03). These results show fewer than half of patients on systemic treatment will be failure-free survivors at one year, and fewer than a third will reach two years without experiencing failure. Better treatments are needed for chronic graft-versus-host disease. Clinicaltrials.gov identifier: NCT00637689. Copyright © 2015, Ferrata Storti Foundation.
    Haematologica 02/2015; DOI:10.3324/haematol.2014.117283 · 5.94 Impact Factor
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    ABSTRACT: Cyclophosphamide (Cy) is a prodrug that depends on bioactivation by hepatic cytochrome P450 (CYP) enzymes for its cytotoxicity. We evaluated the influence of single nucleotide polymorphisms (SNPs) of CYP enzymes on the efficacy of autologous hematopoietic cell transplantation (HCT) for lymphoma. SNPs of 22 genes were analyzed in 93 patients with Hodgkin (n=52) and non-Hodgkin lymphoma (n=41) treated with high-dose Cy followed by autologous HCT between 2004-2012. Preparative regimens contained Cy (120mg/kg) combined with carmustine/etoposide (n=61) or Cy (6000mg/m2) with total body irradiation (n=32). Lack of complete remission as measured by pre-transplant positron emission tomography was the sole clinical factor associated with increased risk of relapse (HR 2.1). In genomic analysis, we identified a single SNP (rs3211371) in exon 9 (C >T) of the CYP2B6 gene (allele designation 2B6*5) that significantly impacted patient outcomes. After adjusting for disease status and conditioning regimen, patients with CYP2B6*1/*5 genotype had a higher 2-year relapse rate (HR 3.3; 95%CI 1.6-6.5; p=0.041) and decreased overall survival (HR 13.5; 95%CI 3.5-51.9; p=0.008) than patients with wild-type allele. Two-year progression-free survival for patients with two hypo-functional CYP2B6 variant genotypes (*5 and *6) was only 11% (95%CI 1-39%) compared to 67% (95% CI 55-77%) for patients with the wild-type CYP2B6*1 allele in exon 9. Our results suggest that CYP2B6 SNPs influence the efficacy of high-dose Cy and significantly reduce the success of autologous HCT for lymphoma patients with the CYP2B6*5 variant.
    Biology of Blood and Marrow Transplantation 02/2015; DOI:10.1016/j.bbmt.2015.02.001 · 3.35 Impact Factor
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    ABSTRACT: Mycophenolate mofetil (MMF) is frequently used in hematopoietic cell transplantation (HCT) for graft-versus-host disease (GVHD) prophylaxis and to facilitate engraftment. We previously reported that a higher level of mycophenolic acid can be achieved with an MMF dose of 3 g/day as compared to 2g/day. Here, we retrospectively compared clinical outcomes of reduced intensity conditioning (RIC) double umbilical cord blood (dUCB) HCT recipients receiving cyclosporine A with MMF 2g (n=93) vs. 3g (n=175) daily. Multiple regression analysis adjusted for ATG in the conditioning revealed that MMF 3g/day led to a 49% relative risk reduction in grade II-IV acute GVHD rate (RR=0.51, 95%CI 0.36-0.72; p<0.01). However, the higher MMF dose was not protective for chronic GVHD. Additionally, MMF dose was not an independent predictor of neutrophil engraftment, treatment-related mortality at 6 months, or 2-year post-transplant disease relapse, disease-free survival, or overall survival. Higher MMF dose did not increase risk of infectious complications and infection-related mortality was similar for both MMF doses. Our data indicate that MMF 3g/day reduces the risk of acute GVHD without affecting other clinical outcomes and should be used for GVHD prophylaxis after RIC dUCBT. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2015; DOI:10.1016/j.bbmt.2015.01.023 · 3.15 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S166-S167. DOI:10.1016/j.bbmt.2014.11.242 · 3.35 Impact Factor
  • Biology of Blood and Marrow Transplantation 02/2015; 21(2):S144-S145. DOI:10.1016/j.bbmt.2014.11.202 · 3.35 Impact Factor
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    ABSTRACT: Various cytogenetic risk scoring systems may determine prognosis for patients with myelodysplastic syndromes (MDS). We evaluated four different risk scoring systems in predicting outcome after allogeneic hematopoietic cell transplantation (alloHCT). We classified 124 patients with MDS using the International prognostic scoring system (IPSS), the revised international prognostic scoring system (R-IPSS), Armand's transplantation-specific cytogenetic grouping (TSCG), and monosomal karyotype (MK) both at the time of diagnosis and alloHCT. After adjusting for other important factors, MK at diagnosis (compared to no MK) was associated with poor 3-year disease-free survival (DFS) (27% (95% CI, 12-42%) versus 39% (95% CI, 28-50%), p=0.02) and overall survival (OS) (29% (95% CI, 14-44%) versus 47% (95% CI, 36-59%), p=0.02). OS but not DFS was affected by MK at HCT. MK frequency was uncommon in low score R-IPPS and IPSS. Although IPSS and R-IPSS discriminated good/very good groups from poor/very poor groups, patients with intermediate risk scores had the worst outcomes and therefore these scores did not show a progressive linear discriminating trend. Cytogenetic risk score change between diagnosis and alloHCT was uncommon and did not influence OS. MK cytogenetics in MDS are associated with poor survival suggesting the need for alternative or intensified approaches to their treatment. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2015; DOI:10.1016/j.bbmt.2015.01.017 · 3.15 Impact Factor
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    ABSTRACT: The success of allogeneic hematopoietic cell transplantation (HCT) is typically assessed as individual complications, including graft-versus-host disease (GVHD), relapse, or death, yet no one factor can completely characterize cure without ongoing morbidity. We examined a novel composite endpoint of GVHD-free/relapse-free survival (GRFS) where events include grade III-IV acute GVHD, systemic therapy-requiring chronic GVHD, relapse, or death in the first post-HCT year. In 907 consecutive University of Minnesota allogeneic HCT recipients (2000-2012), 1-year GRFS was 31% (95% CI 28-34%). Regression analyses showed age, disease risk, and donor type significantly influencing GRFS. Adults age 21+ had two-fold worse GRFS versus children; GRFS did not differ beyond age 21. Adjusted for conditioning intensity, stem cell source, disease risk, age, and transplant year, HLA-matched sibling donor (MSD) marrow resulted in the best GRFS (51%, 95% CI 46-66%), while MSD peripheral blood stem cells (PBSC) were significantly worse (25%, 95% CI 20-30%, p=0.01). GRFS after umbilical cord blood (UCB) transplants and marrow from matched unrelated donors (URD) were similar (31%, 95% CI 27-35% and 32%, 95% CI 22-42%, respectively). Because GRFS measures freedom from ongoing morbidity and represents ideal HCT recovery, GRFS has value as a novel endpoint for benchmarking new therapies. Copyright © 2015 American Society of Hematology.
    Blood 01/2015; DOI:10.1182/blood-2014-10-609032 · 9.78 Impact Factor
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    ABSTRACT: To develop a novel acute graft-versus-host disease (GVHD) Risk Score, we examined the GVHD clinical stage and grade of 1723 patients at the onset of treatment with systemic steroids. Using clinical grouping, descriptive statistics and recursive partitioning, we identified poorly responsive, high-risk (HR) acute GVHD by the number of involved organs and severity of GVHD at onset. The overall response [(complete response/partial response (CR/PR)] rate 28 days after initiation of steroid therapy for acute GVHD was lower in the 269 patients with HR-GVHD than in the 1454 patients with standard risk (SR)-GVHD [44% (95% CI 38-50%) vs. 68% (95% CI 66-70%), p<0.001. Patients with HR-GVHD were less likely to respond at day 28 [odds ratio (OR), 0.3, 95% CI 0.2-0.4, p<0.001], and had higher risks of mortality [relative risk (RR) 2.1, 95% CI 1.7-2.6, P<0.001] and transplant-related mortality (RR 2.5, 95% CI 2.0-3.2%, p<0.001) compared to patients with SR-GVHD. This refined definition of acute GVHD risk is a better predictor of response, survival and transplant-related mortality than other published acute GVHD risk scores. Patients with HR-GVHD are candidates for studies investigating new treatment approaches. Likewise, patients with SR-GVHD are candidates for studies investigating less toxic therapy. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2015; 21(4). DOI:10.1016/j.bbmt.2015.01.001 · 3.15 Impact Factor
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    ABSTRACT: Graft-versus-host disease (GVHD) is the major cause of non-relapse mortality (NRM) after allogeneic hematopoietic stem-cell transplantation (HCT). The severity of symptoms at the onset of GVHD does not accurately define risk, and thus most patients are treated alike with high dose systemic corticosteroids. We aimed to define clinically meaningful risk strata for patients with newly diagnosed acute GVHD using plasma biomarkers. We prospectively collected plasma from 492 HCT patients with newly diagnosed acute GVHD and randomly divided them into training (n=328) and test (n=164) sets. We used the concentrations of three recently validated biomarkers (TNFR1, ST2, and REG3α) to create an algorithm that computed the probability of NRM six months after GVHD onset for individual patients in the training set alone. We rank ordered the probabilities and identified thresholds that created three distinct NRM scores. We evaluated the algorithm in the testset, and again in an independent validation set of 300 additional HCT patients enrolled on multicenter clinical trials of primary therapy for acute GVHD. In all three datasets, the cumulative incidence of twelve month NRM significantly increased as the GVHD score increased (8% [95% confidence interval (CI); 3%, 16%], 27% [95% CI; 20%%, 34%], and 46% [95% CI; 33%, 58%], for scores 1, 2 and 3 respectively in the multicenter validation set, p<0 · 0001). Conversely, the response rates to primary GVHD treatment decreased as the GVHD score increased (86%, 67%, and 46%, for scores 1, 2 and 3 respectively in the multicenter validation set, p<0 · 0001). Biomarker-based scores can be used to guide risk-adapted therapy at the onset of acute GVHD.
    01/2015; 2(1):e21-e29. DOI:10.1016/S2352-3026(14)00035-0
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    ABSTRACT: The 2005 National Institutes of Health (NIH) Consensus Conference proposed new criteria for diagnosing and scoring the severity of chronic GVHD. The 2014 NIH consensus maintains the framework of the prior consensus with further refinement based on new evidence. Revisions have been made to address areas of controversy or confusion, such as the overlap chronic GVHD subcategory and the distinction between active disease and past tissue damage. Diagnostic criteria for involvement of mouth, eyes, genitalia, and lungs have been revised. Categories of chronic GVHD should be defined in ways that indicate prognosis, guide treatment, and define eligibility for clinical trials. Revisions have been made to focus attention on the causes of organ-specific abnormalities. Attribution of organ-specific abnormalities to chronic GVHD has been addressed. This paradigm shift provides greater specificity, more accurately measures the global burden of disease attributed to GVHD, and will facilitate biomarker association studies. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2014; 21(3). DOI:10.1016/j.bbmt.2014.12.001 · 3.15 Impact Factor
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    ABSTRACT: Cyclophosphamide in combination with busulfan (Bu) or total body irradiation (TBI) are the most commonly used myeloablative conditioning regimens in patients with Chronic Myeloid Leukemia (CML). We used data from the Center for International Bone Marrow Transplantation Research to compare outcomes in adults who underwent hematopoietic cell transplantation for CML in first chronic phase following myeloablative conditioning with cyclophosphamide (Cy) in combination with TBI, oral Bu or intravenous (IV) Bu. Four hundred thirty-eight adults received human leukocyte antigen (HLA)-matched sibling grafts and 235 received well-matched grafts from unrelated donors from 2000 through 2006. Important differences existed between the groups in distribution of donor relation, exposure to tyrosine kinase inhibitors and year of transplantation. In multivariate analysis, relapse occurred less frequently among patients receiving IV Bu compared to TBI (RR=0.36; P=0.022) or oral Bu (RR=0.39; P=0.028), but non-relapse mortality and survival were similar. A significant interaction was detected between donor relation and the main effect in leukemia-free survival (LFS). Among recipients of HLA-identical sibling grafts, but not URD grafts, LFS was better in patients receiving IV (RR=0.53; P=0.025) or oral Bu (RR=0.64; P=0.017) compared to TBI. In CML in first chronic phase, Cy in combination with IV Bu was associated with less relapse than TBI or oral Bu. LFS was better following IV or oral Bu compared to TBI. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2014; DOI:10.1016/j.bbmt.2014.12.010 · 3.15 Impact Factor
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    ABSTRACT: We previously reported a risk score that predicted mortality in patients with chronic graft-versus-host disease (CGVHD) after hematopoietic stem cell transplant (HCT) between 1995-2004 and reported to the Center for International Blood and Marrow Transplant Registry (CIBMTR). We sought to validate this risk score in an independent CIBMTR cohort of 1128 patients with CGVHD transplanted between 2005-2007 using the same inclusion criteria and risk-score calculations. According to the sum of the overall risk score (range 1 to 12), patients were assigned to 4 risk-groups (RGs): RG1 (0-2), RG2 (3-6), RG3 (7-8) and RG4 (9-10). RG3 and 4 were combined as RG4 comprised only 1% of the total cohort. Cumulative incidences of non relapse mortality (NRM) and probability of overall survival (OS) were significantly different between each RG (all p<0.01). NRM and OS at five years after CGVHD for each RG were 17% and 72% in RG1, 26% and 53% in RG2, and 44% and 25% in RG 3, respectively (all p<0.01). Our study validates the prognostic value of the CIBMTR CGVHD RGs for OS and NRM in a contemporary transplant population. The CIBMTR CGVHD RGs can be used to predict major outcomes, tailor treatment planning, and enrollment in clinical trials. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 12/2014; DOI:10.1016/j.bbmt.2014.10.022 · 3.15 Impact Factor
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    ABSTRACT: Core binding factor acute myelogenous leukemia (CBF AML) constitutes 15% of adult AML and carries an overall good prognosis. CBF AML encodes two recurrent cytogentic abnormalities referred to as t(8;21) and inv (16). The two CBF AML entities are usually grouped together but there is a considerable clinical, pathologic and molecular heterogeneity within this group of diseases. Recent and ongoing studies are addressing the molecular heterogeneity, minimal residual disease and targeted therapies to improve the outcome of CBF AML. In this article, we present a comprehensive review about CBF AML with emphasis on molecular heterogeneity and new therapeutic options.
    American Journal of Hematology 12/2014; 89(12). DOI:10.1002/ajh.23821 · 3.48 Impact Factor
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    ABSTRACT: Acute myeloid leukemia (AML) relapse after allogeneic hematopoietic cell transplantation (alloHCT) remains a major therapeutic challenge. We studied outcomes of 1788 AML patients relapsing after alloHCT (1990 to 2010) during first or second complete remission (CR) to identify factors associated with longer postrelapse survival. Median time to post-HCT relapse was 7 months (range, 1 to 177). At relapse, 1231 patients (69%) received intensive therapy, including chemotherapy alone (n = 660), donor lymphocyte infusion (DLI) ± chemotherapy (n = 202), or second alloHCT ± chemotherapy ± DLI (n = 369), with subsequent CR rates of 29%. Median follow-up after relapse was 39 months (range, <1 to 193). Survival for all patients was 23% at 1 year after relapse; however, 3-year overall survival correlated with time from HCT to relapse (4% for relapse during the 1- to 6-month period, 12% during the 6-month to 2-year period, 26% during the 2- to 3-year period, and 38% for ≥3 years). In multivariable analysis, lower mortality was significantly associated with longer time from alloHCT to relapse (relative risk, .55 for 6 months to 2 years; relative risk, .39 for 2 to 3 years; and relative risk, .28 for ≥3 years; P < .0001) and a first HCT using reduced-intensity conditioning (relative risk, .77; 95% confidence interval [CI], .66 to .88; P = .0002). In contrast, inferior survival was associated with age >40 years (relative risk, 1.42; 95% CI, 1.24 to 1.64; P < .0001), active graft-versus-host disease at relapse (relative risk, 1.25; 95% CI, 1.13 to 1.39; P < .0001), adverse cytogenetics (relative risk, 1.37; 95% CI, 1.09 to 1.71; P = .0062), mismatched unrelated donor (relative risk, 1.61; 95% CI, 1.22 to 2.13; P = .0008), and use of cord blood for first HCT (relative risk, 1.23; 95% CI, 1.06 to 1.42; P = .0078). AML relapse after alloHCT predicted poor survival; however, patients who relapsed ≥6 months after their initial alloHCT had better survival and may benefit from intensive therapy, such as second alloHCT ± DLI. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2014; 21(3). DOI:10.1016/j.bbmt.2014.11.007 · 3.15 Impact Factor
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    ABSTRACT: The use of alternative donor transplants is increasing as the transplantation-eligible population ages and sibling donors are less available. We evaluated the impact of donor source on transplantation outcomes for adults with acute myeloid leukemia undergoing myeloablative (MA) or reduced-intensity conditioning (RIC) transplantation. Between January 2000 and December 2010, 414 consecutive adult patients with acute myeloid leukemia in remission received MA or RIC allogeneic transplantation from either a matched related donor (n = 187), unrelated donor (n = 76), or umbilical cord blood donor (n = 151) at the University of Minnesota or Hôpital St. Louis in Paris. We noted similar 6-year overall survival across donor types: matched related donor, 47% (95% confidence interval [CI], 39% to 54%); umbilical cord blood, 36% (95% CI, 28% to 44%); matched unrelated donor, 54% (95% CI, 40% to 66%); and mismatched unrelated donor, 51% (95% CI, 28% to 70%) (P < .11). Survival differed based on conditioning intensity and age, with 6-year survival of 57% (95% CI, 47% to 65%), 39% (95% CI, 28% to 49%), 23% (95% CI, 6% to 47%), 47% (95% CI, 36% to 57%), and 28% (95% CI, 17% to 41%) for MA age 18 to 39, MA age 40+, or RIC ages 18 to 39, 40 to 56, and 57 to 74, respectively (P < .01). Relapse was increased with RIC and lowest in younger patients receiving MA conditioning (hazard ratio, 1.0 versus 2.5 or above for all RIC age cohorts), P < .01. Transplantation-related mortality was similar across donor types. In summary, our data support the use of alternative donors as a graft source with MA or RIC for patients with acute myeloid leukemia when a sibling donor is unavailable.
    Biology of Blood and Marrow Transplantation 11/2014; 21(2). DOI:10.1016/j.bbmt.2014.10.030 · 3.35 Impact Factor
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    ABSTRACT: To develop, characterize, and implement a fast patient localization method for total marrow irradiation. Topographic images were acquired using megavoltage computed tomography (MVCT) detector data by delivering static orthogonal beams while the couch traversed through the gantry. Geometric and detector response corrections were performed to generate a megavoltage topogram (MVtopo). We also generated kilovoltage topograms (kVtopo) from the projection data of 3-dimensional CT images to reproduce the same geometry as helical tomotherapy. The MVtopo imaging dose and the optimal image acquisition parameters were investigated. A multi-institutional phantom study was performed to verify the image registration uncertainty. Forty-five MVtopo images were acquired and analyzed with in-house image registration software. The smallest jaw size (front and backup jaws of 0) provided the best image contrast and longitudinal resolution. Couch velocity did not affect the image quality or geometric accuracy. The MVtopo dose was less than the MVCT dose. The image registration uncertainty from the multi-institutional study was within 2.8 mm. In patient localization, the differences in calculated couch shift between the registration with MVtopo-kVtopo and MVCT-kVCT images in lateral, cranial-caudal, and vertical directions were 2.2 ± 1.7 mm, 2.6 ± 1.4 mm, and 2.7 ± 1.1 mm, respectively. The imaging time in MVtopo acquisition at the couch speed of 3 cm/s was <1 minute, compared with ≥15 minutes in MVCT for all patients. Whole-body MVtopo imaging could be an effective alternative to time-consuming MVCT for total marrow irradiation patient localization. Copyright © 2014 Elsevier Inc. All rights reserved.
    International Journal of Radiation OncologyBiologyPhysics 10/2014; 91(1). DOI:10.1016/j.ijrobp.2014.09.014 · 4.18 Impact Factor
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    ABSTRACT: Although transplant practices have changed over the last decades there is no information on trends in incidence and outcome of cGVHD over time. This study utilized the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe the time trends for cGVHD incidence, non-relapse mortality, and the risk factors for cGVHD. The 12-year period was divided into three intervals: 1995-1999, 2000-2003, 2004-2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia and myelodysplastic syndrome. In the multivariate analysis, the incidence of cGVHD was shown to be increased in more recent years (odds ratio= 1.19, p<0.0001) and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, non-relapse mortality has decreased over time, but at 5-years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research. Copyright © 2014 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2014; 21(2). DOI:10.1016/j.bbmt.2014.10.021 · 3.15 Impact Factor
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    ABSTRACT: Purpose: Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year post-transplant at the time when acute GVHD is still active. Experimental design: The current study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7489 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) who were leukemia-free at12 months after myeloablative allogeneic HCT. Results: Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on relapse was present only in patients with CML (RR: 0.47, 95% CI: 0.37-0.59, P <0.0001). cGVHD was significantly associated with higher risk of treatment related mortality, (RR: 2.43, 95% CI: 2.09-2.82, P <0.0001) and inferior overall survival (RR: 1.56, 95% CI: 1.41-1.73, P <0.0001) for all diseases. In patients with CML all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse. Conclusions: These results indicate that clinically relevant anti-leukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL or MDS. Chronic GVHD in patients who are one year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival.

Publication Stats

23k Citations
3,395.32 Total Impact Points

Institutions

  • 1982–2015
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States
    • University of Connecticut
      • Department of Nutritional Sciences
      Storrs, Connecticut, United States
  • 1999–2014
    • Indiana Blood and Marrow Transplantation
      Indianapolis, Indiana, United States
    • University of California, San Francisco
      San Francisco, California, United States
  • 1991–2014
    • University of Minnesota Medical Center, Fairview
      Minneapolis, Minnesota, United States
  • 2013
    • Mayo Foundation for Medical Education and Research
      Rochester, Michigan, United States
    • Hôpital Saint-Louis (Hôpitaux Universitaires Saint-Louis, Laboisière, Fernand-Widal)
      Lutetia Parisorum, Île-de-France, France
    • Carolinas HealthCare System
      Charlotte, North Carolina, United States
    • American Cancer Society
      Atlanta, Georgia, United States
    • Children's Hospitals and Clinics of Minnesota
      Minneapolis, Minnesota, United States
    • Michiana Hematology Oncology
      Indiana, Pennsylvania, United States
  • 2010–2013
    • Moffitt Cancer Center
      • Program in Blood and Marrow Transplantation
      Tampa, FL, United States
    • University Hospitals Bristol NHS Foundation Trust
      Bristol, England, United Kingdom
    • Duke University
      Durham, North Carolina, United States
    • National Institutes of Health
      • Branch of Experimental Transplantation and Immunology
      Maryland, United States
  • 2002–2013
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, Washington, United States
  • 1989–2013
    • University of Minnesota Twin Cities
      • • Division of Hematology, Oncology and Transplantation
      • • Department of Medicine
      • • Division of Pediatric Infectious Diseases
      • • Department of Pediatrics
      Minneapolis, Minnesota, United States
  • 2012
    • Vanderbilt University
      Nashville, Michigan, United States
  • 2011–2012
    • Children's National Medical Center
      • Division of Blood and Marrow Transplantation
      Washington, Washington, D.C., United States
    • Stanford University
      • Division of Blood and Marrow Transplantation
      Stanford, CA, United States
    • Indiana University-Purdue University Indianapolis
      • Department of Medicine
      Indianapolis, IN, United States
    • Emory University
      Atlanta, Georgia, United States
  • 2006–2012
    • University of Toronto
      Toronto, Ontario, Canada
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
    • University of Waterloo
      Ватерлоо, Ontario, Canada
    • Wayne State University
      Detroit, Michigan, United States
    • University of Illinois at Chicago
      Chicago, Illinois, United States
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
    • University of Cincinnati
      Cincinnati, Ohio, United States
  • 2001–2011
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
  • 1998–2011
    • Roswell Park Cancer Institute
      Buffalo, New York, United States
  • 2006–2010
    • University of Michigan
      • • Medical School
      • • Department of Internal Medicine
      Ann Arbor, Michigan, United States
    • City of Hope National Medical Center
      • Department of Population Sciences
      Duarte, CA, United States
  • 2003–2010
    • Mayo Clinic - Rochester
      • Department of Hematology
      Rochester, Minnesota, United States
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      Maryland, United States
  • 2008
    • British Society of Blood and Marrow Transplantation
      Bristol, England, United Kingdom
  • 2003–2008
    • National Marrow Donor Program
      Minneapolis, Minnesota, United States
  • 1995–2008
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, Wisconsin, United States
  • 2007
    • Northwestern University
      Evanston, Illinois, United States
    • Baylor College of Medicine
      Houston, Texas, United States
    • The Children's Hospital of Philadelphia
      Filadelfia, Pennsylvania, United States
  • 2005
    • University of Nebraska Medical Center
      Omaha, Nebraska, United States
    • National Cancer Institute
      Μπογκοτά, Bogota D.C., Colombia
  • 2000–2005
    • The Rockefeller University
      New York, New York, United States
    • Virginia Commonwealth University
      • Division of Hematology/Oncology
      Richmond, VA, United States
  • 2004
    • Harvard University
      Cambridge, Massachusetts, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
  • 2001–2003
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 1988–1993
    • Minnesota Department of Health
      Saint Paul, Minnesota, United States
  • 1981
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States