Daniel J Weisdorf

Indiana Blood and Marrow Transplantation, Indianapolis, Indiana, United States

Are you Daniel J Weisdorf?

Claim your profile

Publications (612)3801.51 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: The effectiveness of NK cell infusions to induce leukemic remission is limited by lack of both antigen specificity and in vivo expansion. To address the first issue we previously generated a bispecific killer engager (BiKE) containing single chain scFV against CD16 and CD33 to create an immunologic synapse between NK cells and CD33+ myeloid targets. We have now incorporated a novel modified human IL-15 crosslinker, producing a 161533 trispecific killer engager (TriKE) to induce expansion, priming, and survival, which we hypothesize will enhance clinical efficacy. Methods: Reagents were tested in proliferation and functional assays and in an in vivo xenograft model of AML. Results: When compared to the 1633 BiKE, the 161533 TriKE induced superior NK cell cytotoxicity, degranulation, and cytokine production against CD33+ HL-60 targets and increased NK survival and proliferation. Specificity was shown by the ability of a 1615EpCAM TriKE to kill CD33-EpCAM+ targets. Using NK cells from patients after allogeneic stem cell transplantation when NK cell function is defective, the 161533 TriKE restored potent NK function against primary AML targets and induced specific NK cell proliferation. These results were confirmed in an immunodeficient mouse HL-60-Luc tumor model where the 161533 TriKE exhibited superior anti-tumor activity and induced in vivo persistence and survival of human NK cells for at least 3 weeks. Conclusions: Off-the-shelf 161533 TriKE imparts antigen specificity and promotes in vivo persistence, activation, and survival of NK cells. These qualities are ideal for NK cell therapy of myeloid malignancies or targeting antigens of solid tumors.
    No preview · Article · Feb 2016 · Clinical Cancer Research
  • [Show abstract] [Hide abstract]
    ABSTRACT: B cell anti-host antibody production plays a central role in chronic graft-vs-host disease (cGVHD). T follicular helper (TFH) cells drive B cell responses and are implicated in this process. Given differences in cGVHD incidence between umbilical cord blood (UCB) and adult donor transplant recipients, we evaluated TFH cell reconstitution kinetics to define graft source differences and their potential pathogenic role in cGVHD. Although we observed significantly fewer TFH cells in the blood of UCB recipients (vs. matched related donors (MRD)) early after transplantation, by 1 year the numbers of TFH cells were similar. Additionally, at both early (day 60) and late (1 year) time points, TFH cell phenotype was predominantly central memory cells in both cohorts. TFH cells were functional and able to produce multiple cytokines (INF-γ, TNF-α, IL-2, IL-17 and IL-21) following stimulation. In contrast to mouse models where an enhanced frequency of splenic TFH cells contributes to cGVHD, patients with cGVHD showed significantly depleted circulating TFH cells following both UCB and MRD transplantation. Low numbers of TFH cells early after UCB transplantation could directly contribute to less cGVHD in this cohort. Additionally, systemic therapy (including steroids and calcineurin inhibitors) may contribute to decreases in TFH cells in patients with cGVHD. These data provide further evidence supporting the importance of TFH cells in cGVHD pathogenesis.
    No preview · Article · Jan 2016 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • [Show abstract] [Hide abstract]
    ABSTRACT: For adults with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) in first complete remission (CR1), allogeneic hematopoietic cell transplantation (HCT) is an established curative strategy. However, pediatric-inspired chemotherapy may also offer durable leukemia free survival in the absence of HCT. We compared 422 HCT recipients aged 18-50 years with Ph-ALL in CR1 reported to the CIBMTR with an age-matched concurrent cohort of 108 Ph- ALL CR1 patients who received a Dana-Farber Consortium pediatric-inspired non-HCT regimen. At four years follow-up, incidence of relapse after HCT was 24% [95% C.I. 19-28] vs. 23% [95% C.I. 15-32] for the non-HCT ("chemo") cohort (p=0.97). Treatment-related mortality (TRM) was higher in the HCT cohort (HCT 37% [95% C.I. 31-42] vs. chemo 6% [95% C.I. 3 - 12], p<0.0001). DFS in the HCT cohort was 40% [95% C.I. 35-45] vs. 71% [95% C.I. 60-79] for chemo, p<0.0001. Similarly, OS favored chemo (HCT 45% [95% C.I. 40-50]) vs. chemo 73% [95% C.I. 63-81], p<0.0001). In multivariable analysis, the sole factor predictive of shorter OS was the administration of HCT (HR 3.12 [1.99 - 4.90], p<0.0001). For younger adults with Ph- ALL, pediatric-inspired chemotherapy had lower TRM, no increase in relapse, and superior overall survival compared to HCT. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · American Journal of Hematology
  • [Show abstract] [Hide abstract]
    ABSTRACT: Advanced systemic mastocytosis (AdvSM) is associated with shortened survival. The only potentially curative therapy in AdvSM is allogeneic hematopoietic cell transplantation (alloHCT) with durable disease-free survival reported in 51% of patients. Veno-occlusive disease (VOD) is a known potential complication of alloHCT and can affect liver and less commonly lung. Severe VOD with multiorgan failure (MOF) is associated with a high mortality (>80%). AdvSM patients may be at high risk for VOD given their frequent liver involvement by SM, the well-known interactions between vascular epithelium and mast cells, and the huge numbers of mast cells in the lung in both normal individuals and patients with SM. This article is protected by copyright. All rights reserved.
    No preview · Article · Dec 2015 · European Journal Of Haematology
  • [Show abstract] [Hide abstract]
    ABSTRACT: There is little data regarding the incidence, clinical manifestations, risk factors and outcomes of late acute GVHD (aGVHD). We evaluated patients with late aGVHD after allogeneic HCT between 2007 and 2012 and compared their outcomes to patients with early onset aGVHD. Of the 511 allogeneic HCT recipients, 75 developed late aGVHD (cumulative incidence: 14.7% (95% CI: 11.6-17.8) versus 248 with early onset aGVHD (cumulative incidence: 49% (95% CI: 45-53). Amongst those with late aGVHD, 52% had persistent, 39% recurrent and 9% de-novo late aGVHD. Advanced (grade III-IV) early onset aGVHD was associated with a higher risk of developing late aGVHD (HR 1.9, 95% CI: 1.2 -3.1, p= 0.01). 48% (95% CI: 36-60%) of late aGVHD versus only 31% (95% CI: 26-37%) of early onset aGVHD progressed to chronic GVHD by 2 years. Higher proportion of persistent (53%) as compared to recurrent (39%) and de-novo (46%) late aGVHD progressed to cGVHD at 2 years. The overall survival was 59% (95% CI: 49-72) in late aGVHD and 50% (95% CI: 44-57%) in early onset aGVHD. Persistent late aGVHD had worse OS and NRM (45% and 39%) as compared to recurrent (74% and 18%) and de-novo (83% and 0%) late aGVHD. Compared to HLA-identical sibling HCT, unrelated donor transplants were associated with a higher risk of mortality in patients developing late aGVHD (HR 6.1, 95% CI: 2.3-16.2, p<0.01). In a landmark analysis (evaluating 100 day survivors among early onset aGVHD), no difference was seen in late mortality (after 100 days) between early onset and late aGVHD (HR 0.96, 95% CI: 0.59-1.55, p= 0.85), however the risk of cGVHD was nearly doubled (HR 1.81, 95% CI: 1.16-2.82, p=0.01) in patients with late aGVHD. Conclusions: Late aGVHD is a relatively common complication after allogeneic HCT. Poorer outcomes in those with persistent late aGVHD imply need for more effective therapy in this group to improve transplant outcomes. A higher risk of subsequent chronic GVHD needs further evaluation and close monitoring.
    No preview · Article · Dec 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • B J Trottier · Z Sachs · T E DeFor · L Shune · M Dolan · D J Weisdorf · C Ustun · E D Warlick
    [Show abstract] [Hide abstract]
    ABSTRACT: Among patients with myelodysplastic syndrome (MDS) undergoing hematopoietic cell transplantation (HCT), the impact of residual pretransplant cytogenetically abnormal cells on outcomes remains uncertain. We analyzed HCT outcomes by time of transplant disease variables, including (1) blast percentage, (2) percentage of cytogenetically abnormal cells and (3) Revised International Prognostic Scoring System (R-IPSS) cytogenetic classification. We included 82 MDS patients (median age 51 years (range 18–71)) transplanted between 1995 and 2013 with abnormal diagnostic cytogenetics. Patients with higher percentages of cytogenetically abnormal cells experienced inferior 5-year survival (37–76% abnormal cells: relative risk (RR) 2.9; 95% confidence interval (CI) 1.2–7.2; P=0.02; and 77–100% abnormal cells: RR 5.6; 95% CI 1.9–19.6; P<0.01). Patients with >10% blasts also had inferior 5-year survival (RR 2.9; 95% CI 1.1–7.2; P=0.02) versus patients with 2% blasts. Even among patients with 2% blasts, patients with 77–100% cytogenetically abnormal cells had poor survival (RR 4.4; 95% CI 1.1–18.3; P=0.04). Increased non-relapse mortality (NRM) was observed with both increasing blast percentages (P<0.01) and cytogenetically abnormal cells at transplant (P=0.01) in multivariate analysis. We observed no impact of disease burden characteristics on relapse outcomes due to high 1-year NRM. In conclusion, both blast percentage and percentage of cytogenetically abnormal cells reflect MDS disease burden and predict post-HCT outcomes.
    No preview · Article · Nov 2015 · Bone Marrow Transplantation
  • [Show abstract] [Hide abstract]
    ABSTRACT: Infection is one of the most common complications after hematopoietic cell transplantation. Many patients experience infectious complications repeatedly after transplant. Existing statistical methods for recurrent gap time data typically assume that patients are enrolled due to the occurrence of an event of interest, and subsequently experience recurrent events of the same type; moreover, for one-sample estimation, the gap times between consecutive events are usually assumed to be identically distributed. Applying these methods to analyze the post-transplant infection data will inevitably lead to incorrect inferential results because the time from transplant to the first infection has a different biological meaning than the gap times between consecutive recurrent infections. Some unbiased yet inefficient methods include univariate survival analysis methods based on data from the first infection or bivariate serial event data methods based on the first and second infections. In this article, we propose a nonparametric estimator of the joint distribution of time from transplant to the first infection and the gap times between consecutive infections. The proposed estimator takes into account the potentially different distributions of the two types of gap times and better uses the recurrent infection data. Asymptotic properties of the proposed estimators are established.
    No preview · Article · Nov 2015 · Biometrics
  • [Show abstract] [Hide abstract]
    ABSTRACT: We studied the safety and clinical outcomes of patients treated with umbilical cord blood (UCB) derived regulatory T cells that expanded in cultures stimulated with K562 cells modified to express the high affinity Fc receptor (CD64) and CD86, the natural ligand of CD28 (KT64/86). Eleven patients were treated with Treg doses from 3 to 100 x 10(6) Treg/kg. The median proportion of CD4+FoxP3+CD127- in the infused product was 87% (r, 78-95%) and we observed no dose limiting infusional adverse events. Clinical outcomes were compared to contemporary controls (n=22) who received the same conditioning regimen with sirolimus and mycophenolate mofetil immune suppression. The incidence of grade II-IV acute graft-vs.-host disease (GVHD) at 100 days was 9% (95%CI, 0-25%) vs. 45% (95%CI, 24-67%) in controls (p=.05). Chronic GVHD at 1 year was zero in Tregs and 14% in controls. Hematopoietic recovery and chimerism, cumulative density of infections, non-relapse mortality, relapse and disease-free survival were similar in the Treg recipients and controls. KT64/86 expanded UCB Tregs were safe and resulted in low risk of acute GVHD.
    No preview · Article · Nov 2015 · Blood
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stringent complete remission (CR) in acute myeloid leukemia (AML) requires the absence of both morphologic and flow cytometric evidence of disease. We have previously shown that persistent AML detected by flow cytometry (FC+) before reduced-intensity conditioning (RIC) allogeneic hematopoietic cell transplantation (alloHCT) was associated with significantly increased relapse, shorter disease-free survival (DFS) and poorer overall survival (OS), independent of morphologic blast count. We evaluated the effect of FC status on outcomes of alloHCT for AML after either myeloablative conditioning (MAC) or RIC regimens. In 203 patients (MAC, n=80 and RIC, n=123) with no morphologic evidence of persistent AML pre-transplant on marrow biopsy. The allografts included 130 umbilical cord blood (UCB) and 73 sibling donors. We performed central review of pre-transplant standard sensitivity flow cytometry to identify detectable FC+. Twenty-five patients were FC+, including 15 (18.7%) receiving MAC and 10 (8.1%) RIC alloHCT. Among RIC patients FC+ was associated with significantly inferior relapse, disease-free survival (DFS), and overall survival (OS) [multiple regression hazard ratio (HR) 3.8, (95% confidence interval (95% CI) 1.7-8.7), p<0.01 for relapse; HR 2.9, (95% CI: 1.4-5.9), p<0.01 for DFS, and HR 3.4 (95%CI: 1.7-7), p<0.01 for OS]. In contrast, FC+ status was not associated with relapse or decreased OS after MAC. These data suggest that MAC, but not RIC, overcomes the negative effect of pretransplant FC+ following sibling or UCB alloHCT. Therefore, a deeper pre-transplant leukemia-free state is preferred for those treated with RIC.
    No preview · Article · Nov 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • C. G. Brunstein · J. E. Wagner · D. J. Weisdorf

    No preview · Article · Nov 2015 · Blood
  • Melhem Solh · Shanna Morgan · Jeffrey McCullough · Ryan Shanley · Daniel J. Weisdorf
    [Show abstract] [Hide abstract]
    ABSTRACT: Background: Transfusion of blood products is an essential component of the hematopoietic cell transplantation (HCT) process. Blood transfusion carries several risks including, but not limited to, lung injury. The effect of transfusions on lung complications after HCT has not been previously investigated. Study design and methods: We retrospectively studied 215 adult allogeneic HCT recipients at the University of Minnesota and examined the association between transfusion of blood components and development of lung complications after HCT. Patients without lung complications were used as the control group. Results: A total of 113 (58%) of the patients developed lung injury events before Day 180 after HCT. Six-month survival was significantly lower in the lung event group (52%) versus the controls (78%; p = 0.01). Patients who eventually developed lung events received more transfusion episodes per week in the first month after HCT (median, 4.3 vs. 2.7 for controls), platelet units per week (3.5 vs. 2.0), and RBC units per week (1.8 vs. 1.4; p < 0.01) for all. In a multivariable analysis, each additional transfusion before Day +30 was associated with a 2.7% higher risk of lung complication (95% confidence interval, 0.8-4.8; p = 0.01), adjusting for time to engraftment, conditioning intensity, and donor type. Blood utilization increased after the lung event and remained high for several months relative to controls. Conclusion: Our data suggest that transfusion of blood products is associated with and may further complicate lung complications after HCT. Cautious use of blood components in the post HCT period is recommended.
    No preview · Article · Nov 2015 · Transfusion
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and purpose: Total body irradiation (TBI) is a common component of hematopoietic cell transplantation (HCT) conditioning regimens. Preclinical studies suggest prolonged bone marrow (BM) injury after TBI could contribute to impaired engraftment and poor hematopoietic function. Materials and methods: We studied the longitudinal changes in the marrow environment in patients receiving allogeneic HCT with myeloablative (MA, n=42) and reduced intensity (RIC, n=56) doses of TBI from 2003-2013, including BM cellularity, histologic features of injury and repair, hematologic and immunologic recovery. Results: Following MA conditioning, a 30% decrease in the marrow cellularity persisted at 1year post-transplant (p=0.03). RIC HCT marrow cellularity transiently decreased but returned to baseline by 6months even though the RIC group received mostly umbilical cord blood (UCB) grafts (82%, vs. 17% in the MA cohort, p<0.01). There was no evidence of persistent marrow vascular damage or inflammation. Recipients of more intensive conditioning did not show more persistent cytopenias with the exception of a tendency for minimal thrombocytopenia. Immune recovery was similar between MA and RIC. Conclusions: These findings suggest that TBI associated with MA conditioning leads to prolonged reductions in marrow cellularity, but does not show additional histological evidence of long-term injury, which is further supported by similar peripheral counts and immunologic recovery.
    No preview · Article · Nov 2015 · Radiotherapy and Oncology
  • [Show abstract] [Hide abstract]
    ABSTRACT: The impact of allele level HLA mismatch is uncertain in recipients of double umbilical cord blood transplantation (dUCBT). We report a single center retrospective study of the clinical effect of using allele-level HLA mismatch HLA-A, -B, -C, -DRB1 and -DQB1 of the two UCB units. We studied 342 patients with hematological malignancy. Donor-recipient pairs were grouped according to the number of matched HLA alleles with 32 matched at 9-10/10, 202 at 6-8/10 and 108 at 2-5/10 alleles. The incidence of hematopoietic recovery, acute and chronic graft-versus-host disease (GVHD), and non-relapse mortality (NRM) and treatment failure was similar between groups. In an exploratory analysis of 174 patients with acute leukemia, after adjusting for length of first remission and cytogenetic risk group, 2-5/10 HLA match was associated with lower risk of relapse and treatment failure. These data indicate that a high degree of allele level HLA mismatch does not adversely affect transplant outcomes and may be associated with reduced relapse risk in patients with acute leukemia.
    No preview · Article · Oct 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • [Show abstract] [Hide abstract]
    ABSTRACT: The maximum age of patients receiving allogeneic hematopoietic stem cell transplantation (alloHCT) has been moving up over time. However, the availability of a suitable HLA-matched sibling donor may limit access of this patient population to alloHCT. We retrospectively investigated the outcomes of umbilical cord blood (UCB) transplantation after reduced intensity conditioning regimen (RIC) in patients with myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML) ≥ 70 years between 2010 and 2014. During this period, 70 patients with AML/MDS were referred to our center for alloHCT consideration. Twenty-two patients (33%) received alloHCT, including 10 UCB transplantation, 9 HLA full-matched sibling donor transplantation, 2 haploidentical alloHCT, and 1 unrelated donor (URD) alloHCT. In UCB transplantation, cumulative incidence of non-relapse mortality and relapse was 20% and 30% at 2 years, respectively. The cumulative incidence of acute graft versus host disease (GVHD) at day +100 and chronic GVHD at 2 years was 10%. Seven patients had viral reactivation/infections. Overall survival and disease-free survival were 60% and 50% at 2 years, respectively. Moreover, these outcomes seem similar to that of patients 60-69 years of age receiving UCB transplantation (n=60) and patients ≥ 70 years receiving HLA full-matched sibling donor transplantation (n=9). These results suggest that UCB transplantation is feasible in selected AML/MDS patients ≥ 70 years. In fact, UCB shortens required time for URD search and thus increases the chance of proceeding with alloHCT, which might contribute to higher rates of alloHCT in the referral group. Outcomes of UCB transplantation are promising; however, larger studies with a longer follow-up are needed.
    No preview · Article · Sep 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • [Show abstract] [Hide abstract]
    ABSTRACT: We have recently described a specialized subset of human natural killer (NK) cells with a CD56(dim)CD57(+)NKG2C(+) phenotype that expand specifically in response to cytomegalovirus (CMV) reactivation in hematopoietic cell transplant (HCT) recipients and exhibit properties characteristic of adaptive immunity. We hypothesize that these cells mediate relapse protection and improve post-HCT outcomes. In 674 allogeneic HCT recipients, we found that those who reactivated CMV had lower leukemia relapse (26% [17-35%], p=0.05) and superior disease-free survival (DFS) (55% [45-65%] p=0.04) 1 year after reduced intensity conditioning (RIC) compared to CMV seronegative recipients who experienced higher relapse rates (35% [27-43%]) and lower DFS (46% [38-54%]). This protective effect was independent of age and graft-versus-host disease (GvHD) and was not observed in recipients who received myeloablative (MA) regimens. Analysis of the reconstituting NK cells demonstrated that CMV reactivation is associated with both higher frequencies and greater absolute numbers of CD56(dim)CD57(+)NKG2C(+) NK cells, particularly after RIC HCT. Furthermore, expansion of these cells at 6 months post-transplant independently trended toward a lower 2-year relapse risk. Together, our data suggest that the protective effect of CMV reactivation on post-transplant relapse is in part driven by adaptive NK cell responses.Leukemia accepted article preview online, 29 September 2015. doi:10.1038/leu.2015.260.
    No preview · Article · Sep 2015 · Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K
  • [Show abstract] [Hide abstract]
    ABSTRACT: Infection is a major complication of hematopoietic cell transplantation. Prolonged neutropenia and graft versus host disease are the two major complications with an associated risk for infection, and these complications differ according to the graft source. A phase 3, multicenter, randomized trial (BMT CTN 0201) of transplantation of bone marrow (BM) versus peripheral-blood stem cells (PBSC) from unrelated donors (URD) showed no significant differences in two-year survival between these graft sources. In an effort to provide data regarding whether bone marrow or peripheral-blood stem cells could be used as a preferential graft source for transplantation, we report a detailed analysis of the infectious complications for 2 years following transplantation from the BMT CTN 0201 trial. A total of 499 patients in this study had full audits of infection data. A total of 1347 infection episodes of moderate or greater severity were documented in 384 (77%) patients; 201/249 (81%) of the evaluable patients had received a BM graft and 183/250 (73%) had received a PBSC graft. Of 1347 infection episodes, 373 were severe and 123 were life-threatening and/or fatal; 710 (53%) of these episodes occurred on the BM arm and 637 (47%) on the PBSC arm, resulting in a two-year cumulative incidence 84.7% (95% confidence interval [CI]: 79.6-89.8) for BM vs. 79.7% (95%CI, 73.9-85.5) for PBSC, P = .013. The majority of these episodes, 810 (60%), were due to bacteria, with a two-year cumulative incidence of 72.1% and 62.9% in BM versus PBSC recipients, respectively (P = .003). The cumulative incidence of bloodstream bacterial infections during the first 100 days was 44.8% (95%CI, 38.5-51.1) for BM vs. 35.0% (95%CI, 28.9-41.1) for PBSC (P = .027). The total infection density (# infection events / 100 patient days at risk) was .67 for BM and .60 for PBSC. The overall infection density for bacterial infections was .4 in both arms; for viral infections was .2 in both arms; and for fungal/parasitic infections was .04 and .05 for BM and PBSC, respectively. The cumulative incidence of infection prior to engraftment was 47.9% (95%CI, 41.5-53.9) for BM vs. 32.8% (95%CI, 27.1-38.7) for PBSC (P = .002), possibly related to quicker neutrophil engraftment using PBSC. Infections remain frequent following URD HCT, particularly following BM grafts.
    No preview · Article · Sep 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation
  • Hartmut Döhner · Daniel J Weisdorf · Clara D Bloomfield

    No preview · Article · Sep 2015 · New England Journal of Medicine
  • [Show abstract] [Hide abstract]
    ABSTRACT: Allogeneic hematopoietic cell transplantation is often complicated by graft-versus-host disease (GVHD). We analyzed the incidence and risk factors for acute and chronic graft-versus-host disease (GVHD), and their impact on disease relapse and survival, among recipients of single umbilical cord blood (sUCB, n=295), double umbilical cord blood (dUCB, n=416), and matched sibling donor (MSD, n=469) allografts. The incidence of grade II-IV aGVHD and chronic GVHD among dUCB, sUCB, and MSD was 56%, 26% and 37% and 26%, 7%, and 40%, respectively. Development of acute GVHD had no effect on relapse, non-relapse mortality, or overall survival among UCB recipients, but was associated with worse non-relapse mortality and survival in MSD recipients. Development of cGVHD was only associated with lower relapse in dUCBT. In multivariate analysis of GVHD incidence, age > 18 years was associated with higher incidence of aGVHD and cGVHD across all cohorts, while worse HLA match and prior aGVHD were associated with higher risks of aGVHD in both UCB cohorts. Non-myeloablative conditioning limited the risk of aGVHD compared to myeloablative conditioning in dUCB recipients. Cyclosporine A and mycophenolate mofetil as GVHD prophylaxis lowered the risk of cGVHD compared to steroids with cyclosporine A among sUCB recipients. This large contemporary analysis suggests similarity of risks and consequences of GVHD for UCB and MSD recipients. Limiting the severity of aGVHD remains important in all groups. Increasing the UCB inventory or developing strategies that reduce the cell-dose threshold and thereby increase the chance of identifying an adequately dosed, better HLA-matched single UCB unit may further limit risks of acute GVHD after UCB transplantation.
    No preview · Article · Sep 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation

  • No preview · Article · Sep 2015
  • [Show abstract] [Hide abstract]
    ABSTRACT: The number of allogeneic hematopoietic stem cell (HSC) transplants performed globally each year continues to increase. Advances in HLA typing, better supportive care and administration of reduced-intensity conditioning regimens allow treatment of older patients with older sibling donors. Pre-transplant donor assessment and testing are very important processes affecting the quality and safety of donation. For unrelated HSC donors detailed recommendations for health assessment have been published allowing donation only if they are unrestrictedly healthy. Eligibility criteria for related donors are less strict and vary significantly between centers. In situations where a family donor does not meet the suitability criteria for unrelated donors, involved physicians often struggle with the decision whether the matched relative is suitable for donation or not. On behalf of the Worldwide Network for Blood and Marrow Transplantation Standing Committee on Donor Issues we intended to develop a consensus document with recommendations for donor work-up and final clearance of family donors who would not be able to serve as unrelated donors due to their age or pre-existing diseases. This manuscript covers different topics intending to support decision-making, with the goal of minimizing medical risk to the donor and protection of the recipient from transmissible diseases. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
    No preview · Article · Aug 2015 · Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation

Publication Stats

32k Citations
3,801.51 Total Impact Points


  • 2007-2015
    • Indiana Blood and Marrow Transplantation
      Indianapolis, Indiana, United States
    • Northwestern University
      Evanston, Illinois, United States
    • City of Hope National Medical Center
      • Department of Population Sciences
      Duarte, CA, United States
    • Baylor College of Medicine
      Houston, Texas, United States
  • 1991-2015
    • University of Minnesota Medical Center, Fairview
      Minneapolis, Minnesota, United States
  • 1982-2015
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States
    • University of Connecticut
      • Department of Nutritional Sciences
      Storrs, Connecticut, United States
  • 2014
    • Universität Regensburg
      Ratisbon, Bavaria, Germany
  • 2000-2014
    • Medical College of Wisconsin
      • • Department of Medicine
      • • Center for International Blood & Marrow Transplant Research
      Milwaukee, Wisconsin, United States
    • The Rockefeller University
      New York, New York, United States
  • 2013
    • American Cancer Society
      Atlanta, Georgia, United States
  • 2011-2012
    • Moffitt Cancer Center
      • Program in Blood and Marrow Transplantation
      Tampa, FL, United States
    • Emory University
      Atlanta, Georgia, United States
  • 2002-2011
    • Roswell Park Cancer Institute
      • Department of Medicine
      Buffalo, New York, United States
    • University of Toronto
      Toronto, Ontario, Canada
  • 1995-2009
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, Washington, United States
  • 2008
    • British Society of Blood and Marrow Transplantation
      Bristol, England, United Kingdom
  • 2006
    • University of Michigan
      • Department of Internal Medicine
      Ann Arbor, Michigan, United States
  • 1995-2006
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 2005
    • Columbia University
      New York, New York, United States
  • 1999-2005
    • National Cancer Institute (USA)
      • • Experimental Transplantation and Immunology Branch
      • • Division of Cancer Epidemiology and Genetics
      베서스다, Maryland, United States
  • 2003
    • National Marrow Donor Program
      Minneapolis, Minnesota, United States
  • 2002-2003
    • University of Minnesota Twin Cities
      • Division of Hematology, Oncology and Transplantation
      Minneapolis, Minnesota, United States
  • 2001-2002
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
  • 1998
    • Children's Hospitals and Clinics of Minnesota
      Minneapolis, Minnesota, United States
  • 1990
    • Children's Hospital Los Angeles
      • Division of Hematology-Oncology
      Los Ángeles, California, United States
  • 1988
    • Minnesota Department of Health
      Saint Paul, Minnesota, United States
  • 1981
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States