Daniel J Weisdorf

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

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Publications (599)3756.94 Total impact

  • B J Trottier · Z Sachs · T E DeFor · L Shune · M Dolan · D J Weisdorf · C Ustun · E D Warlick ·
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    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.
    Bone Marrow Transplantation 11/2015; DOI:10.1038/bmt.2015.274 · 3.57 Impact Factor
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    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.
    Biometrics 11/2015; DOI:10.1111/biom.12439 · 1.57 Impact Factor
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    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.
    Blood 11/2015; DOI:10.1182/blood-2015-06-653667 · 10.45 Impact Factor
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    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.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 11/2015; DOI:10.1016/j.bbmt.2015.10.024 · 3.40 Impact Factor
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    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.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2015; DOI:10.1016/j.bbmt.2015.09.025 · 3.40 Impact Factor
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    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.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2015; DOI:10.1016/j.bbmt.2015.09.020 · 3.40 Impact Factor
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    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.
    Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 09/2015; DOI:10.1038/leu.2015.260 · 10.43 Impact Factor
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    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.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2015; DOI:10.1016/j.bbmt.2015.09.013 · 3.40 Impact Factor
  • Hartmut Döhner · Daniel J Weisdorf · Clara D Bloomfield ·

    New England Journal of Medicine 09/2015; 373(12):1136-52. DOI:10.1056/NEJMra1406184 · 55.87 Impact Factor
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    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.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 09/2015; DOI:10.1016/j.bbmt.2015.09.008 · 3.40 Impact Factor

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    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.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2015; DOI:10.1016/j.bbmt.2015.08.009 · 3.40 Impact Factor
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    ABSTRACT: The presence of monosomal karyotype (MK+) in acute myeloid leukemia (AML) is associated with dismal outcomes. We evaluated the impact of MK+ in AML (MK+AML, N=240) and in myelodysplastic syndrome (MK+MDS, N=221) on hematopoietic cell transplantation (HCT) outcomes compared to other cytogenetically defined groups (AML, N=3,360; MDS, N=1,373) as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) from 1998 to 2011. MK+AML was associated with higher disease relapse (hazard ratio [HR] 1.98, p<0.01), similar transplant related mortality (TRM, HR 1.01, p=0.9) and worse survival (HR 1.67, p<0.01) compared to other cytogenetically defined AML. Among patients with MDS, MK+MDS was associated with higher disease relapse (HR 2.39, p<0.01), higher TRM (HR 1.80, p<0.01) and worse survival (HR 2.02, p<0.01). Subset analyses comparing chromosome 7 abnormalities (del7/7q) with or without MK+ demonstrated higher mortality for MK+ disease in for both AML (HR 1.72, p<0.01) and MDS (HR1.79, p<0.01). The strong negative impact of MK+ in myeloid malignancies was observed in all age groups and using either myeloablative or reduced intensity conditioning regimens. Alternative approaches to mitigate disease relapse in this population are needed. 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 08/2015; DOI:10.1016/j.bbmt.2015.08.024 · 3.40 Impact Factor
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    ABSTRACT: Although hemorrhagic cystitis (HC) is a common complication of allogeneic hematopoietic cell transplantation (alloHCT), its risk factors and effects on survival are not well known. We evaluated HC in a large cohort (n=1321, 2003-2012) receiving alloHCT from all graft sources, including umbilical cord blood (UCB). We compared HC patients with non-HC (control) patients and examined clinical variables at HC onset and resolution. Of these 1321 patients, 219 (16.6%) developed HC at a median of 22 days after alloHCT. BK viruria was detected in 90% of 109 tested HC patients. Median duration of HC was 27 days. At the time of HC diagnosis, acute GVHD, fever, severe thrombocytopenia and steroid use were more frequent than at the time of HC resolution. In univariate analysis, male sex, age <20 years, myeloablative conditioning with cyclophosphamide and acute GVHD were associated with HC. In multivariate analysis, HC was significantly more common in males and HLA-mismatched UCB graft recipients. Severe grade HC (grade III-IV) was associated with increased treatment-related mortality but not with overall survival at 1 year. HC remains hazardous and therefore better prophylaxis, and early interventions to limit its severity are still needed.Bone Marrow Transplantation advance online publication, 13 July 2015; doi:10.1038/bmt.2015.162.
    Bone marrow transplantation 07/2015; DOI:10.1038/bmt.2015.162 · 3.57 Impact Factor
  • Celalettin Ustun · Richard Stone · Daniel Weisdorf ·

    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2015; 21(10). DOI:10.1016/j.bbmt.2015.07.011 · 3.40 Impact Factor
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    ABSTRACT: We studied adults with acute myeloid leukemia (AML) after haploidentical (n=192) and 8/8 HLA-matched unrelated donor (n=1982), transplantation. Data were obtained from the Center for International Blood and Marrow Transplant Research. Haploidentical recipients received calcineurin inhibitor (CNI), mycophenolate and post-transplant cyclophosphamide for graft-versus-host disease (GVHD) prophylaxis; 104 patients received myeloablative and 88, reduced intensity conditioning regimens. Matched unrelated donor transplant recipients received CNI with mycophenolate or methotrexate for GVHD prophylaxis; 1245 patients received myeloablative and 737, reduced intensity conditioning regimens. In the myeloablative setting, day-30 neutrophil recovery was lower after haploidentical compared to matched unrelated donor transplants (90% versus 97%, p=0.02). Corresponding rates after reduced intensity conditioning transplants were 93% and 96%, (p=0.25). In the myeloablative setting, 3-month acute grade 2-4 (16% versus 33%, p<0.0001) and 3-year chronic GVHD (30% versus 53%, p<0.0001) were lower after haploidentical compared to matched unrelated donor transplants. Similar differences were observed after reduced intensity conditioning transplants, 19% versus 28%, (p=0.05) and 34% versus 52%, (p=0.002). Among patients receiving myeloablative regimens, 3-year probabilities of overall survival were 45% (95% CI 36-54) and 50% (95% CI 47-53) after haploidentical and matched unrelated donor transplants (p=0.38). Corresponding rates after reduced intensity conditioning transplants were 46% (95% CI 35-56) and 44% (95% CI 0.40-47) (p=0.71). Although statistical power is limited, these data suggests that survival for patients with AML after haploidentical transplantation with posttransplant cyclophosphamide is comparable with matched unrelated donor transplantation. Copyright © 2015 American Society of Hematology.
    Blood 06/2015; 126(8). DOI:10.1182/blood-2015-04-639831 · 10.45 Impact Factor
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    ABSTRACT: Cytomegalovirus (CMV) reactivates in >30% of CMV seropositive patients after allogeneic hematopoietic cell transplantation (HCT). Previously, we reported an increase of NK cells expressing NKG2C, CD57 and inhibitory killer-cell immunoglobulin-like receptors (KIRs) in response to CMV reactivation post-HCT. These NK cells persist after the resolution of infection and display 'adaptive' or memory properties. Despite these findings, the differential impact of persistent/inactive vs. reactivated CMV on NK vs. T cell maturation following HCT from different graft sources has not been defined. We compared the phenotype of NK and T cells from 292 recipients of allogeneic sibling (n = 118) or umbilical cord blood (UCB; n = 174) grafts based on recipient pre-transplant CMV serostatus and post-HCT CMV reactivation. This cohort was utilized to evaluate CMV-dependent increases in KIR-expressing NK cells exhibiting an 'adaptive' phenotype (NKG2C(+)CD57(+)). Compared to CMV seronegative recipients, those who reactivated CMV (React(+)) had the highest adaptive cell frequencies, while intermediate frequencies were observed in CMV seropositive recipients harboring persistent/non-replicating CMV. The same effect was observed in T cells and CD56(+) T cells. These adaptive lymphocyte subsets were increased in CMV seropositive recipients of sibling, but not UCB grafts, and correlated with lower rates of CMV reactivation (sibling 33% vs. UCB 51%; p<0.01). These data suggest that persistent/non-replicating recipient CMV induces rapid production of adaptive NK and T cells from mature cells from sibling, but not UCB grafts. These adaptive lymphocytes are associated with protection from CMV reactivation. 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 06/2015; 21(9). DOI:10.1016/j.bbmt.2015.05.025 · 3.40 Impact Factor
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    ABSTRACT: Hematopoietic cell transplantation (HCT) has been used as a part of cancer therapy for over half a decade. Beyond the necessity for donor-derived cells to reconstitute hematopoiesis after radiation and chemotherapy, immunologic reconstitution from allogeneic cells is important for the elimination of residual tumor cells. Natural killer (NK) cells are first among lymphocytes to reconstitute post-transplant and protect against cancer relapse. In this review, we provide a historical perspective on the role of NK cells in cancer control in the transplant setting and focus on current research aimed at improving NK cell responses for therapeutic benefit.
    Current topics in microbiology and immunology 06/2015; DOI:10.1007/82_2015_445 · 4.10 Impact Factor
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    ABSTRACT: Natural killer (NK) cells are regulated killer immunoglobulin-like receptor (KIR) interactions with HLA class I ligands. Several models of NK reactivity have been associated with improved outcomes following myeloablative allogeneic hematopoietic cell transplantation (HCT), but this issue has not been rigorously addressed in reduced-intensity conditioning (RIC) unrelated donor (URD) HCT. We studied 909 patients undergoing RIC-URD HCT. Patients with acute myeloid leukemia (AML, n=612) lacking >1 KIR ligands experienced higher grade III-IV acute graft-vs.-host disease (GvHD) (HR 1.6, 95%CI 1.16-2.28, p=0.005) compared to those with all ligands present. Absence of HLA-C2 for donor KIR2DL1 was associated with higher grade II-IV (HR 1.4, p=0.002) and III-IV acute GvHD (HR 1.5, p=0.01) compared to HLA-C2+patients. AML patients with KIR2DS1+, HLA-C2 homozygous donors had greater treatment-related mortality compared to others (HR 2.4, 95%CI 1.4-4.2, p=0.002), but did not experience lower relapse. There were no significant associations with outcomes for AML when assessing donor activating KIRs or centromeric KIR content, nor for any donor-recipient KIR-HLA assessments in patients with myelodysplastic syndrome (n=297). KIR-HLA combinations in RIC-URD HCT recapitulate some but not all KIR-HLA effects observed in myeloablative HCT. 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 05/2015; 21(9). DOI:10.1016/j.bbmt.2015.05.002 · 3.40 Impact Factor
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    ABSTRACT: The impact of extramedullary disease (EMD) in AML on the outcomes of allogeneic hematopoietic cell transplantation (alloHCT) is unknown. Using data from the Center for International Blood and Marrow Transplant Research, we compared the outcomes of patients who had EMD of AML at any time before transplant, with a cohort of AML patients without EMD. We reviewed data from 9797 AML patients including 814 with EMD from 310 reporting centers and 44 different countries, who underwent alloHCT between and 1995 and 2010. The primary outcome was overall survival (OS) after alloHCT. Secondary outcomes included leukemia-free survival (LFS), relapse rate and treatment-related mortality (TRM). In a multivariate analysis, the presence of EMD did not affect either OS (hazard ratio 1.00, 95% confidence interval (CI) 0.91-1.09), LFS (0.98, 0.89-1.09), TRM (relative risk 0.92, 95% CI 0.80-1.16, P=0.23) or relapse (relative risk=1.03, 95% CI, 0.92-1.16; P=0.62). Furthermore, the outcome of patients with EMD was not influenced by the location, timing of EMD, or intensity of conditioning regimen. The presence of EMD in AML does not affect transplant outcomes and should not be viewed as an independent adverse prognostic feature.Bone Marrow Transplantation advance online publication, 27 April 2015; doi:10.1038/bmt.2015.82.
    Bone marrow transplantation 04/2015; 50(8). DOI:10.1038/bmt.2015.82 · 3.57 Impact Factor

Publication Stats

30k Citations
3,756.94 Total Impact Points


  • 2007-2015
    • Indiana Blood and Marrow Transplantation
      Indianapolis, Indiana, United States
    • Northwestern University
      Evanston, Illinois, 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
  • 2013
    • Carolinas HealthCare System
      Charlotte, North Carolina, United States
    • 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
  • 2010
    • University Hospitals Bristol NHS Foundation Trust
      Bristol, England, United Kingdom
  • 2007-2010
    • City of Hope National Medical Center
      • Department of Population Sciences
      Duarte, CA, United States
  • 2002-2010
    • University of Toronto
      Toronto, Ontario, Canada
    • University of Minnesota Twin Cities
      • • Division of Pediatric Blood and Marrow Transplantation (BMT)
      • • Division of Hematology, Oncology and Transplantation
      Minneapolis, Minnesota, United States
  • 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
  • 2000-2008
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, Wisconsin, United States
    • The Rockefeller University
      New York, New York, United States
  • 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
  • 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