Daniel J Weisdorf

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

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Publications (452)2544.88 Total impact

  • [Show abstract] [Hide abstract]
    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; · 3.15 Impact Factor
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    ABSTRACT: We observed similar survival across all donor sources for our cohort of AML patients undergoing allogeneic stem cell transplant.•Our study highlighted superior relapse rates in younger patients receiving myeloablative conditioning.•Treatment related mortality was similar across all donor sources.•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;
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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; · 4.52 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; · 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.
    Clinical cancer research : an official journal of the American Association for Cancer Research. 10/2014;
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    ABSTRACT: Certain mitochondrial haplotypes (mthaps) are associated with disease, possibly through differences in oxidative phosphorylation and/or immunosurveillance. We explored whether mthaps are associated with allogeneic HCT outcomes. Recipient (n=437) and donor (n=327) DNA was genotyped for common European mthaps (H, J, U, T, Z, K, V, X, I, W, K2). HCT outcomes for mthap matched siblings (n=198), all recipients, and all donors were modeled using relative risks (RR) and 95% confidence intervals and compared to mthap H, the most common. Siblings with I and V were significantly more likely to die within 5 years (RR=3.0;1.2-7.9 and 4.6;1.8-12.3, respectively). W siblings experienced higher aGVHD II-IV events (RR=2.1;1.1-2.4) with no events for K or K2. Similar results were observed for all recipients combined, although J recipients experienced lower GVHD and higher relapse. Patients with I donors had a 2.7 fold (1.2-6.2) increased risk of death in five years, while few patients with K2 or W donors died. No patients with K2 donors and few patients with U donors relapsed. Mthap may be an important consideration in HCT outcomes, although validation and functional studies are needed. If confirmed, it may be feasible to select donors based on mthap to increase positive or decrease negative outcomes.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 10/2014; · 3.15 Impact Factor
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    ABSTRACT: Corticosteroids are the accepted primary therapy for acute graft-versus-host disease (GvHD), but durable responses are seen in only about half the patients. BMT-CTN 0802, a phase III multi-center randomized double blinded trial, was designed to test whether mycophenolate mofetil (MMF) plus corticosteroids was superior to corticosteroids alone as initial therapy for acute GvHD. Patients with newly diagnosed acute GvHD were eligible if required systemic therapy. Patients were randomized to receive prednisone with either MMF or placebo. The primary endpoint was acute or chronic GvHD-free survival at day 56 after initiation of therapy. A futility rule for GvHD free survival at day 56 was met at a planned interim analysis after 235 eligible patients (out of 372) were enrolled: 116 to MMF, 119 to placebo. Baseline characteristics were well balanced between treatment groups including grade and organ distribution of GvHD. GvHD free survival at day 56, cumulative incidence of chronic GvHD at 12 months, overall survival, EBV reactivation, cumulative incidence of severe, life threatening infections, cumulative incidence of relapse at 12 months, quality of severe infections were similar. The addition of MMF to corticosteroids as initial therapy of acute GvHD does not improve GvHD-free survival compared with treatment with corticosteroids alone. The study was registered at www.clinicaltrials.gov NCT01002742.
    Blood 08/2014; · 9.78 Impact Factor
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    ABSTRACT: Advanced systemic mastocytosis (SM), a fatal hematopoietic malignancy characterized by drug resistance, has no standard therapy. The effectiveness of allogeneic hematopoietic stem-cell transplantation (alloHCT) in SM remains unknown.
    Journal of Clinical Oncology 08/2014; · 18.04 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 08/2014; · 4.00 Impact Factor
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    ABSTRACT: The National Institutes of Health global score for chronic graft-versus-host disease was devised by experts but was not based on empirical data. We hypothesized that analysis of prospectively collected data would allow derivation of a more accurate model for estimating mortality risk. We analyzed 574 adult patients with chronic graft-versus-host disease enrolled in a multicenter, observational study, using multivariate time-varying analysis accounting for serial changes in severity of eight individual organ sites over time. In the training set, severity of skin, mouth, gastrointestinal tract, liver and lung involvement were independently associated with the risk of nonrelapse mortality. Weighted mortality points were assigned to individual organs based on the hazard ratios and were summed. The population was divided into three risk groups based on the total mortality points. The three new risk groups were validated in an independent validation set, but did not show better discriminative performance than the National Institutes of Health global score. As compared to moderate or mild global score, severe global score was associated with increased risks of nonrelapse and overall mortality across time but not with a decreased risk of recurrent malignancy. The National Institutes of Health global score predicts mortality risk throughout the course of patients with chronic graft-versus-host disease. Further research is required in order to improve outcomes in patients with severe chronic graft-versus-host disease, since their risk of mortality remains elevated.
    Haematologica 07/2014; · 5.94 Impact Factor
  • Shernan G Holtan, Marcelo Pasquini, Daniel J Weisdorf
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    ABSTRACT: Over the past five years, many novel approaches to early diagnosis, prevention, and treatment of acute graft-versus-host disease (aGVHD) have been translated from the bench to the bedside. In this review, we highlight recent discoveries in the context of current aGVHD care. The most significant innovations that have already reached the clinic are prophylaxis strategies based upon a refinement of our understanding of key sensors, effectors, suppressors of the immune alloreactive response and the resultant tissue damage from the aGVHD inflammatory cascade. In the near future, aGVHD prevention and treatment will likely involve multiple modalities, including small molecules regulating immunologic checkpoints, enhancement of suppressor cytokines and cellular subsets, modulation of the microbiota, graft manipulation, and other donor-based prophylaxis strategies. Despite long-term efforts, major challenges in treatment of established aGVHD still remain. Resolution of inflammation and facilitation of rapid immune reconstitution in those with only a limited response to corticosteroids is a research arena that remains rife with opportunity and urgent clinical need.
    Blood 06/2014; · 9.78 Impact Factor
  • Shernan G Holtan, Daniel J Weisdorf
    Blood 06/2014; 123(23):3538-9. · 9.78 Impact Factor
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    ABSTRACT: Although older patients undergoing allogeneic hematopoietic stem cell transplantation (HCT) may experience higher morbidity, the impact of chronic graft-versus-host disease (GVHD) on quality of life (QOL) or survival outcomes for older compared to younger patients is currently unknown. We utilized data of patients with moderate or severe chronic GVHD (N=522, 1661 follow-up visits, a total of 2,183 visits) from the Chronic GVHD Consortium, a prospective observational multicenter cohort. We examined the relationship between age group (adolescent and young adult "AYA" 18-40, "middle-aged" 41-59, and "older" ≥ 60 years) and QOL (FACT-BMT), physical functioning (Human Activity Profile (HAP)), functional status (2-minute walk test (2MWT)), non-relapse mortality and overall survival. Because of multiple testing, p-values <0.01 were considered significant. This study included 115 (22%) AYA, 279 (53%) middle-aged, and 128 (25%) older patients with moderate (58%) or severe (42%) chronic GVHD. Despite more physical limitations in older patients as measured by worse functional status [shorter 2MWT (p<0.001) and lower HAP scores (p<0.001)] relative to AYA and middle-aged patients, older patients reported better QOL [FACT-BMT, p=0.004)] compared to middle-aged patients and similar to AYA patients (p=0.99). Non-relapse mortality and overall survival were similar between the age groups. Therefore, despite higher physical and functional limitations, older patients who are selected to undergo HSCT and survive long enough to develop moderate or severe chronic GVHD have preserved QOL and similar overall survival and non-relapse mortality when compared to younger patients. Therefore, we did not find evidence that older age is associated with worse outcomes in patients with moderate or severe chronic GVHD.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 05/2014; · 3.15 Impact Factor
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    ABSTRACT: Allogeneic hematopoietic cell transplantation (alloHCT) with reduced intensity conditioning is an appealing option for patients with high risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1-21 of 28 days cycles, with intra-patient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age 54 years) with high risk MM were enrolled at 8 centers between 2009 -2012. The median time from alloHCT to LEN initiation was 96 days (66-171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%).Most common reasons for discontinuation were aGVHD (37%) and disease progression (37%). Cumulative incidence of grades III-IV acute GVHD from time of initiation of Len was 17%. . Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplant related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN post alloHCT is feasible at lower doses, although associated with a 38% incidence of aGVHD. Survival outcomes observed in this high risk MM population warrant further study of this approach.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 04/2014; · 3.15 Impact Factor
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    ABSTRACT: Killer cell Ig-like receptors (KIRs) interact with HLA class I ligands to regulate NK cell development and function. These interactions affect the outcome of unrelated donor hematopoietic cell transplantation (HCT). We have shown previously that donors with KIR B versus KIR A haplotypes improve the clinical outcome for patients with acute myelogenous leukemia by reducing the incidence of leukemic relapse and improving leukemia-free survival (LFS). Both centromeric and telomeric KIR B genes contribute to the effect, but the centromeric genes are dominant. They include the genes encoding inhibitory KIRs that are specific for the C1 and C2 epitopes of HLA-C. We used an expanded cohort of 1532 T cell-replete transplants to examine the interaction between donor KIR B genes and recipient class I HLA KIR ligands. The relapse protection associated with donor KIR B is enhanced in recipients who have one or two C1-bearing HLA-C allotypes, compared with C2 homozygous recipients, with no effect due to donor HLA. The protective interaction between donors with two or more, versus none or one, KIR B motifs and recipient C1 was specific to transplants with class I mismatch at HLA-C (RR of leukemia-free survival, 0.57 [0.40-0.79]; p = 0.001) irrespective of the KIR ligand mismatch status of the transplant. The survival advantage and relapse protection in C1/x recipients compared with C2/C2 recipients was similar irrespective of the particular donor KIR B genes. Understanding the interactions between donor KIR and recipient HLA class I can be used to inform donor selection to improve outcome of unrelated donor hematopoietic cell transplantation for acute myelogenous leukemia.
    The Journal of Immunology 04/2014; · 5.52 Impact Factor
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    ABSTRACT: Because the outcome of allogeneic hematopoietic cell transplantation (HCT) is predominantly influenced by disease type and status, it is essential to be able to stratify patients undergoing HCT by disease risk. The Disease Risk Index (DRI) was developed for this purpose. In the present study, we analyzed 13,131 patients reported to the CIBMTR who underwent HCT between 2008 and 2010. The original DRI stratified patients into 4 groups with 2-year OS ranging from 64% to 24% (p<0.0001 for all pair-wise comparisons between groups), and was the strongest prognostic factor regardless of age, conditioning intensity, graft source, or donor type. A randomly selected training subgroup of 9,849 patients (3/4 of the cohort) was used to refine the DRI, using a multivariable regression model for OS. This refined DRI had improved prediction ability for the remaining 3,282 patients, compared with the original DRI or other existing schemes. This validated and refined DRI can be used as a 4- or 3-group index, depending on the size of the cohort under study, for prognostication, to facilitate the interpretation of single-, multi-center or registry studies, to adjust center outcome data, and to stratify patients entering clinical trials that enroll patients across disease categories.
    Blood 04/2014; · 9.78 Impact Factor
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    ABSTRACT: Haploidentical natural killer (NK) cell infusions can induce remissions in some patients with AML but regulatory T-cell (Treg) suppression may reduce efficacy. We treated 57 refractory AML patients with lymphodepleting cyclophosphamide and fludarabine followed by NK cell infusion and interleukin (IL)-2 administration. In 42 patients, donor NK cell expansion was detected in 10%, whereas in 15 patients receiving host Treg depletion with the IL-2-diphtheria fusion protein (IL2DT) the rate was 27%, with a median absolute count of 1000 NK cells/µL blood. IL2DT was associated with improved complete remission rates at day 28 (53% versus 21%; P=0.02) and disease-free survival at 6 months (33% versus 5%; P<0.01). In the IL2DT cohort, NK cell expansion correlated with higher post-chemotherapy serum IL-15 levels (P=0.002), effective peripheral blood Treg depletion (< 5%) at day 7 (P<0.01) and decreased IL-35 levels at day 14 (P=0.02). In vitro assays demonstrated that Tregs co-cultured with NK cells inhibit their proliferation by competition for IL-2, but not for IL-15. Together with our clinical observations this supports the need to optimize the in vivo cytokine milieu where adoptively transferred NK cells compete with other lymphocytes to improve clinical efficacy in patients with refractory AML. This study is registered at clinicaltrials.gov, identifiers: NCT00274846 and NCT01106950.
    Blood 04/2014; · 9.78 Impact Factor
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    ABSTRACT: To investigate the usefulness of various scales for evaluating joint and fascia manifestations in patients with chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation, and to compare the scales in terms of simplicity of use and ability to yield reliable and clinically meaningful results. In a prospective, multicenter, longitudinal, observational cohort of patients with chronic GVHD (n = 567), we evaluated 3 scales proposed for assessing joint status: the National Institutes of Health (NIH) joint/fascia scale, the Hopkins fascia scale, and the Photographic Range of Motion (P-ROM) scale. Ten other scales were also tested for assessment of symptoms, quality of life, and physical functions. Joint and fascia manifestations were present at study enrollment in 164 (29%) of the patients. Limited range of motion was most frequent at the wrists or fingers. Among the 3 joint assessment scales, changes in the NIH scale correlated with both clinician- and patient-perceived improvement of joint and fascia manifestations, with higher sensitivity than the Hopkins fascia scale. Changes in all 3 scales correlated with clinician- and patient-perceived worsening, but the P-ROM scale was the most sensitive in this regard. Onset of joint and fascia manifestations was not associated with subsequent mortality. Joint and fascia manifestations are common in patients with chronic GVHD and should be assessed carefully in these patients. Our results support the use of the NIH joint/fascia scale and P-ROM scale to assess joint and fascia manifestations. The NIH scale better captures improvement, while the P-ROM scale better captures worsening. The utility of these scales could also be tested in the rheumatic diseases.
    Arthritis & rheumatology (Hoboken, N.J.). 04/2014; 66(4):1044-52.
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    ABSTRACT: To identify favored choice of transplantation in patients with acute promyelocytic leukemia in second complete remission. We studied 294 acute promyelocytic leukemia (APL) patients receiving allogeneic (n=232) or autologous (62) hematopoietic cell transplantation (HCT) in second complete remission (CR2) reported to the Center for International Blood and Marrow Transplantation Research (CIBMTR) from 1995 to 2006 including pre-HCT PML/RAR∝ status in 155 (49% of allogeneic and 66% of autologous). Patient characteristics and transplant characteristics including treatment related mortality, overall survival, and disease free survival were collected and analyzed for both univariate and multivariate outcomes. With median follow-up of 115 (allogeneic) and 72 months (autologous), 5-year disease-free survival (DFS) favored autologous 63% (49-75%) compared to allogeneic 50% (44-57%) (p=0.10) and overall survival (OS) 75% (63-85%) vs. 54% (48-61%) (p=.002) Multivariate analysis showed significantly worse DFS after allogeneic HCT (HR=1.88, 95% CI=1.16-3.06, p=0.011) and age >40 years (HR=2.30, 95% CI 1.44-3.67, p=0.0005). OS was significantly worse after allogeneic HCT (HR=2.66, 95%CI 1.52-4.65, p=0.0006; age >40 (HR=3.29, 95% CI 1.95-5.54, p<0.001) and CR1<12 months (HR=1.56 95% CI 1.07-2.26, p=0.021). Positive pre-HCT PML-RAR∝ status in 17/114 allogeneic and 6/41 autologous transplants did not influence relapse, treatment failure or survival in either group. The survival advantage for autografting was attributable to increased 3 years TRM: allogeneic 30%; autologous 2%, and GVHD. We conclude that autologous HCT yields superior overall survival for APL in CR2. Long term DFS in autologous recipients, even with MRD+ grafts remains an important subject for further study.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 03/2014; · 3.15 Impact Factor
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    ABSTRACT: Myelodysplastic syndromes (MDS) are stem cell disorders that can progress to acute myeloid leukemia (AML). While hematopoietic cell transplantation (HCT) can be curative, additional therapies are needed for a disease that disproportionally afflicts the elderly. We tested the ability of a CD16xCD33 BiKE to induce natural killer (NK) cell function from 67 MDS patients. Compared to age-matched normal controls, CD7(+) lymphocytes, NK cells, and CD16 expression were markedly decreased in MDS patients. Despite this, reverse-antibody dependent cell-mediated cytotoxicity (R-ADCC) assays showed potent degranulation and cytokine production when resting MDS-NK cells were triggered with an agonistic CD16 mAb. Blood and marrow MDS-NK cells treated with BiKE significantly enhanced degranulation, TNF-α and IFN-γ production against HL-60 and endogenous CD33(+) MDS targets. MDS patients had a significantly increased proportion of immunosuppressive CD33(+) myeloid derived suppressor cells (MDSC) that negatively correlated with MDS lymphocyte populations and CD16 loss on NK cells. Treatment with the CD16xCD33 BiKE successfully reversed MDSC immunosuppression of NK cells and induced MDSC target cell lysis. Lastly, the BiKE induced optimal MDS-NK cell function irrespective of disease stage. Our data suggest that the CD16xCD33 BiKE functions against both CD33(+) MDS and MDSC targets and may be therapeutically beneficial for MDS patients.
    Blood 03/2014; · 9.78 Impact Factor

Publication Stats

16k Citations
2,544.88 Total Impact Points

Institutions

  • 2004–2014
    • Indiana Blood and Marrow Transplantation
      Indianapolis, Indiana, United States
    • Thomas Jefferson University
      Philadelphia, Pennsylvania, United States
  • 1991–2014
    • University of Minnesota Medical Center, Fairview
      Minneapolis, Minnesota, United States
  • 1982–2014
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States
    • University of Connecticut
      • Department of Nutritional Sciences
      Storrs, CT, 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
    • Michiana Hematology Oncology
      Indiana, Pennsylvania, United States
    • Children's Hospitals and Clinics of Minnesota
      Minneapolis, Minnesota, 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
    • CHU Sainte-Justine
      Montréal, Quebec, Canada
  • 2007–2013
    • City of Hope National Medical Center
      • Department of Population Sciences
      Duarte, CA, United States
    • Cincinnati Children's Hospital Medical Center
      Cincinnati, Ohio, United States
    • Northwestern University
      Evanston, Illinois, 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
    • Emory University
      Atlanta, Georgia, United States
    • Roswell Park Cancer Institute
      Buffalo, New York, 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
  • 2010–2012
    • University of Toronto
      Toronto, Ontario, Canada
  • 2008–2012
    • University of Michigan
      • Comprehensive Cancer Center
      Ann Arbor, MI, United States
    • British Society of Blood and Marrow Transplantation
      Bristol, England, United Kingdom
  • 2008–2011
    • National Institutes of Health
      • Branch of Experimental Transplantation and Immunology
      Bethesda, MD, United States
  • 2002–2011
    • Dana-Farber Cancer Institute
      • Department of Medical Oncology
      Boston, MA, United States
  • 2003–2010
    • National Cancer Institute (USA)
      • Division of Cancer Epidemiology and Genetics
      Maryland, United States
    • Mayo Clinic - Rochester
      • Department of Hematology
      Rochester, Minnesota, United States
    • Georgetown University
      • Department of Oncology
      Washington, D. C., DC, United States
  • 2009
    • Memorial Sloan-Kettering Cancer Center
      New York City, New York, United States
  • 2003–2009
    • National Marrow Donor Program
      Minneapolis, Minnesota, United States
  • 2006–2007
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
    • The Ohio State University
      Columbus, Ohio, United States
    • Cleveland State University
      Cleveland, Ohio, United States
    • University of Cincinnati
      Cincinnati, Ohio, United States
    • University of Illinois at Chicago
      Chicago, Illinois, United States
    • University of British Columbia - Vancouver
      Vancouver, British Columbia, Canada
  • 1995–2007
    • Medical College of Wisconsin
      • Center for International Blood & Marrow Transplant Research
      Milwaukee, WI, United States
  • 2005
    • University of Nebraska Medical Center
      Omaha, Nebraska, United States
    • National Cancer Institute
      Μπογκοτά, Bogota D.C., Colombia
  • 1988–1994
    • Minnesota Department of Health
      Saint Paul, Minnesota, United States
  • 1981
    • Minneapolis Veterans Affairs Hospital
      Minneapolis, Minnesota, United States