Navneet S Majhail

National Marrow Donor Program, Minneapolis, Minnesota, United States

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Publications (137)459.21 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Vancomycin-resistant enterococcus (VRE) is a well-known infectious complication among immunocompromised patients. We performed a retrospective analysis to identify risk factors for the development of VRE bacteremia (VRE-B) within 15 months after allogeneic hematopoietic cell transplantation (alloHCT) and to determine its prognostic importance for other post-transplant outcomes. Eight hundred consecutive adult patients who underwent alloHCT for hematologic diseases from 1997 to 2011 were included. Seventy-six (10%) developed VRE-B at a median of 46 days post transplant. Year of transplant, higher HCT comorbidity score, a diagnosis of ALL, unrelated donor and umbilical cord blood donor were all significant risk factors on multivariable analysis for the development of VRE-B. Sixty-seven (88%) died within a median of 1.1 months after VRE-B, but only four (6%) of these deaths were attributable to VRE. VRE-B was significantly associated with worse OS (hazard ratio 4.28, 95% confidence interval 3.23-5.66, P<0.001) in multivariable analysis. We conclude that the incidence of VRE-B after alloHCT has increased over time and is highly associated with mortality, although not usually attributable to VRE infection. Rather than being the cause, this may be a marker for a complicated post-transplant course. Strategies to further enhance immune reconstitution post transplant and strict adherence to infection prevention measures are warranted.Bone Marrow Transplantation advance online publication, 11 August 2014; doi:10.1038/bmt.2014.150.
    Bone marrow transplantation. 08/2014;
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    ABSTRACT: We examined risk of second solid cancers after allogeneic hematopoietic cell transplantation (AHCT) using reduced intensity/non-myeloablative conditioning (RIC/NMC). RIC/NMC recipients with leukemia/myelodysplastic syndrome (MDS) (n=2833) and lymphoma (n=1436) between 1995-2006 were included. In addition, RIC/NMC recipients 40-60 years of age (n=2138) were compared with patients of the same age receiving myeloablative conditioning (MAC, n=6428). The cumulative incidence of solid cancers was 3.35% at 10-years. There was no increase in overall cancer risk compared to the general population (standardized incidence ratio [SIR] 0.99, P=1.00 for leukemia/MDS and 0.92, P=0.75 for lymphoma). However, risks were significantly increased in leukemia/MDS patients for cancers of lip (SIR 14.28), tonsil (SIR 8.66), oropharynx (SIR 46.70), bone (SIR 23.53), soft tissue (SIR 12.92), and vulva (SIR 18.55) and skin melanoma (SIR 3.04). Lymphoma patients had significantly higher risks of oropharyngeal cancer (SIR 67.35) and skin melanoma (SIR 3.52). Among RIC/NMC recipients, age >50 years was the only independent risk factor for solid cancers (hazard ratio [HR] 3.02, P<0.001). Among patients age 40-60 years, when adjusted for other factors, there was no difference in cancer risks between RIC/NMC and MAC in leukemia/MDS patients (HR 0.98, P=0.905). In lymphoma patients, risks were lower after RIC/NMC (HR 0.51, P=0.047). In conclusion, the overall risks of second solid cancers in RIC/NMC recipients are similar to the general population, although there is an increased risk of cancer at some sites. Studies with longer follow-up are needed to realize the complete risks of solid cancers after RIC/NMC AHCT.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2014; · 3.15 Impact Factor
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    ABSTRACT: Studies show that engaging patients in exercise and/or stress management techniques during hematopoietic cell transplantation (HCT) improves quality of life. The Blood and Marrow Transplant Clinical Trials Network tested the efficacy of training patients to engage in self-directed exercise and stress management during their HCTs. The study randomized 711 patients at 21 centers to receive one of four training interventions before HCT: a self-directed exercise program, a self-administered stress management program, both or neither. Participants completed self-reported assessments at enrollment and up to 180 days after transplant. Randomization was stratified by center and transplant type. There were no differences in the primary endpoints of the physical (PCS) and mental (MCS) component scales of the SF36 at day 100 among the groups based on an intention-to-treat analysis. There were no differences observed in overall survival, hospital days through day 100 post-HCT, or in other patient-reported outcomes, including treatment-related distress, sleep quality, pain, and nausea. Patient randomized to training in stress management reported more use of those techniques; patients randomized to training in exercise did not report more physical activity. Although other studies have reported efficacy of more intensive interventions, brief training in an easy-to-disseminate format for either self-directed exercise or stress management was not effective in our trial.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 06/2014; · 3.15 Impact Factor
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    ABSTRACT: Peripheral blood progenitor cell mobilization practices vary significantly among institutions. Effective mobilization regimens include growth factor alone, chemotherapy and growth factor combined, and more recently incorporation of plerixafor with either approach. Many institutions have developed algorithms to improve stem cell mobilization success rates and cost effectiveness. However, an optimal stem cell mobilization regimen has not been defined. Practical guidelines are needed to address important clinical questions including which growth factor is optimal, what chemotherapy and dose is most effective, and when to initiate leukapheresis. We present recommendations, based on a comprehensive review of the literature, from the American Society of Blood and Marrow Transplantation.
    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: An elevated ferritin before allogeneic hematopoietic cell transplantation (HCT) is an adverse prognostic factor for overall survival (OS) and non-relapse mortality (NRM). Because ferritin is an imperfect surrogate of iron stores, the prognostic role of iron overload remains unclear. We conducted a patient-level meta-analysis of 4 studies that used magnetic resonance imaging to estimate pre-HCT liver iron content (LIC). An elevated LIC was not associated with a significant increase in mortality: the hazard ratio (HR) for mortality associated with LIC>7 mg/gdw (primary endpoint) was 1.4 (p=0.18). In contrast, ferritin >1000 ng/ml was a significant prognostic factor (HR for mortality 1.7, p=0.036). There was, however, no significant association between ferritin>2500 and mortality. This meta-analysis suggests that iron overload, as assessed by LIC, is not a strong prognostic factor for OS in a general adult HCT population. Our data also suggest that ferritin is an inadequate surrogate for iron overload in HCT.
    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: We compared serious early and late events experienced by 2726 BM and 6768 PBSC donors who underwent collection of peripheral blood stem cells (PBSC) or bone marrow (BM) between 2004 and 2009 as part of a prospective study through the National Marrow Donor Program. Standardized FDA definitions for serious adverse events (SAEs) were used and all events were reviewed by an independent physician panel. BM donors had an increased risk of SAEs (2.38% BM vs. 0.56% PBSC; OR 4.13, p < 0.001), and women were twice as likely to experience an SAE (OR for men 0.50, p=0.005). Restricting the analysis to life-threatening, unexpected, or chronic/disabling events, BM donors maintained an increased risk for SAEs (0.99% BM vs. 0.31% PBSC; OR 3.20, p < 0.001). Notably, the incidence of cancer, autoimmune illness, and thrombosis after donation was similar in BM versus PBSC donors. In addition, cancer incidence in PBSC donors was less than that reported in the general population (SEER database). In conclusion, SAEs after donation are rare, but more often occurred in BM donors and women. In addition, there was no evidence of increased risk of cancer, autoimmune illness, and stroke in donors receiving G-CSF during this period of observation.
    Blood 04/2014; · 9.78 Impact Factor
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    ABSTRACT: Variation in Medicaid policies among states may lead to differences in coverage for complex treatments. This article uses hematopoietic cell transplantation (HCT), an established treatment for patients with hematologic cancers, as a case study to highlight state variation in Medicaid coverage of complex oncology treatments. Information on HCT coverage benefits for 2012 was collected from state Medicaid Web sites and was compared with recommended HCT benefits developed by multiple stakeholders. Coverage was reviewed for five categories: one, transplantation procedure; two, donor search; three, prescriptions; four, clinical trials; and five, patient food, lodging, and transportation. Coverage was coded on a three-point scale for each category for each state. States were ranked by the number of variables for which they met recommended benefits criteria (maximum rank score, 5). Detailed information on Medicaid coverage was available for 47 states. No state provided the recommended coverage benefits in all five categories. Prescription coverage most often met the recommended criteria, whereas only a small number of states provided clinical trial coverage for HCT. There was substantial variation in Medicaid coverage for HCT by state. Findings highlight substantial variation in Medicaid coverage for HCT by state, which may increase disparities in access for already medically underserved populations.
    Journal of Oncology Practice 04/2014;
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    ABSTRACT: Adolescents and young adults (AYAs, ages 15-40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival following myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (N=981), AYAs (N=1218) and older adults (N=469) who were transplanted over three time periods: 1990-1995, 1996-2001 and 2002-2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time forolder adults. Survival improvements were primarily related to lower rates of early treatment related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15-25 at 46 pediatric or 49 adult centers werealso analyzed to describe differences by center type. In this subgroup, there were differences in transplant practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.
    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: Hematopoietic cell transplantation (HCT) remains the only known curative therapy for many patients with hematologic, metabolic and immunologic disorders. Furthermore, the use of HCT has increased with the emergence of HCT as a viable therapeutic option for older patients, those with significant co-morbidities, and, with the demonstrated clinical effectiveness of alternative allogeneic donor sources, for those patients without a suitable sibling donor. The National Marrow Donor Program® (NMDP) estimates that by 2020 it will facilitate 10,000 transplants per year, double the number in 2010. To understand the HCT infrastructure needs to facilitate this number of transplants, the NMDP organized the System Capacity Initiative 2020, centered on 6 working groups representing a diverse group of stakeholders. The Physician Workforce Group was tasked with addressing issues relating to recruitment and retention of transplant physicians. We report here the results of our efforts and future initiatives.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 02/2014; · 3.15 Impact Factor
  • ASBMT; 02/2014
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    ABSTRACT: Hematopoietic stem cell transplantation (HCT) is a potentially life-saving therapy for patients with malignant and non-malignant disease states. This article reviews the current published literature on the dosing of pharmacologic agents used for HCT-preparative regimens with specific focus on the obese patient population. The review found that dose adjustments for obesity have, to date, been based empirically or extrapolated from published data in the non-transplant patient population. As a result, the Committee determined that clear standards or dosing guidelines are unable to be made for the obese population because Level I and II evidence is unavailable at this time. Instead, the Committee provides a current published literature review to serve as a platform for conditioning agent dose selection in the setting of obesity. A necessary goal should be to encourage future prospective trials in this patient population because further information is needed to enhance our knowledge of the pharmacokinetics and pharmacodynamics of conditioning agents in the setting of obesity.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2014; · 3.15 Impact Factor
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    ABSTRACT: With broadening indications, more options for hematopoietic cell transplantation (HCT) and improvement in survival, the number of long-term HCT survivors is expected to increase steadily. Infertility is a frequent problem that long-term HCT survivors and their partners face and it can negatively impact on the quality of life. The most optimal time to address fertility issues is before the onset of therapy for the underlying disease; however, fertility preservation should also be addressed before HCT in all children and patients of reproductive age, with referral to a reproductive specialist for patients interested in fertility preservation. In vitro fertilization (IVF) and embryo cryopreservation, oocyte cryopreservation and ovarian tissue banking are acceptable methods for fertility preservation in adult women/pubertal females. Sperm banking is the preferred method for adult men/pubertal males. Frequent barriers to fertility preservation in HCT recipients may include the perception of lack of time to preserve fertility given an urgency to move ahead with transplant, lack of patient-physician discussion because of several factors (for example, time constraints, lack of knowledge), inadequate access to reproductive specialists, and costs and lack of insurance coverage for fertility preservation. There is a need to raise awareness in the medical community about fertility preservation in HCT recipients.Bone Marrow Transplantation advance online publication, 13 January 2014; doi:10.1038/bmt.2013.211.
    Bone marrow transplantation 01/2014; · 3.00 Impact Factor
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    ABSTRACT: Peripheral blood stem cell (PBSC) products have traditionally been transported from the collection center to a transplant center using validated volunteer courier-based procedures. Evolving airline service strategies and security policies have complicated this model of product transport. This study was designed to evaluate the feasibility of transporting PBSC products using commercial overnight shipping services, while maintaining product quality, compared to courier-transported products. Five PBSC products were collected from healthy volunteer donors and divided to evaluate product quality when transported either by volunteer courier or by commercial overnight shipping service. Products were evaluated on the day of collection and at 24, 48, and 72 hours postcollection for total nucleated cell (TNC) count, cell viability, progenitor cell numbers, and progenitor cell lineage growth potential (colony-forming units [CFUs]) to assess product composition and quality associated with each cohort. No delivery delays were encountered and all products were received intact. Measurements of product composition and quality demonstrated no differences in TNC count (p = 0.893), cell viability (p = 0.409), CD34+ progenitor cell content (p = 0.509), or CFU-granulocyte-macrophage growth potential (p = 0.827). We found no difference in product viability, progenitor cell content, or product potency in PBSC products transported either by volunteer courier or by commercial overnight shipping.
    Transfusion 01/2014; · 3.53 Impact Factor
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    ABSTRACT: We conducted a nested case-control study within a cohort of 6,244 patients to assess risk factors for avascular necrosis (AVN) of bone in children and adolescents following allogeneic transplantation. Eligible patients were ≤21 years of age, received their first allogeneic transplant between 1990 and 2008 in the United States and had survived ≥ 6 months from transplantation. Overall, 160 cases with AVN and 478 controls matched by year of transplant, length of followup and transplant center were identified. Cases and controls were confirmed via central review of radiology, pathology and/or surgical procedure reports. Median time from transplant to diagnosis of AVN was 14 months. On conditional logistic regression, increasing age at transplant (≥5 years), female gender and chronic graft-versus-host disease (GVHD) were significantly associated with increased risks of AVN. Compared to patients receiving myeloablative regimens for malignant diseases, lower risks of AVN were seen in patients with non-malignant diseases and those who had received reduced intensity conditioning regimens for malignant diseases. Children at high risk for AVN include those within the age group where rapid bone growth occurs as well as those who experience exposure to myeloablative conditioning regimens and immunosuppression post-HCT for the treatment of GVHD. More research is needed to determine whether screening strategies specifically for patients at high risk for developing AVN with early interventions may mitigate the morbidity associated with this complication.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 01/2014; · 3.15 Impact Factor
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    ABSTRACT: The clinical relevance of mismatches at the major histocompatibility complex class I-related chain A (MICA) in hematopoietic stem cell transplantation (HSCT) remains unclear. We investigated the association of MICA donor/recipient mismatch and whether there is an interaction between these and HLA-DPB1 mismatch on clinical outcomes following unrelated donor HSCT. Our study included 227 patients who underwent unrelated donor allogeneic HSCT at our institution between 2000 and 2010. Among these, 177 (78%) received HSCT from a 10/10 HLA-matched donor. MICA genotyping was performed using commercially available kits. In univariable analysis, the risk of grade II-IV acute GvHD was greater for patients with MICA mismatch (hazard ratio (HR) 1.73, p=0.02) than for HLA-DPB1 mismatch (HR 1.62, p=0.07). When MICA and HLA-DPB1 were assessed simultaneously, patients mismatched at both loci had the greatest risk (HR 2.51, p<0.01) and those mismatched at only one locus had somewhat greater risk (HR 1.53, p=0.12) than patients matched at both loci; this remained significant in multivariable analysis. 100-day incidence was 66%, 45%, and 31% (p=0.03). Results were similar for grade III-IV acute GvHD, with 100-day incidence 34%, 16%, and 8% (p=0.01). These results are clinically pertinent to donor selection strategies and indicate that patients with mismatch at both MICA and HLA-DPB1 are at increased risk for acute GvHD.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 01/2014;
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    ABSTRACT: Several studies have shown comparable survival outcomes among different graft sources, but the relative resource needs of hematopoietic cell transplantation (HCT) by graft source have not been well studied. We compared total hospital length of stay in the first 100 days after HCT in 1577 patients with acute leukemia in remission receiving umbilical cord blood (UCB), matched unrelated donor (MUD) or mismatched unrelated donors (MMUD) HCT from 2008-2011. To ensure a relatively homogenous study population, the analysis was limited to patients with acute myeloid leukemia and acute lymphoblastic leukemia in first or second complete remission who received HCT in the United States. To account for early deaths, we compared the number of days alive and out of hospital in the first 100 days. For children receiving myeloablative conditioning, median days alive and out of hospital in the first 100 days were 50, 54 and 60 days for single UCB, double UCB and MUD bone marrow (BM) recipients, respectively. In multivariate analysis, use of UCB was significantly associated with fewer days alive and out of the hospital compared to MUD BM. For adults receiving HCT using myeloablative conditioning, median days alive and out of hospital in first 100 days were 52 for single UCB, 55 for double UCB, 69 for MUD BM, 75 for MUD peripheral blood stem cells (PBSC), 63 for MMUD BM and 67 days MMUD PBSC recipients. In multivariate analysis, UCB and MMUD BM recipients had fewer days alive and out of the hospital compared to other graft sources. For adults receiving a reduced intensity preparative regimen, median days alive and out of hospital during the first 100 days for single UCB, double UCB, MUD PBSC and MMUD PBSC were 65, 63, 79, and 79, respectively. Similar to the other two groups, use of UCB was associated with a fewer days alive and out of the hospital. In conclusion, length of stay in the first 100 days varies by graft source and is greater for UCB HCT recipients. These data provide insight into the resource needs of transplant patients receiving these graft sources.
    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 01/2014;
  • Brian L McClune, Navneet S Majhail
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    ABSTRACT: With long-term survival for recipients of autologous and allogeneic hematopoietic cell transplantation (HCT) increasing, the recognition of late complications such as decreased bone mineral density leading to osteoporosis (OP) has also increased. With an incidence that is reported to affect as many 50 % of allo HCT recipients, studies continue to mount supporting the need and success in treatment of this HCT complication. In this review, we highlight the major pathological mechanisms behind the development of OP, its diagnosis, and the literature supporting consensus treatment recommendations while noting areas of uncertainty that need further research.
    Current Osteoporosis Reports 11/2013;
  • Navneet S Majhail, Hillard M Lazarus
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 08/2013; · 3.15 Impact Factor
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    ABSTRACT: Advances in hematopoietic cell transplantation (HCT) have led to an increasing number of transplant survivors. In order to adequately support their healthcare needs, there is a need to know the prevalence of HCT survivors. We used data on 170,628 recipients of autologous and allogeneic HCT reported to the Center for International Blood and Marrow Transplant Research from 1968 to 2009 to estimate the current and future number of HCT survivors in the United States. Stacked cohort simulation models were used to estimate the number of HCT survivors in the US in 2009 and make projections for HCT survivors by the year 2030. There were 108,900 (range, 100,500-115,200) HCT survivors in the United States in 2009. This included 67,000 autologous HCT and 41,900 allogeneic HCT survivors. The number of HCT survivors is estimated to increase by 2.5 times by the year 2020 (242,000 survivors) and 5 times by the year 2030 (502,000 survivors). By 2030, the age at transplant will be <18 years for 14% of all survivors (N=64,000), 18-59 years for 61% survivors (N=276,000) and 60 years and older for 25% of survivors (N=113,000). In coming decades, a large number of individuals will be HCT survivors. Transplant center providers, hematologists, oncologists, primary care physicians and other specialty providers will need to be familiar with the unique and complex health issues faced by this population.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2013; · 3.15 Impact Factor
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    ABSTRACT: Autologous hematopoietic cell transplantation (auto-HCT) is performed to treat relapsed and recurrent malignant disorders and as part of initial therapy for selected malignancies. This study evaluated changes in use, techniques, and survival in a population-based cohort of 68,404 patients who underwent first auto-HCT in a US or Canadian center between 1994 and 2005 and were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). The mean annual number of auto-HCTs performed was highest during 1996-1999 (6948), and decreased subsequently 2000-2003 (4783), owing mainly to fewer auto-HCTs done to treat breast cancer. However, the mean annual number of auto-HCTs increased from 5278 annually in 1994-1995 to 5459 annually in 2004-2005, reflecting increased use for multiple myeloma, non-Hodgkin lymphoma, and Hodgkin lymphoma. Despite an increase in the median recipient age from 44 to 53 years, there has been a significant improvement in overall survival (OS) from 1994 to 2005 in patients with chemotherapy-sensitive relapsed non-Hodgkin lymphoma (day +100 OS, from 85% to 96%; 1-year OS, from 68% to 80%; P < .001) and chemotherapy-sensitive multiple myeloma (day +100 OS, from 96% to 98%; 1-year OS, from 83% to 92%; P < .001). This improvement in OS was most pronounced in middle-aged (>40 years) and older (>60 years) individuals.
    Biology of blood and marrow transplantation: journal of the American Society for Blood and Marrow Transplantation 07/2013; 19(7):1116–1123. · 3.15 Impact Factor

Publication Stats

1k Citations
459.21 Total Impact Points

Institutions

  • 2009–2014
    • National Marrow Donor Program
      Minneapolis, Minnesota, United States
    • Fred Hutchinson Cancer Research Center
      • Division of Clinical Research
      Seattle, Washington, United States
    • University of Nebraska at Omaha
      • Department of Internal Medicine
      Omaha, NE, United States
  • 2002–2014
    • Cleveland Clinic
      • Department of Solid Tumor Oncology
      Cleveland, Ohio, United States
  • 2013
    • Roswell Park Cancer Institute
      • Department of Medicine
      Buffalo, New York, United States
  • 2012
    • Children's Hospital of Orange County
      Orange, California, United States
  • 2006–2012
    • University of Minnesota Duluth
      • Medical School
      Duluth, Minnesota, United States
    • Minnesota Oncology
      Saint Paul, Minnesota, United States
  • 2011
    • Massachusetts General Hospital
      Boston, Massachusetts, United States
    • Moffitt Cancer Center
      • Program in Blood and Marrow Transplantation
      Tampa, FL, United States
    • University of Minnesota Medical Center, Fairview
      Minneapolis, Minnesota, United States
    • Emory University
      • Department of Health Policy and Management
      Atlanta, GA, United States
    • University of Pennsylvania
      • "Abramson" Cancer Center
      Philadelphia, PA, United States
  • 2004–2011
    • University of Minnesota Twin Cities
      • • Division of Hematology, Oncology and Transplantation
      • • Department of Pediatrics
      Minneapolis, Minnesota, United States
  • 2010
    • Imperial College London
      Londinium, England, United Kingdom