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  1. Article ; Online: Randomized, Double-Blind, Placebo-Controlled, Global Phase III Trial of Talimogene Laherparepvec Combined With Pembrolizumab for Advanced Melanoma.

    Chesney, Jason A / Ribas, Antoni / Long, Georgina V / Kirkwood, John M / Dummer, Reinhard / Puzanov, Igor / Hoeller, Christoph / Gajewski, Thomas F / Gutzmer, Ralf / Rutkowski, Piotr / Demidov, Lev / Arenberger, Petr / Shin, Sang Joon / Ferrucci, Pier Francesco / Haydon, Andrew / Hyngstrom, John / van Thienen, Johannes V / Haferkamp, Sebastian / Guilera, Josep Malvehy /
    Rapoport, Bernardo Leon / VanderWalde, Ari / Diede, Scott J / Anderson, James R / Treichel, Sheryl / Chan, Edward L / Bhatta, Sumita / Gansert, Jennifer / Hodi, Frank Stephen / Gogas, Helen

    Journal of clinical oncology : official journal of the American Society of Clinical Oncology

    2022  Volume 41, Issue 3, Page(s) 528–540

    Abstract: Purpose: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the ... ...

    Abstract Purpose: The combination of talimogene laherparepvec (T-VEC) and pembrolizumab previously demonstrated an acceptable safety profile and an encouraging complete response rate (CRR) in patients with advanced melanoma in a phase Ib study. We report the efficacy and safety from a phase III, randomized, double-blind, multicenter, international study of T-VEC plus pembrolizumab (T-VEC-pembrolizumab) versus placebo plus pembrolizumab (placebo-pembrolizumab) in patients with advanced melanoma.
    Methods: Patients with stage IIIB-IVM1c unresectable melanoma, naïve to antiprogrammed cell death protein-1, were randomly assigned 1:1 to T-VEC-pembrolizumab or placebo-pembrolizumab. T-VEC was administered at ≤ 4 × 10
    Results: Overall, 692 patients were randomly assigned (346 T-VEC-pembrolizumab and 346 placebo-pembrolizumab). T-VEC-pembrolizumab did not significantly improve PFS (hazard ratio, 0.86; 95% CI, 0.71 to 1.04;
    Conclusion: T-VEC-pembrolizumab did not significantly improve PFS or OS compared with placebo-pembrolizumab. Safety results of the T-VEC-pembrolizumab combination were consistent with the safety profiles of each agent alone.
    MeSH term(s) Humans ; Melanoma/drug therapy ; Oncolytic Virotherapy/methods ; Herpesvirus 1, Human ; Double-Blind Method
    Chemical Substances talimogene laherparepvec ; pembrolizumab (DPT0O3T46P)
    Language English
    Publishing date 2022-08-23
    Publishing country United States
    Document type Randomized Controlled Trial ; Multicenter Study ; Clinical Trial, Phase III ; Clinical Trial, Phase I ; Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 604914-x
    ISSN 1527-7755 ; 0732-183X
    ISSN (online) 1527-7755
    ISSN 0732-183X
    DOI 10.1200/JCO.22.00343
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Response to Letter from Demetrios S. Theodoropoulos, MD, DSc.

    Gajewski, James L / Lill, Michael / Horowitz, Mary / Maziarz, Richard T

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2010  Volume 16, Issue 4, Page(s) 561–562

    MeSH term(s) Hematopoietic Stem Cell Transplantation ; Humans
    Language English
    Publishing date 2010-04
    Publishing country United States
    Document type Letter
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2010.02.001
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Distinct Graft-Specific TCR Avidity Profiles during Acute Rejection and Tolerance.

    Miller, Michelle L / McIntosh, Christine M / Williams, Jason B / Wang, Ying / Hollinger, Maile K / Isaad, Noel J / Moon, James J / Gajewski, Thomas F / Chong, Anita S / Alegre, Maria-Luisa

    Cell reports

    2018  Volume 24, Issue 8, Page(s) 2112–2126

    Abstract: Mechanisms implicated in robust transplantation tolerance at the cellular level can be broadly categorized into those that inhibit alloreactive T cells intrinsically (clonal deletion and dysfunction) or extrinsically through regulation. Here, we ... ...

    Abstract Mechanisms implicated in robust transplantation tolerance at the cellular level can be broadly categorized into those that inhibit alloreactive T cells intrinsically (clonal deletion and dysfunction) or extrinsically through regulation. Here, we investigated whether additional population-level mechanisms control T cells by examining whether therapeutically induced peripheral transplantation tolerance could influence T cell populations' avidity for alloantigens. Whereas T cells with high avidity preferentially accumulated during acute rejection of allografts, the alloreactive T cells in tolerant recipients retained a low-avidity profile, comparable to naive mice despite evidence of activation. These contrasting avidity profiles upon productive versus tolerogenic stimulation were durable and persisted upon alloantigen re-encounter in the absence of any immunosuppression. Thus, peripheral transplantation tolerance involves control of alloreactive T cells at the population level, in addition to the individual cell level. Controlling expansion or eliminating high-affinity, donor-specific T cells long term may be desirable to achieve robust transplantation tolerance in the clinic.
    MeSH term(s) Animals ; Graft Rejection/immunology ; Humans ; Immune Tolerance/immunology ; Mice ; Transplantation Tolerance/immunology
    Language English
    Publishing date 2018-08-22
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2018.07.067
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Emergence of Cunninghamella as a pathogenic invasive mold infection in allogeneic transplant recipients.

    Strasfeld, Lynne / Espinosa-Aguilar, Luis / Gajewski, James L / Stenzel, Peter / Pimentel, Agustin / Mater, Elana / Maziarz, Richard T

    Clinical lymphoma, myeloma & leukemia

    2013  Volume 13, Issue 5, Page(s) 622–628

    MeSH term(s) Adult ; Aged ; Cunninghamella ; Female ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Male ; Middle Aged ; Mucormycosis/complications ; Mucormycosis/diagnosis ; Transplantation, Homologous
    Language English
    Publishing date 2013-10
    Publishing country United States
    Document type Case Reports ; Journal Article ; Review
    ZDB-ID 2540992-X
    ISSN 2152-2669 ; 2152-2650
    ISSN (online) 2152-2669
    ISSN 2152-2650
    DOI 10.1016/j.clml.2013.05.002
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Payment and Care for Hematopoietic Cell Transplantation Patients: Toward a Specialized Medical Home for Complex Care Patients.

    Gajewski, James L / McClellan, Mark B / Majhail, Navneet S / Hari, Parameswaran N / Bredeson, Christopher N / Maziarz, Richard T / LeMaistre, Charles F / Lill, Michael C / Farnia, Stephanie H / Komanduri, Krishna V / Boo, Michael J

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2017  Volume 24, Issue 1, Page(s) 4–12

    Abstract: Patient-centered medical home models are fundamental to the advanced alternative payment models defined in the Medicare Access and Children's Health Insurance Plan Reauthorization Act (MACRA). The patient-centered medical home is a model of healthcare ... ...

    Abstract Patient-centered medical home models are fundamental to the advanced alternative payment models defined in the Medicare Access and Children's Health Insurance Plan Reauthorization Act (MACRA). The patient-centered medical home is a model of healthcare delivery supported by alternative payment mechanisms and designed to promote coordinated medical care that is simultaneously patient-centric and population-oriented. This transformative care model requires shifting reimbursement to include a per-patient payment intended to cover services not previously reimbursed such as disease management over time. Payment is linked to quality measures, including proportion of care delivered according to predefined pathways and demonstrated impact on outcomes. Some medical homes also include opportunities for shared savings by reducing overall costs of care. Recent proposals have suggested expanding the medical home model to specialized populations with complex needs because primary care teams may not have the facilities or the requisite expertise for their unique needs. An example of a successful care model that may provide valuable lessons for those creating specialty medical home models already exists in many hematopoietic cell transplantation (HCT) centers that deliver multidisciplinary, coordinated, and highly specialized care. The integration of care delivery in HCT centers has been driven by the specialty care their patients require and by the payment methodology preferred by the commercial payers, which has included bundling of both inpatient and outpatient care in the peritransplant interval. Commercial payers identify qualified HCT centers based on accreditation status and comparative performance, enabled in part by center-level comparative performance data available within a national outcomes database mandated by the Stem Cell Therapeutic and Research Act of 2005. Standardization across centers has been facilitated via voluntary accreditation implemented by Foundation for the Accreditation of Cell Therapy. Payers have built on these community-established programs and use public outcomes and program accreditation as standards necessary for inclusion in specialty care networks and contracts. Although HCT centers have not been described as medical homes, most HCT providers have already developed the structures that address critical requirements of MACRA for medical homes.
    MeSH term(s) Delivery of Health Care/economics ; Delivery of Health Care/methods ; Hematopoietic Stem Cell Transplantation/economics ; Humans ; Patient Care Management/economics ; Patient Care Management/trends ; Patient Care Team/trends ; Quality of Health Care/standards ; Reimbursement, Incentive/economics
    Language English
    Publishing date 2017-09-28
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2017.09.012
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Standardization of terminology for episodes of hematopoietic stem cell patient transplant care.

    LeMaistre, C Fred / Farnia, Stephanie / Crawford, Stephen / McGuirk, Joseph / Maziarz, Richard T / Coates, James / Irwin, Dennis / Martin, Patricia / Gajewski, James L

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2013  Volume 19, Issue 6, Page(s) 851–857

    Abstract: The nomenclature describing hematopoietic stem cell transplantation has evolved, adding precision and definition in research and regulation. The lack of coordination and standardization in terminology has left some gaps in the definition of episodes of ... ...

    Abstract The nomenclature describing hematopoietic stem cell transplantation has evolved, adding precision and definition in research and regulation. The lack of coordination and standardization in terminology has left some gaps in the definition of episodes of clinical care. These voids have caused particular problems in contracting for payment and billing for services rendered. The purpose of this report is to propose definitions for cell products, cell infusions, and transplantation episodes.
    MeSH term(s) Hematopoietic Stem Cell Transplantation/classification ; Hematopoietic Stem Cell Transplantation/economics ; Humans ; Terminology as Topic ; Transplantation/economics ; Transplantation, Autologous ; Transplantation, Homologous
    Language English
    Publishing date 2013-06
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2013.03.004
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Epacadostat plus pembrolizumab versus placebo plus pembrolizumab in patients with unresectable or metastatic melanoma (ECHO-301/KEYNOTE-252): a phase 3, randomised, double-blind study.

    Long, Georgina V / Dummer, Reinhard / Hamid, Omid / Gajewski, Thomas F / Caglevic, Christian / Dalle, Stephane / Arance, Ana / Carlino, Matteo S / Grob, Jean-Jacques / Kim, Tae Min / Demidov, Lev / Robert, Caroline / Larkin, James / Anderson, James R / Maleski, Janet / Jones, Mark / Diede, Scott J / Mitchell, Tara C

    The Lancet. Oncology

    2019  Volume 20, Issue 8, Page(s) 1083–1097

    Abstract: Background: Immunotherapy combination treatments can improve patient outcomes. Epacadostat, an IDO1 selective inhibitor, and pembrolizumab, a PD-1 inhibitor, showed promising antitumour activity in the phase 1-2 ECHO-202/KEYNOTE-037 study in advanced ... ...

    Abstract Background: Immunotherapy combination treatments can improve patient outcomes. Epacadostat, an IDO1 selective inhibitor, and pembrolizumab, a PD-1 inhibitor, showed promising antitumour activity in the phase 1-2 ECHO-202/KEYNOTE-037 study in advanced melanoma. In this trial, we aimed to compare progression-free survival and overall survival in patients with unresectable stage III or IV melanoma receiving epacadostat plus pembrolizumab versus placebo plus pembrolizumab.
    Methods: In this international, randomised, placebo-controlled, double-blind, parallel-group, phase 3 trial, eligible participants were aged 18 years or older, with unresectable stage III or IV melanoma previously untreated with PD-1 or PD-L1 checkpoint inhibitors, an ECOG performance status of 0 or 1, and had a known BRAF
    Findings: Between June 21, 2016, and Aug 7, 2017, 928 patients were screened and 706 patients were randomly assigned to receive epacadostat plus pembrolizumab (n=354) or placebo plus pembrolizumab (n=352). Median follow-up was 12·4 months (IQR 10·3-14·5). No significant differences were found between the treatment groups for progression-free survival (median 4·7 months, 95% CI 2·9-6·8, for epacadostat plus pembrolizumab vs 4·9 months, 2·9-6·8, for placebo plus pembrolizumab; hazard ratio [HR] 1·00, 95% CI 0·83-1·21; one-sided p=0·52) or overall survival (median not reached in either group; epacadostat plus pembrolizumab vs placebo plus pembrolizumab: HR 1·13, 0·86-1·49; one-sided p=0·81). The most common grade 3 or worse treatment-related adverse event was lipase increase, which occurred in 14 (4%) of 353 patients receiving epacadostat plus pembrolizumab and 11 (3%) of 352 patients receiving placebo plus pembrolizumab. Treatment-related serious adverse events were reported in 37 (10%) of 353 patients receiving epacadostat plus pembrolizumab and 32 (9%) of 352 patients receiving placebo plus pembrolizumab. There were no treatment-related deaths in either treatment group.
    Interpretation: Epacadostat 100 mg twice daily plus pembrolizumab did not improve progression-free survival or overall survival compared with placebo plus pembrolizumab in patients with unresectable or metastatic melanoma. The usefulness of IDO1 inhibition as a strategy to enhance anti-PD-1 therapy activity in cancer remains uncertain.
    Funding: Incyte Corporation, in collaboration with Merck Sharp & Dohme.
    MeSH term(s) Adult ; Aged ; Antibodies, Monoclonal, Humanized/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Double-Blind Method ; Female ; Humans ; Male ; Melanoma/drug therapy ; Middle Aged ; Oximes/administration & dosage ; Progression-Free Survival ; Sulfonamides/administration & dosage
    Chemical Substances Antibodies, Monoclonal, Humanized ; Oximes ; Sulfonamides ; epacadostat (71596A9R13) ; pembrolizumab (DPT0O3T46P)
    Language English
    Publishing date 2019-06-17
    Publishing country England
    Document type Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
    ZDB-ID 2049730-1
    ISSN 1474-5488 ; 1470-2045
    ISSN (online) 1474-5488
    ISSN 1470-2045
    DOI 10.1016/S1470-2045(19)30274-8
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Single and multiple dose MultiStem (multipotent adult progenitor cell) therapy prophylaxis of acute graft-versus-host disease in myeloablative allogeneic hematopoietic cell transplantation: a phase 1 trial.

    Maziarz, Richard T / Devos, Timothy / Bachier, Carlos R / Goldstein, Steven C / Leis, Jose F / Devine, Steven M / Meyers, Gabrielle / Gajewski, James L / Maertens, Johan / Deans, Robert J / Van't Hof, Wouter / Lazarus, Hillard M

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2015  Volume 21, Issue 4, Page(s) 720–728

    Abstract: We conducted a multicenter, phase 1 dose escalation study evaluating the safety of the allogeneic multipotent adult progenitor cell (MAPC, MultiStem, Athersys, Inc., Cleveland, OH) stromal product administered as an adjunct therapy to 36 patients after ... ...

    Abstract We conducted a multicenter, phase 1 dose escalation study evaluating the safety of the allogeneic multipotent adult progenitor cell (MAPC, MultiStem, Athersys, Inc., Cleveland, OH) stromal product administered as an adjunct therapy to 36 patients after myeloablative allogeneic hematopoietic cell transplantation (HCT). Patients received increasing doses of MAPC (1, 5, or 10 million cells per kilogram recipient weight) as a single i.v. dose on day +2 after HCT (n = 18), or once weekly for up to 5 doses (1 or 5 million cells per kilogram; n = 18). Infusional and regimen-related toxicities were assessed for 30 days after the last MAPC dose. Of 36 allogeneic HCT donors (17 related and 19 unrelated), 35 were 6/6 HLA matched. MAPC infusions were well tolerated without associated infusional toxicity, graft failure, or increased incidence of infection. Median times to neutrophil (n = 36) and platelet (n = 31) engraftment were 15 (range, 11 to 25) and 16 (range, 11 to 41) days, respectively. The overall cumulative incidences of grades II to IV and III and IV acute graft-versus-host disease (GVHD) at day 100 were 37% and 14%, respectively (n = 36). In the group that received the highest single MAPC dose (10 million cells/kg), day 100 incidence of grade II to IV GVHD was 11.1% (1 of 9) with no observed cases of grade III and IV GVHD. We found no evidence for MHC class II allogeneic antibody induction, although some patients showed an increase in serum anticlass I titers compared with baseline. MAPC contribution to blood chimerism was negligible. These phase I data support the safety of stromal stem cell therapy and suggest that MAPC should be tested prospectively as a novel therapeutic option for GVHD prophylaxis after HCT.
    MeSH term(s) Acute Disease ; Adolescent ; Adult ; Adult Stem Cells/transplantation ; Aged ; Allografts ; Female ; Graft Survival ; Graft vs Host Disease/prevention & control ; Hematologic Neoplasms/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Multipotent Stem Cells/transplantation
    Language English
    Publishing date 2015-04
    Publishing country United States
    Document type Clinical Trial, Phase I ; Journal Article ; Randomized Controlled Trial
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2014.12.025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: A review of transfusion practice before, during, and after hematopoietic progenitor cell transplantation.

    Gajewski, James L / Johnson, Viviana V / Sandler, S Gerald / Sayegh, Antoine / Klumpp, Thomas R

    Blood

    2008  Volume 112, Issue 8, Page(s) 3036–3047

    Abstract: The increased use of hematopoietic progenitor cell (HPC) transplantation has implications and consequences for transfusion services: not only in hospitals where HPC transplantations are performed, but also in hospitals that do not perform HPC ... ...

    Abstract The increased use of hematopoietic progenitor cell (HPC) transplantation has implications and consequences for transfusion services: not only in hospitals where HPC transplantations are performed, but also in hospitals that do not perform HPC transplantations but manage patients before or after transplantation. Candidates for HPC transplantation have specific and specialized transfusion requirements before, during, and after transplantation that are necessary to avert the adverse consequences of alloimmunization to human leukocyte antigens, immunohematologic consequences of ABO-mismatched transplantations, or immunosuppression. Decisions concerning blood transfusions during any of these times may compromise the outcome of an otherwise successful transplantation. Years after an HPC transplantation, and even during clinical remission, recipients may continue to be immunosuppressed and may have critically important, special transfusion requirements. Without a thorough understanding of these special requirements, provision of compatible blood components may be delayed and often urgent transfusion needs prohibit appropriate consultation with the patient's transplantation specialist. To optimize the relevance of issues and communication between clinical hematologists, transplantation physicians, and transfusion medicine physicians, the data and opinions presented in this review are organized by sequence of patient presentation, namely, before, during, and after transplantation.
    MeSH term(s) Blood Component Removal ; Blood Platelets/cytology ; Blood Transfusion/methods ; Clinical Trials as Topic ; Cytomegalovirus Infections/transmission ; Erythrocytes/cytology ; Gamma Rays ; Hematology/methods ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/cytology ; Humans ; Immune System ; Medical Oncology/methods ; Splenectomy
    Language English
    Publishing date 2008-06-26
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 80069-7
    ISSN 1528-0020 ; 0006-4971
    ISSN (online) 1528-0020
    ISSN 0006-4971
    DOI 10.1182/blood-2007-10-118372
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Challenges and potential solutions for recruitment and retention of hematopoietic cell transplantation physicians: the National Marrow Donor Program's System Capacity Initiative Physician Workforce Group report.

    Burns, Linda J / Gajewski, James L / Majhail, Navneet S / Navarro, Willis / Perales, Miguel-Angel / Shereck, Evan / Selby, George B / Snyder, Edward L / Woolfrey, Ann E / Litzow, Mark R

    Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation

    2014  Volume 20, Issue 5, Page(s) 617–621

    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 ... ...

    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 comorbidities, 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 transplantations per year, double the number in 2010. To understand the needs of the HCT infrastructure to facilitate this number of transplantations, 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 transplantation physicians. We report here the results of our efforts and future initiatives.
    MeSH term(s) Career Choice ; Focus Groups ; Hematologic Diseases/pathology ; Hematologic Diseases/therapy ; Hematopoietic Stem Cell Transplantation ; Humans ; Physicians/supply & distribution ; Registries ; Tissue Donors ; United States
    Language English
    Publishing date 2014-05
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1474865-4
    ISSN 1523-6536 ; 1083-8791
    ISSN (online) 1523-6536
    ISSN 1083-8791
    DOI 10.1016/j.bbmt.2014.01.028
    Database MEDical Literature Analysis and Retrieval System OnLINE

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