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Article: Reduced-intensity versus myeloablative allogeneic transplantation.

Weisdorf, Daniel J

Hematology/oncology and stem cell therapy

2017 Volume 10, Issue 4, Page(s) 321–326

Abstract: Allotransplantation cures patients by cytoreduction and the graft-versus-tumor (leukemia; graft-versus-leukemia [GVL]) alloresponse; both eliminate residual disease. The spectrum of conditioning intensity influences toxicities and non-relapse mortality. ... ...

Abstract	Allotransplantation cures patients by cytoreduction and the graft-versus-tumor (leukemia; graft-versus-leukemia [GVL]) alloresponse; both eliminate residual disease. The spectrum of conditioning intensity influences toxicities and non-relapse mortality. The spectrum of tumor sensitivity to the GVL response influences relapse. Balancing tolerable toxicities (influenced by patients' performance status and comorbidities) is also influenced by the graft. Intense immunosuppression (for engraftment and graft-versus-host disease prevention) may constrain the immunologic potency of the graft and limit the antineoplastic capacity of the transplant, thus requiring more intense or more effective conditioning regimens to limit the risks of relapse and permit satisfactory disease-free survival.
MeSH term(s)	Allografts ; Graft Survival ; Graft vs Host Disease/mortality ; Graft vs Host Disease/prevention & control ; Graft vs Tumor Effect ; Hematopoietic Stem Cell Transplantation/methods ; Humans ; Immunosuppression/methods ; Neoplasms/mortality ; Neoplasms/therapy ; Transplantation Conditioning/methods
Language	English
Publishing date	2017-12
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2651893-4
ISSN	1658-3876
ISSN	1658-3876
DOI	10.1016/j.hemonc.2017.05.002
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Article ; Online: Access to CAR T-cell therapy: Focus on diversity, equity and inclusion.

Odstrcil, Maria S / Lee, Catherine J / Sobieski, Catherine / Weisdorf, Daniel / Couriel, Daniel

Blood reviews

2023 Volume 63, Page(s) 101136

Abstract: Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of hematologic malignancies in patients with relapsed or refractory disease without other treatment options. However, only a very small proportion of patients with an ... ...

Abstract	Chimeric antigen receptor T-cell (CAR T-cell) therapy has revolutionized the treatment of hematologic malignancies in patients with relapsed or refractory disease without other treatment options. However, only a very small proportion of patients with an indication for CAR T-cell can access the treatment. The imbalance between supply and demand is magnified in minority and vulnerable populations. Limited access is multifactorial and in part a result of factors directly related to the cellular product such as cost, complex logistics and manufacturing limitations. On the other hand, the impact of diversity, equity, and inclusion (DEI) and their social and structural context are also key to understanding access barriers in cellular therapy and health care in general. CAR T-cell therapy provides us with a new opportunity to better understand and prioritize this gap, a key step towards proactively and strategically addressing access. The aim of this review is to provide an analysis of the current state of access to CAR T therapy with a focus on the influence of DEI. We will cover aspects related to the cellular product and the inseparable context of social and structural determinants. Identifying and addressing barriers is necessary to ensure equitable access to this and all future novel therapies.
MeSH term(s)	Humans ; Immunotherapy, Adoptive/adverse effects ; Diversity, Equity, Inclusion ; Cell- and Tissue-Based Therapy ; Hematologic Neoplasms
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	639015-8
ISSN	1532-1681 ; 0268-960X
ISSN (online)	1532-1681
ISSN	0268-960X
DOI	10.1016/j.blre.2023.101136
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Zs.A 2207: Show issues

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Article ; Online: Microbiota-based approaches to mitigate infectious complications of intensive chemotherapy in patients with acute leukemia.

Rashidi, Armin / Weisdorf, Daniel J

Translational research : the journal of laboratory and clinical medicine

2020 Volume 220, Page(s) 167–181

Abstract: Despite advances in antimicrobial treatments, infection remains a common complication of intensive chemotherapy in patients with acute leukemia. It has become progressively apparent that the current antimicrobial focus has shortcomings that result from ... ...

Abstract	Despite advances in antimicrobial treatments, infection remains a common complication of intensive chemotherapy in patients with acute leukemia. It has become progressively apparent that the current antimicrobial focus has shortcomings that result from disruption of the commensal microbial communities of the gut. These effects, collectively known as dysbiosis, have been increasingly associated worldwide with growing complications such as Clostridioides difficile infection, systemic infections, and antibiotic resistance. A revision of the current practice is overdue. Several innovative concepts have been proposed and tested in animal models and humans, with the overarching goal of preventing damage to the microbiota and facilitating its recovery. In this review, we discuss these approaches, examine critical knowledge gaps, and explore how they may be filled in future research.
MeSH term(s)	Acute Disease ; Animals ; Anti-Bacterial Agents/therapeutic use ; Antineoplastic Agents/adverse effects ; Bacterial Infections/prevention & control ; Dysbiosis/chemically induced ; Gastrointestinal Microbiome/drug effects ; Gastrointestinal Microbiome/physiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Leukemia/complications ; Leukemia/drug therapy ; Leukemia/microbiology
Chemical Substances	Anti-Bacterial Agents ; Antineoplastic Agents
Language	English
Publishing date	2020-04-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2246684-8
ISSN	1878-1810 ; 1532-6543 ; 1931-5244
ISSN (online)	1878-1810 ; 1532-6543
ISSN	1931-5244
DOI	10.1016/j.trsl.2020.03.011
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Article ; Online: Treatment-Sensitive and Treatment-Dependent Chronic Graft-versus-Host Disease Yield Superior Failure-Free and Overall Survival Compared to Treatment-Resistant Chronic Graft-versus-Host Disease.

El Jurdi, Najla / Herzog, Shannon / Shanley, Ryan / Holtan, Shernan G / MacMillan, Margaret L / Weisdorf, Daniel J

Transplantation and cellular therapy

2024

Abstract: Response to treatment of chronic graft-versus-host disease (cGVHD) may help predict prognosis and outcomes. We hypothesized that the response of cGVHD to treatment and the ability to taper immunosuppression define distinct treatment response categories ... ...

Abstract	Response to treatment of chronic graft-versus-host disease (cGVHD) may help predict prognosis and outcomes. We hypothesized that the response of cGVHD to treatment and the ability to taper immunosuppression define distinct treatment response categories that differ in terms of risk factors and prognosis. Our aim was to determine specific clinical characteristics and outcomes associated with 3 distinct cGVHD treatment response groups based on the response to and duration of immunosuppressive therapy (IST) as treatment-sensitive (TS), treatment-resistant (TR), and treatment-dependent (TD) cGVHD. This retrospective single-institution cohort study included 1142 consecutive adult and pediatric recipients of allogeneic hematopoietic cell transplantation (HCT) performed for malignant and nonmalignant disorders at the University of Minnesota between 2008 and 2016. All donor, graft, conditioning regimen, and GVHD prophylaxis strategies were included, but only patients who commenced systemic treatment within 30 days of cGVHD diagnosis were included. A total of 185 patients who developed cGVHD necessitating IST within 30 days of cGVHD diagnosis were included in this analysis. At 1 year after cGVHD onset, 13% of the patients were TS, 27% were TD, and 60% were TR (including 14% deceased), whereas at 2 years after cGVHD onset, 29% were TS, 5% were TD, and 66% were TR (including 22% deceased). In a landmark analysis starting at 1 year after cGVHD onset, 5-year failure-free survival (FFS) and overall survival (OS) were lowest in the TR group (FFS, 38%; OS, 70%), with comparable outcomes in the TD (74% and 82%, respectively) and TS (79% for both) groups. Compared to no cGVHD, TR cGVHD was associated with worse OS at 5 years after cGVHD (hazard ratio, 2.09 versus no cGVHD; 95% confidence interval, 1.3 to 3.3; P < .01). Our findings suggest that refining cGVHD classification into 3 treatment response states defines important predictors of early and late clinical outcomes and identifies patients needing more effective treatment.
Language	English
Publishing date	2024-03-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2024.03.011
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Zs.A 5082: Show issues

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Article ; Online: Allogeneic Hematopoietic Cell Transplantation and Cellular Therapy.

Kim, Hee-Je / Weisdorf, Daniel / Gottlieb, David J

Blood cell therapy

2021 Volume 4, Issue Spec Edition, Page(s) S20–S27

Abstract: Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) generally require allogeneic hematopoietic cell transplantation (allo-HCT) for a cure, except for patients with favorable genetic genotypes such as those with core-binding ... ...

Abstract	Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) generally require allogeneic hematopoietic cell transplantation (allo-HCT) for a cure, except for patients with favorable genetic genotypes such as those with core-binding factor AML. However, the use of intensive chemotherapy followed by prompt HCT does not fully prevent relapse or refractory disease. Despite improvements in transplant techniques and management of complications, further improvement of HCT outcomes is urgently needed. Moreover, careful patient counseling, donor selection, and choice of transplant type are essential to maximize the benefits of early allografting. Maintenance after HCT focusing on selective immunomodulation combined with targeted immunotherapies that control persisting or relapsed hematologic malignancies is currently under active investigation. To improve the balance between GVHD, relapse, and infection, the use of purified blood stem cell grafts in conjunction with
Language	English
Publishing date	2021-10-14
Publishing country	Japan
Document type	Journal Article
ISSN	2432-7026
ISSN (online)	2432-7026
DOI	10.31547/bct-2021-014
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Article ; Online: Novel Composite Endpoints after Allogeneic Hematopoietic Cell Transplantation.

Kim, Haesook T / Logan, Brent / Weisdorf, Daniel J

Transplantation and cellular therapy

2021 Volume 27, Issue 8, Page(s) 650–657

Abstract: With the recent development of transplant-specific composite endpoints for evaluation of allogeneic hematopoietic cell transplantation (alloHCT) outcomes, the use of these novel endpoints is growing rapidly. Combining multiple endpoints into a single ... ...

Abstract	With the recent development of transplant-specific composite endpoints for evaluation of allogeneic hematopoietic cell transplantation (alloHCT) outcomes, the use of these novel endpoints is growing rapidly. Combining multiple endpoints into a single endpoint, these composite endpoints appear simple and can be used as a summary measure for overall effectiveness of an intervention. However, all component endpoints may not have equal clinical significance, and an intervention may not work proportionally in the same direction for all components of a composite endpoint. This may complicate the interpretation of results, particularly if there are opposing effects of differing component endpoints. We assess the benefits and limitations of various composite endpoints used in alloHCT studies recently and propose guidelines for their use and interpretation. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
MeSH term(s)	Hematopoietic Stem Cell Transplantation ; Retrospective Studies ; United States
Language	English
Publishing date	2021-05-15
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2021.05.005
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Zs.A 5082: Show issues

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Article ; Online: Optimizing Donor Choice and GVHD Prophylaxis in Allogeneic Hematopoietic Cell Transplantation.

Holtan, Shernan G / Versluis, Jurjen / Weisdorf, Daniel J / Cornelissen, Jan J

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

2021 Volume 39, Issue 5, Page(s) 373–385

MeSH term(s)	Donor Selection/methods ; Donor Selection/standards ; Graft vs Host Disease/prevention & control ; Hematopoietic Stem Cell Transplantation/methods ; Histocompatibility Testing/methods ; Humans ; Precision Medicine ; Transplantation, Homologous
Language	English
Publishing date	2021-01-12
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.20.01771
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Zs.A 1847: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 650: Show issues

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Article ; Online: Transplantation provides superior survival high risk myeloid malignancies in older patients.

Ustun, Celalettin / Warlick, Erica / Nathan, Sunita / Burns, Linda J / Weisdorf, Daniel

Leukemia & lymphoma

2022 Volume 63, Issue 10, Page(s) 2494–2498

MeSH term(s)	Aged ; Disease-Free Survival ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Leukemia, Myeloid, Acute ; Neoplasms ; Retrospective Studies ; Transplantation Conditioning ; Vidarabine
Chemical Substances	Vidarabine (FA2DM6879K)
Language	English
Publishing date	2022-05-19
Publishing country	United States
Document type	Letter
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2022.2076851
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Article ; Online: Vorinostat is victorious in GVHD prevention.

Holtan, Shernan G / Weisdorf, Daniel J

Blood

2017 Volume 130, Issue 15, Page(s) 1690–1691

MeSH term(s)	Graft vs Host Disease/prevention & control ; Histone Deacetylase Inhibitors ; Humans ; Hydroxamic Acids ; Vorinostat
Chemical Substances	Histone Deacetylase Inhibitors ; Hydroxamic Acids ; Vorinostat (58IFB293JI)
Language	English
Publishing date	2017-10-11
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood-2017-08-802249
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Article ; Online: Body composition and late-occurring chronic health conditions after autologous stem cell transplantation for lymphoma.

Giri, Smith / Harmon, Christian / Landier, Wendy / Chen, Yanjun / Wu, Jessica / Hageman, Lindsey / Balas, Nora / Francisco, Liton / Bosworth, Alysia / Weisdorf, Daniel J / Forman, Stephen J / Armenian, Saro H / Williams, Grant R / Bhatia, Smita

Cancer

2024

Abstract: Background: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition ...

Abstract	Background: Autologous peripheral blood stem cell transplantation (aPBSCT) is the standard of care for adults with relapsed lymphoma, yet recipients remain at risk of developing chronic health conditions (CHCs). It was hypothesized that body composition measurements of skeletal muscle and fat are associated with late-onset CHCs and nonrelapse mortality after aPBSCT. Methods: Leveraging the Blood or Marrow Transplant Survivor Study, we examined association between pre-aPBSCT body composition and new-onset grade 3-5 CHCs among 187 adults with lymphoma treated with aPBSCT (2011-2014) surviving ≥2 years after aPBSCT. Using computed tomography scans at the L3 level, skeletal muscle mass (skeletal muscle area and skeletal muscle density [SMD]) and body fat (subcutaneous adipose tissue and visceral adipose tissue) were measured and quantified as sex-specific z-scores. Competing risk models were built to study the impact of body composition on incident grade 3 through 5 CHCs and nonrelapse mortality (NRM) adjusting for confounders. Results: The study cohort had a median age at aPBSCT of 57 years with 63% males, 77% non-Hispanic Whites and 81% with non-Hodgkin lymphoma. The 5-year cumulative incidence of grade 3 through 5 CHCs was 47% (95% Confidence Interval, CI, 38%-56%). Each SD increase in SMD was associated with 30% reduced risk of grade 3 through 5 CHCs (95% CI, 0.50-0.96). The 10-year cumulative incidence of NRM was 16% (95% CI, 10-22). No body composition measure was associated with NRM. Conclusions: The association between SMD and grade 3 through 5 CHCs following aPBSCT could inform development of prognostic models to identify adults with lymphoma at greatest risk of morbidity following aPBSCT.
Language	English
Publishing date	2024-04-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	1429-1
ISSN	1097-0142 ; 0008-543X ; 1934-662X
ISSN (online)	1097-0142
ISSN	0008-543X ; 1934-662X
DOI	10.1002/cncr.35298
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