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Article ; Online: Recruitment and Retention of Hematopoietic Cell Transplantation and Cellular Therapy Physicians: A Report from the ASTCT Talent Acquisition Task Force.

Sharma, Akshay / Czechowicz, Agnieszka / Mavers, Melissa / Chao, Nelson / DiPersio, John / Reddy, Pavan / Perales, Miguel-Angel / Smith, Melody

Transplantation and cellular therapy

2024

Abstract: A shortage of transplant and cellular therapy (TCT) physicians is expected given the expansion of TCT indications and the scope of practice of TCT programs in recent years. American Society of Transplantation and Cellular Therapy (ASTCT) conducted a ... ...

Abstract	A shortage of transplant and cellular therapy (TCT) physicians is expected given the expansion of TCT indications and the scope of practice of TCT programs in recent years. American Society of Transplantation and Cellular Therapy (ASTCT) conducted a survey of early career transplant physicians and trainees to assess the factors that prompted them to pursue to career in TCT. This was a cross-sectional survey conducted via emails sent to the ASTCT membership. Fifty-nine respondents completed the survey. The vast majority of respondents decided to pursue a career in TCT during their hematology/oncology fellowship (41%), followed by during residency (25%) or medical school (18%), and a majority of them had some exposure to TCT in their clinical training already. The most common reason for choosing to specialize in TCT was interest in the clinical practice of TCT (81%) closely followed by the scientific allure of the field (75%). Most respondents were extremely committed to remaining in this field of practice. We found that those in the field report high levels of satisfaction despite factors that would otherwise predispose them to burnout. A systematic and sustained effort to promote trainee engagement that could result in improved recruitment and retention in the field of TCT is needed. Professional societies in partnership with educational institutions could conduct outreach and help attract trainees from diverse backgrounds.
Language	English
Publishing date	2024-04-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2024.04.005
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Zs.A 5082: Show issues

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Article ; Online: Hematopoiesis post anti-CD117 monoclonal antibody treatment in wild-type and Fanconi anemia settings.

Denis, Morgane / Swartzrock, Leah / Willner, Hana / Bubb, Quenton R / Haslett, Ethan / Chan, Yan Yi / Chen, Anzhi / Krampf, Mark R / Czechowicz, Agnieszka D

Haematologica

2024

Abstract: Anti-CD117 monoclonal antibody (mAb) agents have emerged as exciting alternative conditioning strategies to traditional genotoxic irradiation or chemotherapy conditioning for both allogeneic and autologous gene-modified hematopoietic stem cell ... ...

Abstract	Anti-CD117 monoclonal antibody (mAb) agents have emerged as exciting alternative conditioning strategies to traditional genotoxic irradiation or chemotherapy conditioning for both allogeneic and autologous gene-modified hematopoietic stem cell transplantation. Further, these agents are concurrently being explored in the treatment of mast cell disorders. Despite promising results in animal models and more recently in patients, the short-term and long-term effects of these treatments have not been fully explored. We conducted rigorous assessments to evaluate the effects of antagonistic anti-mCD117 mAb, ACK2, on hematopoiesis in wild-type (WT) and Fanconi Anemia (FA) mice. Importantly, we found no evidence of short-term DNA damage in either setting following this treatment suggesting that ACK2 does not induce immediate genotoxicity, providing crucial insights into its safety profile. Surprisingly, FA mice exhibited an increase in colony formation post-ACK2 treatment without accompanying DNA damage, indicating a potential targeting of hematopoietic stem cells (HSCs) and expansion of hematopoietic progenitor cells. Moreover, the long-term phenotypic and functional changes in hematopoietic stem and progenitor cells did not significantly differ between the ACK2-treated and control groups, in either setting, supporting that ACK2 does not adversely affect hematopoietic capacity. These finding underscore the safety of these agents when utilized as a short-course treatment in the conditioning context, as they did not induce significant changes in DNA damage amongst hematopoietic stem or progenitor cells. However, through a comparison of gene expression via single-cell RNA sequencing between untreated and treated mice, it was revealed that the ACK2 mAb, via c-Kit downregulation, effectively modulated the MAPK pathway with Fos down-regulation in WT and FA mice. Importantly, this modulation was achieved without causing prolonged disruptions. These findings validate the safety of the treatment and also enhance our understanding of its intricate mode of action at the molecular level.
Language	English
Publishing date	2024-04-04
Publishing country	Italy
Document type	Journal Article
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2023.284275
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Article ; Online: Non-genotoxic Restoration of the Hematolymphoid System in Fanconi Anemia.

Chan, Yan Yi / Ho, Pui Yan / Swartzrock, Leah / Rayburn, Maire / Nofal, Rofida / Thongthip, Supawat / Weinberg, Kenneth I / Czechowicz, Agnieszka

Transplantation and cellular therapy

2022 Volume 29, Issue 3, Page(s) 164.e1–164.e9

Abstract: Hematopoietic stem cell transplantation (HSCT) is a curative treatment for patients with many different blood and immune diseases; however, current treatment regimens contain non-specific chemotherapy and/or irradiation conditioning, which carry both ... ...

Abstract	Hematopoietic stem cell transplantation (HSCT) is a curative treatment for patients with many different blood and immune diseases; however, current treatment regimens contain non-specific chemotherapy and/or irradiation conditioning, which carry both short-term and long-term toxicities. The use of such agents may be particularly harmful for patients with Fanconi anemia (FA), who have genetic mutations resulting in deficiencies in DNA repair, leading to increased sensitivity to genotoxic agents. mAb-based conditioning has been proposed as an alternative conditioning strategy for HSCT that minimizes these toxicities by eliminating collateral tissue damage. Given the high need for improved treatments for FA patients, we aimed to evaluate the efficacy of different αCD117 mAb agents and immunosuppression on hematopoietic stem cell (HSC) depletion and explored their ability to safely establish therapeutic donor hematopoiesis post-HSCT in FA disease models. We evaluated the effects of different concentrations of αCD117 mAbs in vitro and in vivo on HSC growth and depletion. To further assess the efficacy of mAb-based conditioning, Fancd2
MeSH term(s)	Animals ; Mice ; Fanconi Anemia/etiology ; Fanconi Anemia/therapy ; Transplantation Conditioning/methods ; Hematopoietic Stem Cell Transplantation/adverse effects ; Immunosuppressive Agents ; Immunosuppression Therapy/methods ; Antibodies, Monoclonal
Chemical Substances	Immunosuppressive Agents ; Antibodies, Monoclonal
Language	English
Publishing date	2022-08-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	3062231-1
ISSN	2666-6367
ISSN (online)	2666-6367
DOI	10.1016/j.jtct.2022.08.015
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Article ; Online: Physioxia improves the selectivity of hematopoietic stem cell expansion cultures.

Igarashi, Kyomi J / Kucinski, Iwo / Chan, Yan Yi / Tan, Tze-Kai / Khoo, Hwei Minn / Kealy, David / Bhadury, Joydeep / Hsu, Ian / Ho, Pui Yan / Niizuma, Kouta / Hickey, John W / Nolan, Garry P / Bridge, Katherine S / Czechowicz, Agnieszka / Gottgens, Berthold / Nakauchi, Hiromitsu / Wilkinson, Adam C

Blood advances

2023 Volume 7, Issue 14, Page(s) 3366–3377

Abstract: Hematopoietic stem cells (HSCs) are a rare type of hematopoietic cell that can entirely reconstitute the blood and immune system after transplantation. Allogeneic HSC transplantation (HSCT) is used clinically as a curative therapy for a range of ... ...

Abstract	Hematopoietic stem cells (HSCs) are a rare type of hematopoietic cell that can entirely reconstitute the blood and immune system after transplantation. Allogeneic HSC transplantation (HSCT) is used clinically as a curative therapy for a range of hematolymphoid diseases; however, it remains a high-risk therapy because of its potential side effects, including poor graft function and graft-versus-host disease (GVHD). Ex vivo HSC expansion has been suggested as an approach to improve hematopoietic reconstitution in low-cell dose grafts. Here, we demonstrate that the selectivity of polyvinyl alcohol (PVA)-based mouse HSC cultures can be improved using physioxic culture conditions. Single-cell transcriptomic analysis helped confirm the inhibition of lineage-committed progenitor cells in physioxic cultures. Long-term physioxic expansion also afforded culture-based ex vivo HSC selection from whole bone marrow, spleen, and embryonic tissues. Furthermore, we provide evidence that HSC-selective ex vivo cultures deplete GVHD-causing T cells and that this approach can be combined with genotoxic-free antibody-based conditioning HSCT approaches. Our results offer a simple approach to improve PVA-based HSC cultures and the underlying molecular phenotype, and highlight the potential translational implications of selective HSC expansion systems for allogeneic HSCT.
MeSH term(s)	Animals ; Mice ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells/metabolism ; Transplantation, Homologous ; Graft vs Host Disease/etiology ; Graft vs Host Disease/prevention & control ; Graft vs Host Disease/metabolism
Language	English
Publishing date	2023-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2023009668
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Zs.A 7153: Show issues

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Book: Różność w rzeczach

Czechowicz, Agnieszka

o wyobraźni pisarskiej Wacława Potockiego

(Studia staropolskie ; N.S. 16 = 72)

2008

Author's details	Agnieszka Czechowicz
Series title	Studia staropolskie ; N.S. 16 = 72
Language	Polish
Size	189 S.
Publisher	Inst. Badań Literackich
Publishing place	Warszawa
Document type	Book
ISBN	9788361552154 ; 8361552154
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation.

Li, Zhanzhuo / Czechowicz, Agnieszka / Scheck, Amelia / Rossi, Derrick J / Murphy, Philip M

Nature communications

2019 Volume 10, Issue 1, Page(s) 616

Abstract: Hematopoietic chimerism after allogeneic bone marrow transplantation may establish a state of donor antigen-specific tolerance. However, current allotransplantation protocols involve genotoxic conditioning which has harmful side-effects and predisposes ... ...

Abstract	Hematopoietic chimerism after allogeneic bone marrow transplantation may establish a state of donor antigen-specific tolerance. However, current allotransplantation protocols involve genotoxic conditioning which has harmful side-effects and predisposes to infection and cancer. Here we describe a non-genotoxic conditioning protocol for fully MHC-mismatched bone marrow allotransplantation in mice involving transient immunosuppression and selective depletion of recipient hematopoietic stem cells with a CD117-antibody-drug-conjugate (ADC). This protocol resulted in multilineage, high level (up to 50%), durable, donor-derived hematopoietic chimerism after transplantation of 20 million total bone marrow cells, compared with ≤ 2.1% hematopoietic chimerism from 50 million total bone marrow cells without conditioning. Moreover, long-term survival of bone marrow donor-type but not third party skin allografts is achieved in CD117-ADC-conditioned chimeric mice without chronic immunosuppression. The only observed adverse event is transient elevation of liver enzymes in the first week after conditioning. These results provide proof-of-principle for CD117-ADC as a non-genotoxic, highly-targeted conditioning agent in allotransplantation and tolerance protocols.
MeSH term(s)	Animals ; Bone Marrow Cells/drug effects ; Bone Marrow Transplantation/methods ; Graft Rejection/immunology ; Graft Rejection/prevention & control ; Graft Survival ; Hematopoietic Stem Cell Transplantation/methods ; Hematopoietic Stem Cells ; Immune Tolerance ; Immunoconjugates/pharmacology ; Immunosuppression Therapy/methods ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Animal ; Proto-Oncogene Proteins c-kit/immunology ; Skin/pathology ; Skin Transplantation/methods ; Transplantation Chimera ; Transplantation Tolerance/drug effects ; Transplantation, Homologous
Chemical Substances	Immunoconjugates ; Proto-Oncogene Proteins c-kit (EC 2.7.10.1)
Language	English
Publishing date	2019-02-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-018-08202-w
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Clonal-level lineage commitment pathways of hematopoietic stem cells in vivo.

Lu, Rong / Czechowicz, Agnieszka / Seita, Jun / Jiang, Du / Weissman, Irving L

Proceedings of the National Academy of Sciences of the United States of America

2019 Volume 116, Issue 4, Page(s) 1447–1456

Abstract: While the aggregate differentiation of the hematopoietic stem cell (HSC) population has been extensively studied, little is known about the lineage commitment process of individual HSC clones. Here, we provide lineage commitment maps of HSC clones under ... ...

Abstract	While the aggregate differentiation of the hematopoietic stem cell (HSC) population has been extensively studied, little is known about the lineage commitment process of individual HSC clones. Here, we provide lineage commitment maps of HSC clones under homeostasis and after perturbations of the endogenous hematopoietic system. Under homeostasis, all donor-derived HSC clones regenerate blood homogeneously throughout all measured stages and lineages of hematopoiesis. In contrast, after the hematopoietic system has been perturbed by irradiation or by an antagonistic anti-ckit antibody, only a small fraction of donor-derived HSC clones differentiate. Some of these clones dominantly expand and exhibit lineage bias. We identified the cellular origins of clonal dominance and lineage bias and uncovered the lineage commitment pathways that lead HSC clones to different levels of self-renewal and blood production under various transplantation conditions. This study reveals surprising alterations in HSC fate decisions directed by conditioning and identifies the key hematopoiesis stages that may be manipulated to control blood production and balance.
MeSH term(s)	Animals ; Cell Differentiation/physiology ; Cell Lineage ; Clone Cells ; Hematopoiesis/physiology ; Hematopoietic Stem Cells/physiology ; Homeostasis/physiology ; Mice ; Mice, Inbred C57BL
Language	English
Publishing date	2019-01-08
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.1801480116
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Zs.A 1148: Show issues

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Article ; Online: Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation

Zhanzhuo Li / Agnieszka Czechowicz / Amelia Scheck / Derrick J. Rossi / Philip M. Murphy

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 7

Abstract: Transplantation of allogeneic bone marrow helps establish chimerism that may induce tolerance to tissue grafts. Here the authors show that a CD117-antibody-drug-conjugate helps precondition the recipients for inducing mixed chimerism and allo-tolerance ... ...

Abstract	Transplantation of allogeneic bone marrow helps establish chimerism that may induce tolerance to tissue grafts. Here the authors show that a CD117-antibody-drug-conjugate helps precondition the recipients for inducing mixed chimerism and allo-tolerance without clear adverse effects or the need for chronic immune suppression.
Keywords	Science ; Q
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Hematopoietic chimerism and donor-specific skin allograft tolerance after non-genotoxic CD117 antibody-drug-conjugate conditioning in MHC-mismatched allotransplantation

Zhanzhuo Li / Agnieszka Czechowicz / Amelia Scheck / Derrick J. Rossi / Philip M. Murphy

Nature Communications, Vol 10, Iss 1, Pp 1-

2019 Volume 7

Abstract	Transplantation of allogeneic bone marrow helps establish chimerism that may induce tolerance to tissue grafts. Here the authors show that a CD117-antibody-drug-conjugate helps precondition the recipients for inducing mixed chimerism and allo-tolerance without clear adverse effects or the need for chronic immune suppression.
Keywords	Science ; Q
Language	English
Publishing date	2019-02-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Purified hematopoietic stem cell transplantation: the next generation of blood and immune replacement.

Czechowicz, Agnieszka / Weissman, Irving L

Hematology/oncology clinics of North America

2011 Volume 25, Issue 1, Page(s) 75–87

Abstract: Replacement of disease-causing stem cells with healthy ones has been achieved clinically via hematopoietic cell transplantation (HCT) for the last 40 years, as a treatment modality for a variety of cancers and immunodeficiencies with moderate, but ... ...

Abstract	Replacement of disease-causing stem cells with healthy ones has been achieved clinically via hematopoietic cell transplantation (HCT) for the last 40 years, as a treatment modality for a variety of cancers and immunodeficiencies with moderate, but increasing, success. This procedure has traditionally included transplantation of mixed hematopoietic populations that include hematopoietic stem cells (HSC) and other cells, such as T cells. This article explores and delineates the potential expansion of this technique to treat a variety of inherited diseases of immune function, the current barriers in HCT and pure HSC transplantation, and the up-and-coming strategies to combat these obstacles.
Language	English
Publishing date	2011-01-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	93115-9
ISSN	1558-1977 ; 0889-8588
ISSN (online)	1558-1977
ISSN	0889-8588
DOI	10.1016/j.hoc.2010.11.006
Database	MEDical Literature Analysis and Retrieval System OnLINE

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