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Article ; Online: What makes a pediatric or young adult patient an appropriate transplant candidate?

Thakar, Monica S / Sorror, Mohamed L

Hematology. American Society of Hematology. Education Program

2023 Volume 2023, Issue 1, Page(s) 731–736

Abstract: A 3-year-old child with chronic granulomatous disease was brought to the transplant clinic by his parents. The patient has a history of Aspergillus fumigatus pneumonia, which required mechanical ventilation, and sepsis, resulting in several intensive ... ...

Abstract	A 3-year-old child with chronic granulomatous disease was brought to the transplant clinic by his parents. The patient has a history of Aspergillus fumigatus pneumonia, which required mechanical ventilation, and sepsis, resulting in several intensive care stays. He has failure to thrive and developmental delay. His parents are seeking guidance whether allogeneic hematopoietic cell transplantation (HCT) is a reasonable treatment option given concerns about his upfront major health limitations. Based on the original HCT-Comorbidity Index (CI), this child's risk for nonrelapse mortality (NRM) would be negligible with a score of 0. With use of the validated youth-nonmalignant HCT-CI, the score increases to 5, due to prior mechanical ventilation (+3), history of fungal infection (+1), and being underweight (+1), with at least 2-fold increase in risk of NRM. The role of developmental delay is unclear and not currently validated to prognosticate survival. While HCT was ultimately recommended in this case, the family was counseled to have a more realistic sense of NRM risk.
MeSH term(s)	Male ; Adolescent ; Humans ; Child ; Young Adult ; Child, Preschool ; Transplantation, Homologous ; Prognosis ; Comorbidity ; Hematopoietic Stem Cell Transplantation/methods ; Transplantation Conditioning/methods ; Retrospective Studies
Language	English
Publishing date	2023-12-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2084287-9
ISSN	1520-4383 ; 1520-4391
ISSN (online)	1520-4383
ISSN	1520-4391
DOI	10.1182/hematology.2023000519
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Article: Editorial: Current Perspectives, Challenges and Advances in Cell Based Therapies.

Thakar, Monica S / Cruz, Conrad Russell / Trikha, Prashant

Frontiers in oncology

2020 Volume 9, Page(s) 1061

Language	English
Publishing date	2020-02-06
Publishing country	Switzerland
Document type	Editorial
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2019.01061
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Article: Controlling Cytokine Release Syndrome to Harness the Full Potential of CAR-Based Cellular Therapy.

Thakar, Monica S / Kearl, Tyce J / Malarkannan, Subramaniam

Frontiers in oncology

2020 Volume 9, Page(s) 1529

Abstract: Chimeric Antigen Receptor (CAR)-based therapies offer a promising, targeted approach to effectively treat relapsed or refractory B cell malignancies. However, the treatment-related toxicity defined as cytokine-release syndrome (CRS) often develops in ... ...

Abstract	Chimeric Antigen Receptor (CAR)-based therapies offer a promising, targeted approach to effectively treat relapsed or refractory B cell malignancies. However, the treatment-related toxicity defined as cytokine-release syndrome (CRS) often develops in patients, and if uncontrolled, can be fatal. Grading systems have now been developed to further characterize and objectify clinical findings in order to provide algorithm-based guidance on CRS-related treatment decisions. The pharmacological treatments associated with these algorithms suppress inflammation through a variety of mechanisms and are paramount to improving the safety profile of CAR-based therapies. However, fatalities are still occurring, and there are downsides to these treatments, including the possibility of disrupting CAR-T cell persistence. This review article will describe the clinical presentation and current management of CRS, and through our now deeper understanding of downstream signaling pathways, will provide a molecular framework to formulate new hypotheses regarding clinical applications to contain proinflammatory cytokines responsible for CRS.
Language	English
Publishing date	2020-01-31
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2019.01529
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Article ; Online: The impact of pre-transplant respiratory virus detection on post-transplant outcomes in children undergoing hematopoietic cell transplantation.

Kim, Sara Ruth / Nordlander, Anna / Xie, Hu / Kim, Yae-Jean / Ogimi, Chikara / Thakar, Monica S / Leisenring, Wendy / Englund, Janet A / Boeckh, Michael / Waghmare, Alpana

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2024

Abstract: Background: Pre-transplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay due to high-risk RVs, we examined the impact of pre- ...

Abstract	Background: Pre-transplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay due to high-risk RVs, we examined the impact of pre-transplant RV detection on transplant outcomes in a pediatric HCT recipients. Methods: This retrospective cohort study included myeloablative allogeneic HCT recipients from 2010 to 2019. All patients were screened for RV at least once within 90 days before HCT using RT-PCR, regardless of symptoms. Post-transplant outcomes included days alive and out of hospital (DAOH) and progression to lower respiratory tract infection (LRTI). Results: Among 310 patients, 134 had a RV detected in the 90 days prior to HCT. In univariable analysis, transplant factors including younger age, total body irradiation, umbilical cord blood transplantation, lymphocyte count less than 100/mm3, and HCT comorbidity index score ≥3, and viral factors including symptomatic infection, human rhinovirus (HRV) as a virus type, and symptomatic pre-transplant upper respiratory tract infection (URTI) were associated with fewer DAOH. In multivariable analysis, transplant factors remained significant, but not viral factors. There was a higher incidence of progression to post-transplant LRTI with the same pre-transplant RV if the last positive PCR before HCT was ≤30 days compared to >30 days (p=0.007). Conclusion: In the setting of recommending HCT delay for high-risk RVs, symptomatic URTI, including HRV infections, may lead to increased duration of hospitalization and early progression to LRTI when transplantation is performed within 30 days of the last positive PCR test.
Language	English
Publishing date	2024-04-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciae216
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Zs.A 1505: 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)
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Article ; Online: Case Series: Development of Polyps as a Late Effect After Total Body Irradiation-based Hematopoietic Cell Transplantation in Children With High-risk Leukemia.

Knight, Benjamin / Anderson, Lynnette / Lerner, Diana / Phelan, Rachel / Thakar, Monica S

Journal of pediatric hematology/oncology

2021 Volume 43, Issue 8, Page(s) e1159–e1163

Abstract: Advancements in hematopoietic cell transplantation (HCT) have led to increased survivorship rates in many childhood diseases. However, this growing group of long-term survivors face a myriad of late effects. There are currently limited guidelines for ... ...

Abstract	Advancements in hematopoietic cell transplantation (HCT) have led to increased survivorship rates in many childhood diseases. However, this growing group of long-term survivors face a myriad of late effects. There are currently limited guidelines for surveillance of gastrointestinal polyps for pediatric transplant patients. Here we describe 5 patients undergoing HCT with total body irradiation-based conditioning regimens for leukemia who developed symptomatic polyps a median of 4.5 (range: 0.75 to 5.75) years after HCT. Because of limited surveillance guidelines in children, we conclude that the development of new or progressive symptoms related to the gastrointestinal tract deserves prompt recognition and evaluation.
MeSH term(s)	Adolescent ; Age of Onset ; Child ; Child, Preschool ; Disease Progression ; Female ; Follow-Up Studies ; Hematopoietic Stem Cell Transplantation/adverse effects ; Humans ; Infant ; Leukemia/pathology ; Leukemia/therapy ; Male ; Polyps/etiology ; Polyps/pathology ; Prognosis ; Retrospective Studies ; Transplantation Conditioning ; Whole-Body Irradiation/adverse effects
Language	English
Publishing date	2021-03-27
Publishing country	United States
Document type	Case Reports ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1231152-2
ISSN	1536-3678 ; 1077-4114 ; 0192-8562
ISSN (online)	1536-3678
ISSN	1077-4114 ; 0192-8562
DOI	10.1097/MPH.0000000000002152
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Zs.A 1537: Show issues

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Article ; Online: In Vivo Assessment of NK Cell-Mediated Cytotoxicity by Adoptively Transferred Splenocyte Rejection.

Schloemer, Nathan J / Abel, Alex M / Thakar, Monica S / Malarkannan, Subramaniam

Methods in molecular biology (Clifton, N.J.)

2019 Volume 2097, Page(s) 115–123

Abstract: NK cells are innate lymphocytes that are vital to clearance of virally infected or malignantly transformed cells. Assessment of the cytotoxic response is an important component of NK cell research and investigation of human disease. Standard assays of NK ...

Abstract	NK cells are innate lymphocytes that are vital to clearance of virally infected or malignantly transformed cells. Assessment of the cytotoxic response is an important component of NK cell research and investigation of human disease. Standard assays of NK cell-mediated cytotoxicity of CD107a degranulation or
MeSH term(s)	Adoptive Transfer/methods ; Animals ; Antibodies/metabolism ; Cytotoxicity, Immunologic ; Data Analysis ; Killer Cells, Natural/immunology ; Lymphocyte Depletion ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Spleen/cytology
Chemical Substances	Antibodies
Language	English
Publishing date	2019-11-23
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-0203-4_8
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Article: Circulating natural killer cells and their association with breast cancer and its clinico-pathological characteristics.

Marcelin, Homian N'da / Dasse, Romuald S / Yeboah, Richard O / Tariam, Agnès D / Kagambega, Arsène G Z / Oseni, Akandji M / Kouassi, Y K K / Bilé, Michel A / Toure, Moctar / Thakar, Monica / Adoubi, Innocent / Kizub, Darya

Ecancermedicalscience

2023 Volume 17, Page(s) 1567

Abstract: Purpose: Natural killer (NK) cells play a critical role in cancer immunosurveillance and hold promise as both therapies and prognostic markers in advanced disease. We explore factors that may influence NK cell concentration in the peripheral blood of ... ...

Abstract	Purpose: Natural killer (NK) cells play a critical role in cancer immunosurveillance and hold promise as both therapies and prognostic markers in advanced disease. We explore factors that may influence NK cell concentration in the peripheral blood of women with breast cancer in Côte d'Ivoire compared to healthy controls and implications for future research in our context. Methods: In this cross-sectional case-control study, blood samples were taken from 30 women diagnosed with breast cancer within 6 months of diagnosis and fifteen healthy women at University Teaching Hospital [Centre Hospitalier Universitaire (CHU)] Treichville in Abidjan, Côte d'Ivoire, from March to September 2018. The blood draw could take place at any time following diagnosis and through treatment. Demographic and clinical data were collected. NK cells were isolated, stained, analysed and counted using the flow cytometer at the Department of Immunology at CHU of Cocody. All p-values were two-sided. Results: Mean age among 30 women with breast cancer was 49 years old compared to 45 years old for 15 controls ( Conclusion: Although we did not find an association between NK cell concentration, cancer characteristics or treatment, our results be limited by the small sample size and timing of blood draw. Our next steps include a larger study to explore circulating NK cells prior to any treatment and NK cell infiltration within breast cancer tumour and correlating this with response to treatment and prognosis.
Language	English
Publishing date	2023-07-03
Publishing country	England
Document type	Journal Article
ISSN	1754-6605
ISSN	1754-6605
DOI	10.3332/ecancer.2023.1567
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Article ; Online: Differential use of the hematopoietic cell transplantation-comorbidity index among adult and pediatric transplant physicians.

Broglie, Larisa / Friend, Brian D / Chhabra, Saurabh / Bupp, Caitrin / Schiller, Gary J / Logan, Brent / Pasquini, Marcelo C / Savani, Bipin / Stadtmauer, Edward A / Thakar, Monica S / Sorror, Mohamed

Leukemia & lymphoma

2022 Volume 63, Issue 10, Page(s) 2507–2510

MeSH term(s)	Adult ; Child ; Comorbidity ; Hematopoietic Stem Cell Transplantation ; Humans ; Physicians ; Retrospective Studies ; Transplantation Conditioning ; Transplantation, Homologous
Language	English
Publishing date	2022-05-18
Publishing country	United States
Document type	Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1042374-6
ISSN	1029-2403 ; 1042-8194
ISSN (online)	1029-2403
ISSN	1042-8194
DOI	10.1080/10428194.2022.2076848
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Zs.A 2997: Show issues

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Article ; Online: Safety and Efficacy of Hizentra® Following Pediatric Hematopoietic Cell Transplant for Treatment of Primary Immunodeficiencies.

Patel, Niraj C / Torgerson, Troy / Thakar, Monica S / Younger, M Elizabeth M / Sriaroon, Panida / Pozos, Tamara C / Buckley, Rebecca H / Morris, David / Vilkama, Diana / Heimall, Jennifer

Journal of clinical immunology

2023 Volume 43, Issue 7, Page(s) 1557–1565

Abstract: Primary immunodeficiency disease (PIDD) comprises a group of disorders of immune function. Some of the most severe PIDD can be treated with hematopoietic cell transplant (HCT). Hizentra® is a 20% liquid IgG product approved for subcutaneous ... ...

Abstract	Primary immunodeficiency disease (PIDD) comprises a group of disorders of immune function. Some of the most severe PIDD can be treated with hematopoietic cell transplant (HCT). Hizentra® is a 20% liquid IgG product approved for subcutaneous administration in adults and children greater than 2 years of age with PIDD-associated antibody deficiency. Limited information is available on the use of Hizentra® in children following HCT for PIDD. A multicenter retrospective chart review demonstrated 37 infants and children (median age 70.1 [range 12.0 to 176.4] months) with PIDD treated by HCT who received Hizentra® infusions over a median duration of 31 (range 4-96) months post-transplant. The most common indication for HCT was IL2RG SCID (n = 16). Thirty-two patients switched from IVIG to SCIG administration, due to one or more of the following reasons: patient/caregiver (n = 17) or physician (n = 12) preference, discontinuation of central venous catheter (n = 16), desire for home infusion (n = 12), improved IgG serum levels following lower levels on IVIG (n = 10), and loss of venous access (n = 8). Serious bacterial infections occurred at a rate of 0.041 per patient-year while on therapy. Weight percentile increased by a mean of 16% during the observation period, with females demonstrating the largest gains. Mild local reactions were observed in 24%; 76% had no local reactions. One serious adverse event (death from sepsis) was reported. Hizentra® was discontinued in 15 (41%) patients, most commonly due to recovery of B cell function (n = 11). These data demonstrate that Hizentra® is a safe and effective option in children who have received HCT for PIDD.
MeSH term(s)	Adult ; Infant ; Female ; Humans ; Child ; Immunoglobulins, Intravenous ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects ; Infusions, Subcutaneous ; Immunoglobulin G ; Immunologic Deficiency Syndromes/therapy ; Immunologic Deficiency Syndromes/drug therapy ; Primary Immunodeficiency Diseases
Chemical Substances	Hizentra ; Immunoglobulins, Intravenous ; Immunoglobulin G
Language	English
Publishing date	2023-06-02
Publishing country	Netherlands
Document type	Multicenter Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	779361-3
ISSN	1573-2592 ; 0271-9142
ISSN (online)	1573-2592
ISSN	0271-9142
DOI	10.1007/s10875-023-01482-y
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Zs.A 1640: Show issues

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Article: NK Cell Development and Function in Patients with Fanconi Anemia.

Hashemi, Elaheh / Bjorgaard, Stacey / Wang, Dandan / Uyemura, Bradley / Riese, Matthew / Thakar, Monica S / Malarkannan, Subramaniam

Critical reviews in immunology

2021 Volume 41, Issue 2, Page(s) 35–44

Abstract: Fanconi anemia (FA) is an inherited disorder characterized by diverse congenital malformations, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. The role of the Fanconi anemia pathway in DNA repair mechanisms ... ...

Abstract	Fanconi anemia (FA) is an inherited disorder characterized by diverse congenital malformations, progressive pancytopenia, and predisposition to hematological malignancies and solid tumors. The role of the Fanconi anemia pathway in DNA repair mechanisms and genome instability is well studied. However, the consequences of inherited mutations in genes encoding the FA proteins and the acquired mutations due to impaired DNA repair complex in immune cells are far from understood. Patients with FA show bone marrow failure (BMF) and have a higher risk of developing myelodysplasia (MDS) or acute myeloid leukemia (AML) which are directly related to having chromosomal instability in hematopoietic stem cells and their subsequent progeny. However, immune dysregulation can also be seen in FA. As mature descendants of the common lymphoid progenitor line, NK cells taken from FA patients are dysfunctional in both NK cell-mediated cytotoxicity and cytokine production. The molecular bases for these defects are yet to be determined. However, recent studies have provided directions to define the cause and effect of inherited and acquired mutations in FA patients. Here, we summarize the recent studies in the hematopoietic dysfunction, focusing on the impairment in the development and functions of NK cells in FA patients, and discuss the possible mechanisms and future directions.
MeSH term(s)	Fanconi Anemia/genetics ; Humans ; Killer Cells, Natural ; Leukemia, Myeloid, Acute ; Mutation ; Myelodysplastic Syndromes
Language	English
Publishing date	2021-08-04
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1353116-5
ISSN	1040-8401
ISSN	1040-8401
DOI	10.1615/CritRevImmunol.2021037644
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