Community Academic Profiles - Faculty & Researchers

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Use of cardiac radiation therapy as bridging therapy to CAR-T for relapsed pediatric B-cell acute lymphoblastic leukemia. Pediatric blood & cancer Marquez, C. P., Montiel-Esparza, R., Hui, C., Schultz, L. M., Davis, K. L., Hoppe, R. T., Donaldson, S. S., Ramakrishna, S., Hiniker, S. M. 2020: e28870
Abstract

The use of radiotherapy as bridging therapy to chimeric antigen receptor T-cell therapy (CAR-T) in pre-B acute lymphoblastic leukemia (B-ALL) has been minimally explored. Here, we present a boy with B-ALL who relapsed after allogeneic bone marrow transplant with disseminated disease, including significant symptomatic cardiovascular and gastrointestinal (GI) involvement. The cardiac and GI leukemic infiltrates were successfully treated with bridging radiation therapy (BRT) prior to CAR-T infusion. Using this approach, he successfully tolerated CAR-T with no evidence of disease or sequelae on 3-month follow-up. This is the first reported case of safe and effective delivery of cardiac BRT in B-ALL.

View details for DOI 10.1002/pbc.28870

View details for PubMedID 33355997
Use of Chimeric Antigen Receptor Modified T Cells With Extensive Leukemic Myocardial Involvement JACC: CARDIOONCOLOGY Han, B., Montiel-Esparza, R., Chubb, H., Kache, S., Schultz, L. M., Davis, K. L., Ramakrishna, S., Su, L. 2020; 2 (4): 666?70
View details for DOI 10.1016/j.jaccao.2020.08.009

View details for Web of Science ID 000613114700018
Delayed cancer diagnoses and high mortality in children during the COVID-19 pandemic. Pediatric blood & cancer Ding, Y., Ramakrishna, S., Long, A. H., Phillips, C. A., Montiel-Esparza, R., Diorio, C. J., Bailey, L. C., Maude, S. L., Aplenc, R., Batra, V., Reilly, A. F., Rheingold, S. R., Lacayo, N. J., Sakamoto, K. M., Hunger, S. P. 2020: e28427
View details for DOI 10.1002/pbc.28427

View details for PubMedID 32588960
Immunomodulation with pomalidomide at early lymphocyte recovery after induction chemotherapy in newly diagnosed AML and high-risk MDS LEUKEMIA Zeidner, J. F., Knaus, H. A., Zeidan, A. M., Blackford, A. L., Montiel-Esparza, R., Hackl, H., Prince, G. T., Gondek, L. P., Ghiaur, G., Showel, M. M., DeZern, A. E., Pratz, K. W., Smith, B., Levis, M. J., Gore, S., Coombs, C. C., Foster, M. C., Streicher, H., Karp, J. E., Luznik, L., Gojo, I. 2020
Abstract

An immunosuppressive microenvironment promoting leukemia cell immune escape plays an important role in the pathogenesis of AML. Through its interaction with cereblon, a substrate receptor for the E3 ubiquitin ligase complex, pomalidomide leads to selective ubiquitination of transcription factors Aiolos and Ikaros thereby promoting immune modulation. In this phase I trial, 51 newly diagnosed non-favorable risk AML and high-risk MDS patients were enrolled and treated with AcDVP16 (cytarabine 667?mg/m2/day IV continuous infusion days 1-3, daunorubicin 45?mg/m2 IV days 1-3, etoposide 400?mg/m2 IV days 8-10) induction therapy followed by dose- and duration-escalation pomalidomide beginning at early lymphocyte recovery. Forty-three patients (AML: n?=?39, MDS: n?=?4) received pomalidomide. The maximum tolerated dose of pomalidomide was 4?mg for 21 consecutive days. The overall complete remission (CR?+?CRi) rate, median overall survival, and disease-free survival were 75%, 27.1 and 20.6 months, respectively. Subset analyses revealed 86% CR/CRi rate in AML patients with unfavorable-risk karyotype treated with pomalidomide. Pomalidomide significantly decreased Aiolos expression in both CD4+ and CD8+ peripheral blood and bone marrow T cells, promoted T cell differentiation, proliferation, and heightened their cytokine production. Finally, pomalidomide induced�distinct gene expression changes in immune function-related ontologies in CD4+ and CD8+ T cells.

View details for DOI 10.1038/s41375-019-0693-4

View details for Web of Science ID 000508141700001

View details for PubMedID 31900407
Use of Chimeric Antigen Receptor Modified T Cells With Extensive Leukemic Myocardial Involvement JACC: CardioOncology Han, B., Montiel-Esparza, R., Chubb, H., Kache, S., Schultz, L. M., Davis, K. L., Su, L. 2020; 2 (4)
A Novel Case of Carcinoid Tumor in a Pediatric Patient With Short Bowel Syndrome Secondary to Gastroschisis J Pediatr Gastroenterol Nutr Huang, A. C., Montiel-Esparza, R., Scott, G., Martin, B., Bruzoni, M., Kadapakkam, M., Namjoshi, S. S. 2020; 1 (2)
View details for DOI 10.1097/PG9.0000000000000023
A Signature of T Cell Exhaustion Is Enriched in the Bone Marrow (BM) of AML Patients and Shared with Immune Exhaustion Signatures of Solid Tumors Knaus, H. A., Hackl, H., Blackford, A., Berglund, S., Montiel-Esparza, R., Zeidner, J. F., Gojo, I., Luznik, L. AMER SOC HEMATOLOGY. 2019
View details for DOI 10.1182/blood-2019-128742

View details for Web of Science ID 000577160406092
Connecting the Dots From Fever of Unknown Origin to Myelodysplastic Syndrome: GATA2 Haploinsufficiency. Journal of pediatric hematology/oncology Montiel-Esparza, R., Reys, B., Rogers, Z. R., Evans, A. S., Wysocki, C. A., Timmons, C., Dickerson, K. E. 2019
Abstract

Leukemia-predisposing conditions, such as GATA2 haploinsufficiency, are known for their high penetrance and expressivity profiles. These disorders pose a difficult diagnostic challenge to even the most experienced clinician when they first present. We describe the case of a 17-year-old male presenting with features of nontuberculous mycobacterial infection, pulmonary fibrinoid granulomatous vasculitis, and myelodysplasia in the setting of a pathogenic GATA2 frameshift mutation confirmed by next-generation sequencing. The broad differential for GATA2 haploinsufficiency requires prompt recognition of key clinical features and laboratory abnormalities towards directing diagnosis and guiding appropriate and perhaps life-saving therapy.

View details for DOI 10.1097/MPH.0000000000001505

View details for PubMedID 31033783
Effective Immunomodulation with Pomalidomide Beginning at Early Lymphocyte Recovery during Induction Timed Sequential Therapy (TST) for Acute Myeloid Leukemia (AML) and High-Risk Myelodysplasia (HR-MDS) Zeidner, J. F., Knaus, H., Zeidan, A. M., Blackford, A., Montiel-Esparza, R., Prince, G. T., Gondek, L. P., Ghiaur, G., Showel, M. M., DeZern, A. E., Pratz, K. W., Smith, B., Levis, M. J., Foster, M. C., Coombs, C. C., Streicher, H., Karp, J. E., Luznik, L., Gojo, I. AMER SOC HEMATOLOGY. 2018
View details for DOI 10.1182/blood-2018-99-114961

View details for Web of Science ID 000454837601044
Signatures of CD8(+) T cell dysfunction in AML patients and their reversibility with response to chemotherapy JCI INSIGHT Knaus, H. A., Berglund, S., Hackl, H., Blackford, A. L., Zeidner, J. F., Montiel-Esparza, R., Mukhopadhyay, R., Vanura, K., Blazar, B. R., Karp, J. E., Luznik, L., Gojo, I. 2018; 3 (21)
Abstract

Our understanding of phenotypic and functional signatures of CD8+ T cell dysfunction in acute myeloid leukemia (AML) is limited. Deciphering these deranged T cell functional states and how they are impacted by induction chemotherapy is essential for incorporation of novel immune-based strategies to restore and maintain antileukemia immunity.We utilized high-dimensional immunophenotyping, gene expression, and functional studies to characterize peripheral blood and bone marrow CD8+ T cells in 72 AML patients at diagnosis and after induction chemotherapy.Our data suggest that multiple aspects of deranged T cell function are operative in AML at diagnosis, with exhaustion and senescence being the dominant processes. Following treatment, the phenotypic and transcriptional profile of CD8+ T cells diverged between responders and nonresponders. Response to therapy correlated with upregulation of costimulatory, and downregulation of apoptotic and inhibitory, T cell signaling pathways, indicative of restoration of T cell function. In functional studies, AML blasts directly altered CD8+ T cell viability, expansion, co-signaling and senescence marker expression. This CD8+ T cell dysfunction was in part reversible upon PD-1 blockade or OX40 costimulation in vitro.Our findings highlight the uniqueness of AML in sculpting CD8+ T cell responses and the plasticity of their signatures upon chemotherapy response, providing a compelling rationale for integration of novel immunotherapies to augment antileukemia immunity.This work was supported by the Leukemia & Lymphoma Society grant no. 6449-13; NIH grants UM1-CA186691 and R01-HL110907-01; the American Society for Blood and Marrow Transplantation New Investigator Award/Gabrielle's Angel Foundation; the Vienna Fund for Innovative Cancer Research; and by fellowships from the Wenner-Gren Foundation and the Swedish Society for Medical Research.

View details for DOI 10.1172/jci.insight.120974

View details for Web of Science ID 000449225900004

View details for PubMedID 30385732

View details for PubMedCentralID PMC6238744
Acute Myeloid Leukemia (AML) Blasts Influence the Gene Expression Signature and Co-Signaling Receptor Expression of CD8(+) T Cells Knaus, H. A., Berglund, S., Hackl, H., Montiel-Esparza, R., Levis, M. J., Karp, J. E., Gojo, I., Luznik, L. AMER SOC HEMATOLOGY. 2016
View details for DOI 10.1182/blood.V128.22.1700.1700

View details for Web of Science ID 000394452306011
Phase 1 Study of Pomalidomide Given at the Time of Early Lymphocyte Recovery after Induction Timed Sequential Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) and High-Risk Myelodysplastic Syndrome (HR-MDS) Zeidner, J. F., Montiel-Esparza, R., Knaus, H. A., Berglund, S., Zeidan, A. M., McCurdy, S. R., Prince, G. T., Gondek, L. P., Ghiaur, G., Showel, M. M., DeZern, A. E., Pratz, K. W., Smith, B., Levis, M. J., Foster, M. C., Jamieson, K., Van Deventer, H. W., Streicher, H., Karp, J. E., Luznik, L., Gojo, I. AMER SOC HEMATOLOGY. 2016
View details for DOI 10.1182/blood.V128.22.2820.2820

View details for Web of Science ID 000394452305092
Immune Modulation with Pomalidomide after Induction Chemotherapy in Newly Diagnosed Acute Myeloid Leukemia (AML) Montiel-Esparza, R., Knaus, H. A., Zeidner, J. F., Vulic, A., Prince, G. T., Smith, B., Levis, M. J., Streicher, H., Karp, J. E., Luznik, L., Gojo, I. AMER SOC HEMATOLOGY. 2015
View details for Web of Science ID 000368019004151
Tracking Effector T Cell Dynamics and Immune Inhibitory Receptors in Patients with Acute Myeloid Leukemia (AML) Knaus, H. A., Montiel-Esparza, R., Zeidner, J. F., Blackford, A., Kanakry, C. G., Vulic, A., Levis, M. J., Karp, J. E., Luznik, L., Gojo, I. AMER SOC HEMATOLOGY. 2015
View details for Web of Science ID 000368021800106

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Ra�l Montiel-Esparza

Affiliate, Dean's Office Operations - Dean OtherFellow in Pediatrics - Hematology & Oncology

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Affiliate, Dean's Office Operations - Dean Other
Fellow in Pediatrics - Hematology & Oncology

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