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CANCEL
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David Shyr, MD

  • David Chung-Chuan Shyr

Specialties

Hematology-Oncology

Work and Education

Professional Education

Medical College of Wisconsin, Milwaukee, WI, 5/20/2005

Residency

University of California, San Diego, San Diego, CA, 6/30/2008

Fellowship

Baylor College of Medicine-Pediatric Hematology/Oncology Fellowship, Houston, TX, 06/30/2012

Children's Hospital of Orange County Hematology/Oncology Fellowship, Orange, CA, 06/30/2011

Board Certifications

Pediatric Hematology-Oncology, American Board of Pediatrics

All Publications

Precision Delivery of Steroids as a Rescue Therapy for Gastrointestinal Graft-versus-Host Disease in Pediatric Stem Cell Transplant Recipients Journal of Clinical Medicine Levitte, s., Ganguly, A., Frolik, S., Guevara-Tique, A., et al 2023; 12 (4229)

View details for DOI 10.3390/jcm12134229

Correction to: Infections in Infants with SCID: Isolation, Infection Screening and Prophylaxis in PIDTC Centers. Journal of clinical immunology Dorsey, M., Wright, N. A., Chaimowitz, N. S., Davila Saldana, B. J., Miller, H., Keller, M. D., Thakar, M. S., Shah, A. J., Abu-Arja, R., Andolina, J., Aquino, V., Barnum, J. L., Bednarski, J. J., Bhatia, M., Bonilla, F. A., Butte, M. J., Bunin, N. J., Burroughs, L. M., Chandra, S., Chaudhury, S., Chen, K., Chong, H., Cuvelier, G., Dalal, J., DeFelice, M. L., DeSantes, K. B., Forbes, L. R., Gillio, A., Goldman, F., Joshi, A. Y., Kapoor, N., Knutsen, A. P., Kobrynski, L., Lieberman, J. A., Leiding, J. W., Oshrine, B., Patel, K. P., Prockop, S., Quigg, T. C., Quinones, R., Schultz, K. R., Seroogy, C., Shyr, D., Siegel, S., Smith, A. R., Torgerson, T. R., Vander Lugt, M. T., Yu, L. C., Cowan, M. J., Buckley, R. H., Dvorak, C. C., Griffith, L. M., Haddad, E., Kohn, D. B., Logan, B., Notarangelo, L. D., Pai, S., Puck, J., Pulsipher, M. A., Heimall, J. 2020

Abstract

A Correction to this paper has been published: https://doi.org/10.1007/s10875-020-00917-0.

View details for DOI 10.1007/s10875-020-00917-0

View details for PubMedID 33274413

HLA-haplotype loss after TCRalphabeta/CD19-depleted haploidentical HSCT. Bone marrow transplantation Shyr, D. C., Zhang, B. M., Saini, G., Madani, N. D., Schultz, L. M., Patel, S., Kristovich, K., Fernandez-Vina, M., Bertaina, A. 2020

View details for DOI 10.1038/s41409-020-01081-0

View details for PubMedID 33070150

Infections in Infants with SCID: Isolation, Infection Screening, and Prophylaxis in PIDTC Centers. Journal of clinical immunology Dorsey, M. J., Wright, N. A., Chaimowitz, N. S., Davila Saldana, B. J., Miller, H., Keller, M. D., Thakar, M. S., Shah, A. J., Abu-Arja, R., Andolina, J., Aquino, V., Barnum, J. L., Bednarski, J. J., Bhatia, M., Bonilla, F. A., Butte, M. J., Bunin, N. J., Chandra, S., Chaudhury, S., Chen, K., Chong, H., Cuvelier, G. D., Dalal, J., DeFelice, M. L., DeSantes, K. B., Forbes, L. R., Gillio, A., Goldman, F., Joshi, A. Y., Kapoor, N., Knutsen, A. P., Kobrynski, L., Lieberman, J. A., Leiding, J. W., Oshrine, B., Patel, K. P., Prockop, S., Quigg, T. C., Quinones, R., Schultz, K. R., Seroogy, C., Shyr, D., Siegel, S., Smith, A. R., Torgerson, T. R., Vander Lugt, M. T., Yu, L. C., Cowan, M. J., Buckley, R. H., Dvorak, C. C., Griffith, L. M., Haddad, E., Kohn, D. B., Logan, B., Notarangelo, L. D., Pai, S., Puck, J., Pulsipher, M. A., Heimall, J. 2020

Abstract

PURPOSE: The Primary Immune Deficiency Treatment Consortium (PIDTC) enrolled children with severe combined immunodeficiency (SCID) in a prospective natural history study of hematopoietic stem cell transplant (HSCT) outcomes over the last decade. Despite newborn screening (NBS) for SCID, infections occurred prior to HSCT. This study's objectives were to define the types and timing of infection prior to HSCT in patients diagnosed via NBS or by family history (FH) and to understand the breadth of strategies employed at PIDTC centers for infection prevention.METHODS: We analyzed retrospective data on infections and pre-transplant management in patients with SCID diagnosed by NBS and/or FH and treated with HSCT between 2010 and 2014. PIDTC centers were surveyed in 2018 to understand their practices and protocols for pre-HSCT management.RESULTS: Infections were more common in patients diagnosed via NBS (55%) versus those diagnosed via FH (19%) (p=0.012). Outpatient versus inpatient management did not impact infections (47% vs 35%, respectively; p=0.423). There was no consensus among PIDTC survey respondents as to the best setting (inpatient vs outpatient) for pre-HSCT management. While isolation practices varied, immunoglobulin replacement and antimicrobial prophylaxis were more uniformly implemented.CONCLUSION: Infants with SCID diagnosed due to FH had lower rates of infection and proceeded to HSCT more quickly than did those diagnosed via NBS. Pre-HSCT management practices were highly variable between centers, although uses of prophylaxis and immunoglobulin support were more consistent. This study demonstrates a critical need for development of evidence-based guidelines for the pre-HSCT management of infants with SCID following an abnormal NBS.TRIAL REGISTRATION: NCT01186913.

View details for DOI 10.1007/s10875-020-00865-9

View details for PubMedID 33006109

Excellent Outcomes Following Hematopoietic Cell Transplantation for Wiskott-Aldrich Syndrome: A PIDTC Report. Blood Burroughs, L., Petrovic, A., Brazauskas, R., Liu, X., Griffith, L. M., Ochs, H. D., Bleesing, J., Edwards, S., Dvorak, C. C., Chaudhury, S., Prockop, S., Quinones, R., Goldman, F., Quigg, T., Chandrakasan, S., Smith, A. R., Parikh, S. H., Davila Saldana, B. J., Thakar, M. S., Phelan, R., Shenoy, S., Forbes, L. R., Martinez, C. A., Chellapandian, D., Shereck, E., Miller, H., Kapoor, N., Barnum, J. L., Chong, H., Shyr, D., Chen, K., Abu-Arja, R. F., Shah, A., Weinacht, K., Moore, T. B., Joshi, A., DeSantes, K., Gillio, A. P., Cuvelier, G. D., Keller, M. D., Rozmus, J., Torgerson, T. R., Pulsipher, M. A., Haddad, E., Sullivan, K., Logan, B. R., Kohn, D. B., Puck, J. M., Notarangelo, L. D., Pai, S., Rawlings, D., Cowan, M. J. 2020

Abstract

Wiskott-Aldrich syndrome (WAS) is an X-linked disease caused by mutations in the WAS gene leading to thrombocytopenia, eczema, recurrent infections, autoimmune disease, and malignancy. Hematopoietic cell transplantation (HCT) is the primary curative approach, with the goal of correcting the underlying immunodeficiency and thrombocytopenia. HCT outcomes have improved over time, particularly for patients with HLA-matched sibling and unrelated donors. Here we report the outcomes of 129 patients with WAS who underwent HCT at 29 Primary Immune Deficiency Treatment Consortium centers between 2005 and 2015. Median age at HCT was 1.2 years. Most patients (65%) received myeloablative busulfan-based conditioning. With a median follow-up of 4.5 years, the 5-year overall survival (OS) was 91%. Superior 5-year OS was observed in patients <5 vs. 5 years old at the time of HCT (94% vs. 66%, overall p=0.0008). OS was excellent regardless of donor type even in cord blood recipients (90%). Conditioning intensity did not impact OS, but was associated with donor T-cell and myeloid engraftment post-HCT. Specifically, patients who received fludarabine/melphalan-based reduced-intensity regimens were more likely to have donor myeloid chimerism <50% early post-HCT. In addition, higher platelet counts were observed among recipients who achieved full (>95%) versus low-level (5%-49%) donor myeloid engraftment. In summary, HCT outcomes for WAS have improved since 2005 compared to prior reports. HCT at a younger age continues to be associated with superior outcomes supporting the recommendation for early HCT. High-level donor myeloid engraftment is important for platelet reconstitution following either myeloablative or busulfan-containing reduced intensity conditioning. (www.clinicaltrials.gov NCT02064933.).

View details for DOI 10.1182/blood.2019002939

View details for PubMedID 32268350

Experience with Ruxolitinib (Jakafi (R)) As a Salvage Therapy for Graft-Versus-Host Disease in Children and Young Adults Mavers, M., Klinger, E., Shyr, D. C., Shah, A. J., Bertaina, A., Soni, S. ELSEVIER SCIENCE INC. 2020: S179
Transplantation Outcomes for Children with Severe Combined Immune Deficiency (SCID) Have Improved over Time: A 36-Year Summary Report By the Primary Immune Deficiency Treatment Consortium (PIDTC) Thakar, M. S., Logan, B., Buckley, R. H., Haddad, E., Dvorak, C. C., O'Reilly, R. J., Kapoor, N., Satter, L., Martinez, C., Pai, S., Heimall, J., Jyonouchi, S., Sullivan, K. E., Chandra, S., Smith, A. R., Chaudhury, S., Saldana, B., Sunkersett, G., Shyr, D. C., Burroughs, L. M., Petrovic, A., Quigg, T. C., Shenoy, S., Bednarski, J. J., DeSantes, K., Cuvelier, G. E., Chandrakasan, S., Gillio, A. P., Knutsen, A. P., Eissa, H., Goldman, F., Moore, T. B., Aquino, V., Shereck, E., Lugt, M., Caywood, E. H., Yu, L. C., Rozmus, J., Talano, J. M., Malech, H. L., Shah, A. J., Abu-Arja, R., Miller, H. K., Bani-Hashemi, T., Chang, C. K., Dunn, E., Torgerson, T., Pulsipher, M. A., Griffith, L. M., Cowan, M. J., Kohn, D. B., Puck, J., Notarangelo, L. D. ELSEVIER SCIENCE INC. 2020: S18S19
Hematopoietic Cell Transplantation in Patients With Primary Immune Regulatory Disorders (PIRD): A Primary Immune Deficiency Treatment Consortium (PIDTC) Survey. Frontiers in immunology Chan, A. Y., Leiding, J. W., Liu, X., Logan, B. R., Burroughs, L. M., Allenspach, E. J., Skoda-Smith, S., Uzel, G., Notarangelo, L. D., Slatter, M., Gennery, A. R., Smith, A. R., Pai, S., Jordan, M. B., Marsh, R. A., Cowan, M. J., Dvorak, C. C., Craddock, J. A., Prockop, S. E., Chandrakasan, S., Kapoor, N., Buckley, R. H., Parikh, S., Chellapandian, D., Oshrine, B. R., Bednarski, J. J., Cooper, M. A., Shenoy, S., Davila Saldana, B. J., Forbes, L. R., Martinez, C., Haddad, E., Shyr, D. C., Chen, K., Sullivan, K. E., Heimall, J., Wright, N., Bhatia, M., Cuvelier, G. D., Goldman, F. D., Meyts, I., Miller, H. K., Seidel, M. G., Vander Lugt, M. T., Bacchetta, R., Weinacht, K. G., Andolina, J. R., Caywood, E., Chong, H., de la Morena, M. T., Aquino, V. M., Shereck, E., Walter, J. E., Dorsey, M. J., Seroogy, C. M., Griffith, L. M., Kohn, D. B., Puck, J. M., Pulsipher, M. A., Torgerson, T. R. 2020; 11: 239

Abstract

Primary Immune Regulatory Disorders (PIRD) are an expanding group of diseases caused by gene defects in several different immune pathways, such as regulatory T cell function. Patients with PIRD develop clinical manifestations associated with diminished and exaggerated immune responses. Management of these patients is complicated; oftentimes immunosuppressive therapies are insufficient, and patients may require hematopoietic cell transplant (HCT) for treatment. Analysis of HCT data in PIRD patients have previously focused on a single gene defect. This study surveyed transplanted patients with a phenotypic clinical picture consistent with PIRD treated in 33 Primary Immune Deficiency Treatment Consortium centers and European centers. Our data showed that PIRD patients often had immunodeficient and autoimmune features affecting multiple organ systems. Transplantation resulted in resolution of disease manifestations in more than half of the patients with an overall 5-years survival of 67%. This study, the first to encompass disorders across the PIRD spectrum, highlights the need for further research in PIRD management.

View details for DOI 10.3389/fimmu.2020.00239

View details for PubMedID 32153572

SCID genotype and 6-month posttransplant CD4 count predict survival and immune recovery BLOOD Haddad, E., Logan, B. R., Griffith, L. M., Buckley, R. H., Parrott, R. E., Prockop, S. E., Small, T. N., Chaisson, J., Dvorak, C. C., Mumane, M., Kapoor, N., Abdel-Azim, H., Hanson, I. C., Martinez, C., Bleesing, J. H., Chandra, S., Smith, A. R., Cavanaugh, M. E., Jyonouchi, S., Sullivan, K. E., Burroughs, L., Skoda-Smith, S., Haight, A. E., Tumlin, A. G., Quigg, T. C., Taylor, C., Saldana, B., Keller, M. D., Seroogy, C. M., Desantes, K. B., Petrovic, A., Leiding, J. W., Shyr, D. C., Decaluwe, H., Teira, P., Gillio, A. P., Knutsen, A. P., Moore, T. B., Kletzel, M., Craddock, J. A., Aquino, V., Davis, J. H., Yu, L. C., Cuvelier, G. E., Bednarski, J. J., Goldman, F. D., Kang, E. M., Shereck, E., Porteus, M. H., Connelly, J. A., Fleisher, T. A., Malech, H. L., Shearer, W. T., Szabolcs, P., Thakar, M. S., Vander Lugt, M. T., Heimall, J., Yin, Z., Pulsipher, M. A., Pai, S., Kohn, D. B., Puck, J. M., Cowan, M. J., O'Reilly, R. J., Notarangelo, L. D. 2018; 132 (17): 173749

Abstract

The Primary Immune Deficiency Treatment Consortium (PIDTC) performed a retrospective analysis of 662 patients with severe combined immunodeficiency (SCID) who received a hematopoietic cell transplantation (HCT) as first-line treatment between 1982 and 2012 in 33 North American institutions. Overall survival was higher after HCT from matched-sibling donors (MSDs). Among recipients of non-MSD HCT, multivariate analysis showed that the SCID genotype strongly influenced survival and immune reconstitution. Overall survival was similar for patients with RAG, IL2RG, or JAK3 defects and was significantly better compared with patients with ADA or DCLRE1C mutations. Patients with RAG or DCLRE1C mutations had poorer immune reconstitution than other genotypes. Although survival did not correlate with the type of conditioning regimen, recipients of reduced-intensity or myeloablative conditioning had a lower incidence of treatment failure and better T- and B-cell reconstitution, but a higher risk for graft-versus-host disease, compared with those receiving no conditioning or immunosuppression only. Infection-free status and younger age at HCT were associated with improved survival. Typical SCID, leaky SCID, and Omenn syndrome had similar outcomes. Landmark analysis identified CD4+ and CD4+CD45RA+ cell counts at 6 and 12 months post-HCT as biomarkers predictive of overall survival and long-term T-cell reconstitution. Our data emphasize the need for patient-tailored treatment strategies depending upon the underlying SCID genotype. The prognostic significance of CD4+ cell counts as early as 6 months after HCT emphasizes the importance of close follow-up of immune reconstitution to identify patients who may need additional intervention to prevent poor long-term outcome.

View details for PubMedID 30154114

View details for PubMedCentralID PMC6202916

Genotype, Phenotype and T Cell Counts at One Year Predict Survival and Long Term Immune Reconstitution after Transplantation in Severe Combined Immune Deficiency (SCID)-The Primary Immune Deficiency Treatment Consortium (PIDTC) Haddad, E., Logan, B. R., Griffith, L. M., Buckley, R. H., Parrott, R. E., Dvorak, C. C., Puck, J., Prockop, S. E., Kapoor, N., Abdel-Azim, H., Hanson, I. C., Martinez, C., Bleesing, J., Chandra, S., Smith, A. R., Pai, S., Jyonouchi, S., Sullivan, K., Haight, A. E., Tumlin, A. G., Burroughs, L., Saldana, B., Seroogy, C., Petrovic, A., Shyr, D. C., Quigg, T. C., Gillio, A. P., Decaluwe, H., Kletzel, M., Knutsen, A., Moore, T. B., Aquino, V., Davis, J. H., Yu, L. C., Kang, E. M., Schroeder, M. L., Shereck, E., Craddock, J. A., Connelly, J. A., Bednarski, J. J., Goldman, F., Porteus, M. H., Fleisher, T., Kohn, D. B., Malech, H. L., Pulsipher, M. A., Shearer, W., Szabolcs, P., Thakar, M., Lugt, M., Yin, Z., Notarangelo, L. D., Cowan, M. J., O'Reilly, R. J. ELSEVIER SCIENCE INC. 2017: S101S102