Karen Chao

All Publications

• Access to CARe: A Narrative of Real-World Medical Decision-Making to Access Chimeric Antigen Receptor (CAR) T-Cell Therapy in Children, Adolescents, and Young Adults. Pediatric blood & cancer Steineck, A., Chao, K., Hall, A. G., Jacoby, E., Leahy, A. B., Ligon, J. A., Luciani, K., Schultz, L. M., Summers, C. N., Ward, L., Winestone, L. E., Shah, N. N. 2025: e31516

  Abstract

  Chimeric antigen receptor (CAR) T-cell therapy is a potentially life-saving treatment for children with relapsed/refractory B-cell hematologic malignancies, and remains an important investigational therapy for other childhood cancers. Yet, access to this class of therapies remains suboptimal through both commercial use and clinical trials, especially in children, adolescents, and young adults. Using a series of case-based discussions, we outline guidance on real-world medical decision-making, and offer potential solutions to enhancing access to CAR T-cell therapy as a treatment modality.

  View details for DOI 10.1002/pbc.31516

  View details for PubMedID 39844726

• Establishing Costs for Commercial Chimeric Antigen Receptor T-Cell (Tisagenlecleucel; Kymriah) in Children and Young Adult B-Cell Acute Lymphoblastic Leukemia; A Merged Analysis from the Prwcc and PHIS Satwani, P., Chao, K., Lopez-Garcia, M., Hall, M., Jin, Z., Winestone, L. E., Friedman, D., Phelan, R., Baggott, C., John, S., Pacenta, H. L., Laetsch, T. W., Phillips, C. L., Verneris, M. R., Fabrizio, V. A., Keating, A., Talano, J., Moskop, A., Baumeister, S. C., Qayed, M., Myers, D., Hall, E., Prabhu, S., Khanh Nguyen, Carr, C. A., Mackall, C. L., Lin, J. K., Goldhaber-Fiebert, J., Schultz, L. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-187462

  View details for Web of Science ID 001159900806281

• INSPIRED Symposium Part 4A: Access to CAR T cell Therapy in Unique Populations with B-cell Acute Lymphoblastic Leukemia. Transplantation and cellular therapy Winestone, L. E., Bhojwani, D., Ghorashian, S., Muffly, L., Leahy, A. B., Chao, K., Steineck, A., Rossig, C., Lamble, A., Maude, S. L., Myers, R., Rheingold, S. R. 2023

  Abstract

  Tisagenlecleucel's approval in children with B-cell acute lymphoblastic leukemia (B-ALL) was based on the phase 2 ELIANA trial, a global registration study. The ELIANA trial, however, excluded specific subsets of patients facing unique challenges and did not include enough patients to adequately evaluate outcomes in rare sub-populations. Since commercialization of tisagenlecleucel, data has become available that supports therapeutic indications beyond the specific cohorts previously eligible for Chimeric Antigen receptor targeted to CD19 (CD19 CAR) cell therapy on the registration clinical trial. Substantial real-world data and aggregate clinical trial data have addressed gaps in our understanding of response rates, longer-term efficacy, and toxicities associated with CD19 CAR T cells in special populations and rare clinical scenarios. This includes patients with central nervous system-relapsed disease, as they were excluded from ELIANA and other early CAR T cell trials due to concerns about risk of neurotoxicity that have not been born out. There is also interest in the use of CD19 CAR T cells for very high risk patients earlier in the course of therapy, such as patients with persistent minimal residual disease after two cycles of upfront chemotherapy and patients with first relapse of B-ALL. However, these indications are not part of the label for tisagenlecleucel and were historically not included in eligibility criteria for most clinical trials; data addressing these populations is needed. Populations at high risk of relapse, including patients with high-risk cytogenetic lesions, infants with B-ALL, patients with trisomy 21, and young adults with B-ALL may also benefit from earlier treatment with CD19 CAR T cell therapy. It is important to prospectively study patient-reported outcomes given the differential toxicity expected between CD19 CAR T cell therapy and the historic standard of care, hematopoietic cell transplant. Now that CD19 CAR T cell therapy is commercially available, studies evaluating potential access disparities created by this very expensive novel therapy are increasingly pressing.

  View details for DOI 10.1016/j.jtct.2023.10.005

  View details for PubMedID 37821078

• Potential clinical use of azacitidine and MEK inhibitor combination therapy in PTPN11-mutated juvenile myelomonocytic leukemia. Molecular therapy : the journal of the American Society of Gene Therapy Pasupuleti, S. K., Chao, K., Ramdas, B., Kanumuri, R., Palam, L. R., Liu, S., Wan, J., Annesley, C., Loh, M. L., Stieglitz, E., Burke, M. J., Kapur, R. 2023

  Abstract

  Juvenile myelomonocytic leukemia (JMML) is a rare myeloproliferative neoplasm of childhood. The molecular hallmark of JMML is hyperactivation of the Ras/MAPK pathway with the most common cause being mutations in the gene PTPN11, encoding the protein tyrosine phosphatase SHP2. Current strategies for treating JMML include using the hypomethylating agent, 5-azacitidine (5-Aza) or MEK inhibitors trametinib and PD0325901 (PD-901), but none of these are curative as monotherapy. Utilizing an Shp2E76K/+ murine model of JMML, we show that the combination of 5-Aza and PD-901 modulates several hematologic abnormalities often seen in JMML patients, in part by reducing the burden of leukemic hematopoietic stem and progenitor cells (HSC/Ps). The reduced JMML features in drug-treated mice were associated with a decrease in p-MEK and p-ERK levels in Shp2E76K/+ mice treated with the combination of 5-Aza and PD-901. RNA-sequencing analysis revealed a reduction in several RAS and MAPK signaling-related genes. Additionally, a decrease in the expression of genes associated with inflammation and myeloid leukemia was also observed in Shp2E76K/+ mice treated with the combination of the two drugs. Finally, we report two patients with JMML and PTPN11 mutations treated with 5-Aza, trametinib, and chemotherapy who experienced a clinical response because of the combination treatment.

  View details for DOI 10.1016/j.ymthe.2023.01.030

  View details for PubMedID 36739480

• Real-world experience in treating pediatric relapsed/refractory or therapy-related myeloid malignancies with decitabine, vorinostat, and FLAG therapy based on a phase 1 study run by the TACL consortium PEDIATRIC BLOOD & CANCER Schafer, E. S., Chao, K., Stevens, A. M., Jo, E., Hilsenbeck, S. G., Gossai, N. P., Doan, A., Colace, S. I., Guinipero, T., Otterson, D., Kaplan, J. A., Hinson, A., Pommert, L., Wayne, A. S., Bhojwani, D., Burke, M. J. 2022; 69 (10)

  View details for DOI 10.1002/pbc.29812

  View details for Web of Science ID 000813817300001

  View details for PubMedID 35726868

• Outcomes of Hispanic and non-Hispanic white pediatric and young adult patients with B-cell acute lymphoblastic leukemia after commercial tisagenlecleucel. Vandris, P., Chao, K., Baggott, C., Phillips, C. L., Qayed, M., Rossoff, J., Lim, S., Winestone, L. E., Stefanski, H. E., Talano, J. M., Margossian, S., Verneris, M. R., Myers, G., Karras, N. A., Brown, P. A., Satwani, P., Mackall, C., Curran, K. J., Laetsch, T., Schultz, L. M. LIPPINCOTT WILLIAMS & WILKINS. 2022

  View details for Web of Science ID 000863680300019