My research uses a bedside-to-bench-to-bedside approach to translate novel immunotherapies for high risk leukemias and to understand and influence complications of hematopoietic cell transplantation (HCT), such as graft versus host disease and graft failure. I recently received R01 funding to use blood and imaging biomarkers to identify graft failure after transplantation. The imaging modality is an investigational nuclear medicine modality, F18-labeled thymidine, which we previously showed identified subclinical engraftment early after HCT.
I have two projects in the space of immunotherapy: a genetically modified T cell platform and one that relies on expanded T cells specific for tumor antigens. We are initiating a novel chimeric antigen receptor T cell therapy within Children's Healthcare of Atlanta (using the Prodigy) with plans to study this novel therapy (thanks to the Peach Bowl LegACy fund). In addition, thanks to Leukemia Lymphoma Society funding, we are expanding T cells to multiple tumor antigens, enhancing their activity through a novel cytokine release system, to treat relapsed refractory acute myeloid leukemia and myelodysplastic syndrome. These studies will utilize novel biomarkers of disease burden and immune response. Finally, I have conducted biomarker and treatment studies to treat a rare but deadly complication of HCT, lung graft versus host disease, and am fortunate to continue this work with national collaborators.
Williams KM, Holter Chakrabarty J. Imaging haematopoietic stem cells and microenvironment dynamics through transplantation. Lancet Haematology. February 2020
Williams KM and Holter Chakrabarty J, Lindenberg L, Duong Q, Vesely S, Nguyen CT, Havlicek JP, Kurdziel K, Gea-Banacloche J, Lin FI, Avila DN, Selby G, Kanakry CG, Li S, Scordino T, Adler S, Bollard CM, Choyke P, and Gress RE. Imaging of subclinical haemopoiesis after stem-cell transplantation in patients with haematological malignancies: a prospective pilot study. Lancet Haematolog. 2018. 5(1):44-52.
Williams KM. How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. Blood, 2017. 129(4):448-455.
Cheng GS, Storer B, Chein JW, Jagasia M, Hubbard JJ, Burns L, Ho VT, Pidala J, Palmer L, Mayer S, Crothers K, Pusic I, Lee SJ, Williams KM. Lung function trajectory in bronchiolitis obliterans syndrome after allogeneic hematopoietic transplant. Ann. Am. Thoracic Soc. 2016. 13(11):1932-1939.
Williams KM, Cheng GC, Pusic I, Jagasia M, Burns L, Ho V, Pidala J, Palmer J, Johnston L, Mayer S, Chien JW, Jacobsohn DA, Pavletic SZ, Martin PJ, Storer BE, Inamoto Y, Chai X, Flowers MED, Lee SJ. FAM treatment for new onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016. 22(4):710-716.
Williams KM, Chien JW, Gladwin MT, Pavletic SZ. Bronchiolitis Obliterans After Allogeneic Hematopoieitc Stem Cell Transplantation- An Increasingly Recognized Manifestation of Chronic Graft-versus-Host Disease. Journal of American Medical Association. 2009. 302(2):206-214.
Williams KM and Gress RE. Immune Reconstitution and Implications for Immunotherapy Following Hematopoietic Stem Cell Transplantation. Best Practice and Research Clinical Haematology. 2008. 21(3):579-596.
Leukemia and Lymphoma Society LLS TRP – 07/01/2018-10/31/2021
Initiation of a Novel Immunotherapeutic to Safely Eradicate Acute Leukemia
NHLBI/NIH - 1R01HL146668-01 – 08/26/2019-07/31/2024
Imaging and Blood Biomarkers to Predict Graft Failure after Hematopoietic Stem Cell Transplantation
Peach Bowl LegACy Fund – 03/24/2020-12/31/2020
CD19/22 CARPOOL: Phase I trial of CD19/22 Chimeric Antigen Receptor Protocol with Objective of Tolerability in Relapsed/Refractory B-ALL