OncoTargets and Therapy (Jan 2023)
Post-Hematopoietic Cell Transplantation Relapsed Acute Lymphoblastic Leukemia: Current Challenges and Future Directions
Abstract
Indumathy Varadarajan,1 Eric Pierce,1 Lisa Scheuing,1 Amy Morris,2 Firas El Chaer,1 Michael Keng1 1Department of Medicine, Division of Hematology and Oncology, University of Virginia, Charlottesville, VA, USA; 2Department of Pharmacy Services, University of Virginia, Charlottesville, VA, USACorrespondence: Michael Keng, Division of Hematology & Oncology, University of Virginia Comprehensive Cancer Center, West Complex Room 6009, 1300 Jefferson Park Ave, PO Box 800716, Charlottesville, VA, 22908, USA, Tel +1 434 924 4257, Fax +1 434- 243 6068, Email [email protected]: Allogeneic hematopoietic cell transplantation (allo-HCT) represents an important and potentially curative treatment option for adult patients with acute lymphoblastic leukemia. Relapse continues to remain the most important factor influencing overall survival post allo-HCT. We discuss early identification, clinical manifestations, and management of relapsed disease. Routine evaluation of measurable residual disease (MRD) and change in donor chimerism play a crucial role in early detection. Pivotal clinical trials have led to FDA approval of multiple novel agents like blinatumomab and inotuzumab. Combining targeted therapy with cellular immunotherapy serves as the backbone for prolonging overall survival in these patients. Donor lymphocyte infusions have traditionally been used in relapsed disease with suboptimal outcomes. This review provides insight into use of cellular therapy in MRD positivity and decreasing donor chimerism. It also discusses various modalities of combining cellular therapy with novel agents and discussing the impact of chimeric antigen receptor T-cell therapy in the setting of post allo–HCT relapse both as consolidative therapy and as a bridge to second transplant.Keywords: acute lymphoblastic leukemia, hematopoietic cell transplantation, relapsed disease, measurable residual disease, MRD, ALL, CART, DLI
