Our Science – Wayne Website
Alan S. Wayne, M.D.
The primary mission of the clinical research program of the Hematologic Diseases Section is to develop new treatment strategies for hematologic malignancies, the most frequent cancer type in pediatrics. Although cure rates are excellent for many subtypes of childhood leukemia and lymphoma, new approaches are needed to overcome resistance to standard therapies and to decrease treatment-associated side-effects. The Section leads novel clinical trials and conducts correlative biologic studies and pre-clinical investigations into the biology of leukemias and lymphomas in collaboration with intramural and extramural investigators.
A major focus of the Hematologic Diseases Section research program is the development of targeted agents for childhood leukemias and lymphomas. Among the most active programs is the study of anti-CD22 immunotoxin agents RFB4(dsFv)-PE38 developed at the NCI in the therapy of drug-resistant acute lymphoblastic leukemia (ALL). A pediatric Phase I trial of a first-generation agent (BL22, CAT-3888) was conducted at the NCI (Wayne et al, Clin Cancer Res 2010;16:1894). BL22 was shown to have an acceptable safety profile and clinical activity was observed in children with multiply relapsed chemotherapy resistant ALL. Studies of a modified agent with higher CD22 binding affinity (moxetumomab pasudotox, HA22, CAT-8015) showed improved in vitro cytotoxicity against childhood ALL blasts (Mussai et al, Br J Haematol 2010, Epub ahead of print 2010 Jun 7, PMID: 20528877). A pediatric Phase I trial of HA22 is in progress at the NCI, St. Jude Children's Research Hospital, and the Dana-Farber Cancer Institute/Children's Hospital, Boston. Complete remissions in chemotherapy-refractory ALL have been achieved with this new agent (Wayne et al, Blood 2009;114(22):345a).
Another major area of investigation is in allogeneic hematopoietic stem cell transplantation (AlloSCT) for pediatric leukemias and lymphomas. Relapse remains a major cause of failure of AlloSCT in the treatment of children and adolescents with leukemia. The Section investigates methods to direct allogeneic anti-cancer responses in attempt to enhance graft-versus-leukemia effects after AlloSCT. The Section also serves in a leadership role in a broad NCI program that addresses the problem of relapse after AlloSCT. These efforts include an NCI-sponsored International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation (Bishop et al, Biol Blood Marrow Transplant 2010;16:564) and specific studies of the natural history, biology, and treatment of relapse after AlloSCT. The Section also conducts investigations in the area of graft-versus-host disease, a frequent and complex biologic consequence of AlloSCT.
The clinical trial development activities of the Section are conducted in collaboration with a number of pediatric oncology consortia and cooperative groups including the Children's Oncology Group and the Pediatric Blood and Marrow Transplant Consortium.
This page was last updated on 3/5/2013.