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 Childrens Research Hospital, and the Dana-Farber Cancer Institute/Childrens Hospital, Boston. Complete remissions in chemotherapy-refractory ALL have been achieved with this new agent (Wayne et al, Blood 2009;114(22):345a;Wayne et al, Blood 2010;116:3246a). 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 clinical trial development activities of the Section are conducted in collaboration with a number of pediatric oncology consortia and cooperative groups including the Childrens Oncology Group and the Pediatric Blood and Marrow Transplant Consortium.

National Institute of Health (NIH)
National Cancer Institute (NCI)
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Mehta, Neha; Wayne, Alan S; Kim, Youn H et al. (2012) Bexarotene is active against subcutaneous panniculitis-like T-cell lymphoma in adult and pediatric populations. Clin Lymphoma Myeloma Leuk 12:20-5
Wei, Hui; Xiang, Laiman; Wayne, Alan S et al. (2012) Immunotoxin resistance via reversible methylation of the DPH4 promoter is a unique survival strategy. Proc Natl Acad Sci U S A 109:6898-903
Shah, Nirali N; Bacher, Ulrike; Fry, Terry et al. (2012) Myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: diagnostic and therapeutic challenges. Am J Hematol 87:916-22
Larochelle, Andre; Gillette, Jennifer M; Desmond, Ronan et al. (2012) Bone marrow homing and engraftment of human hematopoietic stem and progenitor cells is mediated by a polarized membrane domain. Blood 119:1848-55
Sokolic, Robert; Maric, Irina; Kesserwan, Chimene et al. (2011) Myeloid dysplasia and bone marrow hypocellularity in adenosine deaminase-deficient severe combined immune deficiency. Blood 118:2688-94
Bishop, Michael R; Alyea 3rd, Edwin P; Cairo, Mitchell S et al. (2011) National Cancer Institute's First International Workshop on the Biology, Prevention, and Treatment of Relapse after Allogeneic Hematopoietic Stem Cell Transplantation: summary and recommendations from the organizing committee. Biol Blood Marrow Transplant 17:443-54
Zhang, Hua; Cui, Yongzhi; Voong, Nga et al. (2011) Activating signals dominate inhibitory signals in CD137L/IL-15 activated natural killer cells. J Immunother 34:187-95
Jasper, Gregory A; Arun, Indu; Venzon, David et al. (2011) Variables affecting the quantitation of CD22 in neoplastic B cells. Cytometry B Clin Cytom 80:83-90
FitzGerald, David J; Wayne, Alan S; Kreitman, Robert J et al. (2011) Treatment of hematologic malignancies with immunotoxins and antibody-drug conjugates. Cancer Res 71:6300-9
Cohen, Jeffrey I; Jaffe, Elaine S; Dale, Janet K et al. (2011) Characterization and treatment of chronic active Epstein-Barr virus disease: a 28-year experience in the United States. Blood 117:5835-49

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