Frederick R. Appelbaum
M.D., Tufts University, 1972.
A.B. (cum laude), Dartmouth College, 1968.
Our group is interested in developing an improved understanding of the biology of acute myeloid leukemia (AML) and using this knowledge to create novel therapeutic approaches. The following are several examples of such studies: (1) In one group of studies, we had previously shown that higher dose total body irradiation given in conjunction with hematopoietic cell transplantation was able to more reliably eradicate AML, but was associated with increased transplant-related toxicities. We have since shown the feasibility of targeting radiation therapy specifically to sites of normal and abnormal hematopoiesis using monoclonal antibodies against CD45 radiolabeled with 131I, and phase II trials incorporating this approach in transplant preparative regimens have yielded encouraging results. Current studies are aimed at further improving the specificity of targeting radiotherapy and defining the optimal way to apply this technique. (2) In a second group of experiments, we found that following exposure to cell-damaging agents, AML cells dramatically increase cellular cholesterol content and that blocking this response specifically sensitizes cells to chemotherapy. Subsequent clinical trials have demonstrated the feasibility of adding high dose pravastatin to leukemia induction therapy with encouraging clinical outcomes. We are currently attempting to conclusively define the role of cholesterol synthesis blockade in AML treatment. (3) In collaboration with the Southwest Oncology group, we have found that MDR1 mediated drug efflux in AML is increased in older patients and in patients with recurrent disease, and is tightly associated with drug resistance. We have completed studies showing an advantage of the use of MDR1 inhibition in patients with recurrent AML and are currently conducting clinical trials in the up-front treatment of older patients. In addition, we have identified novel compounds that inhibit not only drug efflux but the effects of BCL-2 overexpression and are attempting to define the optimal way in which to apply such therapy.
Banker, D.E., Mayer, S.J., Li, H.Y., Willman, C.L., Appelbaum, F.R., Zager, R.A. Cholesterol synthesis and import contribute to protective cholesterol increments in acute myeloid leukemia cells. Blood 104: 1816-1824, 2004.
Appelbaum,F.R., Gundacker,H., Head,D.R., Slovak,M.L., Willman,C.L., Godwin,J.E., Anderson,J.E., Petersdorf,S.H. Age and acute myeloid leukemia. Blood 107:3481-3485, 2006.
Larson,R.A., Sievers,E.L., Stadtmauer,E.A., Lowenberg,B., Estey,E.H., Dombret,H., Theobald,M., Voliotis,D., Bennett,J.M., Richie,M., Leopold,L.H., Berger,M.S., Sherman,M.L., Loken,M.R., van Dongen,J.J.M., Bernstein,I.D., Appelbaum,F.R. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 104: 1442-1452, 2005.
Pagel,J.M., Appelbaum,F.R., Eary,J.F., Rajendran,J., Fisher,D.R., Gooley,T., Ruffner,K., Nemecek,E., Sickle,E., Durack,L., Carreras,J., Horowitz,M.M., Press,O.W., Gopal,A.K., Martin,P.J., Bernstein,I.D., Matthews,D.C. 131I-anti-CD45 antibody plus busulfan and cyclophosphamide before allogeneic hematopoietic cell transplantation for treatment of acute myeloid leukemia in first remission. Blood 107: 2184-2191, 2006.
Walter,R.B., Pirga,J.L., Cronk,M.R., Mayer,S., Appelbaum,F.R., Banker,D.E. PK11195, a peripheral benzodiazepine receptor (pBR) ligand, broadly blocks drug efflux to chemosensitize leukemia and myeloma cells by a pBR-independent, direct transporter-modulating mechanism. Blood 106: 3584-3593, 2005.
In addition to overseeing a laboratory focused on the biology of acute myeloid leukemia and chairing the Leukemia Committee of the Southwest Oncology Group, Dr. Appelbaum is the head of the Program in Clinical Transplant Research at the Fred Hutchinson Cancer Research Center. The overall goal of the Program in Clinical Transplant Research is to improve the therapy of cancer in children and adults through the conduct of clinical trials, many of which involve marrow and stem cell transplantation. Major topics of these trials include the eradication of malignancy, control of graft-vs-host disease, and prevention of transplant related complications.
Alpha Omega Alpha
American Association for Cancer Research
American Society of Clinical Oncology
American Society of Hematology
International Society for Experimental Hematology
Gastrointestinal and hepatic complications. Thomas’ Hematopoietic Cell Transplantation.. In Press.
Radiolabeled Anti-CD45 Antibody with Reduced-Intensity Conditioning and Allogeneic Transplantation for Younger Patients with Advanced Acute Myeloid Leukemia or Myelodysplastic Syndrome.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2014.
SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukaemia.. British journal of haematology.. 2014.
Multi-Center Biologic Assignment Trial Comparing Reduced Intensity Allogeneic Hematopoietic Cell Transplant to Hypomethylating Therapy or Best Supportive Care in Patients Aged 50-75 with Intermediate-2 and High Risk Myelodysplastic Syndrome Blood and Marr. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2014.
Treosulfan, Fludarabine, and 2-Gy Total Body Irradiation Followed by Allogeneic Hematopoietic Cell Transplantation in Patients with Myelodysplastic Syndrome and Acute Myeloid Leukemia.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2014.
Unsuccessful diagnostic cytogenetic analysis is a poor prognostic feature in acute myeloid leukaemia.. British journal of haematology. 164(2):245-50.. 2014.
Myeloablative I-131-Tositumomab with Escalating Doses of Fludarabine and Autologous Hematopoietic Transplantation for Adults Aged ≥ 60 Years with B-Cell Lymphoma.. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.. 2014.
Prognostic factors and outcomes of severe gastrointestinal GVHD after allogeneic hematopoietic cell transplantation.. Bone marrow transplantation.. 2014.
Impact of minimal residual disease, detected by flow cytometry, on outcome of myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia.. Leukemia research and treatment. 2014:421723.. 2014.
Indications for allogeneic hematopoietic cell transplantation for acute myeloid leukemia in the genomic era.. American Society of Clinical Oncology educational book / ASCO. American Society of Clinical Oncology. Meeting. 34:e327-33.. 2014.
Acute myeloid leukemia, version 2.2013.. Journal of the National Comprehensive Cancer Network : JNCCN. 11(9):1047-55.. 2013.
Measurement of minimal residual disease before and after myeloablative hematopoietic cell transplantation for acute leukemia.. Best practice & research. Clinical haematology. 26(3):279-84.. 2013.