Center for Stem Cell Transplantation
Hematopoietic stem cell transplantation is a procedure that involves the infusion of stem cells to treat patient malignancies or to repair diseased or defective bone marrow. This procedure starts with the patient receiving intensive chemotherapy with or without total body irradiation in an attempt to kill all cancerous cells. The high doses of therapy lead to the destruction of the patient’s marrow and immune system, which is then replaced by healthy marrow from self (autologous) or donor (allogeneic) hematopoietic stem cells that have been harvested from bone marrow or peripheral blood before therapy.
Highlights Of Our Stem Cell Transplantation Program:
- The research team is working to reduce treatment toxicity and improve patient outcomes using leading-edge research to advance hematopoietic stem cell transplant methods.
- Physicians and scientists work side by side to set standards for stem cell transplantation and improve long-term outcomes for both pediatric and adult patients.
- The team has access to a large transplant patient population, rich historical data and a clinical department with a reputation for outstanding transplant outcomes for the past 12 consecutive years.
- The team focuses its research on donor types, treatment complications (such as graft-vs-host disease), cytomegalovirus vaccination and regimens designed to reduce the risk of relapse.
Research Highlights
- Novel conditioning regimens (TMLI-based higher-intensity conditioning regimens, clofarabine in combination with melphalan)
- Application of CAR T cells in HCT in collaboration with T Cell Therapy Center
- CMV vaccine trials
- Human lysozyme-rich milk produced by transgenic goats, Artemis.
- GVHD biomarker-based stratified treatments (natalizumab, JAK1 inhibitor)
- Personalized use of chemotherapeutic agents based on population pharmacokinetics and metabolomics analyses
- Tolerance induction with haploidentical donor HCT using nonmyeloablative conditioning for sickle cell anemia
Featured Grant Funding
Grant Support
- R21 for radio-immunotherapy
- TMLI grant
- CMV vaccine development; 1) CMV PepVax 1R01CA181045-02 (Diamond, Nakamura), 2) CMV-MVA Triplex 5R01 CA077544-14 (Diamond, Nakamurs)
- BMT CTN U01; 2UG1HL069278-17 (Nakamura)
- Lymphoma SPORE; CA107399
- DeFu Zeng lab (R01)
- Wenek Family Foundation (Sickle cell project; Zeng, Rosenthal, Nakamura)
- COH/TGEN Initiative (Dadwal, Marcucci)
Training/Career-Development Grants
- ASBMT New Investigator Award (Dr. Khaled)
- ASBMT Clinical Research Training Course (Dr. Sandhu)
- ASCO/Conquer Cancer Foundation Merit Award (Dr. Pham)
- ISCT-ASBMT Training Course (Dr. Al Malki)
- ASH HONORS (Hematology Opportunities for the Next Generation of Research Scientists) Award (Nikeshan Jeyakumar)
Publication Highlights
Stein A, Palmer J, Tsai NC, Al Malki MM, Aldoss I, Ali H, Aribi A, Farol L, Karanes C, Khaled S, Liu A, O'Donnell M, Parker P, Pawlowska A, Pullarkat V, Radany E, Rosenthal J, Sahebi F, Salhotra A, Sanchez JF, Schultheiss T, Spielberger R, Thomas SH, Snyder D, Nakamura R, Marcucci G, Forman SJ, Wong J. Phase I Trial of Total Marrow and Lymphoid Irradiation Transplantation Conditioning in Patients with Relapsed/Refractory Acute Leukemia. Biol Blood Marrow Transplant. 2017 Apr;23(4):618-624. PMCID: PMC5382014
Aldoss I, Pham A, Li SM, Gendzekhadze K, Afkhami M, Telatar M, Hong H, Padeganeh A, Bedell V, Cao T, Khaled SK, Al Malki MM, Salhotra A, Ali H, Aribi A, Palmer J, Aoun P, Spielberger R, Stein AS, Snyder D, O'Donnell MR, Murata-Collins J, Senitzer D, Weisenburger D, Forman SJ, Pullarkat V, Marcucci G, Pillai R, Nakamura R. Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of TP53 mutational status. Haematologica. 2017 Sep 29. pii: haematol.2017.172544. PMID: 28971906
Nakamura R, La Rosa C, Longmate J, Drake J, Slape C, Zhou Q, Lampa MG, O'Donnell M, Cai JL, Farol L, Salhotra A, Snyder DS, Aldoss I, Forman SJ, Miller JS, Zaia JA, Diamond DJ. Viraemia, immunogenicity, and survival outcomes of cytomegalovirus chimeric epitope vaccine supplemented with PF03512676 (CMVPepVax) in allogeneic haemopoietic stem-cell transplantation: randomised phase 1b trial. Lancet Haematol. 2016 Feb;3(2):e87-98. PMC4926626
Khaled SK, Palmer JM, Herzog J, Stiller T, Tsai NC, Senitzer D, Liu X, Thomas SH, Shayani S, Weitzel J, Forman SJ, Nakamura R. Influence of Absorption, Distribution, Metabolism, and Excretion Genomic Variants on Tacrolimus/Sirolimus Blood Levels and Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation. Biol Blood Marrow Transplant. 2016 Feb;22(2):268-276. PMCID: PMC4716887
Wang X, Wong CW, Urak R, Mardiros A, Budde LE, Chang WC, Thomas SH, Brown CE, La Rosa C, Diamond DJ, Jensen MC, Nakamura R, Zaia JA, Forman SJ. CMVpp65 Vaccine Enhances the Antitumor Efficacy of Adoptively Transferred CD19-Redirected CMV-Specific T Cells. Clin Cancer Res. 2015 Jul 1;21(13):2993-3002. PMCID: PMC4489991
Ni X, Song Q, Cassady K, Deng R, Jin H, Zhang M, Dong H, Forman S, Martin PJ, Chen YZ, Wang J, Zeng D. PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor CD8+ T cells. J Clin Invest. 2017 May 1;127(5):1960-1977. PMC5409099
Anderlini P, Wu J, Gersten I, Ewell M, Tolar J, Antin JH, Adams R, Arai S, Eames G, Horwitz ME, McCarty J, Nakamura R, Pulsipher MA, Rowley S, Leifer E, Carter SL, DiFronzo NL, Horowitz MM, Confer D, Deeg HJ, Eapen M Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. Lancet Haematol. 2015 Sep;2(9):e367-75. PMCID: 26685770
Alvarnas JC, Le Rademacher J, Wang Y, Little RF, Akpek G, Ayala E, Devine S, Baiocchi R, Lozanski G, Kaplan L, Noy A, Popat U, Hsu J, Morris LE Jr, Thompson J, Horowitz MM, Mendizabal A, Levine A, Krishnan A, Forman SJ, Navarro WH, Ambinder R. Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial. Blood. 2016 Aug 25;128(8):1050-8. PMCID: PMC5000843
Bashey A, Zhang MJ, McCurdy SR, St Martin A, Argall T, Anasetti C, Ciurea SO, Fasan O, Gaballa S, Hamadani M, Munshi P, Al Malki MM, Nakamura R, O'Donnell PV, Perales MA, Raj K, Romee R, Rowley S, Rocha V, Salit RB, Solh M, Soiffer RJ, Fuchs EJ, Eapen M. Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell-Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide. J Clin Oncol. 2017 Sep 10;35(26):3002-3009. PMCID: PMC5590802
Faculty
Monzr M. Al Malki, M.D., is a professor in the Department of Hematology & Hematopoietic Cell Transplantation and is board certified in internal medicine, hematology and medical oncology at City of Hope.
Ibrahim T. Aldoss, M.D., is a hematologist-oncologist and board-certified in internal medicine, medical oncology and hematology. His clinical expertise is in acute lymphoblastic leukemia and acute myeloid leukemia.
Haris Ali, M.D., is a hematologist-oncologist and associate professor in the Department of Hematology & Hematopoietic Cell Transplantation.
Sanjeet Singh Dadwal, M.D., is chief, Division of Infectious Diseases, and professor in the Department of Medicine, with a clinical focus on infectious diseases.
Don J. Diamond, Ph.D., is Professor in the Department of Hematology & Hematopoietic Cell Transplantation.
Susanta Hui, Ph.D., is a Professor, Department of Radiation Oncology at City of Hope in Duarte, CA.
Percy Lee, M.D., is delighted to increase City of Hope's reach and help establish its radiation oncology research network in his role as medical director of Orange County and coastal region radiation oncology and vice chair for clinical research in the Department of Radiation Oncology.
Dermatologist Badri Modi, M.D., focuses on high-risk skin cancers and melanoma and is an associate clinical professor in the Division of Dermatology.
Ryotaro Nakamura, M.D., is the Jan & Mace Siegel Professor in Hematology & Hematopoietic Cell Transplantation professor and a hematologist/oncologist at City of Hope.
Raju Pillai, M.D., is a hematopathologist and molecular pathologist in the Department of Pathology at City of Hope.
Amandeep Salhotra, M.D., is a hematologist-oncologist and Associate Professor in the Division of Leukemia, Department of Hematology and Hematopoietic Cell Transplantation.
Defu Zeng, is a professor of immunology & theranostics and hematologist. His focus is on transplantation immune tolerance.