Photo of Eva C. Guinan,  MD

Eva C. Guinan, MD

Dana-Farber Cancer Institute

Dana-Farber Cancer Institute
Phone: (617) 632-4932
Fax: (617) 632-3770


eva_guinan@dfci.harvard.edu

Eva C. Guinan, MD

Dana-Farber Cancer Institute

EDUCATIONAL TITLES

  • Professor, Radiation Oncology, Harvard Medical School
  • Associate in Medicine, Hematology/Oncology, Boston Children's Hospital
  • Director, Translational Research, Radiation Oncology, Dana-Farber Cancer Institute

DF/HCC PROGRAM AFFILIATION

Research Abstract

Our research laboratory focuses on two issues: 1)overcoming problems related to allogenicity in transplantation and 2) the role of endotoxin neutralization in mitigating the toxicity of radiotherapy.



In regard to the first, allogeneic transplantation is limited by immune attacks between donor and host. Global immunosuppression has been an incomplete and highly toxic approach to this problem. Current understanding of T cell activation suggests that blocking B7-CD28 interactions of the costimulatory pathway for human T helper cells provides an innovative way of producing antigen-specific T cell hyporesponsiveness and generation of regulatory T cells. We are applying these various strategies to the transplant setting.



In regard to the second area, we have found that a human endotoxin neutralizing molecule, bacteriacidal permeability increasing protein (BPI), has the capacity to dramatically decrease the side effects of radiation. We are pursing these observations both for emergency use (such as a nuclear accident) but also in terms of effects on chemoradiotherapy of cancer.

Publications

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  • Bechard LJ, Gordon C, Feldman HA, Venick R, Gura K, Guinan EC, Duggan C. Bone loss and vitamin D deficiency in children undergoing hematopoietic cell transplantation. Pediatr Blood Cancer 2015; 62:687-92. PubMed
  • Heinze KE, Rodday AM, Nolan MT, Bingen K, Kupst MJ, Patel SK, Syrjala K, Harris L, Recklitis C, Schwartz L, Davies S, Guinan EC, Noll R, Chang G, Parsons SK. The impact of pediatric blood and marrow transplant on parents: introduction of the parent impact scale. Health Qual Life Outcomes 2015; 13:46. PubMed
  • Barbon CM, Davies JK, Voskertchian A, Kelner RH, Brennan LL, Nadler LM, Guinan EC. Alloanergization of human T cells results in expansion of alloantigen-specific CD8(+) CD28(-) suppressor cells. Am J Transplant 2014; 14:305-18. PubMed
  • Guinan EC, Palmer CD, Mancuso CJ, Brennan L, Stoler-Barak L, Kalish LA, Suter EE, Gallington LC, Huhtelin DP, Mansilla M, Schumann RR, Murray JC, Weiss J, Levy O. Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin. Innate Immun 2013. PubMed
  • Ayas M, Saber W, Davies SM, Harris RE, Hale GA, Socie G, Lerademacher J, Thakar M, Deeg HJ, Al-Seraihy A, Battiwalla M, Camitta BM, Olsson R, Bajwa RS, Bonfim CM, Pasquini R, Macmillan ML, George B, Copelan EA, Wirk B, Al Jefri A, Fasth AL, Guinan EC, Horn BN, Lewis VA, Slavin S, Stepensky P, Bierings M, Gale RP. Allogeneic Hematopoietic Cell Transplantation for Fanconi Anemia in Patients With Pretransplantation Cytogenetic Abnormalities, Myelodysplastic Syndrome, or Acute Leukemia. J Clin Oncol 2013. PubMed
  • Myers LC, Sun P, Brennan LL, London WB, Guinan EC. Effect of weight on outcomes of children undergoing hematopoietic cell transplantation. Pediatr Hematol Oncol 2013; 30:116-30. PubMed
  • Lakhani KR, Boudreau KJ, Loh PR, Backstrom L, Baldwin C, Lonstein E, Lydon M, MacCormack A, Arnaout RA, Guinan EC. Prize-based contests can provide solutions to computational biology problems. Nat Biotechnol 2013; 31:108-11. PubMed
  • Guinan EC, Agarwal S. A young adult with aplastic anemia and gray hair. Clin Chem 2013; 59:47-50. PubMed
  • Bechard LJ, Feldman HA, Venick R, Gura K, Gordon C, Sonis A, Mehta N, Guinan EC, Duggan C. Attenuation of resting energy expenditure following hematopoietic SCT in children. Bone Marrow Transplant 2012; 47:1301-6. PubMed
  • Davies JK, Barbon CM, Voskertchian A, Nadler LM, Guinan EC. Ex vivo alloanergization with belatacept: a strategy to selectively modulate alloresponses after transplantation. Cell Transplant 2013; 21:2047-61. PubMed
  • Davies JK, Barbon CM, Voskertchian AR, Nadler LM, Guinan EC. Induction of Alloantigen-specific Anergy in Human Peripheral Blood Mononuclear Cells by Alloantigen Stimulation with Co-stimulatory Signal Blockade. 2011. PubMed
  • Richardson PG, Soiffer RJ, Antin JH, Uno H, Jin Z, Kurtzberg J, Martin PL, Steinbach G, Murray KF, Vogelsang GB, Chen AR, Krishnan A, Kernan NA, Avigan DE, Spitzer TR, Shulman HM, Di Salvo DN, Revta C, Warren D, Momtaz P, Bradwin G, Wei LJ, Iacobelli M, McDonald GB, Guinan EC. Defibrotide for the treatment of severe hepatic veno-occlusive disease and multi-organ failure post stem cell transplantation: a multi-center, randomized, dose-finding trial. Biol Blood Marrow Transplant 2010; 16:1005-17. PubMed
  • Davies JK, Singh H, Huls H, Yuk D, Lee DA, Kebriaei P, Champlin RE, Nadler LM, Guinan EC, Cooper LJ. Combining CD19 redirection and alloanergization to generate tumor-specific human T cells for allogeneic cell therapy of B-cell malignancies. Cancer Res 2010; 70:3915-24. PubMed
  • Guinan EC, Hewett EK, Domaney NM, Margossian R. Outcome of hematopoietic stem cell transplant in children with congenital heart disease* Pediatr Transplant 2010. PubMed
  • Bechard LJ, Feldman HA, Gordon C, Gura K, Sonis A, Leung K, Venick R, Guinan EC, Duggan C. A multi-center, randomized, controlled trial of parenteral nutrition titrated to resting energy expenditure in children undergoing hematopoietic stem cell transplantation ("PNTREE"): rationale and design. Contemp Clin Trials 2010; 31:157-64. PubMed
  • Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A, Guinan E, Vogelsang G, Krishnan A, Giralt S, Revta C, Carreau NA, Iacobelli M, Carreras E, Ruutu T, Barbui T, Antin JH, Niederwieser D. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant 2010; 16:157-68. PubMed
  • Davies JK, Nadler LM, Guinan EC. Expansion of allospecific regulatory T cells after anergized, mismatched bone marrow transplantation. Sci Transl Med 2010; 1:1ra3. PubMed
  • Guinan EC. Acquired aplastic anemia in childhood. Hematol Oncol Clin North Am 2009; 23:171-91. PubMed
  • Kurtzberg J,Prasad VK,Carter SL,Wagner JE,Baxter-Lowe LA,Wall D,Kapoor N,Guinan EC,Feig SA,Wagner EL,Kernan NA. Results of the Cord Blood Transplantation Study (COBLT): clinical outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with hematologic malignancies. Blood 2008; 112:4318-27. PubMed
  • Davies JK,Yuk D,Nadler LM,Guinan EC. Induction of alloanergy in human donor T cells without loss of pathogen or tumor immunity. Transplantation 2008; 86:854-64. PubMed
  • Davies JK,Gribben JG,Brennan LL,Yuk D,Nadler LM,Guinan EC. Outcome of alloanergized haploidentical bone marrow transplantation after ex vivo costimulatory blockade: results of 2 phase 1 studies. Blood 2008; 112:2232-41. PubMed
  • Duro D,Bechard LJ,Feldman HA,Klykov A,O'Leary A,Guinan EC,Duggan C. Weekly measurements accurately represent trends in resting energy expenditure in children undergoing hematopoietic stem cell transplantation. JPEN J Parenter Enteral Nutr 2008; 32:427-32. PubMed
  • Bechard LJ, Guinan EC, Feldman HA, Tang V, Duggan C. Prognostic factors in the resumption of oral dietary intake after allogeneic hematopoietic stem cell transplantation (HSCT) in children. JPEN J Parenter Enteral Nutr 2007; 31:295-301. PubMed
  • Guinan EC, Kalish LA, Berry WS, McDaniel S, Lehmann LE, Diller LR. A novel pattern of transaminase elevation associated with autologous transplant for neuroblastoma. Pediatr Transplant 2006; 10:669-76. PubMed
  • Berman JN, Wang M, Berry W, Neuberg DS, Guinan EC. Herpes zoster infection in the post-hematopoietic stem cell transplant pediatric population may be preceded by transaminitis: an institutional experience. Bone Marrow Transplant 2005; 37:73-80. PubMed
  • Treister NS, Woo SB, O'Holleran EW, Lehmann LE, Parsons SK, Guinan EC. Oral chronic graft-versus-host disease in pediatric patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11:721-31. PubMed
  • Haining WN, Neuberg DS, Keczkemethy HL, Evans JW, Rivoli S, Gelman R, Rosenblatt HM, Shearer WT, Guenaga J, Douek DC, Silverman LB, Sallan SE, Guinan EC, Nadler LM. Antigen-specific T-cell memory is preserved in children treated for acute lymphoblastic leukemia. Blood 2005; 106:1749-54. PubMed
  • Peters BA, Diaz LA, Polyak K, Meszler L, Romans K, Guinan EC, Antin JH, Myerson D, Hamilton SR, Vogelstein B, Kinzler KW, Lengauer C. Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med 2005; 11:261-2. PubMed
  • Haining WN, Cardoso AA, Keczkemethy HL, Fleming M, Neuberg D, DeAngelo DJ, Stone RM, Galinsky I, Silverman LB, Sallan SE, Nadler LM, Guinan EC. Failure to define window of time for autologous tumor vaccination in patients with newly diagnosed or relapsed acute lymphoblastic leukemia. Exp Hematol 2005; 33:286-94. PubMed
  • Antin JH, Guinan EC, Avigan D, Soiffer RJ, Joyce RM, Martin VJ, Molrine DC. Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2005; 11:213-22. PubMed
  • Hirano N, Butler MO, Guinan EC, Nadler LM, Kojima S. Presence of anti-kinectin and anti-PMS1 antibodies in Japanese aplastic anaemia patients. Br J Haematol 2005; 128:221-3. PubMed
  • Hirano N, Butler MO, Von Bergwelt-Baildon MS, Maecker B, Schultze JL, O'Connor KC, Schur PH, Kojima S, Guinan EC, Nadler LM. Autoantibodies frequently detected in patients with aplastic anemia. Blood 2003; 102:4567-75. PubMed
  • Levy O, Teixeira-Pinto A, White ML, Carroll SF, Lehmann L, Wypij D, Guinan E. Endotoxemia and elevation of lipopolysaccharide-binding protein after hematopoietic stem cell transplantation. Pediatr Infect Dis J 2003; 22:978-81. PubMed
  • Thornley I, Lehmann L, Ferguson WS, Davis I, Forman EN, Guinan EC. Homozygous alpha-thalassemia treated with intrauterine transfusions and postnatal hematopoietic stem cell transplantation. Bone Marrow Transplant 2003; 32:341-2. PubMed
  • Duggan C, Bechard L, Donovan K, Vangel M, O'Leary A, Holmes C, Lehmann L, Guinan E. Changes in resting energy expenditure among children undergoing allogeneic stem cell transplantation. Am J Clin Nutr 2003; 78:104-9. PubMed
  • Gibbons RD, Duan N, Meltzer D, Pope A, Penhoet ED, Dubler NN, Francis C, Gill B, Guinan E, Henderson M, Ildstad ST, King PA, Martinez-Maldonado M, McLain GE, Murray J, Nelkin D, Spellman MW, Pitluck S,. Waiting for organ transplantation: results of an analysis by an Institute of Medicine Committee. Biostatistics 2003; 4:207-22. PubMed
  • Tse WT, Pendleton JD, Beyer WM, Egalka MC, Guinan EC. Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transplantation 2003; 75:389-97. PubMed
  • Molrine DC, Antin JH, Guinan EC, Soiffer RJ, MacDonald K, Malley R, Malinoski F, Trocciola S, Wilson M, Ambrosino DM. Donor immunization with pneumococcal conjugate vaccine and early protective antibody responses following allogeneic hematopoietic cell transplantation. Blood 2002; 101:831-6. PubMed
  • Richardson PG, Murakami C, Jin Z, Warren D, Momtaz P, Hoppensteadt D, Elias AD, Antin JH, Soiffer R, Spitzer T, Avigan D, Bearman SI, Martin PL, Kurtzberg J, Vredenburgh J, Chen AR, Arai S, Vogelsang G, McDonald GB, Guinan EC. Multi-institutional use of defibrotide in 88 patients after stem cell transplantation with severe veno-occlusive disease and multisystem organ failure: response without significant toxicity in a high-risk population and factors predictive of outcome. Blood 2002; 100:4337-43. PubMed
  • Levy O, Sisson RB, Fryer HE, Goldmann D, Valore E, Ganz T, White ML, Carroll SF, Lehmann L, Guinan EC. Neutrophil defense in patients undergoing bone marrow transplantation: bactericidal/permeability-increasing protein (BPI) and defensins in graft-derived neutrophils. Transplantation 2002; 73:1522-6. PubMed
  • D'Andrea AD, Dahl N, Guinan EC, Shimamura A. Marrow failure. Hematology Am Soc Hematol Educ Program 2002. PubMed
  • Richardson P, Guinan E. Hepatic veno-occlusive disease following hematopoietic stem cell transplantation. Acta Haematol 2001; 106:57-68. PubMed
  • Parsons SK, Levine KJ, Hoorntje LE, Eichelberger WJ, Mayer DK, Guinan EC. Impact of pharmacy practices on the cost of colony-stimulating factor use in pediatric stem cell transplantation: an institution-based analysis. J Pediatr Hematol Oncol 2001; 23:19-24. PubMed
  • Parsons SK, Hoorntje LE, Levine KJ, Mayer DK, Eichelberger WJ, Guinan EC. Balancing efficacy with cost: antiemetic control in the pediatric stem cell transplant (SCT) population. Bone Marrow Transplant 2000; 25:553-7. PubMed
  • Richardson P, Guinan E. The pathology, diagnosis, and treatment of hepatic veno-occlusive disease: current status and novel approaches. Br J Haematol 1999; 107:485-93. PubMed
  • Guinan EC, Boussiotis VA, Neuberg D, Brennan LL, Hirano N, Nadler LM, Gribben JG. Transplantation of anergic histoincompatible bone marrow allografts. N Engl J Med 1999; 340:1704-14. PubMed
  • Taylor DS, Lee Y, Sieff CA, Homans A, Garrison L, Guinan EC. Phase I/II trial of PIXY321 (granulocyte-macrophage colony stimulating factor/interleukin-3 fusion protein) for treatment of inherited and acquired marrow failure syndromes. Br J Haematol 1998; 103:304-7. PubMed
  • Vance E, George S, Guinan EC, Wheeler C, Antin JH, Ambrosino DM, Molrine DC. Comparison of multiple immunization schedules for Haemophilus influenzae type b-conjugate and tetanus toxoid vaccines following bone marrow transplantation. Bone Marrow Transplant 1998; 22:735-41. PubMed
  • Richardson PG, Elias AD, Krishnan A, Wheeler C, Nath R, Hoppensteadt D, Kinchla NM, Neuberg D, Waller EK, Antin JH, Soiffer R, Vredenburgh J, Lill M, Woolfrey AE, Bearman SI, Iacobelli M, Fareed J, Guinan EC. Treatment of severe veno-occlusive disease with defibrotide: compassionate use results in response without significant toxicity in a high-risk population. Blood 1998; 92:737-44. PubMed
  • Pulsipher M, Kupfer GM, Naf D, Suliman A, Lee JS, Jakobs P, Grompe M, Joenje H, Sieff C, Guinan E, Mulligan R, D'Andrea AD. Subtyping analysis of Fanconi anemia by immunoblotting and retroviral gene transfer. Mol Med 1998; 4:468-79. PubMed
  • Guinan EC. Clinical aspects of aplastic anemia. Hematol Oncol Clin North Am 1998; 11:1025-44. PubMed
  • Ballen KK, Gilliland DG, Guinan EC, Hsieh CC, Parsons SK, Rimm IJ, Ferrara JL, Bierer BE, Weinstein HJ, Antin JH. Bone marrow transplantation for therapy-related myelodysplasia: comparison with primary myelodysplasia. Bone Marrow Transplant 1998; 20:737-43. PubMed
  • Laufer MR, Townsend NL, Parsons KE, Brody KA, Diller LR, Emans SJ, Guinan EC. Inducing amenorrhea during bone marrow transplantation. A pilot study of leuprolide acetate. J Reprod Med 1997; 42:537-41. PubMed
  • Trede NS, Warwick AB, Rosoff PM, Rohrer R, Bierer BE, Guinan E. Tacrolimus (FK506) in allogeneic bone marrow transplantation for severe aplastic anemia following orthotopic liver transplantation. Bone Marrow Transplant 1997; 20:257-60. PubMed
  • Chan CY, Molrine DC, Antin JH, Wheeler C, Guinan EC, Weinstein HJ, Phillips NR, McGarigle C, Harvey S, Schnipper C, Ambrosino DM. Antibody responses to tetanus toxoid and Haemophilus influenzae type b conjugate vaccines following autologous peripheral blood stem cell transplantation (PBSCT). Bone Marrow Transplant 1997; 20:33-8. PubMed
  • Wheeler C, Eickhoff C, Elias A, Ibrahim J, Ayash L, McCauley M, Mauch P, Schwartz G, Eder JP, Mazanet R, Ferrara J, Rimm IJ, Guinan E, Bierer B, Gilliland G, Churchill WH, Ault K, Parsons S, Antman K, Schnipper L, Tepler I, Gaynes L, Frei E 3rd, Kadin M, Antin J. High-dose cyclophosphamide, carmustine, and etoposide with autologous transplantation in Hodgkin's disease: a prognostic model for treatment outcomes. Biol Blood Marrow Transplant 1997; 3:98-106. PubMed
  • Lehmann LE, Guinan EC, Halpern SL, Donovan MJ, Bierer BE, Parsons SK. Isolated testicular relapse in an adolescent 5 years following allogeneic bone marrow transplantation for acute myelogenous leukemia. Bone Marrow Transplant 1997; 19:849-51. PubMed
  • Rifai N, Sakamoto M, Lafi M, Guinan E. Measurement of plasma busulfan concentration by high-performance liquid chromatography with ultraviolet detection. Ther Drug Monit 1997; 19:169-74. PubMed
  • Platt OS, Guinan EC. Bone marrow transplantation in sickle cell anemia--the dilemma of choice. N Engl J Med 1996; 335:426-8. PubMed
  • Molrine DC, Guinan EC, Antin JH, Wheeler C, Parsons SK, Weinstein HJ, McGarigle C, Blanding P, Phillips NR, Ciamarra A, George S, Ambrosino DM. Haemophilus influenzae type b (HIB)-conjugate immunization before bone marrow harvest in autologous bone marrow transplantation. Bone Marrow Transplant 1996; 17:1149-55. PubMed
  • Gribben JG, Guinan EC, Boussiotis VA, Ke XY, Linsley L, Sieff C, Gray GS, Freeman GJ, Nadler LM. Complete blockade of B7 family-mediated costimulation is necessary to induce human alloantigen-specific anergy: a method to ameliorate graft-versus-host disease and extend the donor pool. Blood 1996; 87:4887-93. PubMed
  • Nichols K, Parsons SK, Guinan E. Long-term follow-up of 12 pediatric patients with primary myelodysplastic syndrome treated with HLA-identical sibling donor bone marrow transplantation. Blood 1996; 87:4020-2. PubMed
  • Molrine DC, Guinan EC, Antin JH, Parsons SK, Weinstein HJ, Wheeler C, McGarigle C, Blanding P, Phillips NR, Kinsella K, Deans K, Ciamarra A, Goorin A, George S, Ambrosino DM. Donor immunization with Haemophilus influenzae type b (HIB)-conjugate vaccine in allogeneic bone marrow transplantation. Blood 1996; 87:3012-8. PubMed
  • Janov AJ, Leong T, Nathan DG, Guinan EC. Diamond-Blackfan anemia. Natural history and sequelae of treatment. Medicine (Baltimore) 1996; 75:77-8. PubMed
  • Lopez KD, Guinan EC. GM-CSF clinical trials: pediatric aplastic anemia and Fanconi's anemia. Pediatr Nurs 1995; 21:345-9. PubMed
  • Guinan EC, Gribben JG, Boussiotis VA, Freeman GJ, Nadler LM. Pivotal role of the B7:CD28 pathway in transplantation tolerance and tumor immunity. Blood 1994; 84:3261-82. PubMed
  • Antin JH, Weinstein HJ, Guinan EC, McCarthy P, Bierer BE, Gilliland DG, Parsons SK, Ballen KK, Rimm IJ, Falzarano G. Recombinant human interleukin-1 receptor antagonist in the treatment of steroid-resistant graft-versus-host disease. Blood 1994; 84:1342-8. PubMed
  • Guinan EC, Molrine DC, Antin JH, Lee MC, Weinstein HJ, Sallan SE, Parsons SK, Wheeler C, Gross W, McGarigle C. Polysaccharide conjugate vaccine responses in bone marrow transplant patients. Transplantation 1994; 57:677-84. PubMed
  • Guinan EC, Lopez KD, Huhn RD, Felser JM, Nathan DG. Evaluation of granulocyte-macrophage colony-stimulating factor for treatment of pancytopenia in children with fanconi anemia. J Pediatr 1994; 124:144-50. PubMed
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