Faculty Profile

Dr. Peter D. Cole, M.D.

Peter D. Cole, M.D.

Associate Professor, Department of Pediatrics (Pediatric Hematology-Oncology)

Areas of Research: Improving treatment for children, adolescents and young adults with acute lymphoblastic leukemia or Hodgkin’s lymphoma. Reducing the toxic side effects of cancer therapy, particularly those that can affect cognitive function.

Professional Interests

My clinical research focuses on improving treatment for children, adolescents and young adults with acute lymphoblastic leukemia or Hodgkin’s lymphoma.

My laboratory background is in the molecular pharmacology of antifolates, such as methotrexate, drugs that exert their antineoplastic effects by interfering with cellular processes dependent on the vitamin folic acid.  My current laboratory research centers on reducing the toxicity of anticancer therapy, including that caused by antifolates.  Although cure rates for patients with cancer continue to increase, many cancer patients report symptoms suggestive of impaired cognitive function while receiving therapy, including fatigue, short-term memory loss, and diminished concentration.  For children, whose brains are continuing to undergo important phases of structural development, the neurotoxic effects of anticancer therapy can be lifelong.  The focus of our translational research is studying how cognitive impariment is caused by the complex intersection of host factors (genetic variation), environmental factors (e.g. dietary intake of micro nutrients, such as folate), and treatment factors (chemotherapy and radiation therapy).  We are establishing animal models that will improve our understanding of the pathophysiology of treatment-induced neurotoxicity, and allow us to test interventions to eliminate it.  In addition, we are attempting to delineate measurable factors in the blood or CSF collected from patients during therapy that will be predictive of neurological impairment after completion of therapy.  Once validated prospectively, these predictors can then be used to identify the subset of patients who might derive the greatest benefit from interventions aimed at reducing neurotoxicity.

Selected Publications

    1. Thomsen AM, Gulinello ME, Vijayanathan V, Wen J, Schmiegelow K, Cole PD. Liposomal Cytarabine Induces Less Neurocognitive Dysfunction than Intrathecal Methotrexate in an Animal Model. Journal of Pediatric Hematology / Oncology. 2017; published online July 17 2017. PMID: 28654460.
    2. Maxwell RR, Cole PD. Pharmacogenetic Predictors of Treatment-Related Toxicity among Children with Acute Lymphoblastic Leukemia. Current Hematologic Malignancy Reports. 2017; 23(3): 176-86 PMID: 28317081
    3. Finkelstein Y, Blonquist TM, Vijayanathan V, Stevenson KE, Neuberg DS, Silverman LB, Vrooman LM, Sallan SE, Cole PD. A Thymidylate Synthase Polymorphism is Associated with Increased Risk for Bone Toxicity Among Children Treated for Acute Lymphoblastic Leukemia. Pediatric Blood & Cancer. 2017; 64(7): e26393; Published online 13 Dec. 2016. PMID: 27957785
    4. Sands SA, Harel BT, Savone M, Kelly K, Vijayanathan V, Welch JG, Vrooman L, Silverman LB, Cole PD. Feasibility of Baseline Neurocognitive Assessment using Cogstate During the First Month of Therapy for Childhood Leukemia. Supportive Care in Cancer. 2016; published online October 12. PMID: 27726029
    5. Kahn J, Athale, UH, Clavell LA, Cole PD, Leclerc J-M, Laverdiere C, Michon B, Schorin MA, Welch JG, Sallan SE, Silverman LB, Kelly KM. How variable is our delivery of information? A survey of medical providers assessing provider-driven patient teaching about oral chemotherapy regimens for pediatric patients with acute lymphoblastic leukemia. Journal of Pediatric Health Care. 2016, published online July 25. PMID: 27461368
    6. Ladas EJ, Orjuela M, Stevenson K, Cole PD, Lin M, Athale UH, Clavell LA, Leclerc J-M, Michon B, Schorin MA, Welch JG, Asselin B, Sallan S, Silverman LB, Kelly KM. The Diet and Acute Lymphoblastic Leukemia Treatment (DALLT) Cohort Study: Rationale, Design, and Baseline Characteristics. Nutrition. 2016; published online March 28. PMID: 27318855
    7. Figueiredo L, Cole PD, Drachtman RA. Asparaginase Erwinia chrysanthemi as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to E. coli-derived asparaginase. Expert Rev Hematol. 2016 Mar;9(3):227-34.
    8. Drachtman RA, Masterson M, Shenkerman A, Vijayanathan V, Cole PD. Long-term outcomes for children with acute lymphoblastic leukemia (ALL) treated on the Cancer Institute of New Jersey ALL trial (CINJALL). Leukemia and Lymphoma 2016; 57(10):2275-80. PMID: 26879921
    9. Place AE, Stevenson KE, Vrooman LM, Harris MH, Hunt SK, Supko J, Asselin B, Athale UH, Clavell LA, Cole PD, Kelly KM, Laverdiere C, Leclerc J-M, Michon B, Schorin MA, Welch J, Lipshultz SE, Blonquist T, Neuberg DS, Sallan E, Silverman LB. Phase III Randomized Comparison of Intravenous Pegasparaginase and Intramuscular Native E.coli L-Asparaginase in Newly Diagnosed Childhood ALL: Results of DFCI Protocol 05-001. Lancet Oncology; 2015; 16(16): 1677-90. PMID: 26549586.
    10. Cole PD, Finkelstein Y, Stevenson KE, Blonquist TM, Vijayanathan V, Silverman LB, et al. Polymorphisms in Genes Related to Oxidative Stress Are Associated with Inferior Cognitive Function after Therapy for Childhood Acute Lymphoblastic Leukemia. Journal of Clinical Oncology. 2015; 33(19):2205-11. PMID: 25987702
    11. Horton TM, Drachtman R, Chen L, Cole PD, McCarten K, Voss SD, et al. A Phase 2 Study of Bortezomib in Combination with Ifosfamide/Vinorelbine in Pediatric Patients and Young Adults with Refractory/Recurrent Hodgkin Lymphoma: A Children’s Oncology Group (COG) Study. British Journal of Haematology. 2015 Jul;170(1):118-22. PMID: 25833390
    12. Perales M-A, Ceberio P, Burns L, Chen R, Cole PD, Evens AM, et al. The Role of Cytotoxic Therapy with Hematopoietic Cell Transplantation in the Treatment of Hodgkin Lymphoma: An Evidence-Based Review by the American Society for Blood and Marrow Transplantation Committee on Practice Guideline. Biology of Blood and Marrow Transplantation. 2015; 21(6):971-983. doi: 10.1016/j.bbmt.2015.02.022.
    13. Kim S-E, Hinoue T, Kim MS, Sohn K-J, Cho RC, Cole PD, Weisberger DJ, Laird PW, Kim YI. g-Glutamyl hydrolase modulation significantly influences global and gene-specific DNA methylation and gene expression in human colon and breast cancer cells. Genes and Nutrition, 2015; 10(1): 444. PMID: 25502219
    14. Harker-Murray P, Drachtman RA, Hodgson DC, Chauvenet AR, Kelly KM, Cole PD. Stratification of treatment intensity in relapsed pediatric Hodgkin lymphoma. Pediatric Blood & Cancer, 2014; 61(4): 579-586. PMID: 24504790
    15. Kim S-E, Cole PD, Cho R, Ly A, Ishiguro L, Sohn K-J, Croxford R, Kamen B, Kim Y-I. γ-Glutamyl hydrolase modulation and folate influence chemosensitivity of cancer cells to 5-fluorouracil and methotrexate. British Journal of Cancer 2013; 109: 2175-88. PMID: 24045662
    16. Cole PD, Vijayanathan V, Ali NF, Wagshul ME, Tanenbaum EJ, Price J, Dalal V, Gulinello ME. “Memantine protects rats treated with intrathecal methotrexate from developing spatial memory deficits,” Clinical Cancer Research 2013: 19(16):4446-54. PMID: 23833301.
    17. Becton LJ, Goilav B, Wang Y, Cole PD, Kaskel F. 18 year old with nephrotic syndrome and chest pain. Pediatric Nephrology. 2015; 30(2): 267-71. Published online Nov. 22, 2013. DOI: 10.1007/s00467-013-2646-x. PMID: 24263532.
    18. Kelly KM, Hodgson D, Appel B, Chen L, Cole PD, Horton T, Keller FG, on behalf of the, 'Children's Oncology Group's 2013 Blueprint for Research: Hodgkin Lymphoma', Pediatric Blood & Cancer (2012), 60(6):972-8. PMID: 23255501.
    19. Vijayanathan V, Ali N, Gulinello M, Cole PD. Persistent cognitive deficits, induced by intrathecal methotrexate, are associated with elevated CSF concentrations of excitotoxic glutamate analogs and can be reversed by an NMDA antagonist. Behavioural Brain Research. 2011;225(2):491-7.
    20. Vrooman LM, Neuberg DS, Stevenson KE, Asselin BL, Athale UH, Clavell L, Cole PD, Kelly KM, Larsen EC, Laverdiere C, Michon B, Schorin M, Schwartz CL, Cohen HJ, Lipshultz SE, Silverman LB, and Sallan SE. The low incidence of secondary acute myelogenous leukaemia in children and adolescents treated with dexrazoxane for acute lymphoblastic leukaemia: a report from the Dana-Farber Cancer Institute ALL Consortium. European Journal of Cancer 2011;47: 1373-1379.
    21. Mahadeo KM, Wolgast L, McMahon C, Cole PD. Systemic Mastocytosis in a Child With t(8;21) Acute Myeloid Leukemia. Pediatric Blood & Cancer, 2011; 27(8):650-7.
    22. Cole PD, McCarten KM, Drachtman RA, de Alarcon P, Chen L, Trippett TM, Schwartz CL. Early FDG-PET-based Response Evaluation After Treatment with Gemcitabine and Vinorelbine for Refractory Hodgkin Disease: A Children’s Oncology Group Report. Pediatric Hematology and Oncology; 2010; 27(8): 650-7.
    23. Mahadeo KM, Cole PD. Successful treatment using omacetaxine for a patient with CML and BCR-ABL1 35INS. Blood 2010; 115(18): 3852.
    24. Li Y, Vijayanathan V, Gulinello M, Cole PD. Intrathecal Methotrexate Induces Focal Cognitive Deficits and Increases Cerebrospinal Fluid Homocysteine. Pharmacology, Biochemistry and Behavior;2010; 95 (4): 428-33.
    25. Silverman LB, Supko JG, Stevenson KE, Woodward C, Vrooman LM, Neuberg DS, Asselin  BL, Athale UH, Clavell L, Cole PD, Kelly K, Laverdiere C, Michon B, Schorin M, Schwartz CL, O’Brien JE, Cohen HJ, Sallan SE.  Intravenous PEG-Asparaginase During Remission Induction in Children and Adolescents with Newly Diagnosed Acute Lymphoblastic Leukemia.   Blood 2010; 115(7):1351-3.
    26. Li Y, Vijayanathan V, Gulinello ME, Cole PD. Systemic Methotrexate Induces Spatial Memory Deficits and Depletes Cerebrospinal Fluid Folate in Rats. Pharmacology, Biochemistry and Behavior 2010: 94(3):454-63.
    27. Silverman LB, Stevenson K, O’Brien JE, Asselin BL, Athale UH, Clavell L, Cole PD, Kelly K,  Laverdiere C, Michon B, Schorin M, Schwartz CL, O’Holleran EW, Neuberg DS, Cohen HJ,  Sallan SE. Long-term results of Dana-Farber Cancer Institute ALL Consortium protocols for children with newly diagnosed acute lymphoblastic leukemia (1981-1995).  Leukemia 2010; 24(2): 320-34.
    28. Cole PD, Beckwith KA, Vijayanathan V, Roychowdhury S, Smith AK, Kamen BA. CSF Folate Homeostasis During Therapy for Acute Lymphoblastic Leukemia. Pediatric Neurology 2009; 40(1): 34-41.
    29. Cole PD, Schwartz CL, Drachtman RA, de Alarcon PA, Chen L, Trippett T. Phase 2 Study of Weekly Gemcitabine and Vinorelbine for Children with Recurrent or Refractory Hodgkin Disease, A Children's Oncology Group Report. Journal of Clinical Oncology. 2009; 27(9): 1456-61.
    30. Wollack JB, Makori B, Ahlawat S, Koneru R, Picinich S, Smith AK, Goldman ID, Qiu A, Cole PD, Glod J, Kamen BA.  Characterization of folate uptake by choroid plexus epithelial cells in a rat primary culture model. Journal of Neurochemistry, 2008; 104(6): 1494-503.
    31. Cho RC, Cole PD, Sohn KJ, Gaisano G, Croxford R, Kamen BA, Kim YI.  Effects of folate and folylpolyglutamyl synthase modulation on chemosensitivity of breast cancer cells.  Molecular Cancer Therapeutics, 2007; 6(11): 2909-20.
    32. Vijayanathan V. Smith AK, Zebala JA, Kamen BA, Cole PD. HPLC Separation of Aminopterin Polyglutamates Within Red Blood Cells of Children Treated for Acute Lymphoblastic Leukemia. Translational Research, 2007; 150(6) 367-73.
    33. Cole PD, Drachtman RA, Masterson M, Smith AK, Glod J, Zebala JA, Lisi S, Drapala D-A, Kamen BA.  Phase IIB Trial Of Aminopterin In Multiagent Therapy For Children With Newly Diagnosed Acute Lymphoblastic Leukemia at High Risk of Relapse. Cancer Chemotherapy and Pharmacology, 2008; 62:65-75.
    34. Cole PD, Kamen BA.  Delayed Neurotoxicity Associated with Therapy for Patients with Childhood Leukemia.  Mental Retardation and Developmental Disabilities Research Reviews. 2006; 12(3): 174-83.
    35. Cole PD, Drachtman RA, Smith AK, Cate S, Larson RA, Hawkins DS, Holcenberg J, Kelly K, Kamen BA.  Phase II Trial of Oral Aminopterin for Adults and Children with Refractory Acute Leukemia.  Clinical Cancer Research 2005; 11(22): 8089-96.
    36. Cole PD, Alcaraz MJ, Smith AK, Tan J, Kamen BA.  Pharmacodynamic properties of methotrexate and Aminotrexate during weekly therapy.  Cancer Chemotherapy and Pharmacology. 2006; 57(6):826-34. Epub 2005 Sep 17.
    37. Hochhauser CJ, Lewis M, Kamen BA, Cole PD. Steroid Induced Alterations of Mood and Behavior in Children During Treatment for Acute Lymphoblastic Leukemia.  Supportive Care in Cancer. 2005; 13(12): 967-74.
    38. Li WW, Su D, Mizobuchi H, Martin DS, Gu B, Gorlick R, Cole P, and Bertino JR. Status of methylthioadenosine phosphorylase and its impact on cellular response to l-alanosine and methylmercaptopurine riboside in human soft tissue sarcoma cells. Oncology Research, 2004; 14: 373-379.
    39. Kaufman Y, Drori S, Cole PD, Kamen BA, Sirota J, Ifergan I, Ben Arush MW, Elhasid R, Sahar D, Kaspers GJL, Jansen G, Matherly LH, Rechavi G, Toren A, Assaraf YG.  Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia. Cancer. 2004; 100(4): 773-82.
    40. Cole PD, Smith AK, Kamen BA. Osteosarcoma cells, resistant to methotrexate due to nucleoside and nucleobase salvage, are sensitive to nucleoside analogs.  Cancer Chemotherapy and Pharmacology 2002; 50(2): 111-6.
    41. Drachtman RA, Cole PD, Golden CB, James SJ, Melnyk S, Aisner J, Kamen BA. Dextromethorphan is effective in the treatment of subacute methotrexate neurotoxicity. Pediatric Hematology and Oncology, 2002; 19(5): 319-327.
    42. Cole PD, Gorlick R, Banerjee D, Magill L, Smith A, Kamen BA, Bertino JR. Effects Of Overexpression Of g-Glutamyl Hydrolase (GGH) On Methotrexate Metabolism And Resistance.  Cancer Research, 2001; 61(11): 4599-4604.
    43. Cole PD, Suh JS, Onel K, Stiles J, Armstrong D, Dunkel IJ. Benign Outcome Of RSV Infection In Children with Cancer.  Medical and Pediatric Oncology, 2001; 37(1): 24-9.
    44. Cole PD, Stiles J, Boulad F, Small TN, O’Reilly RJ, George D, Szabolcs P, Kiehn TE, Kernan NA.  Successful treatment of Human Herpes Virus-6 encephalitis in a bone marrow transplantation recipient.  Clinical Infectious Diseases, 1998; 27:653-4.
    45. Cole P, Ladanyi M, Gerald WL, Cheung N-K V, Kramer K, LaQuaglia MP, Kushner BH.  Synovial sarcoma mimicking desmoplastic small round-cell tumor: critical role for molecular diagnosis.  Medical and Pediatric Oncology, 1999; 32: 97-101.
    46. Gorlick R, Cole P, Banerjee D, Longo G, Li WW, Hochhauser D, Bertino JR. Mechanisms of methotrexate resistance in acute leukemia: Decreased transport and polyglutamylation. Advances in Experimental Medicine & Biology, 1999:457:543-50.

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