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Hematology/Oncology

Division Photo

HemOnc600

First Row: F. Smith, T. Kalfa, R. Gruppo; Second Row:  S. Wells, M. Fouladi, T. Cripe; Third Row:  K. Burns, S. Joshi, P. Mehta, L. Wagner; Fourth Row: K. Kalinyak; Fifth Row:  R. Nagarajan, B. Weiss; Sixth Row: C. Joiner, R. Drissi, T. Hummel; Seventh Row:  J. Perentesis, P. Malik

Division Data Summary
Research and Training Details
Number of Faculty28
Number of Joint Appointment Faculty7
Number of Research Fellows3
Number of Research Students1
Number of Support Personnel187
Direct Annual Grant Support $4,397,168
Direct Annual Industry Support $143,650
Peer Reviewed Publications55
Clinical Activities and Training
Number of Clinical Staff4
Number of Clinical Fellows12
Number of Other Students1
Inpatient Encounters1,197
Outpatient Encounters13,753

Faculty Members

Franklin O. Smith, MD,  Professor ; Marjory J. Johnson Endowed Chair; Director, Hematology/Oncology
Research Interests: Acute myeloid leukemia
Michael Absalon, MD, PhD,  Assistant Professor Clinical
Research Interests: New therapeutics; ataxia telangiectasia; DNA damage response mechanisms
Denise M. Adams, MD,  Associate Professor Clinical ; Inpatient Clinical Director; Medical Director of Comprehensive Hemangiomas and Vascular Malformation Clinic;
Research Interests: Research in angiogenesis, endothelial cell proliferation, vascular anomalies.
Vinod Balasa, MBBS,  Assistant Professor Clinical
Research Interests: Research activities related to sickle cell disease and Thrombophilia
Jacob Bleesing, MD, PhD,  Assistant Professor Clinical
Research Interests: Clinical Investigation of Primary Immunodeficiency Disorders, with emphasis on disorders of immunodysregulation and B-cell disorders
Karen Burns, MD,  Assistant Professor Clinical
Research Interests: Outcomes following cancer therapy and outcomes following bone sarcomas
Timothy Cripe, MD, PhD,  Associate Professor ; Director, Musculoskeletal Tumor Comprehensive Clinic; Director, Translational Research Trials Office
Research Interests: Transcriptional regulation; genetic perturbations in cancer; gene therapy of cancer; gene transfer; transcriptional targeting; antiangiogenesis; viral oncolysis; viral oncogenesis
Stella M. Davies, MBBS, PhD, MRCP,  Professor ; Jacob G. Schmidlapp Endowed Chair; Director, Blood and Marrow Transplant Program
Rachid Drissi, PhD,  Assistant Professor
Research Interests: Examine telomere disruption signaling to DNA damage pathway
Alexandra Filipovich, MD,  Professor ; Ralph J. Stolle Chair in Clinical Immunology; Director, Immunodeficiency and Histiocytosis Program; Medical Director, Diagnostic Laboratory
Research Interests: Immunoreconstitution Following Pediatric Stem Cell Transplantation
Maryam Fouladi, MD, FRCP,  Associate Professor
Research Interests: Developing novel drugs for the treatment of children with recurrent or poor prognosis brain tumors
James I. Geller, MD,  Assistant Professor Clinical
Research Interests: Solid and brain tumors, with a specific interest in new drug development. Leads renal, liver and retinoblastoma initiative
Ralph A Gruppo, MD,  Professor Clinical ; Director, Hemophilia Thrombosis Center
Research Interests: Coagulation; hemophilia; thrombosis
Matthew  Hansen, MD,  Assistant Professor Clinical
Research Interests: Studying outcomes in Hurler’s syndrome patients receiving hematopoietic stem cell transplants.
Richard E. Harris, MD,  Adjunct Professor Clinical
Research Interests: Transplantation for children with bone marrow failure syndromes and aplastic anemia
Sonata Jodele, MD,  Assistant Professor Clinical
Research Interests: Phase I clinical trials; new anticancer drug development; stem cell transplantation; high risk pediatric malignancies; childhood neuroblastoma
Clinton H. Joiner, MD, PhD,  Professor ; Director, Comprehensive Sickle Cell Center
Research Interests: Sickle cell disease and other hemoglobinopathies
Theodosia Kalfa, MD, PhD,  Assistant Professor
Research Interests: study of erythropoiesis and red blood cell structural membrane biology
Karen Ann Kalinyak, MD,  Professor Clinical ; Hematology Clinical Director
Research Interests: Hematology; bone marrow failure; sickle cell anemia; hemoglobinopathy
Beatrice Lampkin, MD,  Professor Emerita
Parinda  Mehta, MD,  Assistant Professor
Research Interests: Blood and Marrow Transplant, Fanconi anemia, Pharmacogenetics and Pharmacokinetics
Rajaram Nagarajan, MD,  Assistant Professor Clinical
Research Interests: Outcomes following cancer therapy and outcomes following bone sarcomas
Joseph S. Palumbo, MD,  Research Assistant Professor
Research Interests: Interactions between the hemostatic system and innate immunity effecting tumor progression
John Perentesis, MD,  Professor ; Director, Oncology Program
Research Interests: Recombinant cancer therapeutics and molecular mechanisms for drug action
Janos Sumegi, MD, PhD,  Professor
Research Interests: Lymphoproliferative disease, Hemphagocytic Lymphohisstiocytosis, Usher syndrom
Lars Wagner, MD,  Associate Professor Clinical
Research Interests: Treatment of neuroblastoma, sarcomas, and brain tumors
Brian D. Weiss, MD,  Assistant Professor Clinical
Research Interests: Targeted Agents for Neurofibromatosis Type 1-Related Malignancies (including plexiform neurofibromas, optic pathway gliomas, and Juvenile Myelomonocytic Leukemia)
Susanne Wells, PhD,  Associate Professor
Research Interests: Papillomavirus biology, molecular mechanisms of cellular growth and senescence

Joint Appointment Faculty Members

Michael Jordan, MD,  Assistant Professor
Immunobiology
Regulation of the immune response; immunotherapy of cancer
Mi-Ok Kim, PhD,  Assistant Professor
Center for Epidemiology and Biostatistics
Punam  Malik, MD,  Associate Professor
Experimental Hematology and Cancer Biology
Laura  Stadler, MEd, MD, MS,  Assistant Professor
Infectious Disease
Epidemiology of infectious diseases; cytomegalovirus (CMV); infections in immunocompromised hosts; international adoption; medical education
Sualius Sumanas, PhD,  Assistant Professor
Developmental Biology
Mary  Sutton, MD,  Assistant Professor
Neurology
David Williams, MD,  Professor
Experimental Hematology
Translational Research

Clinical Staff Members

  • Sarita Joshi, MBBS, MD
  • Teresa  Finke, MD
  • Grant  Mussman, MD
  • Gregory Wallace, DO

Trainees

  • Trent Hummel, MD,  PL-VII,  Children's Hospital Medical Center - Akron
  • Eric Mullins, MD,  PL-VII,  Vanderbilt University
  • Francis Eshun, MD,  PL-VI,  Lincoln Medical Center
  • Sabine  Mellor-Heineke, MD,  PL-VI,  Staedtisches Klinikum Braunschweig
  • Ajay Perumbeti, MD,  PL-VI,  Upstate Medical University
  • Philip Roehrs, MD,  PL-VI,  Medical University of South Carolina
  • Lars Mueller, MD,  PL-V,  Cincinnati Children's Hospital
  • Christine Phillips, MD,  PL-V,  Children's Memorial Hospital Chicago
  • Melissa Rayburg, MD,  PL-V,  University of Texas Health Science Center
  • Adrienne  Hammill, MD, PhD,  PL-IV,  Cincinnati Children's Hospital
  • Theodore Johnson, MD, PhD,  PL-IV,  Medical College of Georgia
  • Kasiani Myers, MD,  PL-IV,  Cincinnati Children's Hospital
  • Benjamin Mizukawa, MD,  PL-IV,  Cincinnati Children's Hospital

Significant Accomplishments in FY08

Oncology Program Summary:   Leukemia/Lymphoma Programs                                        

A key focus of the Oncology Program is the translational development of new anti-cancer therapies built upon a foundation of investigation into the basic mechanisms of oncogenesis in childhood cancers. Fundamental cancer research is based in the Divisions of Hematology/Oncology and Experimental Hematology, along with integrated collaborations including other CCHMC Divisions, the University of Cincinnati, and the Ohio State University Comprehensive Cancer Center.

Leukemia and lymphoma are the most common pediatric malignancies and accounts for approximately 40% to 45% of all childhood cancer. In coordinated efforts, CCHMC faculty members from the Divisions of Hematology/Oncology and Experimental Hematology lead an impressive array of research initiatives in the biology and therapy of leukemias and lymphomas which have been benchmarked by ability to gain competitive National Institutes of Health funding. Dr. Yi Zheng’s NIH-funded laboratory is developing novel small molecular inhibitors of pathological signaling in leukemia cells. His group studies the function and mechanism of regulation of the Rho family small GTP-binding proteins of Ras superfamily. The Rho GTPases are a class of intracellular signal transducers that play important roles in the regulation of diverse cellular activities including action cytoskeleton reorganization, transcription activation, and DNA synthesis. The NIH-funded research group of Dr. Lee Grimes is studying the regulation of expression of cancer causing genes in leukemias through multiple NIH funded awards and is using this work to develop an understanding of the molecular bases of acute myeloid leukemia. He is also actively identifying and refining new drug targets for clinical intervention in leukemias. Dr. Hartmut Geiger is identifying the role of tumor suppressor genes in leukemias and therapeutic opportunities to exploit this pathway. Dr. John Perentesis' NIH-funded laboratory program is identifying molecular targets in leukemias in high-risk pediatric populations such as children with Down syndrome, as well a molecular predictors of outcome in leukemia and Hodgkin’s lymphoma. His lab has also been active in the development of targeted therapies for leukemia. Dr. Andreassen is NIH funded to analyze and dissect the role of cancer gene checkpoint dysregulation in leukemias. Dr. Filippi is NIH-funded to understand some of the role of similar small molecules affecting normal and malignant hematopoietic stem cells as well as how these molecules impact the function of normal cells. Dr. Meetei is also funded through the NIH to study the function and regulation of DNA repair genes in blood cell precursors. Dr. James Mulloy’s NIH-funded group is studying the role of specific core binding factor and other fusion target genes in the regulation of normal and leukemia cells. Dr. Stella Davies leads an extensive NIH-funded program to identify genetic risk factors for the development of leukemia as well as a parallel extensive effort in pharmacogenetics to provide a foundation for the optimization of personalized cancer therapies as well as new targeted agents. Her NIH funded laboratory is the center for national pharmacogenetic studies on the children treated on leukemia regimens through the National Children's Oncology Group, and 20,000 survivors of pediatric cancer through the Childhood Cancer Survivor Study. This work is a key element for the future development of personalized and predictive medicine efforts in pediatric and adult cancers. Translational clinical activities in the Oncology and Blood/Marrow Transplantation Programs are investigating the use of new targeted anti-cancer therapies and antibodies in the treatment of high-risk and relapsed pediatric leukemias and lymphomas.

Blood and Marrow Transplantation Program Summary: Reducing the Side Effects of Bone Marrow Transplantation

Bone marrow transplantation is the only available cure for children with a variety of genetic diseases that cause metabolic abnormalities or bone marrow failure. The availability of better matched donors has improved the results of bone marrow transplantation have improved markedly in recent years. However, the short and long term side effects of transplant can still be severe, or even fatal. Faculty members of the stem cell transplant program at Cincinnati Children’s Hospital have investigated the use of a less intense pre-transplant chemotherapy regimen and have shown that the results are excellent, with successful engraftment and reduced side-effects of treatment. The new reduced-intensity regimen has been used successfully to treat children with Schwachman-Diamond syndrome and Seckel syndrome, two bone marrow failure syndromes in which genetic instability commonly leads to severe side effects, or even death after treatment with conventional regimens. All the children treated with the new regimen had successful engraftment of their stem cells and survived their transplant. Outcomes were similarly in children with Hurler syndrome, a progressive and fatal metabolic disease. The investigators are hopeful that the new approach will allow preservation of fertility for at least a proportion of children, but long term follow-up is needed to confirm this.

Hematology Program Summary: Comprehensive Sickle Cell Center

Sickle cell disease is one of the most common “single gene” disorders in the US, seriously affecting the health and well-being of almost 100,000 children and adults, and significantly shortening their life expectancy. The past two decades of basic and clinical research have generated a new opportunities for treating this disease of red blood cells. The Comprehensive Sickle Cell Center, led by Dr. Clinton Joiner, is fully engaged across a full spectrum of basic, translational, clinical and outcomes/adherence research. Over the past decade, the Sickle Cell Center has received over $22 M in extramural research funding. In 2008 the Sickle Cell Center was awarded a new $6.4 M four-year grant from NHLBI to conduct three major projects: 1. Basic science research into ways to improve the hydration state of sickle red blood cells via gene transfer to hematopoietic stem cells (Dr. Clinton Joiner, PI). 2. Translational research to develop methodogies to alter hemoglobin expression via gene transfer to hematopoietic stem cells (Dr. Punam Malik, PI, Division of Experimental Hematology). 3. A project aimed at improving adherence to hydroxyurea therapy for sickle cell disease via individualized psychosocial interventions (Dr. Monica Mitchell, PI, Division of Psychology and Behavioral Medicine). The grant also funds a career development program for research faculty in hematology and a summer program to introduce high school students to laboratory research. Other NIH-funded, collaborative clinical research projects focus on therapies to prevent strokes in sickle cell disease; on pharmacological treatments for Hemoglobin SC disease; on the correlation between genetic polymorphisms and phenotypic diversity in sickle cell disease (Dr. Karen Kalinyak, PI). Another NHLBI-funded translational research project, in collaboration with the Divisions of Experimental Hematology and Pulmonary Medicine, investigates the relationships among sickle cell disease, inflammation, and lung disease (Dr. Malik).

Significant Publications in FY08

 Leukemia 22(2): 265-72

Bhatla, D., R. B. Gerbing, T. A. Alonzo, P. A. Mehta, K. Deal, J. Elliott, S. Meshinchi, H. Geiger, J. P. Perentesis, B. J. Lange and S. M. Davies (2008). "DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group."

This study demonstrated that patients with acute myeloid leukemia who were hetergeneous for the XRCC3 Thr241 Met allele has improved post-induction disease-free survival compared to children homozygous for the major or minor allele.

Mol Ther16(5): 879-85

Currier, M. A., R. A. Gillespie, N. M. Sawtell, Y. Y. Mahller, G. Stroup, M. H. Collins, H. Kambara, E. A. Chiocca and T. P. Cripe (2008). "Efficacy and safety of the oncolytic herpes simplex virus rRp450 alone and combined with cyclophosphamide."

This study suggest that the oncolytic herpes simplex virus, rRP450/CPA, is safe and should be studied further in childen with recurrent solid tumors. 

Cancer110(11): 2535-41

Fouladi, M., H. S. Nicholson, T. Zhou, F. Laningham, K. J. Helton, E. Holmes, K. Cohen, R. A. Speights, J. Wright and I. F. Pollack (2007). "A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: a Children's Oncology Group study."

This phase II study of the farnesyl transferase inhibitor, tipifarnib, was not found to be effective in children with recurrent central nervous system malignancies.

Blood110(1): 133-41

Palumbo, J. S., K. E. Talmage, J. V. Massari, C. M. La Jeunesse, M. J. Flick, K. W. Kombrinck, Z. Hu, K. A. Barney and J. L. Degen (2007). "Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms."

This study showed that tumor-associated tissue factor is linked to metastasis throught a fibrinogen-dependent and platelet-dependent restriction in natural killer cell mediated clearance of micro-metastases.

Clin Cancer Res13(18 Pt 1): 5418-25

Wagner, L. M., R. E. McLendon, K. J. Yoon, B. D. Weiss, C. A. Billups and M. K. Danks (2007). "Targeting methylguanine-DNA methyltransferase in the treatment of neuroblastoma."

This study showed that methylguanine-DNA methyltransferase is widely expressed in primary neuroblastoma tumors and may be a relevant therapeutic target.

Division Highlights

New viral and gene therapies for high-risk brain and other pediatric solid tumors

Brain tumors and other pediatric solid tumors including neuroblastoma and rhabdomyosarcoma that cannot be completely resected are often fatal, and desperately need new approaches to therapy. CCHMC researchers are developing genetically engineered viruses, called “oncolytic viruses,” that show potent effects in killing cancer cells. In leading edge discoveries published in Molecular Therapy, Cancer Research, and Cancer Gene Therapy, CCHMC investigators have shown that oncolytic herpes simplex viruses can specifically target malignant sarcomas, inhibiting tumor growth and angiogenesis. In parallel clinical trials, patients at CCHMC with highly malignant brain tumors called glioblastoma multiforme are being treated with gene therapy that allows normal healthy blood cells to become resistant to the chemotherapies needed to treat these tumors. In these studies, a patient’s normal healthy blood stem cells are genetically modified to carry genes conferring resistance for the brain tumor chemotherapy drug temozolomide, allowing the patients to safely receive higher doses of the drug. Patients receive the genetically modified blood cells as well as high-dose temozolomide therapy and radiation for treatment of the glioblastoma multiforme. In related studies, our investigators have discovered the molecular mechanisms involved in events leading to the development of gene therapy-related complications, including leukemia. This work provides background for the development of safer gene therapy technologies.

References

Howe SJ, Mansour MR, Schwarzwaelder K, Bartholomae C, Hubank M, Kempski H, Brugman MH, Pike-Overzet K, Chatters SJ, de Ridder D, Gilmour KC, Adams S, Thornhill SI, Parsley KL, Staal FJ, Gale RE, Linch DC, Bayford J, Brown L, Quaye M, Kinnon C, Ancliff P, Webb DK, Schmidt M, von Kalle C, Gaspar HB, Thrasher AJ. Insertional mutagenesis combined with acquired somatic mutations causes leukemogenesis following gene therapy of SCID-X1 patients.

J Clin Invest. 2008 Sep:118(9):3143-50.

Mahller YY, Vaikunth SS, Currier MA, Miller SJ, Ripberger MC, Hsu Y-H, Mehrian-Shai R, Collins MH, Crombleholme TM, Ratner N, Cripe TP. Oncolytic HSV and Erlotinib Inhibit Tumor Growth and Angiogenesis in a Novel Malignant Peripheral Nerve Sheath Tumor Xenograft Model. Mol Ther 15:279-286, 2007

Mahller YY, Vaikunth SS, Ripberger MC, Baird WH, Saeki Y, Cancelas JA, Crombleholme TM, Cripe TP. Tissue inhibitor of metalloproteinase-3 via oncolytic herpes virus inhibits tumor growth and vascular progenitors. Cancer Res 68:1170-1179, 2008

Modlich U, Schambach A, Brugman MH, Wicke DC, Knoess S, Li Z, Maetzig T, Rudolph C, Schlegelberger B, Baum C. Leukemia induction after a single retroviral vector insertion in Evi1 or Prdm16. Leukemia. 22(8):1519-28, 2008

Leading-edge advances in leukemia research

CCHMC leukemia researchers are among the first to successfully transform normal human blood stem cells into leukemia stem cells. This work is providing a new understanding of what causes pediatric leukemia, the most common cancer affecting children. When researchers programmed normal benign human umbilical cord blood cells to express a fusion of two genes important in childhood mixed-lineage leukemia (MLL), they were able to create leukemia stem cells able to transform into either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL) cells depending on the growth factor proteins present in the cell culture. By manipulating these growth factor proteins in the cells, they were also able to transform ALL cells into AML cells and vice versa. In order to facilitate research into new therapies, this same team of researchers used the human leukemia stem cells they developed to create new and more useful mouse models of MLL-associated ALL and mixed myeloid/lymphoid disease. This work has highlighted the critical importance of leukemia cells’ environment to the progression and form of the disease and has suggested exciting new targets for future drug development. Published in the prestigious journal Cancer Cell, this research has garnered significant national attention. In integrated parallel investigations, CCHMC scientists have developed novel drugs for targeting signaling pathways in these leukemias as well as other cancers. Importantly, these new drugs work to kill leukemia cells by targeting the core processes that make them malignant and spare normal cells. These new drugs also kill leukemia cells that have become otherwise resistant to traditional chemotherapy and are currently being refined for clinical trials.

References

Thomas EK, Cancelas JA, Zheng Y, Williams DA. Rac GTPases as key regulators of p210-BCR-ABL-dependent leukemogenesis. Leukemia. 22(5):898-904, 2008

Wei J. Wunderlich M. Fox C. Alvarez S. Cigudosa JC. Wilhelm JS. Zheng Y. Cancelas JA. Gu Y. Jansen M. Dimartino JF. Mulloy JC. Microenvironment determines lineage fate in a human model of MLL-AF9 leukemia. Cancer Cell. 13(6):483-95, 2008

Williams DA, Zheng Y, Cancelas JA. Rho GTPases and regulation of hematopoietic stem cell localization. Methods Enzymol. 439:365-93, 2008

Division Collaboration

Collaboration with Experimental Hematology & Cancer Biology; Pediatric & Thoracic Surgery; Developmental Biology-Students

Collaborating Faculty: J. Cancelas; T. Crombleholme; W. Baird

Tissue inhibitor of metalloproteinase-3 via oncolytic herpesvirus inhibits tumor growth and vascular progenitors. Cancer Res 68:1170-1179, 2008  (T. Cripe; Y. Mahller)

Collaboration with Translational Research Trials Office; Infectious Diseases; Immunobiology

Collaborating Faculty: R. Gillespie; N. Sawtell; D. Hildeman

Efficacy and safety of the oncolytic herpes simplex virus rRp450 alone and combined with cyclophosphamide. Mol Ther 16:879-885, 2008  (T. Cripe; M. Currier; Y. Mahller)

Collaboration with Biomedical Informatics; Developmental Biology-Students

Collaborating Faculty: B. Sakthivel; B. Aronow; W. Baird

Molecular analysis of human cancer cells infected by a multi-mutated oncolytic HSV-1 reveals a role for SOCS1 in virus replication. Cancer Gene Therapy, in press 2008  T. Cripe; Y. Mahller)

Collaboration with Experimental Hematology & Cancer Biology; Pathology; Biostatistics & Epidemiology; Experimental Hematology & Cancer Biology

Collaborating Faculty: G. Johansson; M. Collins; K. Mi-Ok; N. Ratner

Effective in vivo targeting of the mTOR pathway in malignant peripheral nerve sheath tumors. Mol Cancer Ther 7:1237-1245, 2008.  (T. Cripe; Y. Mahller; J. Perentesis)

Collaboration with Endocrinology; Behavioral Medicine & Clinical Psychology

Collaborating Faculty: S. Rose; Doug Ris

A pilot study of oxandrolone in children with Fanconi Anemia and severe bone marrow failure  (F. Smith)

Collaboration with Surgical Services

Collaborating Faculty: R. Azizkhan

COG, Surgery services for Oncology patients

Collaboration with UC Radiation Oncology

Collaborating Faculty: J. Breneman

Radiation Oncology clinical services for Hem/Onc patients; COG

Collaboration with Human Genetics

Collaborating Faculty: Liming Bao; T Smolarek

COG; Genetic services for HemOnc Patients

Collaboration with Pathology

Collaborating Faculty: M. Collins

COG; Pathology services

Collaboration with Behavioral Medicine and Clinical Psychology

Collaborating Faculty: D. Drotar

COG; Adherence Research

Collaboration with Behavioral Medicine & Clinical Psychology

Collaborating Faculty: D. Ris

COG; NeuroPsych services, Neuropsychology research, Fanconi Anemia research

Collaboration with Radiology

Collaborating Faculty: M. Gelfand

COG; Cancer Nuclear Mecine services

Collaboration with Orthopaedics

Collaborating Faculty: CT Mehlman

COG; Brain Tumor research and clinical services

Collaboration with Experimental Hematology

Collaborating Faculty: J. Mulloy

Leukemia Research; COG

Collaboration with Endocrinology

Collaborating Faculty: S. Rose

COG; FA research, NeurOncology Research, Endocrinology services as part of clinic

Collaboration with University of Cincinnati

Collaborating Faculty: George Thomas

COG; Drug Development

Collaboration with Pediatric & Thoracic Surgery

Collaborating Faculty: G. Tiao

COG; Cancer Surgery

Collaboration with Clinical Pharmacology

Collaborating Faculty: A. Vinks

COG; Developmental Therapeutics research

Collaboration with Anesthesia

Collaborating Faculty: N. Weidner

COG; Paliative care and pain

Collaboration with PM&R

Collaborating Faculty: D. Pruit

NeuroOncology Clinic

Collaboration with University of Cincinnati - Oncology

Collaborating Faculty: M Gerena-Lewis

Medical Oncology and NeuroOncology services

Mentions in Consumer Media

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Division Publications

  1. Absalon MJ, McCarville MB, Liu T, Santana VM, Daw NC, Navid F. Pulmonary nodules discovered during the initial evaluation of pediatric patients with bone and soft-tissue sarcoma. Pediatr Blood Cancer. 2008; 50: 1147-53.
  2. Adams DM, Wentzel MS. The role of the hematologist/oncologist in the care of patients with vascular anomalies. Pediatr Clin North Am. 2008; 55: 339-55.
  3. Adams DM, Zhou T, Berg SL, Bernstein M, Neville K, Blaney SM. Phase 1 trial of O6-benzylguanine and BCNU in children with CNS tumors: a Children's Oncology Group study. Pediatr Blood Cancer. 2008; 50: 549-53.
  4. Friedlander SL, Dooms KT, Seroogy CM, Voss CY, Agger WA, Zhang K, Bleesing J, Filipovich AH. Adolescent presentation of x-linked lymphoproliferative disease. Ann Allergy Asthma Immunol. 2008; 100: 398-400.
  5. Kahwash SB, Fung B, Savelli S, Bleesing JJ, Qualman SJ. Autoimmune lymphoproliferative syndrome (ALPS): a case with congenital onset. Pediatr Dev Pathol. 2007; 10: 315-9.
  6. Cripe TP. Can less really be more? Using lessons from leukemia and cancer stem cells to make sense of oral maintenance for metastatic sarcoma. Pediatr Blood Cancer. 2008; 50: 737-8.
  7. Currier MA, Gillespie RA, Sawtell NM, Mahller YY, Stroup G, Collins MH, Kambara H, Chiocca EA, Cripe TP. Efficacy and safety of the oncolytic herpes simplex virus rRp450 alone and combined with cyclophosphamide. Mol Ther. 2008; 16: 879-85.
  8. Mahller YY, Vaikunth SS, Ripberger MC, Baird WH, Saeki Y, Cancelas JA, Crombleholme TM, Cripe TP. Tissue inhibitor of metalloproteinase-3 via oncolytic herpesvirus inhibits tumor growth and vascular progenitors. Cancer Res. 2008; 68: 1170-9.
  9. Blanco JG, Leisenring WM, Gonzalez-Covarrubias VM, Kawashima TI, Davies SM, Relling MV, Robison LL, Sklar CA, Stovall M, Bhatia S. Genetic polymorphisms in the carbonyl reductase 3 gene CBR3 and the NAD(P)H:quinone oxidoreductase 1 gene NQO1 in patients who developed anthracycline-related congestive heart failure after childhood cancer. Cancer. 2008; 112: 2789-95.
  10. Davies S. Who evaluates and counsels related donors?. Biol Blood Marrow Transplant. 2007; 13: 1526-7.
  11. Davies SM, Borowitz MJ, Rosner GL, Ritz K, Devidas M, Winick N, Martin PL, Bowman P, Elliott J, Willman C, Das S, Cook EH, Relling MV. Pharmacogenetics of minimal residual disease response in children with B-precursor acute lymphoblastic leukemia: a report from the Children's Oncology Group. Blood. 2008; 111: 2984-90.
  12. Gardner SL, Carreras J, Boudreau C, Camitta BM, Adams RH, Chen AR, Davies SM, Edwards JR, Grovas AC, Hale GA, Lazarus HM, Arora M, Stiff PJ, Eapen M. Myeloablative therapy with autologous stem cell rescue for patients with Ewing sarcoma. Bone Marrow Transplant. 2008; 41: 867-72.
  13. Lee SJ, Joffe S, Artz AS, Champlin RE, Davies SM, Jagasia M, Kernan NA, Loberiza FR, Jr., Soiffer RJ, Eapen M. Individual physician practice variation in hematopoietic cell transplantation. J Clin Oncol. 2008; 26: 2162-70.
  14. Mulrooney DA, Dover DC, Li S, Yasui Y, Ness KK, Mertens AC, Neglia JP, Sklar CA, Robison LL, Davies SM. Twenty years of follow-up among survivors of childhood and young adult acute myeloid leukemia: a report from the Childhood Cancer Survivor Study. Cancer. 2008; 112: 2071-9.
  15. Pentz RD, Haight AE, Noll RB, Barfield R, Pelletier W, Davies S, Alderfer MA, Hinds PS. The ethical justification for minor sibling bone marrow donation: a case study. Oncologist. 2008; 13: 148-51.
  16. Bullock JZ, Villanueva JM, Blanchard C, Filipovich AH, Putnam PE, Collins MH, Risma KA, Akers RM, Kirby CL, Buckmeier BK, Assa'ad AH, Hogan SP, Rothenberg ME. Interplay of adaptive th2 immunity with eotaxin-3/c-C chemokine receptor 3 in eosinophilic esophagitis. J Pediatr Gastroenterol Nutr. 2007; 45: 22-31.
  17. Filipovich AH. Diagnosis and manifestations of chronic graft-versus-host disease. Best Pract Res Clin Haematol. 2008; 21: 251-7.
  18. Filipovich AH. Hemophagocytic lymphohistiocytosis and other hemophagocytic disorders. Immunol Allergy Clin North Am. 2008; 28: 293-313, viii.
  19. Hazen MM, Woodward AL, Hofmann I, Degar BA, Grom A, Filipovich AH, Binstadt BA. Mutations of the hemophagocytic lymphohistiocytosis-associated gene UNC13D in a patient with systemic juvenile idiopathic arthritis. Arthritis Rheum. 2008; 58: 567-70.
  20. Horne A, Trottestam H, Arico M, Egeler RM, Filipovich AH, Gadner H, Imashuku S, Ladisch S, Webb D, Janka G, Henter JI. Frequency and spectrum of central nervous system involvement in 193 children with haemophagocytic lymphohistiocytosis. Br J Haematol. 2008; 140: 327-35.
  21. Nicolaou SA, Szigligeti P, Neumeier L, Lee SM, Duncan HJ, Kant SK, Mongey AB, Filipovich AH, Conforti L. Altered dynamics of Kv1.3 channel compartmentalization in the immunological synapse in systemic lupus erythematosus. J Immunol. 2007; 179: 346-56.
  22. Stein ML, Villanueva JM, Buckmeier BK, Yamada Y, Filipovich AH, Assa'ad AH, Rothenberg ME. Anti-IL-5 (mepolizumab) therapy reduces eosinophil activation ex vivo and increases IL-5 and IL-5 receptor levels. J Allergy Clin Immunol. 2008; 121: 1473-83, 1483 e1-4.
  23. Fouladi M, Laningham F, Wu J, O'Shaughnessy MA, Molina K, Broniscer A, Spunt SL, Luckett I, Stewart CF, Houghton PJ, Gilbertson RJ, Furman WL. Phase I study of everolimus in pediatric patients with refractory solid tumors. J Clin Oncol. 2007; 25: 4806-12.
  24. Fouladi M, Nicholson HS, Zhou T, Laningham F, Helton KJ, Holmes E, Cohen K, Speights RA, Wright J, Pollack IF. A phase II study of the farnesyl transferase inhibitor, tipifarnib, in children with recurrent or progressive high-grade glioma, medulloblastoma/primitive neuroectodermal tumor, or brainstem glioma: a Children's Oncology Group study. Cancer. 2007; 110: 2535-41.
  25. Haas-Kogan DA, Banerjee A, Kocak M, Prados MD, Geyer JR, Fouladi M, McKnight T, Poussaint TY, Broniscer A, Blaney SM, Boyett JM, Kun LE. Phase I trial of tipifarnib in children with newly diagnosed intrinsic diffuse brainstem glioma. Neuro Oncol. 2008; 10: 341-7.
  26. Helton KJ, Weeks JK, Phillips NS, Zou P, Kun LE, Khan RB, Gajjar A, Fouladi M, Broniscer A, Boop F, Li CS, Ogg RJ. Diffusion tensor imaging of brainstem tumors: axonal degeneration of motor and sensory tracts. J Neurosurg Pediatrics. 2008; 1: 270-6.
  27. Laughton SJ, Merchant TE, Sklar CA, Kun LE, Fouladi M, Broniscer A, Morris EB, Sanders RP, Krasin MJ, Shelso J, Xiong Z, Wallace D, Gajjar A. Endocrine outcomes for children with embryonal brain tumors after risk-adapted craniospinal and conformal primary-site irradiation and high-dose chemotherapy with stem-cell rescue on the SJMB-96 trial. J Clin Oncol. 2008; 26: 1112-8.
  28. Shih CS, Hale GA, Gronewold L, Tong X, Laningham FH, Gilger EA, Srivastava DK, Kun LE, Gajjar A, Fouladi M. High-dose chemotherapy with autologous stem cell rescue for children with recurrent malignant brain tumors. Cancer. 2008; 112: 1345-53.
  29. Geller JI, Argani P, Adeniran A, Hampton E, De Marzo A, Hicks J, Collins MH. Translocation renal cell carcinoma: lack of negative impact due to lymph node spread. Cancer. 2008; 112: 1607-16.
  30. Wu SW, Graham B, Gelfand MJ, Gruppo RE, Dinopolous A, Gilbert DL. Clinical and positron emission tomography findings of chorea associated with primary antiphospholipid antibody syndrome. Mov Disord. 2007; 22: 1813-5.
  31. Hansen MD, Filipovich AH, Davies SM, Mehta P, Bleesing J, Jodele S, Hayashi R, Barnes Y, Shenoy S. Allogeneic hematopoietic cell transplantation (HCT) in Hurler's syndrome using a reduced intensity preparative regimen. Bone Marrow Transplant. 2008; 41: 349-53.
  32. Harris RE. Management of the hematologic abnormalities of Shwachman Diamond Syndrome. Kernersville, NC; Shwachman Diamond America
  33. Joiner CH. Gardos pathway to sickle cell therapies?. Blood. 2008; 111: 3918-9.
  34. Lindsell CJ, Franco RS, Smith EP, Joiner CH, Cohen RM. A method for the continuous calculation of the age of labeled red blood cells. Am J Hematol. 2008; 83: 454-7.
  35. Roszell NJ, Danton MJ, Jiang M, Witte D, Daugherty C, Grimes T, Girdler B, Anderson KP, Franco RS, Degen JL, Joiner CH. Fibrinogen deficiency, but not plasminogen deficiency, increases mortality synergistically in combination with sickle hemoglobin SAD in transgenic mice. Am J Hematol. 2007; 82: 1044-8.
  36. Goodman SR, Joiner CH. "Damage to the RBC membrane in sickle cell disease." In: B Pace, ed. Renaissance of sickle cell disease research in the genome era. London: Imperial College Press; 2007: 153-172.
  37. Daria D, Filippi MD, Knudsen ES, Faccio R, Li Z, Kalfa T, Geiger H. The retinoblastoma tumor suppressor is a critical intrinsic regulator for hematopoietic stem and progenitor cells under stress. Blood. 2008; 111: 1894-902.
  38. Yang L, Wang L, Kalfa TA, Cancelas JA, Shang X, Pushkaran S, Mo J, Williams DA, Zheng Y. Cdc42 critically regulates the balance between myelopoiesis and erythropoiesis. Blood. 2007; 110: 3853-61.
  39. Bhatla D, Gerbing RB, Alonzo TA, Mehta PA, Deal K, Elliott J, Meshinchi S, Geiger H, Perentesis JP, Lange BJ, Davies SM. DNA repair polymorphisms and outcome of chemotherapy for acute myelogenous leukemia: a report from the Children's Oncology Group. Leukemia. 2008; 22: 265-72.
  40. Mehta PA, Davies SM. Allogeneic transplantation for childhood ALL. Bone Marrow Transplant. 2008; 41: 133-9.
  41. Zebrack BJ, Zevon MA, Turk N, Nagarajan R, Whitton J, Robison LL, Zeltzer LK. Psychological distress in long-term survivors of solid tumors diagnosed in childhood: a report from the childhood cancer survivor study. Pediatr Blood Cancer. 2007; 49: 47-51.
  42. Flick MJ, LaJeunesse CM, Talmage KE, Witte DP, Palumbo JS, Pinkerton MD, Thornton S, Degen JL. Fibrin(ogen) exacerbates inflammatory joint disease through a mechanism linked to the integrin alphaMbeta2 binding motif. J Clin Invest. 2007; 117: 3224-35.
  43. Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, Hu Z, Barney KA, Degen JL. Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms. Blood. 2007; 110: 133-41.
  44. Johansson G, Mahller YY, Collins MH, Kim MO, Nobukuni T, Perentesis J, Cripe TP, Lane HA, Kozma SC, Thomas G, Ratner N. Effective in vivo targeting of the mammalian target of rapamycin pathway in malignant peripheral nerve sheath tumors. Mol Cancer Ther. 2008; 7: 1237-45.
  45. Aplenc R, Alonzo TA, Gerbing RB, Lange BJ, Hurwitz CA, Wells RJ, Bernstein I, Buckley P, Krimmel K, Smith FO, Sievers EL, Arceci RJ. Safety and efficacy of gemtuzumab ozogamicin in combination with chemotherapy for pediatric acute myeloid leukemia: a report from the Children's Oncology Group. J Clin Oncol. 2008; 26: 2390-3295.
  46. Brown P, Smith FO. Molecularly targeted therapies for pediatric acute myeloid leukemia: progress to date. Paediatr Drugs. 2008; 10: 85-92.
  47. Kamani N, Spellman S, Hurley CK, Barker JN, Smith FO, Oudshoorn M, Bray R, Smith A, Williams TM, Logan B, Eapen M, Anasetti C, Setterholm M, Confer DL. State of the art review: HLA matching and outcome of unrelated donor umbilical cord blood transplants. Biol Blood Marrow Transplant. 2008; 14: 1-6.
  48. Lange BJ, Smith FO, Feusner J, Barnard DR, Dinndorf P, Feig S, Heerema NA, Arndt C, Arceci RJ, Seibel N, Weiman M, Dusenbery K, Shannon K, Luna-Fineman S, Gerbing RB, Alonzo TA. Outcomes in CCG-2961, a children's oncology group phase 3 trial for untreated pediatric acute myeloid leukemia: a report from the children's oncology group. Blood. 2008; 111: 1044-53.
  49. Rubnitz JE, Gibson B, Smith FO. Acute myeloid leukemia. Pediatr Clin North Am. 2008; 55: 21-51, ix.
  50. Trizzino A, zur Stadt U, Ueda I, Risma K, Janka G, Ishii E, Beutel K, Sumegi J, Cannella S, Pende D, Mian A, Henter JI, Griffiths G, Santoro A, Filipovich A, Arico M. Genotype-phenotype study of familial haemophagocytic lymphohistiocytosis due to perforin mutations. J Med Genet. 2008; 45: 15-21.
  51. Wagner LM, Crews KR, Stewart CF, Rodriguez-Galindo C, McNall-Knapp RY, Albritton K, Pappo AS, Furman WL. Reducing irinotecan-associated diarrhea in children. Pediatr Blood Cancer. 2008; 50: 201-7.
  52. Wagner LM, Garrett JK, Ballard ET, Hill DA, Perry A, Biegel JA, Collins MH. Malignant rhabdoid tumor mimicking hepatoblastoma: a case report and literature review. Pediatr Dev Pathol. 2007; 10: 409-15.
  53. Wagner LM, McLendon RE, Yoon KJ, Weiss BD, Billups CA, Danks MK. Targeting methylguanine-DNA methyltransferase in the treatment of neuroblastoma. Clin Cancer Res. 2007; 13: 5418-25.
  54. Blanchard C, Mingler MK, Vicario M, Abonia JP, Wu YY, Lu TX, Collins MH, Putnam PE, Wells SI, Rothenberg ME. IL-13 involvement in eosinophilic esophagitis: transcriptome analysis and reversibility with glucocorticoids. J Allergy Clin Immunol. 2007; 120: 1292-300.
  55. Wise-Draper TM, Wells SI. Papillomavirus E6 and E7 proteins and their cellular targets. Front Biosci. 2008; 13: 1003-17.
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Grants, Contracts, and Industry Agreements

Grant and Contract Awards Annual Direct / Project Period Direct

Browne, A

Delivery and Production of a Secretable Universal Cancer Biomarker and its Detection in the Blood by a Novel Continuous Sampling Microtechnology
05/01/08 - 04/30/09 $35,000 / $35,000

Burns, K.

Survivorship Conference Grant
11/01/07 - 10/31/08 $20,000 / $20,000

Cripe, T

Identifying and Targeting the Source of Neuroblastoma Metastasis
05/01/08 - 04/30/09 $25,000 / $25,000
Oncolytic HSV Therapy in Immunocompetent Sarcoma Models
R01 CA 11400407/01/06 - 05/31/11 $172,353 / $866,912
Cincinnati NF1 Preclinical Testing Center
12/01/07 - 05/31/11 $25,000 / $720,000
Cincinnati NF1 Preclinical Testing Center
06/01/08 - 05/31/11 $232,000 / $720,000

Davies, S

The Children's Oncology Group Chairs Grant
U10 CA 09854303/01/08 - 02/28/13 $11,663 / $58,465
The Children's Oncology Group Chairs Grant - Methotrexate
U10 CA 098543-S103/01/08 - 02/28/13 $11,693 / $58,468
COG Pediatric Blood and Marrow Transplant (Per Patient)
U01 HL 06929409/01/06 - 08/31/08 $4,763 / $22,610
Predictors Of Adult Leukemia
R01 CA 10714304/01/05 - 02/28/10 $11,712 / $56,904
Genetic Epidemiology of Basal Cell Carcinoma in Childhood Cancer Survivors
04/01/08 - 03/31/09 $25,000 / $25,000
Novel Molecular and Cellular Therapies in Fanconi Anemia
R01 HL 08149904/01/08 - 03/31/10 $166,839 / $333,678
Childhood Cancer Survivor Study
U54 CA 05572712/01/05 - 11/30/10 $50,000 / $643,729
Antileukemic Effect of NK Cells in HCT for Pediatric AML
R01 CA 12058308/01/07 - 06/30/12 $8,716 / $43,580

Fouladi, M

Children's Oncology Group Phase I/Pilot Consortium
U01 CA 09745208/01/07 - 07/31/12 $21,877 / $21,877
The Pediatric Brain Tumor Consortium
U01 CA 08145704/01/08 - 03/31/09 $11,127 / $11,127

Glass, D.

Fascanto II Flow Cytometer and SVC Fascanto II Violet
C76 HF 0997806/01/08 - 05/31/09 $473,707 / $473,707

Gruppo, R

Hemophilia Comprehensive Care & Prevention Core Center for Bleeding Disorders
5H30MC0015-1110/01/97 - 05/31/09 $14,760 / $124,190
Hemophilia Prevention Network
U27 CCU 5138210/01/97 - 09/29/08 $22,295 / $134,771
Hemophilia and Thrombosis Center
06/01/03 - 05/31/09 $58,200 / $239,458

Joiner, C

Cincinnati Sickle Cell Project
31-6-006-1-CC-0807/01/07 - 06/30/08 $117,368 / $117,368
Cincinnati Comprehensive Sickle Cell Center
U54 HL 07087106/15/08 - 03/31/12 $1,005,115 / $4,067,809
Mitchell, MProject 3108,644
Joiner, CProject 4298,056
Malik, PProject 5389,734
Joiner, CAdmin Core103,681
Joiner, CScholar105,000
Cincinnati Comprehensive Sickle Cell Center
U54 HL070871-05S06/15/08 - 03/31/09 $184,862 / $184,862

Kalfa, T

Rac1 and Rac2 Guanosine Triphosphatases in Erythroid Function and Differentiation
K08 HL 08812602/11/08 - 11/30/12 $119,125 / $595,625

Kalinyak, K

Silent Cerebral Infarct Multi-Center Clinical Trial
U01 NS 04280409/30/03 - 06/30/10 $3,665 / $502,371
Stroke With Transfusions Changing To Hydroxyurea
U01 HL 07878704/01/06 - 06/30/11 $28,975 / $138,180

Marsh, R

Investigation into the Clinical and Molecular Pathogenesis of XIAP Deficiency
11/01/07 - 10/31/08 $48,500 / $48,500

Muller, L

Optimization of Gene Therapy Technology for FA, an Inherited Cancer Predisposition and Bone Marrow Failure Syndrome
07/01/07 - 06/30/08 $61,875 / $61,875

Nagarajan, R

Genetic Epidemiology of Osteosarcoma
U01 CA 12237105/01/07 - 04/30/11 $9,013 / $36,607

Palumbo, J

Hemostatic Factors and Tumor Biology
K08 HL 07436307/15/03 - 06/30/08 $120,750 / $603,750
Mechanisms Linking Metastasis to Tumor Procoagulant and Innate Immunity
R01 HL 08554507/20/06 - 06/30/11 $242,750 / $1,221,000

Partin-Welch, P

Oncology Education and Support Group/Family Specials Needs Program
07/01/07 - 06/30/08 $5,000 / $5,000

Perentesis, J

Children's Oncology Group Phase I Consortium
U01 CA 09754208/01/07 - 07/31/12 $21,250 / $106,250
Children's Oncology Group Phase I Consortium (Per Patient)
U01 CA 09754208/01/07 - 07/31/12 $23,354 / $116,772
Children's Oncology Group - Committee
U01 CA 09754208/01/07 - 07/31/12 $11,441 / $57,205
Molecular Studies of Down Syndrome Leukemia
R01 CA 11177801/01/05 - 12/31/08 $178,395 / $652,146
Personalized Neuroblastoma Cancer Signatures and Targeted Therapy
05/01/08 - 04/30/09 $40,000 / $40,000
Chairman's Award Children's Oncology Group
U10 CA 09854303/01/08 - 02/28/13 $23,325 / $116,625
Chairman's Award Children's Oncology Group (Per Patient)
U10 CA 09854303/01/03 - 02/28/13 $97,909 / $418,715

Shook, L

Cincinnati Sickle Cell Newborn Screening Network
H46 MC 0923306/01/08 - 05/31/11 $185,000 / $555,000

Smith, F.

The Children's Oncology Group Chairs Grant
U10 CA 09854303/01/08 - 02/28/13 $108,925 / $544,628

Sumegi, J

Molecular Characterization of Novel Variant Translocation in Sarcomas of Children
09/01/07 - 08/31/08 $25,000 / $25,000
Search for Growth Inhibitory Genes in Ewing's Sarcoma by Epigentic Profiling
01/01/08 - 12/31/08 $46,262 / $92,524

Wagner, L.

Children's Oncology Group Phase I ADVL0414 Study Chair
U01 CA 09745208/01/07 - 07/31/12 $20,251 / $101,255
Identification of Response Markers in Children Receiving Combination Therapy with Chemotherapy and Bevacizumab
05/01/08 - 04/30/09 $20,000 / $20,000

Wells, S.

Fanconi Anemia and HPV Associated Disease
01/01/07 - 12/31/08 $75,000 / $150,000
Role and Regulation of the Human DEK Proto-Oncogene
R01 CA 11631304/01/06 - 02/28/11 $172,353 / $916,579
Current Year Direct$4,397,168
Industry Contracts

Balasa, V

$ 36,599

Cripe, T

$ 38,078

Gruppo, R

$ 11,562
$ 12,570

Harris, R

$ 2,118
$ 6,622

Joiner, C

$ 2,257

Smith, F

$ 33,844
Current Year Direct Receipts$143,650
Current Year Direct$143,650
Total$4,540,818
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