Infectious complications are a significant cause of morbidity and mortality after HCT. HCT patients are recognized to be the most immunosuppressed of patients and to have the highest infectious death rate, and they are an excellent sentinel source of emerging pathogens and resistant organisms. Although much progress has been made in preventing infections with various prophylaxis strategies for specific infections, infectious death remains a major complication after HCT due to the following:
• increasing significance of Aspergillus, respiratory virus, and adenovirus infections
• an emergence of resistant pathogens and late infections
• transplantation of patients at higher risk for transplantation
• new transplantation practices, such as non-myeloablative conditioning regimens
Therefore, a better understanding of the current epidemiology of infectious complications is required. All faculty members at the Program in Infectious Diseases in collaboration with the clinical labs, molecular labs and the pathology labs are involved in studies aimed at:
These aims are addressed in both retrospective and prospective observational studies using large computerized databases. Infection data include results from standard bacteriologic, fungal and virologic tests, direct antigen detection methods, quantitative molecular test methods for viral pathogens and mutations associated with antiviral resistance, blood-based fungal diagnostic tests and antifungal resistance tests using NCCLS methods. Information from tissues (including autopsies) uses immunohistochemistry, in situ hybridization as well as standard histology and culture-based techniques. Trends in the incidence of infections, infection-related death, and antimicrobial resistance over the last decade will be analyzed using regression models for longitudinal data. Associations of underlying transplantation and patient conditions as well as antimicrobial prophylaxis will be examined using appropriate multivariate regression techniques. These studies provide important clinical information and generate preliminary data for future laboratory studies and novel interventions.
Recent References
Crippa, F., Corey, L., Sale, G, Chuang, E., Boeckh, M . Virological, Clinical, and Ophthalmologic Features of Cytomegalovirus (CMV) Chorioretinitis after Hematopoietic Stem Cell Transplantation. Clin Inf Dis 32 :214-219, 2001 .
Junghanss, C., Boeckh, M., Sandmaier, B.M., Malony, d., Chnaucey, T., McSweeny, P., Little, M.T., Corey, L., Storb, R. Incidence and outcome of viral infections following nonmyeloablative compared to myeloablative allogeneic stem cell transplantation, a matched control study. Blood 99 : 1978-1985, 2002.
Crippa, F., Holmberg, L., Carter, R., Hooper, H., Marr, K., Thomas, C., Bensinger, W, Corey, L., M. Boeckh. Infectious complications in recipients of CD34-selected autologous peripheral blood stem cell transplants. Biol Blood Marrow Transplant 8 :281-289, 2002 .
Boeckh, M ., Leisenring,W., Riddell, S.R., Bowden R.A., Huang, M., Myerson, D., Stevens-Ayers, T., Cunningham, T., Flowers, M., Corey, L. Late Cytomegalovirus Disease And Mortality In Allogeneic Marrow Transplant Recipients: Importance Of Viral Load And CMV-Specific T Cell Immunity. Blood 101 :407-414, 2003 .
Marr, K., Carter, R.A., Boeckh, M ., Martin, P., Corey, L. Invasive Aspergillosis in Allogeneic Stem Cell Transplant Recipients: Changes in Epidemiology and Risk Factors. Blood , 100 :4348-4356, 2002.
Hübel, K., Carter, R., Liles, C., Dale, D.C., Price, T.H., Bowden, R.A., Rowley, S., Bensinger, W., Boeckh, M. Use of granulocyte donors versus related donors for granulocyte transfusion therapy of infections in hematopoietic stem cell transplant recipients: a comparative analysis of feasibility and outcome. Transfusion , 42 ; 1414-21, 2002 .
Chen, C.S., Boeckh, M. , Seidel, K., Clark, J.G., Kansu, E., Madtes, D.K., Wagner, J.L., Witherspoon, R.P., Anasetti, C., Appelbaum, F.R., Bensinger, W., Deeg, H.J, Martin, P.J., Sanders, J.E., Storb, R., Wade, J., Siadak, M., Flowers, M.E.D., Sullivan, K.M. Incidence, Risk Factors And Mortality Of Pneumonia Developing Late After Hematopoietic Stem Cell Transplantation. Bone Marrow Transplant , 32 :515-22, 2003 .
Fukuda, T., Hackman, R.C., Guthrie, K.A., Sandmaier, B.M., Boeckh, M ., Maris, M.B., Maloney, D.G., Deeg, H.J., Martin, P.J., Storb, R.F., Madtes, D.K. Risks and Outcomes of Idiopathic Pneumonia Syndrome After Nonmyeloablative Compared to Conventional Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplantation. Blood 102 :2777-85, 2003 .
Fukuda, T., Boeckh, M. , Guthrie, K.A., Owens, S.M., Mattson, D.K., Wald, A., Corey, L., Storb, R.F., Marr, K.A. Allogeneic Hematopoietic Stem Cell Transplantation in Patients with a History of Prior Invasive Aspergillosis: 10-year Experience at a Single Transplant Center. Biol Blood Marrow Transplant 10 : 494-503, 2004 .
Weinstock, D.M., Boeckh, M., Boulad, F., Eagan, J.A., Fraser, V.J., Henderson, D.A., Perl, T., Yokoe, D., Sepkowitz, K.A. Post-exposure prophylaxis against VZV infection among hematopoietic stem cell transplant recipients: unresolved questions. Infection Control Hospital Epidemiol 25 : 603-8, 2004 .
Marr, K.A., Boeckh, M., Kim, H., Carter, R., Corey, L. Combination antifungal therapy for invasive aspergillosis. Clin Inf Dis 39 :797-802, 2004.
Sangiolo, D., Storer, B., Nash, R., Corey, l., Davis, C., Flowers, M., Hackman, R., Boeckh, M. Toxicity and Efficacy of Daily Dapsone as Pneumocystis Jerovici Prophylaxis after Hematopoietic Stem Cell Transplantation: a Case-Control Study. Biol Blood Marrow Transplant, in press.
Review Articles
Marr, K., Boeckh, M . Commentary to “Prophylaxis against deep fungal infections and CMV endorgan disease in bone marrow transplant recipients: a review” (A. Wilkin and J. Feinberg), Oncology, 14:1712, 2001.
Boeckh, M ., Marr, K. Infections in hematopoietic stem cell transplantation. In: Clinical Approach to Infection in the compromised Host (chapter 16). 4 th Edition. Eds. Rubin, R. and Young, L.S. Plenum Medical Book Company , New York. Pages 527-72, 2002 .
Boeckh, M., Nichols, W.G., Papanicolaou, G., Rubin, R., Wingard, J.R., Zaia. J. Cytomegalovirus in Hematopoietic Stem Cell Transplant Recipients: Current Status, Known Challenges, and Future Strategies. Biol Blood Marrow Transplant 9 :543-58, 2003
Boeckh, M. CMV diagnosis and resistance. Blood Marrow Transplant Reviews 13 (2) :6-10, 2003. (CME)
Boeckh, M. Pneumocystis carinii Pneumonia: Current Prevention and Treatment Strategies. Blood Marrow Transplant Reviews 13 (3) :8-10, 2003. (CME)
Marr KA . (editorial). Empirical antifungal therapy: new options, new trade-offs. New Eng J Med 346(4): 278-80 (2002).
Marr KA . New Approaches To Invasive Fungal Infections. Curr Opin Hematol 10:445-50 (2003).
Marr KA . Antifungals for Febrile Neutropenia: Issues in Trial Design. Curr Opin Invest Drugs 5(2):202-7 (2004).
