Patients undergoing bone marrow transplantation (BMT) are at risk for granulocytopenia, impairment of barrier defenses, and impairment of cell-mediated immunity (CMI) and humoral immunity. This impairment leads to an immunocompromised state, allowing microorganisms to cause infection more easily, even those with limited pathogenicity. Patients undergoing BMT experience a sequential suppression of host defenses, allowing for various infectious processes at different phases of the transplantation process.
BMTs are classified as either autologous or allogeneic, based on the source of the hematopoietic stem cells.
Placental or umbilical cord blood obtained immediately after birth has been used to harvest stem cells for transplantation, [2, 3] primarily for use in allogeneic transplantations in children.  Whether parents should create their own stem cell donor for the purpose of treating another of their children is currently an issue of ethical debate.
Infection and GVHD remain the major source of morbidity and mortality in patients who undergo BMT. [5, 13, 14, 15, 16, 17, 18] According to the National Marrow Donor Program, of 462 patients in the United States who underwent an unrelated allogeneic BMT between December 1987 and November 1990, 66% had died by 1991, with infection as the most common primary and secondary cause of death (37% of 307 patients). [3, 19] This article is focused on the common infections in patients who have undergone BMT, the risk factors for these infections, and the approaches to their prevention and treatment.
Certain risk factors place patients undergoing bone marrow transplantation (BMT) at increased risk for infections. Host factors, type of transplant (allogeneic vs autologous, peripheral blood vs bone marrow), immunosuppressive regimen, and graft reactions are the major categories of risk factors to consider.  The baseline medical status of the BMT recipient can lead to an increased predilection to infection. Underlying medical state, previous immune status, prior colonization, prior latent infections, and medications all determine the recipient's baseline medical status.  Patients with malignant conditions probably have a higher risk of infection than patients with nonmalignant conditions because of the immunosuppression associated with the malignancy.
History of vaccination during the 4 weeks before donation: The donation should be deferred for 4 weeks after the donor receives any live-attenuated vaccine.
Travel history: Determine whether the donor has resided in or traveled to countries in which endemic disease that can be transmitted by BMT could have been acquired, eg, malaria.
Similarly, for the transplant recipient, screening must include a complete history, physical examination, and serologic testing. This helps to establish the presence of chronic viral infections (herpes group) and to assess susceptibility for reactivation of pathogens that appear during BMT.  The serology serves as a baseline by which future events can be compared.
Infections during the pretransplantation period are very heterogeneous, as are the conditions necessitating BMT.  Baseline host status and medication therapy determine risk of infection during this period. Preexisting neutropenia or compromised barrier defenses lead to infections at this stage. Before transplantation, screening is needed to identify potential infectious agents that may put the patient at risk of death following the immunosuppression that precedes the BMT.
In the preengraftment period, the major risk for acquiring infection is neutropenia and altered barrier defenses resulting from the BMT conditioning regimen. [2, 3, 4, 5] Another factor is the need for vascular access in this group of patients. [2, 3, 21] The sources of pathogens for infection during this period are the patient's skin flora, oral flora, and GI tract flora.  The disruption of the normal barrier defenses allows microorganisms that normally colonize these areas to invade, rendering them pathogenic.
The predominant infections during the preengraftment phase of transplantation are bacterial, occurring in 15%-50% of recipients of BMT.  The first fever that develops in the BMT recipient posttransplantation is usually caused by a bacterial pathogen; however, isolating the responsible organism or determining the source of infection is unusual.  Just as in the febrile neutropenic patient, a shift in the etiologic agents of bacteremia has occurred in these patients.
The next most common fungal infections are with Aspergillus species; infections with these exogenous fungi/molds appear to have increased during the past decade. Aspergillus infections occur in 4%-20% of BMT recipients.  These fungi are ubiquitous in the environment, but increased amounts are found around areas of recent construction within hospitals. Aspergillus is acquired through inhalation of spores into the respiratory tract or into the sinus tracts. The most common clinical syndromes associated with Aspergillus are pulmonary and sinus disease. However, in immunocompromised patients, this mold can invade into the circulation and disseminate widely.
The virus most commonly documented during the preengraftment phase is HSV, and the usual mechanism of appearance is reactivation of prior latent infection.  A large proportion (80%) of patients who were seropositive for HSV before the transplantation develop clinical disease if prophylaxis is not provided. [4, 21] The most common clinical presentation in this phase is gingivostomatitis (85%).  Pneumonia and HSV-2 genital ulcers or extragenital vesicles (eg, perianal) also occasionally occur. Human herpesvirus 6 (HHV-6) infection may also be a cause of undiagnosed fevers during the preengraftment period. VZV infections, although less common during this phase, may also reactivate.
Other important causes of impaired immunity include acute graft versus host disease (GVHD) and the use of immunosuppressive agents as part of the management of GVHD episodes in allogeneic transplantation.  GVHD prevents recovery of immune function and damages epithelial cells in multiple organ systems, leading to further breakdown of barrier defenses.
CMV disease due to infection occurs more commonly in allogeneic BMT (compared to autologous) with associated risk factors that include recipient seropositivity, histocompatibility differences (between donor and recipient), T-cell depletion of the donated stem cells, graft source unrelated donor, older age, intense GVHD prophylaxis, and intensity of cytoreductive conditioning regimens.  To prevent development of CMV disease, both prophylaxis and early empiric therapy of CMV viremia have been used at BMT centers and is discussed below (see Viral infections). Risk for acquiring CMV in patients who are seronegative comes not only from the bone marrow donor, but also from transfusion of blood products and from close sexual contact in adolescents in the postengraftment phase of transplant.
Respiratory virus infections were found to be a common problem (11%) in a pediatric population who underwent BMT and were associated with substantial morbidity (28% developed pneumonia, approximately 5% had complications with croup) and mortality (9.4%).  Parainfluenza type 3 was found to be the most common. Risk factors for the acquisition of respiratory viral infections depend on the type of BMT (higher risk with allogeneic BMT than with autologous BMT) and the degree of GVHD present.  Enteroviral infections have also been reported to occur in the postengraftment period of transplantation.
Parasitic infections also tend to occur during this period. Pneumocystis jiroveci pneumonia (PCP) was a major opportunistic infection leading to significant morbidity and mortality. However, with the use of trimethoprim-sulfamethoxazole (TMP-SMZ) prophylaxis, PCP is now uncommon except in patients who are not compliant with prophylaxis or are taking inferior prophylaxis.  Toxoplasmosis has also been described in a small number of patients during this phase of transplantation.
The late posttransplantation period is heralded by the recovery of CMI and humoral immunity. This phase begins at day 100 and continues until the BMT recipient stops all immunosuppressive medication for GVHD, which is approximately 18-36 months posttransplantation.  In the absence of chronic GVHD, infection is unusual in this period.
VZV infections are most likely to occur in patients who have undergone BMT during the late posttransplantation period and are usually secondary to reactivation. The median time for occurrence of VZV is 5 months after transplantation.  Eighty-five percent of patients develop shingles, whereas approximately 15% develop chickenpox.  Patients who develop chickenpox are at an increased risk of systemic dissemination (eg, leading to pneumonia), but it can also occur with shingles. Chronic GVHD leads to functional asplenia in these patients and, therefore, to increased susceptibility to encapsulated bacteria (eg, Streptococcus pneumoniae, Neisseria meningitidis).  Systemic fungemia is not commonly observed at this stage, but oropharyngeal candidiasis and Aspergillus sinopulmonary and disseminated infections may occur.
The Centers for Disease Control and Prevention (CDC) produced a report in its Morbidity and Mortality Weekly Report (RR-10) that provides guidelines for preventing opportunistic infections in patients undergoing bone marrow transplantation (BMT).  These guidelines are a good resource for reviewing the variety of techniques available for preventing these infections.
Hospitals that perform BMTs should have appropriately designed facilities that have rooms with more than 12 air exchanges per hour and point-of-use high-efficiency particulate air (HEPA) filtration.  The HEPA filters should be able to remove particles down to at least 0.3 µm in diameter.  Laminar airflow rooms, in which air moves in one direction, have been shown to protect patients from Aspergillus infections during outbreaks. [52, 53] Rooms should have positive air pressure compared to the hallway unless it is housing a patient who has active disease with a pathogen that has airborne transmission; in that case, a negative pressure room is recommended.
Policies and procedures should be in the hospital infection-control manual to address issues of construction and renovation, cleaning, and isolation and barrier precautions. Hand washing should be strongly emphasized to prevent nosocomial transmission of infection. Most researchers recommend that plants and dried or fresh flowers should not be allowed in rooms, although exposure has not been conclusively proven to cause fungal infections. Health care workers should follow a policy with regard to their immunizations and vaccinations.
The major concern with the use of prophylactic antibiotics is the development of resistant organisms. Reports of fluoroquinolone resistance in coagulase-negative staphylococci and in E coli have emerged. [55, 57] Streptococcal species are showing increased resistance to penicillin, ciprofloxacin, and imipenem.  Pseudomonas species have been found to be more resistant to agents such as ceftazidime.  Another concern with the use of prophylactic antimicrobial therapy is the increase in C difficile as a pathogen.
In the late posttransplantation period, because of the increased infection rate related to encapsulated organisms, some centers suggest the use of penicillin prophylaxis and vaccination with the 23-valent polysaccharide S pneumoniae vaccine.  However, the role of this vaccine in infants and younger children is absent or limited, as it is ineffective in this age group. The role of the newer conjugate pneumococcal vaccines in younger children who have undergone BMT remains to be elucidated.
The treatment of bacterial infections in the preengraftment phase is usually empiric, with broad-spectrum antibiotic therapy begun upon the onset of any fever. Treatment is tailored upon the isolation of organisms but remains suitably broad spectrum for continued coverage of all other pathogens that are likely in patients with neutropenic risk. Treatment with empiric antibiotics usually continues until neutrophil count recovery occurs. Generally, empiric coverage consists of one or more antipseudomonal agents, either alone or in combination with an antistaphylococcal antibiotic. Common choices include antipseudomonal penicillins (eg, piperacillin, ticarcillin) in combination with an aminoglycoside (eg, gentamicin, tobramycin), ceftazidime alone or in combination with vancomycin, piperacillin-tazobactam, or meropenem. Knowledge and consideration of the local antimicrobial resistance patterns of the institution are essential when choosing the specific antimicrobial agents.
Fluconazole has been recommended as a prophylactic agent in patients who have undergone BMT. However, with more widespread use of prophylactic fluconazole, an increase has occurred in infections secondary to resistant C albicans and in the isolation of Candida species (ie, C glabrata, C krusei) that are not usually sensitive to fluconazole. [4, 5, 21, 33] Fluconazole possesses no significant activity against Aspergillus; thus, increased infections with Aspergillus are emerging.
The agent micafungin is also approved for prophylaxis of Candida infections in BMT recipients as young as 4 months old. The dose for prophylaxis is 1 mg/kg IV once daily; not to exceed 50 mg/day.
With improved CMV control, Aspergillus species are now the most common cause of infectious mortality in BMT.  Fungal prophylaxis must be addressed, with a focus on the fungi and molds now observed and the resistance patterns. New antifungal agents (eg, voriconazole, caspofungin), which are effective against the resistant candidal species and have activity against Aspergillus, are likely to play a role in future prophylaxis measures.
To improve the poor response seen with conventional therapy, combination therapy has been used in the treatment of invasive aspergillosis. The basis of these regimens has been in vitro studies revealing synergy of the antifungals against Aspergillus. [83, 90, 91, 92] There has been no randomized controlled trial to address the efficacy of this approach. Studies consist of case reports and case series. [93, 94, 95, 96] With no proof that this is a better regimen in terms of efficacy or survival, important considerations arguing against the use of combination therapy include the additive toxicity, as well as the added costs of therapy.
When febrile neutropenia persists for more than 5-7 days despite empiric therapy, most centers currently rely on amphotericin B (0.5 mg/kg/d IV once daily for systemic candidiasis, 1-1.5 mg/kg/d once daily for invasive aspergillosis) or an equivalent dose of a liposomal formulation. [97, 98] This therapy is continued until the fever has abated and, generally, until the neutrophil count has recovered. Search for fungi must go hand in hand with empiric therapy.
Acyclovir (5-10 mg/kg IV q8h for 7-14 d) is also the treatment of choice when HSV infection does develop.  When patients do not respond to acyclovir, foscarnet (80-120 mg/kg/d IV divided q8-12h) is used until infection resolves.  If foscarnet is unsuccessful, therapy with cidofovir (limited data exist, check most recent protocol for dose) should be attempted.
CMV was the leading cause of morbidity and mortality in patients after BMT. The advent of ganciclovir for prophylaxis has profoundly decreased severe CMV disease. The highest risk for disease is in recipients who are CMV negative and who received transplantation from a donor who is CMV positive. The group at next highest risk is recipients who are CMV positive, and the lowest risk is in BMT recipients who are CMV negative receiving transplantation from a donor who is CMV negative. Minimal risk exists if a CMV-negative recipient receives filtered leukocytes and irradiated filtered blood products for all transfusions.
The disadvantage of prophylaxis is that all patients are treated, leading to unnecessary therapy, and ganciclovir has the adverse effect of myelosuppression and is associated with an increased risk of fungal infections. The other approach is to perform active surveillance to evaluate for evidence of CMV in the body by antigenemia assays (pp 65) or by PCR.  Because of the side effects of prophylactic medication and good tests on which to base early preemptive therapy, the preference at most transplant centers is to use this preemptive approach.
CMV viremia develops at rates in autologous BMTs that are as high as with allogeneic BMTs, but much less CMV disease occurs; therefore, patients with autologous BMT are not administered prophylactic therapy.  However, patients with autologous BMT do need ongoing screening and early therapy upon evidence of CMV reactivation.
A second meta-analysis, by Wittes in 1996,  described a very heterogenous group of patients. Patients who have undergone BMT as well as solid organ transplants were included in the meta-analysis. Randomized controlled trials, prospective controlled trials, and retrospective controlled trials were included, totaling 23 studies. The studies included 295 BMT and 321 solid organ transplant patients. Twelve papers were randomized, with one blinded. CMV infection and CMV disease/pneumonia were examined as separate outcomes. The benefit of CMVIG prophylaxis was statistically significant when all studies were examined (pooled OR 0.56, 95% CI: 0.41, 0.77) and also when only randomized studies were considered (pooled OR 0.56, 95% CI: 0.37, 0.84). Prevention of severe CMV-related disease or CMV-related pneumonia was also statistically significant with all studies considered (pooled OR 0.59, 95% CI: 0.40, 0.86) and with only the randomized studies (pooled OR 0.47, 95% CI: 0.29, 0.76).
Rimantadine or amantadine has been used for prophylaxis or early preemptive therapy for influenza A infections. However, circulating influenza A viruses worldwide have rapidly developed resistance to these agents over the past several years, and these medications are no longer recommended for influenza prevention or treatment. Amantadine and rimantadine are not recommended by the CDC for the 2008-2009 influenza season because of resistance. Preliminary CDC data from the 2007-2008 influenza season showed resistance to amantadine remains high among influenza A isolates, with approximately 99% of tested influenza A (H3N2) isolates and approximately 10% of influenza A (H1N1) isolates resistant to amantadine (CDC Prevention and Control of Influenza 2008).
HHV-6–associated meningoencephalitis has been treated both with ganciclovir and foscarnet. [138, 139, 140, 141, 142] Ganciclovir has also been used as prophylaxis to prevent HHV-6 disease. [143, 138] There are no randomized controlled trials to prove treatment or prophylaxis with ganciclovir is effective.
Infection remains a major cause of mortality in patients who undergo BMT, despite recent advances in supportive care, growth factors, more potent antimicrobials, prophylaxis strategies, and new diagnostic techniques. Prevention of infection in these patients remains the optimal method of decreasing morbidity and mortality. Once infections occur in a bone marrow recipient, the mortality rate is high. Pathogens that are benign in an immunocompetent host can lead to significant mortality in these patients.
Aspergillus infection, which is generally benign in the immunocompetent host, carries a mortality rate of close to 100% in BMT recipients.  Adenovirus, which generally causes a mild self-limited illness in the immunocompetent host, can lead to a mortality rate of 18%-60%.  Appropriate management of infectious diseases in this population involves understanding transplantation techniques, clinical syndromes, the stages of immunosuppression, the natural history of certain infections, immune system reconstitution, early empiric therapy, and different antimicrobial agents.
Boulad F, Sands S, Sklar C. Late complications after bone marrow transplantation in children and adolescents. Curr Probl Pediatr. 1998 Oct. 28(9):273-97. [Medline].
van Burik J, Weisdorf D. Infections in recipients of blood and marrow transplantation. Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000. 3136-47.
CDC. Guidelines for preventing opportunistic infections among hematopoietic stem cell transplant recipients. MMWR Recomm Rep. 2000 Oct. 49(RR-10):1-125, CE1-7. [Medline].
Leather HL, Wingard JR. Infections following hematopoietic stem cell transplantation. Infect Dis Clin North Am. 2001 Jun. 15(2):483-520. [Medline].
Sable CA, Donowitz GR. Infections in bone marrow transplant recipients. Clin Infect Dis. 1994 Mar. 18(3):273-81; quiz 282-4. [Medline].
Appelbaum FR. The use of bone marrow and peripheral blood stem cell transplantation in the treatment of cancer. CA Cancer J Clin. 1996 May-Jun. 46(3):142-64. [Medline].
Zittoun RA, Mandelli F, Willemze R, de Witte T, Labar B, Resegotti L, et al. Autologous or allogeneic bone marrow transplantation compared with intensive chemotherapy in acute myelogenous leukemia. European Organization for Research and Treatment of Cancer (EORTC) and the Gruppo Italiano Malattie Ematologiche Maligne dell'Adulto (GIMEMA) Leukemia Cooperative Groups. N Engl J Med. 1995 Jan 26. 332(4):217-23. [Medline].
Thomas ED, Clift RA, Fefer A, et al. Marrow transplantation for the treatment of chronic myelogenous leukemia. Ann Intern Med. 1986 Feb. 104(2):155-63. [Medline].
Storb R, Longton G, Anasetti C, et al. Changing trends in marrow transplantation for aplastic anemia. Bone Marrow Transplant. 1992. 10 Suppl 1:45-52. [Medline].
Marmont AM, Horowitz MM, Gale RP, et al. T-cell depletion of HLA-identical transplants in leukemia. Blood. 1991 Oct 15. 78(8):2120-30. [Medline].
Rowlings PA. 1996 summary slides show current use and outcome of blood and marrow transplantation. Autologous Blood & Marrow Transplant Registry-North America. ABMTR Newsletter. 1996. 3:6-12.
Engels EA, Ellis CA, Supran SE, et al. Early infection in bone marrow transplantation: quantitative study of clinical factors that affect risk. Clin Infect Dis. 1999 Feb. 28(2):256-66. [Medline].
Ninin E, Milpied N, Moreau P, et al. Longitudinal study of bacterial, viral, and fungal infections in adult recipients of bone marrow transplants. Clin Infect Dis. 2001 Jul 1. 33(1):41-7. [Medline].
Collin BA, Leather HL, Wingard JR, Ramphal R. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis. 2001 Oct 1. 33(7):947-53. [Medline].
Woo PC, Wong SS, Lum PN, et al. Cell-wall-deficient bacteria and culture-negative febrile episodes in bone-marrow-transplant recipients. Lancet. 2001 Mar 3. 357(9257):675-9. [Medline].
Busca A, Saroglia EM, Giacchino M, et al. Analysis of early infectious complications in pediatric patients undergoing bone marrow transplantation. Support Care Cancer. 1999 Jul. 7(4):253-9. [Medline].
Kruger W, Russmann B, Kroger N, et al. Early infections in patients undergoing bone marrow or blood stem cell transplantation--a 7 year single centre investigation of 409 cases. Bone Marrow Transplant. 1999 Mar. 23(6):589-97. [Medline].
Kernan NA, Bartsch G, Ash RC, et al. Analysis of 462 transplantations from unrelated donors facilitated by the National Marrow Donor Program. N Engl J Med. 1993 Mar 4. 328(9):593-602. [Medline].
Dummer JS, Ho M. Risk factors and approaches to infections in transplant recipients. Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases. 5th ed. Philadelphia, Pa: Churchill Livingstone; 2000. 3126-36.
van Burik JA, Weisdorf DJ. Infections in recipients of blood and marrow transplantation. Hematol Oncol Clin North Am. 1999 Oct. 13(5):1065-89, viii. [Medline].
Stem Cell Trialists' Collaborative Group. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol. 2005 Aug 1. 23(22):5074-87. [Medline].
Jansen J., Hanks S., Thompson JM. Transplantation of hematopoietic stem cells from the peripheral blood. Journal of cellular and molecular medicine. 2005. 9:37-50. [Medline].
National Marrow Donor Program. Standards: effective September 1, 1999. 17th ed. National Marrow Donor Program. 1999:1-35.
Aronchick JM. Pulmonary infections in cancer and bone marrow transplant patients. Semin Roentgenol. 2000 Apr. 35(2):140-51. [Medline].
Hughes WT. Mycobacterial infections in bone marrow transplant recipients. Biol Blood Marrow Transplant. 2000. 6(4):359-60. [Medline].
Yamazaki R, Mori T, Nakazato T, Aisa Y, Imaeda H, Hisamatsu T, et al. Non-tuberculous mycobacterial infection localized in small intestine developing after allogeneic bone marrow transplantation. Intern Med. 2010. 49(12):1191-3. [Medline].
van Burik JA, Hackman RC, Nadeem SQ, et al. Nocardiosis after bone marrow transplantation: a retrospective study. Clin Infect Dis. 1997 Jun. 24(6):1154-60. [Medline].
Baddley JW, Stroud TP, Salzman D, Pappas PG. Invasive mold infections in allogeneic bone marrow transplant recipients. Clin Infect Dis. 2001 May 1. 32(9):1319-24. [Medline].
Dictar MO, Maiolo E, Alexander B, et al. Mycoses in the transplanted patient. Med Mycol. 2000. 38 Suppl 1:251-8. [Medline].
Ribaud P, Chastang C, Latge JP, et al. Survival and prognostic factors of invasive aspergillosis after allogeneic bone marrow transplantation. Clin Infect Dis. 1999 Feb. 28(2):322-30. [Medline].
Hovi L, Saarinen-Pihkala UM, Vettenranta K, Saxen H. Invasive fungal infections in pediatric bone marrow transplant recipients: single center experience of 10 years. Bone Marrow Transplant. 2000 Nov. 26(9):999-1004. [Medline].
Wingard JR. Fungal infections after bone marrow transplant. Biol Blood Marrow Transplant. 1999. 5(2):55-68. [Medline].
Castagnola E, Machetti M, Bucci B, Viscoli C. Antifungal prophylaxis with azole derivatives. Clin Microbiol Infect. 2004 Mar. 10 Suppl 1:86-95. [Medline].
Greenberg RN, Scott LJ, Vaughn HH. Zygomycosis (mucormycosis): emerging clinical importance and new treatments. Current Opinion in Infectious Diseases. 2004. 17:517-25. [Medline].
Kontoyiannis DP, Lionakis MS, Lewis RE. Zygomycosis in a tertiary-care cancer center in the era of Aspergillus-active antifungal therapy: a case-control observational study of 27 recent cases. Journal of Infectious Diseases. 2005. 191:1350-60. [Medline].
Shigematsu A, Yamamoto S, Sugita J, Kondo T, Onozawa M, Kahata K, et al. Increased risk of bacterial infection after engraftment in patients treated with allogeneic bone marrow transplantation following reduced-intensity conditioning regimen. Transpl Infect Dis. 2010 Oct. 12(5):412-20. [Medline].
Hale GA, Heslop HE, Krance RA, et al. Adenovirus infection after pediatric bone marrow transplantation. Bone Marrow Transplant. 1999 Feb. 23(3):277-82. [Medline].
Howard DS, Phillips II GL, Reece DE, et al. Adenovirus infections in hematopoietic stem cell transplant recipients. Clin Infect Dis. 1999 Dec. 29(6):1494-501. [Medline].
Baldwin A, Kingman H, Darville M, et al. Outcome and clinical course of 100 patients with adenovirus infection following bone marrow transplantation. Bone Marrow Transplant. 2000 Dec. 26(12):1333-8. [Medline].
La Rosa AM, Champlin RE, Mirza N, et al. Adenovirus infections in adult recipients of blood and marrow transplants. Clin Infect Dis. 2001 Mar 15. 32(6):871-6. [Medline].
Davis D, Henslee PJ, Markesbery WR. Fatal adenovirus meningoencephalitis in a bone marrow transplant patient. Ann Neurol. 1988 Apr. 23(4):385-9. [Medline].
Lujan-Zilbermann J, Benaim E, Tong X, et al. Respiratory virus infections in pediatric hematopoietic stem cell transplantation. Clin Infect Dis. 2001 Oct 1. 33(7):962-8. [Medline].
Oliveira R, Machado A, Tateno A, Boas LV, Pannuti C, Machado C. Frequency of human metapneumovirus infection in hematopoietic SCT recipients during 3 consecutive years. Bone Marrow Transplant. 2008 Aug. 42(4):265-9. [Medline].
Zerr DM, Gooley TA, Yeung L, et al. Human herpesvirus 6 reactivation and encephalitis in allogeneic bone marrow transplant recipients. Clin Infect Dis. 2001 Sep 15. 33(6):763-71. [Medline].
Cone RW, Huang ML, Corey L, et al. Human herpesvirus 6 infections after bone marrow transplantation: clinical and virologic manifestations. J Infect Dis. 1999 Feb. 179(2):311-8. [Medline].
Zerr DM, Gupta D, Huang ML, et al. Effect of antivirals on human herpesvirus 6 replication in hematopoietic stem cell transplant recipients. Clin Infect Dis. 2002 Feb 1. 34(3):309-17. [Medline].
Yoshikawa T, Asano Y, Ihira M, Suzuki K, Ohashi M, Suga S, et al. Human herpesvirus 6 viremia in bone marrow transplant recipients: clinical features and risk factors. J Infect Dis. 2002 Apr 1. 185(7):847-53. [Medline].
Clark DA. Human herpesvirus 6 and human herpesvirus 7: emerging pathogens in transplant patients. International Journal of Hematology. 2002. 76 Suppl 2:246-52. [Medline].
Gorczynska E, Turkiewicz D, Rybka K, Toporski J, Kalwak K, Dyla A, et al. Incidence, clinical outcome, and management of virus-induced hemorrhagic cystitis in children and adolescents after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2005 Oct. 11(10):797-804. [Medline].
Barnes RA, Rogers TR. Control of an outbreak of nosocomial aspergillosis by laminar air-flow isolation. J Hosp Infect. 1989 Aug. 14(2):89-94. [Medline].
Sherertz RJ, Belani A, Kramer BS, et al. Impact of air filtration on nosocomial Aspergillus infections. Unique risk of bone marrow transplant recipients. Am J Med. 1987 Oct. 83(4):709-18. [Medline].
Cruciani M, Rampazzo R, Malena M, et al. Prophylaxis with fluoroquinolones for bacterial infections in neutropenic patients: a meta-analysis. Clin Infect Dis. 1996 Oct. 23(4):795-805. [Medline].
Murphy M, Brown AE, Sepkowitz KA, et al. Fluoroquinolone prophylaxis for the prevention of bacterial infections in patients with cancer--is it justified?. Clin Infect Dis. 1997 Aug. 25(2):346-8. [Medline].
Engels EA, Lau J, Barza M. Efficacy of quinolone prophylaxis in neutropenic cancer patients: a meta-analysis. J Clin Oncol. 1998 Mar. 16(3):1179-87. [Medline].
Cometta A, Calandra T, Bille J, Glauser MP. Escherichia coli resistant to fluoroquinolones in patients with cancer and neutropenia. N Engl J Med. 1994 Apr 28. 330(17):1240-1. [Medline].
Vose JM, Armitage JO. Clinical applications of hematopoietic growth factors. J Clin Oncol. 1995 Apr. 13(4):1023-35. [Medline].
Spitzer G, Adkins DR, Spencer V, et al. Randomized study of growth factors post-peripheral-blood stem-cell transplant: neutrophil recovery is improved with modest clinical benefit. J Clin Oncol. 1994 Apr. 12(4):661-70. [Medline].
Goodman JL, Winston DJ, Greenfield RA, et al. A controlled trial of fluconazole to prevent fungal infections in patients undergoing bone marrow transplantation. N Engl J Med. 1992 Mar 26. 326(13):845-51. [Medline].
Rotstein C, Bow EJ, Laverdiere M, et al. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. The Canadian Fluconazole Prophylaxis Study Group. Clin Infect Dis. 1999 Feb. 28(2):331-40. [Medline].
Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of fluconazole prophylaxis for fungal infections after marrow transplantation--a prospective, randomized, double-blind study. J Infect Dis. 1995 Jun. 171(6):1545-52. [Medline].
Peterson PK, McGlave P, Ramsay NK, et al. A prospective study of infectious diseases following bone marrow transplantation: emergence of Aspergillus and Cytomegalovirus as the major causes of mortality. Infect Control. 1983 Mar-Apr. 4(2):81-9. [Medline].
Denning DW, del Favero A, Gluckman E. UK-109,496, a novel, wide-spectrum triazole derivative for the treatment of fungal infections: clinical efficacy in acute invasive aspergillosis. Program and Abstracts of the 35th Interscience Conference on Antimicrobial Agent. 1995. 126.
Jezequel SG, Clark M, Evans K. UK-109,496, a novel, wide-spectrum triazole derivative for the treatment of fungal infections: Disposition in animals. Program and Abstracts of the 35th Interscience Conference on Antimicrobial Agent. 1995. 126.
Martin MV, Yates J, Hitchcock CA, et al. Comparison of voriconazole (UK-109,496) and itraconazole in prevention and treatment of Aspergillus fumigatus endocarditis in guinea pigs. Antimicrob Agents Chemother. 1997 Jan. 41(1):13-6. [Medline].
Murphy M, Bernard EM, Ishimaru T, Armstrong D. Activity of voriconazole (UK-109,496) against clinical isolates of Aspergillus species and its effectiveness in an experimental model of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 1997 Mar. 41(3):696-8. [Medline].
Kirkpatrick WR, McAtee RK, Fothergill AW, et al. Efficacy of voriconazole in a guinea pig model of disseminated invasive aspergillosis. Antimicrob Agents Chemother. 2000 Oct. 44(10):2865-8. [Medline].
Schwartz S, Milatovic D, Thiel E. Successful treatment of cerebral aspergillosis with a novel triazole (voriconazole) in a patient with acute leukaemia. Br J Haematol. 1997 Jun. 97(3):663-5. [Medline].
Pfaller MA, Yu WL. Antifungal susceptibility testing. New technology and clinical applications. Infect Dis Clin North Am. 2001 Dec. 15(4):1227-61. [Medline].
Hoffman HL, Ernst EJ, Klepser ME. Novel triazole antifungal agents. Expert Opin Investig Drugs. 2000 Mar. 9(3):593-605. [Medline].
Kappe R. Antifungal activity of the new azole UK-109, 496 (voriconazole). Mycoses. 1999. 42 Suppl 2:83-6. [Medline].
Espinel-Ingroff A, Boyle K, Sheehan DJ. In vitro antifungal activities of voriconazole and reference agents as determined by NCCLS methods: review of the literature. Mycopathologia. 2001. 150(3):101-15. [Medline].
Herbrecht R, Denning DW, Patterson TF. Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med. 2002. 347:408-15. [Medline].
Perfect JR, Marr KA, Walsh TJ. Voriconazole treatment for less-common, emerging, or refractory fungal infections. Clin Infect Dis. 2003. 36:1122-31. [Medline].
Walsh TJ, Lutsar I, Driscoll T. Voriconazole in the treatment of aspergillosis, scedosporiosis and other invasive fungal infections in children. Pediatr Infect Dis J. 2002. 21:240-8. [Medline].
Walsh TJ, Karlsson MO, Driscoll T. Pharmacokinetics and safety of intravenous voriconazole in children after single- or multiple-dose administration. Antimicrob Agents Chemother. 2004. 48:2166-72. [Medline].
Vehreschild JJ, Böhme A, Buchheidt D, Arenz D, Harnischmacher U, Heussel CP, et al. A double-blind trial on prophylactic voriconazole (VRC) or placebo during induction chemotherapy for acute myelogenous leukaemia (AML). J Infect. 2007 Nov. 55(5):445-9. [Medline].
Keating GM, Jarvis B. Caspofungin. Drugs. 2001. 61(8):1121-9; discussion 1130-1. [Medline].
Pfaller MA, Messer SA, Mills K, et al. Evaluation of Etest method for determining caspofungin (MK-0991) susceptibilities of 726 clinical isolates of Candida species. J Clin Microbiol. 2001 Dec. 39(12):4387-9. [Medline].
Abruzzo GK, Gill CJ, Flattery AM, et al. Efficacy of the echinocandin caspofungin against disseminated aspergillosis and candidiasis in cyclophosphamide-induced immunosuppressed mice. Antimicrob Agents Chemother. 2000 Sep. 44(9):2310-8. [Medline].
Arikan S, Lozano-Chiu M, Paetznick V, Rex JH. In vitro susceptibility testing methods for caspofungin against Aspergillus and Fusarium isolates. Antimicrob Agents Chemother. 2001 Jan. 45(1):327-30. [Medline].
Arikan S, Lozano-Chiu M, Paetznick V, Rex JH. In vitro synergy of caspofungin and amphotericin B against Aspergillus and Fusarium spp. Antimicrob Agents Chemother. 2002 Jan. 46(1):245-7. [Medline].
Mora-Duarte J, Betts R, Rotstein C. Comparison of caspofungin and amphotericin B for invasive candidiasis. N Engl J Med. 2002. 347:2020-9. [Medline].
Arathoon EG, Gotuzzo E, Noriega LM. Randomized, double-blind, multicenter study of caspofungin versus amphotericin B for treatment of oropharyngeal and esophageal candidiases. Antimicrob Agents Chemother. 2002. 46:451-7. [Medline].
Villanueva A, Arathoon EG, Gotuzzo E. A randomized double-blind study of caspofungin versus amphotericin for the treatment of candidal esophagitis. Clin Infect Dis. 2001. 33:1529-35. [Medline].
Maertens J, Raad I, Petrikkos G. Efficacy and safety of caspofungin for treatment of invasive aspergillosis in patients refractory to or intolerant of conventional antifungal therapy. Clin Infect Dis. 2004. 39:1563-71. [Medline].
Kartsonis NA, Saah AJ, Joy Lipka C. Salvage therapy with caspofungin for invasive aspergillosis: results from the caspofungin compassionate use study. J Infect. 2005. 50:196-205. [Medline].
Franklin JA, McCormick J, Flynn PM. Retrospective study of the safety of caspofungin in immunocompromised pediatric patients. Pediatr Infect Dis J. 2003. 22:747-9. [Medline].
Shalit I, Shadkchan Y, Samra Z. In vitro synergy of caspofungin and itraconazole against Aspergillus spp.: MIC versus minimal effective concentration end points. Antimicrob Agents Chemother. 2003. 47:1416-8. [Medline].
Dannaoui E, Lortholary O, Dromer F. In vitro evaluation of double and triple combinations of antifungal drugs against Aspergillus fumigatus and Aspergillus terreus. Antimicrob Agents Chemother. 2004. 48:970-8. [Medline].
Cuenca-Estrella M, Gomez-Lopez A, Garcia-Effron G. Combined activity in vitro of caspofungin, amphotericin B, and azole agents against itraconazole-resistant clinical isolates of Aspergillus fumigatus. Antimicrob Agents Chemother. 2005. 49:1232-5. [Medline].
Kontoyiannis DP, Hachem R, Lewis RE. Efficacy and toxicity of caspofungin in combination with liposomal amphotericin B as primary or salvage treatment of invasive aspergillosis in patients with hematologic malignancies. Cancer. 2003. 98:292-9. [Medline].
Castagnola E, Machetti M, Capelli B. Caspofungin associated with liposomal amphotericin B or voriconazole for treatment of refractory fungal pneumonia in children with acute leukaemia or undergoing allogeneic bone marrow transplant. Clin Microbiol Infect. 2004. 10:255-7. [Medline].
Marr KA, Boeckh M, Carter RA, Kim HW, Corey L. Combination antifungal therapy for invasive aspergillosis. Clin Infect Dis. 2004 Sep 15. 39(6):797-802. [Medline].
Pancham S, Hemmaway C, New H. Caspofungin for invasive fungal infections: combination treatment with liposomal amphotericin B in children undergoing hemopoietic stem cell transplantation. Pediatr Transplant. 2005. 9:254-7. [Medline].
Edwards JE Jr, Bodey GP, Bowden RA, et al. International Conference for the Development of a Consensus on the Management and Prevention of Severe Candidal Infections. Clin Infect Dis. 1997 Jul. 25(1):43-59. [Medline].
American Academy of Pediatrics. Aspergillosis. Pickering LK, ed. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. American Academy of Pediatrics; 2006. 219-22.
Bowden RA. Fungal infections after hematopoietic cell transplantation. Thomas ED, Blume KG, Forman SJ, eds. Hematopoietic Cell Transplantation. 2nd ed. Malden, Mass: Blackwell Science Inc; 1998. 550-9.
Trifilio SM, Bennett CL, Yarnold PR, McKoy JM, Parada J, Mehta J, et al. Breakthrough zygomycosis after voriconazole administration among patients with hematologic malignancies who receive hematopoietic stem-cell transplants or intensive chemotherapy. Bone Marrow Transplant. 2007 Apr. 39(7):425-9. [Medline].
Leather HL, Correll TA, Meyer CL, Schmalfuss IM, Wingard JR. Treatment of zygomycosis with posaconazole in a patient with acute myeloid leukemia. Clin Adv Hematol Oncol. 2005 Oct. 3(10):773-7. [Medline].
Jacobs P, Wood L, Du Toit A. Eradication of invasive mucormycosis--effectiveness of the Echinocandin FK463. Hematology. 2003. 8:119-23. [Medline].
Groll AH, Lehrnbecher T. Posaconazole for paediatric patients: status of development and future perspectives. Mycoses. 2008 Sep. 51 Suppl 2:5-11. [Medline].
Cornely OA, Maertens J, Winston DJ, Perfect J, Ullmann AJ, Walsh TJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007 Jan 25. 356(4):348-59. [Medline].
Ullmann AJ, Lipton JH, Vesole DH, Chandrasekar P, Langston A, Tarantolo SR, et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007 Jan 25. 356(4):335-47. [Medline].
American Academy of Pediatrics. Antiviral drugs for non-human immunodeficiency virus infections. Pickering LK, ed. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. American Academy of Pediatrics; 2006. 785-9.
Goodrich JM, Mori M, Gleaves CA, et al. Early treatment with ganciclovir to prevent cytomegalovirus disease after allogeneic bone marrow transplantation. N Engl J Med. 1991 Dec 5. 325(23):1601-7. [Medline].
Hong KM, Najjar H, Hawley M. Quantitative real-time PCR with automated sample preparation for diagnosis and monitoring of cytomegalovirus infection in bone marrow transplant patients. Clinical Chemistry. 2004. 50:846-56. [Medline].
Yaghobi R, Behzad-Behbahani A, Sabahi F, Roustaee MH, Alborzi A, Ramzi M, et al. Comparative analysis of a double primer PCR assay with plasma, leukocytes and antigenemia for diagnosis of active human cytomegalovirus infection in bone marrow transplant patients. Bone Marrow Transplant. 2005 Mar. 35(6):595-9. [Medline].
Boeckh M, Huang M, Ferrenberg J. Optimization of quantitative detection of cytomegalovirus DNA in plasma by real-time PCR. Journal of Clinical Microbiology. 2004. 42:1142-8. [Medline].
Diaz-Pedroche C, Lumbreras C, Del Valle P. Efficacy and safety of valgancyclovir as preemptive therapy for the prevention of cytomegalovirus disease in solid organ transplant recipients. Transplantation Proceedings. 2005. 37:3766-7. [Medline].
van der Heiden PL, Kalpoe JS, Barge RM, Willemze R, Kroes AC, Schippers EF. Oral valganciclovir as pre-emptive therapy has similar efficacy on cytomegalovirus DNA load reduction as intravenous ganciclovir in allogeneic stem cell transplantation recipients. Bone Marrow Transplant. 2006 Apr. 37(7):693-8. [Medline].
Gilbert DN, Moellering Jr RC, Sande MA. Antiviral therapy (non-HIV). Sanford Guide to Antimicrobial Therapy 2001. 31st ed. Hyde Park, Vt: Antimicrobial Therapy Inc; 2001. 98-107.
Avery RK, Bolwell BJ, Yen-Lieberman B. Use of leflunomide in an allogeneic bone marrow transplant recipient with refractory cytomegalovirus infection. Bone Marrow Transplantation. 2004. 34:1071-5. [Medline].
Wittes JT, Kelly A, Plante KM. Meta-analysis of CMVIG studies for the prevention and treatment of CMV infection in transplant patients. Transplant Proc. 1996 Dec. 28(6 Suppl 2):17-24. [Medline].
Messori A, Rampazzo R, Scroccaro G, Martini N. Efficacy of hyperimmune anti-cytomegalovirus immunoglobulins for the prevention of cytomegalovirus infection in recipients of allogeneic bone marrow transplantation: a meta-analysis. Bone Marrow Transplant. 1994 Feb. 13(2):163-7. [Medline].
Jurado Chacon M, Hernandez Mohedo F, Navarro Mari JM, et al. Adenovirus pneumonitis successfully treated with intravenous ribavirin. Haematologica. 1998 Dec. 83(12):1128-9. [Medline].
Kapelushnik J, Or R, Delukina M, et al. Intravenous ribavirin therapy for adenovirus gastroenteritis after bone marrow transplantation. J Pediatr Gastroenterol Nutr. 1995 Jul. 21(1):110-2. [Medline].
Liles WC, Cushing H, Holt S, et al. Severe adenoviral nephritis following bone marrow transplantation: successful treatment with intravenous ribavirin. Bone Marrow Transplant. 1993 Oct. 12(4):409-12. [Medline].
Cassano WF. Intravenous ribavirin therapy for adenovirus cystitis after allogeneic bone marrow transplantation. Bone Marrow Transplant. 1991 Mar. 7(3):247-8. [Medline].
Jurado M, Navarro JM, Hernandez J, et al. Adenovirus-associated haemorrhagic cystitis after bone marrow transplantation successfully treated with intravenous ribavirin. Bone Marrow Transplant. 1995 Apr. 15(4):651-2. [Medline].
Chakrabarti S, Collingham KE, Fegan CD, Milligan DW. Fulminant adenovirus hepatitis following unrelated bone marrow transplantation: failure of intravenous ribavirin therapy. Bone Marrow Transplant. 1999 Jun. 23(11):1209-11. [Medline].
Mann D, Moreb J, Smith S, Gian V. Failure of intravenous ribavirin in the treatment of invasive adenovirus infection following allogeneic bone marrow transplantation: a case report. J Infect. 1998 Mar. 36(2):227-8. [Medline].
Hromas R, Clark C, Blanke C, et al. Failure of ribavirin to clear adenovirus infections in T cell-depleted allogeneic bone marrow transplantation. Bone Marrow Transplant. 1994 Oct. 14(4):663-4. [Medline].
Bordigoni P, Carret AS, Venard V, et al. Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2001 May 1. 32(9):1290-7. [Medline].
Ribaud P, Scieux C, Freymuth F, et al. Successful treatment of adenovirus disease with intravenous cidofovir in an unrelated stem-cell transplant recipient. Clin Infect Dis. 1999 Mar. 28(3):690-1. [Medline].
Legrand F, Berrebi D, Houhou N, et al. Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children. Bone Marrow Transplant. 2001 Mar. 27(6):621-6. [Medline].
Hoffman JA, Shah AJ, Ross LA, Kapoor N. Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001. 7(7):388-94. [Medline].
Ljungman P, Ribaud P, Eyrich M. Cidofovir for adenovirus infections after allogeneic hematopoietic stem cell transplantation: a survey by the Infectious Diseases Working Party of the European Group for Blood and Marrow Transplantation. Bone Marrow Transplantation. 2003. 31:481-6. [Medline].
Sparrelid E, Ljungman P, Ekelof-Andstrom E, et al. Ribavirin therapy in bone marrow transplant recipients with viral respiratory tract infections. Bone Marrow Transplant. 1997 May. 19(9):905-8. [Medline].
Bowden RA. Respiratory virus infections after marrow transplant: the Fred Hutchinson Cancer Research Center experience. Am J Med. 1997 Mar 17. 102(3A):27-30; discussion 42-3. [Medline].
Lewinsohn DM, Bowden RA, Mattson D, Crawford SW. Phase I study of intravenous ribavirin treatment of respiratory syncytial virus pneumonia after marrow transplantation. Antimicrob Agents Chemother. 1996 Nov. 40(11):2555-7. [Medline].
Nichols WG, Gooley T, Boeckh M. Community-acquired respiratory syncytial virus and parainfluenza virus infections after hematopoietic stem cell transplantation: the Fred Hutchinson Cancer Research Center experience. Biol Blood Marrow Transplant. 2001. 7 Suppl:11S-15S. [Medline].
Adams RH. Preemptive treatment of pediatric bone marrow transplant patients with asymptomatic respiratory syncytial virus infection with aerosolized ribavirin. Biol Blood Marrow Transplant. 2001. 7 Suppl:16S-18S. [Medline].
DeVincenzo JP, Hirsch RL, Fuentes RJ, Top FH Jr. Respiratory syncytial virus immune globulin treatment of lower respiratory tract infection in pediatric patients undergoing bone marrow transplantation - a compassionate use experience. Bone Marrow Transplant. 2000 Jan. 25(2):161-5. [Medline].
Boeckh M, Berrey MM, Bowden RA, et al. Phase 1 evaluation of the respiratory syncytial virus-specific monoclonal antibody palivizumab in recipients of hematopoietic stem cell transplants. J Infect Dis. 2001 Aug 1. 184(3):350-4. [Medline].
Machado CM, Boas LS, Mendes AV. Use of Oseltamivir to control influenza complications after bone marrow transplantation. Bone Marrow Transplantation. 2004. 34:111-4. [Medline].
Tokimasa S, Hara J, Osugi Y, Ohta H, Matsuda Y, Fujisaki H, et al. Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in allogeneic stem cell transplantation. Bone Marrow Transplant. 2002 Apr. 29(7):595-8. [Medline].
Carvajal E, Verdeguer A, Fernandez JM. Herpesvirus-6 encephalitis complicated by Wernicke-Korsakoff syndrome in a pediatric recipient of unrelated cord blood transplantation. Journal of Pediatric Hematology/Oncology. 2001. 23:626-8. [Medline].
Mookerjee BP, Vogelsang G. Human herpes virus-6 encephalitis after bone marrow transplantation: successful treatment with ganciclovir. Bone Marrow Transplant. 1997 Nov. 20(10):905-6. [Medline].
Janoly-Duménil A, Galambrun C, Basset T, Mialou V, Bertrand Y, Bleyzac N. Human herpes virus-6 encephalitis in a paediatric bone marrow recipient: successful treatment with pharmacokinetic monitoring and high doses of ganciclovir. Bone Marrow Transplant. 2006 Dec. 38(11):769-70. [Medline].
Vu T, Carrum G, Hutton G, Heslop HE, Brenner MK, Kamble R. Human herpesvirus-6 encephalitis following allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2007 Jun. 39(11):705-9. [Medline].
American Academy of Pediatrics. Drugs for parasitic infections. Pickering LK, ed. 2006 Red Book: Report of the Committee on Infectious Diseases. 27th ed. American Academy of Pediatrics; 2006. 790-817.
Sauerbrei A, Prager J, Hengst U, Zintl F, Wutzler P. Varicella vaccination in children after bone marrow transplantation. Bone Marrow Transplant. 1997 Sep. 20(5):381-3. [Medline].
National Advisory Committee on Immunization (NACI). An Advisory Committee Statement (ACS)National Advisory Committee on Immunization (NACI):Update on Varicella. Canada Communicable Disease Report. 2004. 30 ACS-1:1-28. [Full Text].
Ljungman P, Avetisyan G. Influenza vaccination in hematopoietic SCT recipients. Bone Marrow Transplant. 2008 Nov. 42(10):637-41. [Medline].
Gratwohl A, Brand R, Frassoni F. Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time. Bone Marrow Transplantation. 2005. 36:757-69. [Medline].
Duell T, van Lint MT, Ljungman P, et al. Health and functional status of long-term survivors of bone marrow transplantation. EBMT Working Party on Late Effects and EULEP Study Group on Late Effects. European Group for Blood and Marrow Transplantation. Ann Intern Med. 1997 Feb 1. 126(3):184-92. [Medline].
Notteghem P, Soler C, Dellatolas G, Kieffer-Renaux V, Valteau-Couanet D, Raimondo G, et al. Neuropsychological outcome in long-term survivors of a childhood extracranial solid tumor who have undergone autologous bone marrow transplantation. Bone Marrow Transplant. 2003 Apr. 31(7):599-606. [Medline].
Riches ML, Trifilio S, Chen M, Ahn KW, Langston A, Lazarus HM, et al. Risk factors and impact of non-Aspergillus mold infections following allogeneic HCT: a CIBMTR infection and immune reconstitution analysis. Bone Marrow Transplant. 2016 Feb. 51 (2):277-82. [Medline]. [Full Text].
Nikolajeva O, Mijovic A, Hess D, Tatam E, Amrolia P, Chiesa R, et al. Single-donor granulocyte transfusions for improving the outcome of high-risk pediatric patients with known bacterial and fungal infections undergoing stem cell transplantation: a 10-year single-center experience. Bone Marrow Transplant. 2015 Jun. 50 (6):846-9. [Medline]. [Full Text].


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Paintings as Experiments in Natural and Moral Philosophy
Posted on February 28, 2011 by Juan Manuel Gomez Paris
About a month ago I published a post on George Turnbull's Treatise on ancient Painting. There I briefly commented that Turnbull thought that paintings could work as proper samples or experiments for natural and moral philosophy (understood as the 'science of man'). I want to expand on this issue in this post.
Engraving by Camillo Paderni, first edition of Turnbull's 'Treatise'
The whole of Turnbull's Treatise, as he comments at the beginning of chapter seven, is designed to show the usefulness of the imitative arts for philosophy and education in general. After a recollection of the thoughts of the ancient philosophers on these arts, Turnbull dedicates the last two chapters of the book to sketch the reasons for incorporating the arts in the Liberal education program. This is where paintings can serve as samples or experiments.
To understand the role of paintings, it is necessary to point out a general characteristic of Turnbull's philosophy. He believed that human beings were made to contemplate and to imitate nature, and their happiness was mainly achieved through these two activities. If we take a look and examine all our faculties and powers, we will see that we are perfectly constituted for the study of nature. We acquire knowledge through the observation of nature, and the desire to imitate it leads us to perform experiments that will enhance our understanding of it.
Nature is also the source for the work of the artist:
The Artist derives all his Ideas from Nature, and does not make Laws and Connexions agreeably to which he works in order to produce certain Effects, but conforms himself to such as he finds to be necessarily and unchangeably established in Nature. (Treatise on Ancient Painting, p. 137)
From this it follows that the paintings of an artist should represent (imitate) nature as it is in reality, following all its laws. With this in mind Turnbull goes on to tell us that paintings in fact serve as samples or experiments for natural and moral philosophy:
Philosophy is rightly divided into natural and moral; and in like manner, Pictures are of two Sorts, natural and moral: The former belong to natural, and the other to moral Philosophy. For if we reflect upon the End and Use of Samples or Experiments in Philosophy, it will immediately appear that Pictures are such, or that they must have the same Effect. What are Landscapes and Views of Nature, but Samples of Nature's visible Beauties, and for that Reason Samples and Experiments in natural Philosophy? And moral Pictures, or such as represent parts of human Life, Men Manners, Affections, and Characters; are they not Samples of moral Nature, or of the Laws and Connexions of the moral World, and therefore Samples or Experiments in moral Philosophy? (Treatise, p. 145)
Since the paintings are supposed to represent nature, it is impossible to appreciate them without comparing them to the original (reality). In this sense paintings will provide us with a proper sample of nature that will enhance our knowledge of it. Turnbull's theory relies on the artist making exact 'copies' of nature, and only then can they serve as proper samples. In the case of natural pictures, he allows two sorts of 'copies': either exact representations of nature (like a photograph), or imaginary scenes, as long as they conform to the Laws of Nature. If they are not in these categories, then they shouldn't be taken as proper samples for the study of nature, and in Turnbull's case, not even as good works of art. Those works of art that do not imitate nature do not give us the pleasure derived from those that do.
Turnbull prescribes a parallel form of realism for moral paintings. These pictures should depict human nature as it really is, and through them we can gain knowledge of our actions and characters:
Moral Pictures, as well as moral Poems, are indeed Mirrours in which we may view our inward Features and Complexions, our Tempers and Dispositions, and the various Workings of our Affections. 'Tis true, the Painter only represents outward Features, Gestures, Airs, and Attitudes; but do not these, by an universal Language, mark the different Affections and Dispositions of the Mind? (Treatise, p. 147)
As long as the sole purpose of the arts is to imitate nature, and all the works follow the laws of nature (even in cases of imaginary scenes), Turnbull can count them as having the same effect 'real' samples and experiments have.
Posted in Ideas	| Tagged experiment, George Turnbull, Moral Philosophy, painting
Locke's Master-Builders were Experimental Philosophers
Posted on February 21, 2011 by Peter Anstey
Peter Anstey says…
In one of the great statements of philosophical humility the English philosopher John Locke characterised his aims for the Essay concerning Human Understanding (1690) in the following terms:
The Commonwealth of Learning, is not at this time without Master-Builders, whose mighty Designs, in advancing the Sciences, will leave lasting Monuments to the Admiration of Posterity; But every one must not hope to be a Boyle, or a Sydenham; and in an age that produces such Masters, as the Great – Huygenius, and the incomparable Mr. Newton, with some other of that Strain; 'tis Ambition enough to be employed as an Under-Labourer in clearing Ground a little, and removing some of the Rubbish, that lies in the way to Knowledge (Essay, 'Epistle to the Reader').
Locke regarded his project as the work of an under-labourer, sweeping away rubbish so that the 'big guns' could continue their work. But what is it that unites Boyle, Sydenham, Huygens and Newton as Master-Builders? It can't be the fact that they are all British, because Huygens was Dutch. It can't be the fact that they were all friends of Locke, for when Locke penned these words he almost certainly had not even met Isaac Newton. Nor can it be the fact that they were all eminent natural philosophers, after all, Thomas Sydenham was a physician.
In my book John Locke and Natural Philosophy, I contend that what they had in common was that they all were proponents or practitioners of the new experimental philosophy and that it was this that led Locke to group them together. In the case of Boyle, the situation is straightforward: he was the experimental philosopher par excellence. In the case of Newton, Locke had recently reviewed his Principia and mentions this 'incomparable book', endorsing its method in later editions of the Essay itself. Interestingly, in his review Locke focuses on Newton's arguments against Descartes' vortex theory of planetary motions, which had come to be regarded as an archetypal form of speculative philosophy.
In the case of Huygens, little is known of his relations with Locke, but he was a promoter of the method of natural history and he remained the leading experimental natural philosopher in the Parisian Académie. In the case of Sydenham, it was his methodology that Locke admired and, especially those features of his method that were characteristic of the experimental philosophy. Here is what Locke says of Sydenham's method to Thomas Molyneux:
I hope the age has many who will follow [Sydenham's] example, and by the way of accurate practical observation, as he has so happily begun, enlarge the history of diseases, and improve the art of physick, and not by speculative hypotheses fill the world with useless, tho' pleasing visions (1 Nov. 1692, Correspondence, 4, p. 563).
Note the references to 'accurate practical observation', the decrying of 'speculative hypotheses' and the endorsement of the natural 'history of diseases' – all leading doctrines of the experimental philosophy in the late seventeenth century. So, even though Sydenham was a physician, he could still practise medicine according to the new method of the experimental philosophy. In fact, many in Locke's day regarded natural philosophy and medicine as forming a seamless whole in so far as they shared a common method. It should be hardly surprising to find that Locke held this view, for he too was a physician.
If it is this common methodology that unites Locke's four heroes then we are entitled to say 'Locke's Master-Builders were experimental philosophers'. I challenge readers to come up with a better explanation of Locke's choice of these four Master-Builders.
Posted in Ideas	| Tagged Boyle, experimental philosophy, Huygens, Locke, Master-Builders, Newton, Sydenham
Galileo and Experimental Philosophy
Posted on February 14, 2011 by Greg Dawes
Greg Dawes writes…
In a recent conference paper I have argued that in some key respects Galileo's natural philosophy anticipates the experimental philosophy of the later seventeenth century. I am not claiming that Galileo uses the term "experimental philosophy." Nor do I claim that he makes any distinction comparable to that between experimental and speculative natural philosophy. His Italian followers in the Accademia del Cimento would later do so, but he does not. Nonetheless, the way in which Galileo undertakes natural philosophy displays at least two of the features that Peter Anstey and his collaborators have argued are characteristic of experimental philosophy.
Galileo's sketch of a device to demonstrate the power of a vacuum.
The first of these has to do with the role of experiment. Much of the twentieth-century debate centred on whether Galileo actually performed the experiments about which he writes. But the more important question has to do with the role of experiments in Galileo's thought. Like his Aristotelian predecessors, Galileo seeks to construct a demonstrative natural philosophy: one in which the conclusions follow with certainty from the premises. But unlike the Aristotelian, he relies on geometrical proofs. Like any mathematical proofs, these can be elaborated in an a priori fashion, without any reference to experience. But whether a particular proof applies to the world of experience – or, better still, whether it accurately describes the structure of the world – can only be ascertained experimentally. It is experiment which tells us which geometrical proof is to be used, even if the geometrical proof itself can be developed independently of experience. (I am relying here on the work of Martha Féher, Peter Machamer, and others.)
Perhaps more importantly, Stephen Gaukroger has argued that experimentation shaped the very way in which Galileo's physical theories are framed and formulated. Alexander Koyré and others have argued that the laws of Galilean physics are "abstract" laws which refer to an ideal reality. It is true, of course, that in setting aside "impediments" (impedimenti), such as the resistance of the air, Galileo's proofs do not refer to the world of everyday experience. But it is unhelpful to think of them as an idealisations of, or abstractions from, experienced reality. There is an experienced reality to which they conform. It may not be that of everyday experience, but it is that of carefully controlled physical experiments. It follows that in Galileo's work, the task of natural philosophy is being rethought. It is no longer the study of reality as revealed to everyday observation; it is the study of that reality revealed in experimental situations.
The second way in which Galileo's natural philosophy anticipates the later experimental philosophy is in its comparative lack of interest in the mechanisms thought to underlie phenomena. It is not that Galileo was a positivist in our modern sense. There are passages in which he engages in speculation regarding matter theory and on these occasions he favours a corpuscularian view. But such speculations are, as Salviati says in the Two New Sciences, a mere "digression." Galileo does not consider that his new science requires them. Indeed his work on motion is almost entirely a kinematics – as he freely admits, it says nothing about the causes of motion – but Galileo does not consider it any less significant as a result.
Galileo's solution of the "rota Aristotelis" paradox, demonstrating that a body could be composed of an infinite number of unquantifiable atoms.
This should not be interpreted as a general lack of interest in causation, as Stillman Drake suggests. Galileo shares the ancient desire cognoscere rerum causas (to know the causes of things). But the causal properties Galileo seeks are different from those sought by his predecessors. His causes are the mathematically describable properties of the objects whose behaviour is being explained, properties that no Aristotelian would regard as essential. (Even his atoms are more akin to mathematical points than physical objects.) It is, once again, experimentation that allows us to pick up which of those mathematically describable properties are generally operative and therefore the proper subject of a science. It is this move that allows Galileo, as it would later allow Newton, to be content with a causal account that remains on the level of phenomena, rather than speculating about a realm inaccessible to observation.
In an early dialogue, Galileo has two rustics (contadini) speculating about the new star of 1605. One of them advises his companion to listen to the mathematicians rather than the philosophers, for they can measure the sky the way he himself can measure a field. It doesn't matter of what material the heavens are made. "If the sky were made of polenta," he says, "couldn't they still see it alright?" This is surely something new in the history of natural philosophy.
While I would still defend the individual claims contained here, my continued study of Galileo has made me increasingly cautious about the usefulness of a distinction between experimental and speculative natural philosophy. It is certainly the case that many late seventeenth-century thinkers made such a distinction, but is it a useful one for us to make? I'm not confident that it is.
Experiment certainly played an important role in Galileo's work, although precisely what that role was continues to be contested. And it is true that Galileo has little interest in speculating about the underlying structure of the world: even if, as he writes, the sky were made of polenta, the mathematicians could still measure it. The problem is that the classical, mathematical tradition out of which he comes — that of astronomy, statics, optics, and (after Galileo) the study of local motion — cannot be helpfully characterized as either experimental or speculative. It certainly uses experiment, but it also reasons a priori, in ways that seem independent of experience.
So perhaps it would be better to have a threefold classification of early modern scientific traditions. (A classification of this kind is suggested by Casper Hakfoort in the last chapter of his Optics in the Age of Euler.) A first tradition would be that of matter theory, which is inevitably speculative insofar as it deals with matters not accessible to direct observation. (This is the realm of Newton's "hypotheses.") Corpuscularian proposals would fall into this category, as would Descartes's vortex theory. A second tradition would be that of experimental natural philosophy, which regarded the results of experiment as themselves significant forms of knowledge, whether or not they could be connected with an underlying theory of the nature of matter. Finally, there is the mathematical tradition that Galileo transformed, so successfully, by producing a mathematical account of local motion.
Individual natural philosophers could engage in all three kinds of activities, but will differ according to the emphasis they place on one or other of them. So although Galileo certainly engaged in experiments, his emphasis was on the kind of reasoning characteristic of the mathematical tradition. It is this form of reasoning, I have come to believe, that cannot be easily fitted into the experimental-speculative scheme.
Posted in Ideas	| Tagged experiment, experimental philosophy, Galileo, history of science
Newton's Early Queries are not Hypotheses
Posted on February 9, 2011 by Kirsten Walsh
In an earlier post I demonstrated that, in his early optical papers, Newton is working with a clear distinction between theory and hypothesis. Newton takes a strong anti-hypothetical stance, giving theories higher epistemic status than hypotheses. Newton's corpuscular hypothesis appears to challenge his commitment to this anti-hypothetical position. Today I will discuss a second challenge to this anti-hypotheticalism: Newton's use of queries.
Newton's queries have often been interpreted as hypotheses-in-disguise. But in his early optical papers, Newton's queries are not hypotheses. In fact, he is building on the method of queries prescribed by Francis Bacon, for whom assembling queries is a specific step in the acquisition and development of natural philosophical knowledge.
To begin, what is Newton's method of queries? In a letter to Oldenburg, Newton explains that
"the proper Method for inquiring after the properties of things is to deduce them from Experiments."
Having obtained a theory in this way, one should proceed as follows: (1) specify queries that suggest experiments that will test the theory; and (2) carry out those experiments.
He then lists eight queries relating to his theory of light and colours, e.g.:
"4. Whether the colour of any sort of rays apart may be changed by refraction?
"5. Whether colours by coalescing do really change one another to produce a new colour, or produce it by mixing onely?"
He ends the letter, saying:
"To determin by experiments these & such like Queries which involve the propounded Theory seemes the most proper & direct way to a conclusion. And therefore I could wish all objections were suspended, taken from Hypotheses or any other Heads than these two; Of showing the insufficiency of experiments to determin these Queries or prove any other parts of my Theory, by assigning the flaws & defects in my Conclusions drawn from them; Or of producing other Experiments which directly contradict me, if any such may seem to occur. For if the Experiments, which I urge be defective it cannot be difficult to show the defects, but if valid, then by proving the Theory they must render all other Objections invalid."
While Newton's method of queries is experimental, it does not appear to be strictly Baconian. For the Baconian-experimental philosopher, queries serve "to provoke and stimulate further inquiry". Thus, for the Baconian-experimental philosopher, queries are part of the process of discovery. However, for Newton, queries serve to test the theory and to answer criticisms. Thus, they are part of the process of justification.
Newton uses queries to identify points of difference between his theory and its opponents. For example, in a letter to Hooke he writes:
"I shall now in the last place proceed to abstract the difficulties involved in Mr Hooks discourse, & without having regard to any Hypothesis consider them in general termes. And they may be reduced to these three Queries. [1] Whether the unequal refractions made without respect to any inequality of incidence, be caused by the different refrangibility of several rays, or by the splitting breaking or dissipating the same ray into diverging parts; [2] Whether there be more then two sorts of colours; & [3] whether whitenesse be a mixture of all colours."
And in a letter to Huygens, Newton says:
"Meane time since M. Hu[y]gens seems to allow that white is a composition of two colours at least if not of more; give me leave to rejoyn these Quæres.
"1. Whether the whiteness of the suns light be compounded of the like colours?
"2. Whether the colours that emerg by refracting that light be those component colours separated by the different refrangibility of the rays in which they inhere?"
In both cases, Newton is using queries to steer the debate towards claims that can be tested and resolved by experiment. On both occasions, Newton devotes a considerable amount of space to discussing the experiments that might determine these queries.
These early queries are not hypotheses. Rather, they are empirical questions that may be resolved by experiment. This is not merely a matter of semantics. In the same letter to Hooke, Newton demonstrates this by distinguishing between philosophical queries and hypothetical queries. A philosophical query is one that can be determined by experiment, a hypothetical query cannot. Newton argues that philosophical queries are the only acceptable queries. He equates hypothetical queries with begging the question.
In his later work, Newton's queries become increasingly speculative, suggesting that they function as de facto hypotheses. Does Newton ultimately reject his early 'method of queries'?
Next Monday we'll have a guest post from Greg Dawes on Galileo and the Experimental Philosophy.
Posted in Ideas	| Tagged Baconian, hypothesis, Newton, optics, queries
Symposium on Experimental Philosophy and the Origins of Empiricism
Posted on February 7, 2011 by Alberto Vanzo
St Margaret's College, University of Otago, 18-19 April 2011
9.00 Introductory Session (Peter Anstey and Alberto Vanzo)
9.30 Discussion of Peter Anstey, The Origins of the Experimental/Speculative Distinction
Discussant: Gideon Manning
Chair: Alberto Vanzo
11:30 Discussion of Juan Gomez, The Experimental Method and Moral Philosophy in the Scottish Enlightenment
Discussant: Charles Pigden
Chair: Kirsten Walsh
14:30 Discussion of Kirsten Walsh, De Gravitatione and Newton's Mathematical Method
Discussant: Keith Hutchison
Chair: Philip Catton
20:00 European Panel of Experts (video conference)
Chair: Peter Anstey
Tuesday 19 April
9:30 Discussion of Peter Anstey, Jean Le Rond d'Alembert and the Experimental Philosophy
Discussant: Anik Waldow
Chair: Juan Gomez
11:30 Discussion of Alberto Vanzo, Empiricism vs Rationalism: Kant, Reinhold, and Tennemann
Discussant: Tim Mehigan
14:30 Discussion of Alberto Vanzo, Experimental Philosophy in Eighteenth Century Germany
Discussant: Eric Watkins
16:30 Final plenary session, led by Gideon Manning
17:00 Conclusion
Attendance at the symposium is free. However, space is limited, so we advise you to register early. To register and for information, please email peter.anstey@otago.ac.nz.
Abstracts of all papers are available here. If you cannot attend, but would like to read some of the papers, send us an email.
Posted in Events	| Tagged Conferences, empiricism, experimental philosophy, George Turnbull, German philosophy, history of science, Kant, Newton, Wolff

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