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The CDC Guidelines for Prevention of Infections: rule with reason
Cytotherapy (2001) Vol. 3, No. 1, 37–39
The CDC Guidelines for Prevention of Infections: rule with reason D Przepiorka From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
The Centers for Disease Control and Prevention (CDC) in collaboration with the Infectious Diseases Society of America (ISDA) and the American Society of Blood and Marrow Transplantation (ASBMT) have reported the consensus guidelines for reducing the risk of infections in hematopoietic stem cell transplant recipients. The guidelines were published in a recent edition of the Morbidity and Mortality Weekly Report (MMWR)[1]. Experts in transplantation and infectious diseases were included in the panel assembling these guidelines. Additional input was sought from interested groups other than the ISDA and ASBMT — including ISHAGE. The resulting compilation provides guidance covering patient treatment, hospital infection control, hematopoietic stem cell safety and patient activities. Regulatory oversight in the field of hematopoietic stemcell transplantation has been part of our daily existence for less than a decade, yet our bookshelves and servers are overflowing with rules, regulations, standards and forms. The CDC guidelines, which are voluntary, distinguish themselves from the usual regulations in two ways. First, the guidelines are not dry rules to be followed without question, but include a nearly exhaustive overview of the relevant literature. One can thus review the primary data and formulate one’s own opinion as well. Second, the recommendations provided are coded according to the strength of the published data available to support or refute a claim (Tables 1 and 2) [2], allowing the reader to make thoughtful decisions. Although some may have strong feelings about a few of the recommendations in the guidelines, it is precisely because of the inclusive but insightful approach of the CDC that the Legal and Regulatory Affairs Committee chose not to act as censor for any part of this publication.
The section on Hematopoietic Stem Cell Safety has been endorsed by the Executive Committee of ISHAGE and this section is published below for review by the members of ISHAGE. The stem cell safety section deals with donor screening and testing, special issues for pediatric donors, and the potential sources of infection in the cell-processing laboratory. The donor screening and testing recommendations largely reflect the FAHCT standards and the FDA draft rule on stem cell donors. The CDC rightly recognized, however, that ‘No person should be denied a potentially life-saving HSCT procedure solely on the basis of the risk for an infectious disease. However, HSCT physicians should avoid transplanting any infected or infectious donor hematopoietic stemcell product unless no other stem cell product can be obtained and the risk for death from not undergoing transplantation is deemed to be greater than the risk for morbidity or death from the infection that could potentially be transmitted’. Over 35,000 patients worldwide receive hematopoietic stem cell products annually, and many more components are collected, processed and/or banked. Yet, interestingly, of the 23 AI recommendations in the guidelines, none is in the stem cell safety section, and of the 38 AII recommendations, only one is in this section. Moreover, despite extensive experience in this country with cord blood banking, no guidance at all is provided for cord blood cell screening, collection, processing and release. The lack of good publications to support strong recommendations for hematopoietic stem cell safety should be a wake-up call to health research funding agencies and to the investigators at collection centers and in the cell processing laboratory. It is up to us to provide the peer-reviewed data that will relieve us of burdensome and arbitrary regulations.
Correspondence to: Donna Przepiorka, Center for Cell and Gene Therapy, 6565 Fannin St., M964, Houston, TX 77030, USA. © 2001 ISHAGE
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D Przepiorka
Table 1. Evidence-based rating system used to determine strength of recommendations Category
Definition
Recommendation
A
Strong evidence for efficacy and substantial clinical benefit Strong or moderate evidence for efficacy, but only limited clinical benefit Insufficient evidence for efficacy; or efficacy does not outweigh possible adverse consequences (e.g., drug toxicity or interactions) or cost of chemoprophylaxis or alternative approaches Moderate evidence against efficacy or for adverse outcome Strong evidence against efficacy or of adverse outcome
Strongly recommended
B C
D E
Generally recommended Optional
Generally not recommended Never recommended
Editor’s note Dr Przepiorka’s article on the Centers for Disease Control and Prevention Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients [1] was written from her perspective as one of many transplant professionals who participated in that ambitious undertaking. The 95-page document was published October 20, 2000. As a service to our readers, we have reprinted the ‘Introduction’, ‘Background’, and ‘Hematopoietic Stem Cell Safety’ chapters, along with Tables 1 and 2 explaining the rating system used in the article and the abbreviations used in the document (Cytotherapy designation Table 3). The references for the reprinted sections follow at the end. The bulk of the document encompasses commentary on specific infections (bacterial, viral, fungal, protozoal, helminthic) and sections on hospital infection control, ‘safe living’ recommendations and vaccinations. It makes fascinating reading. The entire text may be obtained electronically at www.cdc.gov/mmwr/preview/mmwrhtml/rr4910a1.htm .
Table 2. Evidence-based rating system used to determine quality of evidence supporting recommendation Category I II
III
Definition Evidence from at least one well-executed randomized, controlled trial Evidence from at least one welldesigned clinical trial without randomization; cohort or case-controlled analytic studies (preferably from more than one center); multiple time-series studies; or dramatic results from uncontrolled experiments Evidence from opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees
The CDC Guidelines for Prevention of Infections: rule with reason
Table 3. Abbreviations used in this section ANC BAL CDA CJD CMV CRV DNA EBV EPA FDA G-CSF GM-CSF GVHD HCW HEPA Hib HIV HLA HSCT
HSV HTLV IgA IgG IgM IVIG LAF LD LRI MIC MRSA nvCJD OI PCP PCR PZA/RIF RNA RSV TB TMP-SMZ TST UCB URI VRE VZIG VZV
Absolute neutrophil count Bronchoalveolar lavage Chlorodeoxyadenosine Creutzfeldt–Jakob disease Cytomegalovirus Community-acquired respiratory virus Deoxyribonucleic acid Epstein–Barr virus Environmental Protection Agency Food and Drug Administration Granulocyte colony-stimulating factor (filgastrim) Granulocyte-macrophage colonystimulating factor (sargramostim) Graft-versus-host disease Health-care worker Filter high-efficiency (> 90%) particulate air filter Haemophilus influenzae type b Human immunodeficiency virus Human lymphocyte antigen Hematopoietic stem cell transplant; for this report, includes all blood- and marrow-derived hematopoietic stem cell transplants Herpes simplex virus Human T-lymphotropic virus Immunoglobulin A Immunoglobulin G Immunoglobulin M Intravenous immunoglobulin Laminar air flow Legionnaires’ disease Lower respiratory infection Minimum inhibitory concentration Methicillin-resistant Staphylococcus aureus New variant Creutzfeldt–Jakob disease Opportunistic infection Pneumocystis carinii pneumonia Polymerase chain reaction Pyrazinamide/rifampin Ribonucleic acid Respiratory syncytial virus Mycobacteria tuberculosis Trimethoprim-sulfamethasaxole Tuberculin skin test Umbilical cord blood Upper respiratory infection Vancomycin-resistant Enterococcus Varicella-zoster immunoglobulin Varicella-zoster virus
39
The CDC Guidelines for Prevention of Infections: rule with reason D Przepiorka From the Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, Texas, USA
The Centers for Disease Control and Prevention (CDC) in collaboration with the Infectious Diseases Society of America (ISDA) and the American Society of Blood and Marrow Transplantation (ASBMT) have reported the consensus guidelines for reducing the risk of infections in hematopoietic stem cell transplant recipients. The guidelines were published in a recent edition of the Morbidity and Mortality Weekly Report (MMWR)[1]. Experts in transplantation and infectious diseases were included in the panel assembling these guidelines. Additional input was sought from interested groups other than the ISDA and ASBMT — including ISHAGE. The resulting compilation provides guidance covering patient treatment, hospital infection control, hematopoietic stem cell safety and patient activities. Regulatory oversight in the field of hematopoietic stemcell transplantation has been part of our daily existence for less than a decade, yet our bookshelves and servers are overflowing with rules, regulations, standards and forms. The CDC guidelines, which are voluntary, distinguish themselves from the usual regulations in two ways. First, the guidelines are not dry rules to be followed without question, but include a nearly exhaustive overview of the relevant literature. One can thus review the primary data and formulate one’s own opinion as well. Second, the recommendations provided are coded according to the strength of the published data available to support or refute a claim (Tables 1 and 2) [2], allowing the reader to make thoughtful decisions. Although some may have strong feelings about a few of the recommendations in the guidelines, it is precisely because of the inclusive but insightful approach of the CDC that the Legal and Regulatory Affairs Committee chose not to act as censor for any part of this publication.
The section on Hematopoietic Stem Cell Safety has been endorsed by the Executive Committee of ISHAGE and this section is published below for review by the members of ISHAGE. The stem cell safety section deals with donor screening and testing, special issues for pediatric donors, and the potential sources of infection in the cell-processing laboratory. The donor screening and testing recommendations largely reflect the FAHCT standards and the FDA draft rule on stem cell donors. The CDC rightly recognized, however, that ‘No person should be denied a potentially life-saving HSCT procedure solely on the basis of the risk for an infectious disease. However, HSCT physicians should avoid transplanting any infected or infectious donor hematopoietic stemcell product unless no other stem cell product can be obtained and the risk for death from not undergoing transplantation is deemed to be greater than the risk for morbidity or death from the infection that could potentially be transmitted’. Over 35,000 patients worldwide receive hematopoietic stem cell products annually, and many more components are collected, processed and/or banked. Yet, interestingly, of the 23 AI recommendations in the guidelines, none is in the stem cell safety section, and of the 38 AII recommendations, only one is in this section. Moreover, despite extensive experience in this country with cord blood banking, no guidance at all is provided for cord blood cell screening, collection, processing and release. The lack of good publications to support strong recommendations for hematopoietic stem cell safety should be a wake-up call to health research funding agencies and to the investigators at collection centers and in the cell processing laboratory. It is up to us to provide the peer-reviewed data that will relieve us of burdensome and arbitrary regulations.
Correspondence to: Donna Przepiorka, Center for Cell and Gene Therapy, 6565 Fannin St., M964, Houston, TX 77030, USA. © 2001 ISHAGE
37
38
D Przepiorka
Table 1. Evidence-based rating system used to determine strength of recommendations Category
Definition
Recommendation
A
Strong evidence for efficacy and substantial clinical benefit Strong or moderate evidence for efficacy, but only limited clinical benefit Insufficient evidence for efficacy; or efficacy does not outweigh possible adverse consequences (e.g., drug toxicity or interactions) or cost of chemoprophylaxis or alternative approaches Moderate evidence against efficacy or for adverse outcome Strong evidence against efficacy or of adverse outcome
Strongly recommended
B C
D E
Generally recommended Optional
Generally not recommended Never recommended
Editor’s note Dr Przepiorka’s article on the Centers for Disease Control and Prevention Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients [1] was written from her perspective as one of many transplant professionals who participated in that ambitious undertaking. The 95-page document was published October 20, 2000. As a service to our readers, we have reprinted the ‘Introduction’, ‘Background’, and ‘Hematopoietic Stem Cell Safety’ chapters, along with Tables 1 and 2 explaining the rating system used in the article and the abbreviations used in the document (Cytotherapy designation Table 3). The references for the reprinted sections follow at the end. The bulk of the document encompasses commentary on specific infections (bacterial, viral, fungal, protozoal, helminthic) and sections on hospital infection control, ‘safe living’ recommendations and vaccinations. It makes fascinating reading. The entire text may be obtained electronically at www.cdc.gov/mmwr/preview/mmwrhtml/rr4910a1.htm .
Table 2. Evidence-based rating system used to determine quality of evidence supporting recommendation Category I II
III
Definition Evidence from at least one well-executed randomized, controlled trial Evidence from at least one welldesigned clinical trial without randomization; cohort or case-controlled analytic studies (preferably from more than one center); multiple time-series studies; or dramatic results from uncontrolled experiments Evidence from opinions of respected authorities based on clinical experience, descriptive studies or reports of expert committees
The CDC Guidelines for Prevention of Infections: rule with reason
Table 3. Abbreviations used in this section ANC BAL CDA CJD CMV CRV DNA EBV EPA FDA G-CSF GM-CSF GVHD HCW HEPA Hib HIV HLA HSCT
HSV HTLV IgA IgG IgM IVIG LAF LD LRI MIC MRSA nvCJD OI PCP PCR PZA/RIF RNA RSV TB TMP-SMZ TST UCB URI VRE VZIG VZV
Absolute neutrophil count Bronchoalveolar lavage Chlorodeoxyadenosine Creutzfeldt–Jakob disease Cytomegalovirus Community-acquired respiratory virus Deoxyribonucleic acid Epstein–Barr virus Environmental Protection Agency Food and Drug Administration Granulocyte colony-stimulating factor (filgastrim) Granulocyte-macrophage colonystimulating factor (sargramostim) Graft-versus-host disease Health-care worker Filter high-efficiency (> 90%) particulate air filter Haemophilus influenzae type b Human immunodeficiency virus Human lymphocyte antigen Hematopoietic stem cell transplant; for this report, includes all blood- and marrow-derived hematopoietic stem cell transplants Herpes simplex virus Human T-lymphotropic virus Immunoglobulin A Immunoglobulin G Immunoglobulin M Intravenous immunoglobulin Laminar air flow Legionnaires’ disease Lower respiratory infection Minimum inhibitory concentration Methicillin-resistant Staphylococcus aureus New variant Creutzfeldt–Jakob disease Opportunistic infection Pneumocystis carinii pneumonia Polymerase chain reaction Pyrazinamide/rifampin Ribonucleic acid Respiratory syncytial virus Mycobacteria tuberculosis Trimethoprim-sulfamethasaxole Tuberculin skin test Umbilical cord blood Upper respiratory infection Vancomycin-resistant Enterococcus Varicella-zoster immunoglobulin Varicella-zoster virus
39