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Blackwell Science, LtdOxford, UKTRFTransfusion0041-11322003 American Association of Blood BanksOctober 20034310Original Article

BOOK REVIEWSBOOK REVIEWS

B O O K R E V I E W S

PATHOGEN INACTIVATION OF LABILE BLOOD PRODUCTS

Committee of Experts on Blood Transfusion and Immuno-haematology, Council of Europe. Strasbourg: Council ofEurope Publishing, 2001. 75 pages. Price: US$20.00. Soft-cover. ISBN: 92-871-4560-1.

Blood transfusion is not safe; it is, however, almost cer-tainly low risk. Over the past two decades, these risks havebeen minimized by the implementation of donor screen-ing, good manufacturing processes, and viral marker test-ing. Nevertheless, transfusion is known to occasionallytransmit viruses (e.g., CMV, parvovirus B19, TT virus, andHepatitis G virus), bacteria, and protozoa (e.g., malaria,

Babesia

spp., trypanosomes). Given the futility of develop-ing specific tests for all possible microbial contaminants,many of which are of uncertain clinical relevance, therehas been a concerted world-wide effort to extend theexperience of pathogen inactivation of plasma derivativesto FFP and RBC and platelet components.

Pathogen Inactivation of Labile Blood Products

is theoutcome of a coordinated research study approved by theEuropean Health Committee of the Council of Europe,with the express purpose of reviewing the field of patho-gen inactivation and assessing the implications for bloodtransfusion services. A group of experts, under thedirectorship of Professor Andreas Morell (Berne), havecompiled a state-of-the-art report covering the scientificdevelopment and clinical testing of a wide range of meth-ods. These extend from WBC reduction, gamma irradia-tion, and S/D treatment to processing with photodynamicand photochemical agents, such as methylene blue, pso-ralens, Inactine (ethylene amines), and FRALEs (frangibleanchor linker effector compounds; S-303). A detailedaddendum describes the scientific basis of the latter drugtreatments. Tables are used to great effect to detail thebroad range of chemicals that have been tested for patho-gen inactivation properties, as well as the tests utilized toensure component function after treatment.

Written as a technical monograph, rather than anexhaustive review of the literature, the report provides asuccinct background on pathogen inactivation that will beinvaluable as an introduction to a rapidly burgeoningfield. Already, many of the pathogen inactivation strate-gies are in clinical trial and soon we are likely to be delugedwith clinical information. This report will rapidly outdateas results are reported and the commercial sponsors beginmarketing, however, it bears essential background infor-mation that will allow for better interpretation of the newfindings. In particular, institutions and governments willneed to base implementation of individual pathogen inac-tivation technologies on rational cost-benefit arguments.

As outlined by the authors in a brief, but concise sectionon pharmacoeconomics, the costs of pathogen inactiva-tion include not only the purchase price of the new tech-nologies but also the toxicologic risk of the agent utilized,the increased donor exposure risk if components arepooled, and an often unavoidable partial loss of efficacy.Benefits include not only small but measurable increasesin quality-adjusted life expectancy but also the perceivedreduction in risk of as yet unknown infections, a quantitythat is difficult to measure. With the recent history ofimplementation of blood safety technologies based onpolitical and absolutists agendas, it would serve the trans-fusion community well to be educated as to the facts ofpathogen inactivation. In this setting, we may providewise council to our administrators and colleagues as theyare promised the prospect of a pathogen risk-free bloodsupply.

Richard J. Benjamin, MBChB, PhD

Brigham and Women’s HospitalBoston, MA

e-mail: rbenjamin@partners.org

October 20034310Original Article

BOOK REVIEWBOOK REVIEW

HEMATOLOGIC MALIGNANCIES:METHODS AND TECHNIQUES

Guy B. Faguet, ed. Totowa, NJ: Humana Press, 2001. Price:US$99.50. Hardcover. ISBN: 0-896-03543-3.

Hematologic Malignancies: Methods and Techniques

isone of the recent additions to the series entitled,“Methods in Molecular Medicine.” However, this text ofprotocols may have been better entitled, “HematologicMalignancies: Molecular and Immunologic Methods andTechniques.” Such a title would better reflect the scope ofthe book, as both flow cytometry and immunohis-tochemistry are also covered in addition to molecularmethods.

The goals stated in the preface are to “review thosemethods most useful for the diagnosis and subsequentmanagement of hematologic malignancies.” In addition,the authors are to “discuss the pathophysiologic bases andthe diagnostic usefulness to underscore each method’sclinical relevance.” Overall, the latter goal seems to havebeen accomplished more fully than the first goal. A goodfeature of the text is the inclusion of hints and trouble-shooting notes at the end of each chapter. However, theinconsistent use of headings does not enable the reader tolook for specific notes that might correlate with problemsin their own laboratory.

There are 16 chapters divided into five parts. The firstpart on Cytogenetics covers fluorescent in situ hybridiza-tion analyses (FISH), comparative genomic hybridization

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(CGH), and spectral karyotyping (SKY). The protocol onfluorescent in situ hybridization appears to be complete,however, there is no list of FISH probes that are currentlyuseful in the analysis of myeloid and lymphoid tumors.The inclusion of comparative genomic hybridization,although a good research technique, is not currently usedas a diagnostic technique in clinical practice. It is morelikely that M-FISH or SKY, which are adequately ex-plained, will be more frequently used over CGH to identifycryptic rearrangements.

The second part on Polymerase Chain Reaction cov-ers applications ranging from Southern Blot to RT-PCR.The two chapters that have the greatest current use inmolecular diagnostics are “Molecular Genetics Methods inDiagnosis and Treatment” and “Detecting MonoclonalImmunoglobulin and T-Cell Receptor Gene Rearrange-ments in B- and T-Cell Malignancies by Polymerase ChainReaction” (Chapters 5 and 6). Although the protocoldetails in these two chapters are acceptable, there is somelack of attention to detail in the descriptive paragraphs.The authors indicate in the introduction that mutationtests will be included, although no mutation tests arepresented. The authors do not identify that the use ofSouthern blotting of T-cell receptor gamma (TCR) generearrangements is not done routinely due to the knownlimitations of TCR. Only one of two possible rearrange-ments of the BCR/ABL fusion of the t(9; 22) are described.No recommendation for duplicate analyses is presented inChapter 5, however, their use is illustrated in the figures.The authors suggest that the inability to amplify DNA is tobe reported as “technical problems,” as opposed to theusual practice of “inadequate DNA.” The authors in Chap-ter 5 suggest that PAGE is not considered to be a standarddiagnostic protocol, although the authors in Chapter 6recommend utilizing 6-percent polyacrylamide gels.Chapter 6 is written in a somewhat disjointed mannerwith an insufficient explanation of the background andwith no mention of a T-cell receptor beta PCR protocol.High-resolution techniques that separate on the basis ofsequence, such as single-strand conformation polymor-phism analysis (SSCP), are not identified, nor is the cur-rent migration to the capillary electrophoresis platformsmentioned. A recommendation to standardize tissuerequirements for paraffin-embedded tissue similar to thefresh cell counting for the lysate procedure would havebeen helpful.

The third part on Flow Cytometry contains well-written chapters on the diagnostic uses and current prac-tices in flow cytometry. They are not strictly molecular inapplication. In the chapter on

in situ

hybridization in flowcytometry (Chapter 11), there is a paucity of samples ofhow this technology might be used, as the only onepresented was on HIV RNA.

Part Four, Special Histopathology Stains, is oncytochemistry stains for aspirate smears and immuno-

histochemistry of tissues. Both are adequate summa-ries of these techniques but contain no molecularapplications.

Part Five is Molecular Genetics and Cytokines. Thereis one focused chapter on apoptosis that briefly mentionsresearch protocols. The last chapter on cytokines focuseson immunologic research methods. The protocols used indetection of fusion transcripts in the myeloid leukemiasare completely absent from this text with the exception ofthe t(9; 22). This is unfortunate because these are used farmore frequently in hematologic malignancies than RT-PCR for the rare anaplastic large-cell lymphoma to detectthe t(2;5), a focus of an entire chapter. This may have beenan editorial decision because the myeloid translocationsare covered in a chapter of another book in the seriesentitled, “Molecular Pathology Protocols.” Thus, oneneeds to read both books to find the major protocols nec-essary for hematologic malignancies.

In summary, the text could be chosen as an additionto a laboratory’s library, if one desires protocols for bothmolecular and immunologic methods in hematology.

Timothy C. Greiner, MD

Molecular Diagnostics LaboratoryDepartment of Pathology and Microbiology

University of Nebraska Medical CenterOmaha, NE

e-mail: tgreiner@unmc.edu

October 20034310Original Article

BOOK REVIEWBOOK REVIEW

PRACTICAL TRANSFUSION MEDICINE

Michael F. Murphy and Derwood H. Pamphilon, eds.Oxford, Blackwell Science, 2001. Price: US$110. ISBN:0-632-05114-0.

Without question, the editors’ goal of using a “practicaland didactic approach” in the editing of this comprehen-sive guide to transfusion medicine is met. In a concise, yetthorough, style most practical aspects of blood therapy arediscussed. As expected in a multidisciplinary textbook, thework is a compilation of chapters from many authors (allof them practitioners in the United Kingdom), but the edi-tors must be congratulated on the extraordinary workdone in maintaining a consistent style and formatthroughout the book.

The text is divided into five main sections: Basic Prin-ciples of Transfusion, Clinical Transfusion Practice, Com-plications of Transfusion, Practice in Blood Centers andHospitals, and Developments in Transfusion Medicine.The first three sections cover the subjects from basic sci-entific knowledge to everyday practical aspects in dealingwith patient therapy. Well-designed tables and unclut-tered, clear graphics aid in conveying information to thereader. Algorithms depicting decision-making processesare placed throughout these sections and provide excel-

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lent guidance without having to go over pages of text. Tomaintain the editors’ goal of focusing on the practicalaspects of transfusion therapy, discussion on the patho-physiologic basis of the clinical entities covered in the textis sparse. Recommendations for management are goal ori-ented and to the point.

Part 4 (Practice in Blood Centers and Hospitals) hassome limitations because, with the exception of the dis-cussion on production and storage of blood componentsand the last chapter dealing with autologous transfusions,most of the information deals with administrative andmedico-legal aspects that are relevant only to practice inthe UK. Likewise, the chapter on testing of blood donationssuffers from the information limited mostly to testing per-formed in that area of the world. (It must be stressed that,as a very rapidly evolving field, the highly perishable natureof the knowledge base on the subject of donor testing pre-

sents a challenge to most textbooks.) The last section ofthe book covers adequately the rapidly evolving fields ofblood substitutes, cord blood banking, stem cell and genetherapy, tissue banking, and therapeutic apheresis.

Although the authors do not provide references, auseful list of suggested reading materials is provided at theend of each chapter. Those who seek an in-depth coverageof transfusion medicine subjects typically found in refer-ence textbooks will be disappointed. Nevertheless, thisbook is an excellent addition to any blood establishment,particularly those who train professionals in the field,given its breadth of scope, practical approach, and highdidactic value.

Germán F. Leparc, MD

Florida Blood ServicesSt. Petersburg, FL

e-mail: gleparc@fbsblood.org