Delayed hemolytic transfusion reaction in the French hemovigilance system.

In France, reporting of adverse events related, or likely to be related, to transfusion is mandatory. Since its creation in 1993, the French hemovigilance system has contributed to a better recognition of unappreciated risks like delayed hemolytic transfusion reactions (DHTR) in sickle-cell disease (SCD) patients. Long under-reported or misclassified, reports of this serious complication of transfusion have improved, particularly through the dissemination of information within the hemovigilance network. To our knowledge, the French hemovigilance system has one of the largest series of DHTR in SCD patients. Guidelines for diagnosis and reporting to hemovigilance system as well as a specific reporting form are being developed, which should contribute to the quality of data essential for epidemiological studies.

[Is the research of posttransfusional alloantibodies still relevant?] / Est-ce que la réalisation de la recherche d'anticorps antiérythrocytaires post­transfusionnelle est toujours pertinente ?

The decision of November 6th, 2006 defining the principles of best practices recommends that posttransfusional red cell alloantibodies research is performed after one to three months after. In the University hospital of Brest, the haemovigilance unit takes charge of sending the medical prescription within the required time and centralizing the results. We wished to estimate if the realization of this research still remains relevant. METHODS: A prospective analysis was performed in 2015. We evaluated the realization rate, the red cell alloantibodies rate and the recipient adverse reactions with the diagnostic category: alloimmunization (delayed serological transfusion reaction, DSTR). RESULTS: In 2015, 2162 prescriptions were sent to the 3271 transfused patients. One thousand and eighteen red cell alloantibodies research were done, i.e. a return rate of 61%. Among them, 12 alloantibodies appeared (0.9%) within an average of 56 days. Thirty-three other alloantibodies appeared and were discovered most frequently before a new transfusion. In 10 cases, a posttransfusional research was done that was negative. A survey was conducted among GHCOH members to describe the practices in these health institutions. Twelve questionnaires were analysed. Ten institutions performed a posttransfusional alloantibodies research by issuing a prescription at the patient's exit with a return rate between 0.14 and 16%; 1 institution has a centralized organization with a return rate of 68.3%; 1566 red cell alloantibodies research were performed and among them, 24 alloantibodies appeared (1.53%). CONCLUSION: These results indicate that to be effective, the management of this biological test must be centralized. Despite this, the red cell alloantibodies rate remains very low (0.9 and 1.53%) and raises the question of the relevance of this systematic testing after transfusion, which is in any case mandatory before a new transfusion of red blood cells.

[Delayed hemolytic transfusion reaction in sicle cell disease patients: a new challenge for the Hemovigilance network]. / Les hémolyses retardées post-transfusionnelles chez les patients drépanocytaires : un nouveau défi pour le réseau d'hémovigilance.

Delayed hemolytic reaction transfusion in patients with sickle cell disease (SCD) is a serious and still under diagnosed event. Clinical and biological presentation mimics an acute SCD complication. It is a life-threatening event, especially in hyperhemolysis syndrome (HS) characterized by a massive destruction of both the donor's and patient's red blood cells. The main cause is related to the presence of alloantibodies directed against red blood cell antigens, more rarely autoantibodies. In approximately a third of the cases, no new antibody is highlighted. Pathophysiological hypotheses are still under debate but most of the authors agree on the role played by the SCD inflammatory state. Several therapeutic approaches are used but the data are still insufficient to estimate their efficiency. It is admitted that a new transfusion may exacerbate the phenomenon and the benefit-risk of any transfusion must be carefully evaluated. Measures limiting alloimmunization and rigorous follow-up of SCD patients and their immunohematologic status can prevent some of these accidents. The Hemovigilance network has a role to play in the recognition and the description of this risk. A first analysis realized on the French national Hemovigilance database of the French National Agency for Medicines and Health Products Safety (ANSM) over the period 2000-2013, shows us interesting information but some inadequacies, described here, must be taken into account to strengthen these data and insure in the future a better reporting quality.

[Biological diagnosis of resistance to erlotinib in a malignant pleural effusion]. / Diagnostic biologique de résistance à l'erlotinib sur une pleurésie.

INTRODUCTION: The characterization of genetic abnormalities in non-small cell lung cancer (NSCLC) constitutes a theranostic revolution which is leading to rapid progress in the personalized management of this condition. CASE REPORT: We present the case of a patient with NSCLC harboring an activating mutation of the Epidermal Growth Factor Receptor (EGFR). After two years of treatment with a tyrosine kinase inhibitor (TKI), the development of a pleural effusion demonstrated that the NSCLC had progressed. The T790M mutation was identified in tumour cells from the pleural aspirate. This anomaly had not been observed in the initial lung biopsy sample. CONCLUSION: The genetic study of tumour cells contained in a biological fluid could be used to initiate molecular monitoring of the NSCLC tumour, without requiring repeated tissue biopsies and to customize the treatment in some patients with NSCLC.

[Transfusion-associated circulatory overload]. / Œdèmes aigus pulmonaires de surcharge post-transfusionnels.

A working group of the French National Hemovigilance Committee has been in charge of heightening awareness of Transfusion-Associated Circulatory Overload (TACO) among physicians and nurses. This multidisciplinary group has produced the present document that focuses on epidemiological data provided by the French haemovigilance network, physiopathology, diagnosis, treatment and specific actions that could prevent or minimize the risk of TACO.

[Are the indications and choice of labile blood products adapted? National survey on prescriber's knowledge]. / Les indications et le choix des produits sanguins labiles sont-ils adaptés? Enquête nationale sur les connaissances des prescripteurs.

OBJECTIVE: There is little data available on current practice related to prescription of labile blood products (LBP) by French physicians. The aim of this study was to assess whether prescriptions were conform to Anaes (French Medicine's agency) guidelines, with regard not only to indications but also quality of the products, so as to define the improvements that could be made. METHOD: Thirty-four clinical case reports, classified by specialties were sent to prescribing physicians working in the regional health centers, from 17 different blood banks, from October 1997 to February 1998. The prescribers were requested to answer only the questions that were specific to their particular field of experience. Each case description included multiple choice questions on the indication for transfusion of concentrated of red blood cells (RBC) and/or platelets (CP) and/or plasma, and the possible requirements for specification or modification of the guidelines applicable to these products. The primary end point of analysis was the adequation of the answers to the Anaes recommendations. RESULTS: Answers were obtained regarding 5092 clinical cases from 818 physicians. The participation rate was of 30%. The specialties were as follows: 34% anesthesiologists, 14% oncologists-haematologists, 13% internal medicine specialists, 11% emergency physicians, 10% paediatricians, 8% obstetricians, 7% geriatricians, and 3% transplantation surgeons. Eighty-two percent of the answers came from physicians working in the public health services. The adequation with the indication for transfusion was of 90.3% for RBC, 92.3% for platelets and 93.8% for plasma. The percentages of correct answers regarding the indications for specification or modification of the LBP were as follows: 90.3% were correct for irradiation (of either RBC or platelets); 68.8% and 53.2% respectively for leukocyte depletion from RBC and platelets; 64% for phenotyped RBC; 68.2% for compatibilized RBC; and 57.3% for apheresis platelet concentrates. There was no difference in results depending on the type of center, private or public, and the quality of LBP prescribed. The answers obtained from the anaesthesiologists' clinical cases were less accurate with regard to RBC but more accurate with regard to PC compared with other specialists. CONCLUSION: This study shows the correct management of the indications for transfusion by the prescribing physicians who participated in the study, but the lack of knowledge with regard to the indications for specifications and/or transformations of LBP. The respect of the indications for transfusion is the corner stone of safe transfusion and this phase should be optimized with improved dissemination of information on transfusion and training for the physicians and programs that would improve the quality.

Analysis of immunohistochemical label of Fos protein in the suprachiasmatic nucleus: comparison of different methods of quantification.

The induction of the proto-oncogene c-fos, and its phosphoprotein product Fos, has been extensively used to study the effects of light on the circadian pacemaker in the suprachiasmatic nucleus (SCN). Experimental approaches to the quantification of Fos induction have mainly been based on immunohistochemistry and subsequent measure of Fos immunoreactivity (IR) in sections of the SCN. In this study, the authors compare several methods of quantification using optical density image analysis or counts of Fos-IR labeled cells. To assess whether optical density measures using image analysis reflect the amount of Fos in brain tissue, the authors developed standards of known concentrations of Fos protein in an agar matrix. The agar standards were sectioned and treated simultaneously with sections of the SCN from animals exposed to different levels of irradiance. Optical density was found to be proportional to the quantity of Fos in the sections, indicating that this measure accurately reflects relative levels of Fos protein induction. Quantification by optical density analysis allows an objective measure in which the various parameters, conditions of illumination, and threshold can be maintained constant throughout the analysis. Counting cells by visual observation is more subjective because threshold values cannot be precisely defined and can vary according to the observer, illumination, degree of label, and other factors. In addition, cell counts involving direct visual observation, automated cell counts, or stereological methods do not take into account the difference in the density of label between cells, thus giving equal weight to lightly or densely stained cells. These measures are more or less weakly correlated with measures of optical density and thus do not accurately reflect the amount of bound Fos protein in the tissue sections. In contrast, labeled surface area as measured by image analysis shows a linear relationship with optical density. The main outcome of this study is that computer-assisted image analysis provides an accurate and rapid method to determine the relative amount of Fos protein in the SCN and the effects of light on intracellular signaling mechanisms involved in the circadian clock.

[Evaluation of an information document about patients and transfusion]. / Evaluation du document d'information des patients sur la transfusion.

OBJECTIVE: To evaluate the understanding of written information contained in the information sheet for patients intended to receive an homologous transfusion and to know their opinion about this document. TYPE OF THE STUDY: A prospective cohort survey carried out by people unrelated to clinical units and transfusion services. METHODS: A document divided in two parts, the first one summarized, the second detailed, was distributed to transfused adult patients. The patients were hospitalized in the general surgery and orthopedic wards of two hospitals and in the hematology and oncology wards of two different hospitals. A questionnaire was filled out in the presence of the inquirer. RESULTS: Sixty one subjects have been enrolled, among them 53 considered the information as adequate; 53 as comforting and neutral. 53 patients considered a written information as essential and 52 estimated that both part of the information sheet (summarized and detailed) were mandatory. Conversely, a more in depth investigation revealed there was a gap between patients statements and their true understanding. CONCLUSION: The value of a written information for the patients is confirmed by the study. In addition, patients were not generally worried by this information. The partition of the document has been appreciated. It is noteworthy that a gap exist between the patient's perception of the information and their actual level of understanding.

A UMLS-based knowledge acquisition tool for rule-based clinical decision support system development.

Decision support systems in the medical field have to be easily modified by medical experts themselves. The authors have designed a knowledge acquisition tool to facilitate the creation and maintenance of a knowledge base by the domain expert and its sharing and reuse by other institutions. The Unified Medical Language System (UMLS) contains the domain entities and constitutes the relations repository from which the expert builds, through a specific browser, the explicit domain ontology. The expert is then guided in creating the knowledge base according to the pre-established domain ontology and condition-action rule templates that are well adapted to several clinical decision-making processes. Corresponding medical logic modules are eventually generated. The application of this knowledge acquisition tool to the construction of a decision support system in blood transfusion demonstrates the value of such a pragmatic methodology for the design of rule-based clinical systems that rely on the highly progressive knowledge embedded in hospital information systems.

High resolution HLA class I and II typing and CTLp frequency in unrelated donor transplantation: a single-institution retrospective study of 69 BMTs.

UNLABELLED: The results of unrelated donor transplantation (URD-BMT) are difficult to analyze since the continuous advances in HLA typing technology allow the detection of new mismatches unknown at the time of transplantation. We sought to confirm that matched recipient-donor pairs are in fact often mismatched when advanced HLA typing techniques are used. We retrospectively studied the impact of the results of high resolution HLA typing for HLA class I (-A, -B, -C) and HLA class II (-DR, -DQ, -DP) loci, and cytotoxic T lymphocyte precursor (CTLp) frequency, on the outcome of 69 URD-BMT procedures. At the time of transplant, six (6/69) and two (2/69) donor-recipient pairs were mismatched for HLA class I (-A and -B by serology) and HLA class II, respectively, while one pair was mismatched for both HLA class I and II. Using high resolution DNA typing, HLA class I mismatches were found in 31 (45%) pairs and HLA class II mismatches in nine (13%) pairs. Twenty-three of the 69 pairs were HLA-C mismatched. Low CTLp frequencies were found among the 19 HLA class I matched pairs tested, and also in 5/14 mismatched pairs (of whom three had severe aGVHD). The overall survival of the cohort was 28 +/- 6%. Among the 33 patients who were fully matched with their donors, the survival rate was 66% in the 18 patients with a standard hematological risk and 9% in the 15 high risk patients. Only two of the 33 patients developed severe aGVHD, and only one had graft rejection. Among the 36 mismatched pairs, the survival rate was 31% in the 13 patients with a standard hematological risk and 8% in the 23 high risk patients. Sixteen of these 36 patients died from severe aGVHD and four had graft failure or rejection. Three of the 10 patients with only an HLA-C mismatch died from severe aGVHD, and two had graft rejection. IN CONCLUSION: (1) donor-recipient matching based on high resolution HLA class I and II DNA typing is associated with significantly better outcome after URD-BMT; (2) the results of URD-BMT with classical GVHD prevention are comparable to those of geno-identical BMT when donor and recipient are fully matched for HLA-A, -B, -C, -DRB1 and -DQB1 on the basis of high resolution typing; (3) CTLp frequencies do not correlate constantly with HLA class I matching, and our results fail to show that CTLp assay can distinguish between permissible and non-permissible class I mismatches; (4) clinical trials involving donor-recipient pairs with known HLA class I mismatches are needed to improve aGVHD prevention without increasing graft failure rate.

Tandem autotransplant as first-line consolidative treatment in poor-risk aggressive lymphoma: a pilot study of 36 patients.

PURPOSE: In the previous LNH87-2 study, consolidative high-dose therapy followed by stem cell transplantation (HDT) improved disease-free survival, as well as survival for patients (pts) presenting with two or three factors of the age-adjusted international prognostic index (Aa-IPI) in first complete remission (CR). In order to improve further the outcome of such patients, we conducted a pilot study of consolidative tandem autotranplant. PATIENTS AND METHODS: Thirty-six patients (pts) under 60 years of age with two or three factors of the Aa-IPI were enrolled. Their main characteristics were: diffuse large B-cell lymphoma (83%), Aa-IPI three factors (50%), and marrow involved (36)%. The procedure consisted of 1) induction with four cycles of ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone) 2) in responding pts, peripheral blood stem cell (PBSC) collection after the fourth cycle of ACVBP (11 pts) or after an additional mobilization regimen (Cyclophosphamide-VP16) (17 pts) 3) a first HDT (mitoxantrone, cyclophosphamide, VP16 and carmustine) followed by PBSC infusion 4) a second HDT (busulfan, carboplatin and melphalan) followed by PBSC infusion. Among the 29 patients responding to induction, 28 received the first HDTand 24 the second. RESULTS: The rates of three-year-event free survival and survival are 47% (95% confidence interval (95% CI: 31%-63%) and 50% (95% CI: 37%-69%), respectively. Eighteen patients remained free of evolutive disease and 18 patients have died, 15 from disease progression and three from treatment-related toxicity after tandem transplant (two veno-occlusive disease and one cerebral toxoplasmosis). CONCLUSION: We conclude that tandem transplant did not improve the results of the LNH87-2 study in which patients received a single consolidative HDT.

Radiation-induced bone sarcoma following total body irradiation: role of additional radiation on localized areas.

A 44-year-old patient who had had acute monoblastic leukemia developed an osteosarcoma of the pelvic bones 5 years after an allogeneic bone marrow transplant from his HLA-identical sister. He had additionally received superficial cutaneous radiation of the legs and pelvis, over the 3 weeks prior to total body irradiation (TBI), because of cutaneous leukemic lesions. The tumor was a fibrohistiocytomatous osteogenic sarcoma. The first lesion was in the right ilium, and a second lesion appeared 18 months later, symmetrically on the left ilium. Despite treatment, the patient died from metastases. At the time of diagnosis of radiation-induced sarcoma, the patient was free of leukemia and had several risk factors already reported to favor the development of solid tumors in stem cell recipients. These include acute leukemia, TBI and graft-versus-host disease. As he developed symmetrical lesions of the pelvic bone, and because of the histology of the radiation-induced tumor, we assumed that the additional radiation of the skin prior to TBI may have contributed to the pathogenesis of this malignant fibrous histiocytoma. Therefore, the risk/benefit ratio should be carefully considered in unusual indications. These patients should benefit from a close follow-up of the superimposed areas.

Knowledge acquisition environment for the design of a decision support system: application in blood transfusion.

Blood transfusion is a medical domain where decision support systems (DSSs) could be very helpful to the physicians but must easily and continuously be maintained. We have developed a knowledge acquisition tool that allows the construction and the maintenance of such a system by the domain expert. The methodology used could be applied to another highly evolutive medical domain. In this paper, we detail our knowledge acquisition tool, its use and the final DSS obtained, which is fully integrated into our hospital information network.

Infections following peripheral blood progenitor cell transplantation for lymphoproliferative malignancies: etiology and potential risk factors.

PURPOSE: We sought to describe the infections that occur after large-dose chemotherapy, which was followed by autologous peripheral blood progenitor cell transplantation, and to determine their risk factors. PATIENTS AND METHODS: We retrospectively analyzed the occurrence and the characteristics of infections in 277 consecutive patients who received intensive chemotherapy for non-Hodgkin's lymphoma (n = 207), Hodgkin's disease (n = 27), or multiple myeloma (n = 43) in a single institution. Conditioning regimens included total body irradiation in 47% of the cases. Infections occurring within the 30 days after transplant were defined as early infections, whereas infections after that time in patients who had achieved a neutrophil count greater than 1.0 x 10(9)/L (1,000 per microL) were considered as late infections. RESULTS: Within the first 30 days, 172 patients had unexplained fever (62%); infections were documented in 83 patients (30%), most commonly bacteremia (57 patients). Late infections occurred in 64 (26%) of 244 evaluable patients and consisted mainly of varicella zoster virus infections (n = 36) and pneumonia (n = 16). Administration of total body irradiation [odds ratio (OR) = 2.50; 95% confidence interval (CI) 1.4 to 4.5; P = 0.002) and previous use of fludarabine (OR 2.5; CI 1.2 to 5.2; P = 0.02) and a diagnosis of myeloma (OR 2.6; CI 1.2 to 5.6; P = 0.04) were significantly associated with late infections. CONCLUSIONS: This study confirms that infectious toxicity after peripheral blood progenitor cell transplantation is usually moderate, although bacteremia remains a serious problem. Late infections are encountered in about 25% of patients and are more common in those with myeloma, or those who received total body irradiation or fludarabine.

Posttransplantation lymphoproliferative disorder mimicking a nonspecific lymphocytic pleural effusion in a bone marrow transplant recipient. A case report.

BACKGROUND: Serous effusions are rare complications of bone marrow transplantation (BMT) and result mainly from infections or tumor relapse. CASE: We report a case of posttransplantation lympho-proliferative disorder (PTLD) revealed by cytodiagnostic examination of serous effusions in a BMT recipient. The effusion was initially considered reactive, but morphologic, immunocytologic and molecular studies subsequently revealed PTLD. CONCLUSION: This case demonstrates the importance of cytologic examination of effusions in BMT or organ recipients. Since most PTLDs are Epstein-Barr virus (EBV)-associated B-cell lymphoproliferative disorders and T cells predominate in reactive effusions, appropriate initial immunostaining, including CD3, CD79a and EBV latent membrane protein, should aid in their early detection.

CD4+ CD56+ cutaneous neoplasms: a distinct hematological entity? Groupe Français d'Etude des Lymphomes Cutanés (GFELC).

We report seven cases of particular cutaneous tumors selected from the register of the French Study Group on Cutaneous Lymphomas. The patients (three men, four women) were aged 37-86 years. They initially presented with cutaneous nodules or papules. Three cases presented with regional lymph nodes. Stagings were negative, except for one patient with bone marrow involvement. Histological features were relevant with pleomorphic medium T-cell lymphoma, but these cells exhibited a distinguishing phenotype. They were positive for CD4, CD56, and also CD45, CD43, and HLA-DR. All other T-cell and B-cell markers were negative. The myelomonocytic markers (CD13, CD14, CD15, CD33, CD117, myeloperoxidase, and lysozyme) were negative excepted CD68, which was clearly positive in four cases and weakly in two cases. Others natural killer cell markers (CD16, CD57, TiA1, granzyme B), TdT, and CD34 were negative. Polymerase chain reaction studies did not detect any B or T clonal rearrangement. The cytogenetic studies, performed in five cases, showed a del(5q) in two cases. All patients were treated successfully by polychemotherapy, but relapsed quickly in the skin, between 4 and 28 months. Five patients developed bone marrow involvement, with leukemia in three cases, and they died in 5-27 months. One patient died at 17 months with skin progression. The seventh patient is alive at 33 months, with cutaneous progression. The origin of these cells is unclear. Despite expression of CD4 or CD56, we failed to demonstrate a T-cell, natural killer cell origin. However, CD4 and CD56 are not specific for T or natural killer lineages. Although these two markers are also known to be expressed by monocytic cells, classic myeloid antigens were negative. These seven cases, together with other rare similar cases already reported, seem to represent a distinct entity likely developed from hematological precursor cells.

[Transfusion of platelet concentrates]. / Transfusion de concentrés plaquettaires.

Although a number of research have been realized in the aim of decreasing the use of platelet concentrates, these blood products remain absolutely necessary for patients with therapeutic aplasia and for some surgical patients. After the description of the main rules of platelet transfusion procedures, we will discuss some controversial issues: threshold value for platelet transfusion, platelet doses, place of curative and prophylactic strategies, refractoriness to platelet transfusion, HLA alloimmunization. Then we will focus our review on the future alternatives for platelet transfusion.

Reverse seroconversion of hepatitis B after allogeneic bone marrow transplantation: a retrospective study of 37 patients with pretransplant anti-HBs and anti-HBc.

BACKGROUND: Reverse seroconversion to hepatitis B virus (HBV), i.e., HBV reactivation in patients with pretransplant antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc), is rarely re-ported after allogeneic bone marrow transplantation. METHODS: To determine this risk, we studied clinical outcome and serological changes in 37 patients with pretransplant anti-HBs and anti-HBc. RESULTS: In 33 cases, no change in HBV markers was observed in the posttransplant period. In four cases, anti-HBs and anti-HBc were lost, and hepatitis B surface antigen, hepatitis B e antigen, and HBV DNA emerged together with acute hepatitis, after cessation of immunosuppression. The actuarial risk of reactivation in the 37 patients was 20.5% (median follow-up 20 months). No reactivation occurred in patients with anti-HBs-positive donors. CONCLUSION: Although few cases of postallogeneic bone marrow transplantation reverse seroconversion to HBV have been reported, this study demonstrates that the actuarial risk is relatively high and suggests that donor vaccination might be proposed prophylactically or that HBs-specific immunoglobulin infusions might be warranted.

Platelet transfusion: a dose-response study.

Early recommendations on prophylactic transfusion of thrombocytopenic patients involved a standard platelet dose of about 0.5 x 10(11)/10 kg body weight. Given the lack of data supporting this dose, we prospectively studied the dose response to platelet transfusions in adults and children with hematologic malignancies. Each patient received, in similar clinical conditions, a medium, high, and very high dose of fresh (< 24 hours old) ABO-compatible platelets, in the form of apheresis platelet concentrates (APC). For the adults, the medium dose was defined as APC containing between 4 and 6 x 10(11) platelets, the high dose between 6 and 8 x 10(11), and the very high dose > 8 x 10(11); for the children, the three doses corresponded to 2 to 4, 4 to 6, and > 6 x 10(11) platelets. The end points were the platelet increment, platelet recovery, and the transfusion interval, and the results were compared with a paired t-test. Sixty-nine adults and 13 children could be assessed. Recoveries in the adults were similar with the three doses (from 28% to 30%), but the high and very high doses led to a significantly better platelet increment (52 and 61 x 10(9)/L, respectively) than the medium dose (33 x 10(9)/L, P < .01). The main difference was in the transfusion interval, which increased with the dose of platelets transfused, from 2.6 days with the medium dose to 3.3 and 4.1 days with the high and very high doses, respectively (P < .01). The positive effect of the high dose was observed regardless of pretransfusional clinical status, but was more marked in patients with no clinical factors known to impair platelet recovery. In these patients, a platelet dose of 0.07 x 10(11) per kg of body weight led to a transfusion interval of more than 2 days in 95% of cases. In patients with clinical factors favoring platelet consumption, the proportion of transfusions yielding an optimal platelet increment and transfusion interval increased with the dose of platelets. The platelet dose-effect was also significant in the children, in whom the high and very high doses led to 1.5-fold to twofold higher posttransfusion platelet counts and transfusion intervals. We conclude that transfusion of high platelet doses can reduce the number of platelet concentrates required by thrombocytopenic patients and significantly reduce donor exposure.

Human herpesvirus-6 meningoencephalitis in a recipient of an unrelated allogeneic bone marrow transplantation.

BACKGROUND: Human herpesvirus-6 (HHV-6) has been implicated in bone marrow suppression, interstitial pneumonitis, and fatal meningoencephalitis in bone marrow transplant (BMT) recipients. METHODS: We describe the case of a woman with acute myeloid leukemia in second remission who developed febrile meningoencephalitis 8 months after a second unrelated BMT. RESULTS: Computed tomography and magnetic resonance images of the brain were nonspecific. Analysis of cerebrospinal fluid (CSF) revealed lymphocytosis and an increased protein level. Using polymerase chain reaction methods, HHV-6 was the only pathogen detected in CSF, peripheral blood mononuclear cells, and bone marrow. The patient was treated with ganciclovir and foscarnet for 3 months. All clinical manifestations resolved and HHV-6 polymerase chain reaction analysis of CSF became negative 40 days after the beginning of antiviral treatment. CONCLUSIONS: This observation strongly suggests that HHV-6 should be sought in BMT patients with neurological complications and that HHV-6 meningoencephalitis may respond to ganciclovir and foscarnet therapy.