Allogeneic marrow transplantation for chronic granulocytic leukemia

Six patients with Philadelphia-chromosome (Ph' +)-positive chronic granulocytic leukemia were transplanted from their HLA-identical siblings after conditioning with cyclophosphamide and 1'000 rad total body irradiation. All received cyclosporin-A for prophylaxis of Graft-versus-Host disease. All patients showed prompt engraftment and all are cytogenetically and clinically in complete remission. Two patients had transient mild signs of Graft-versus-Host-disease and one patient had unilateral facial nerve paresis of unknown origin. All are ambulatory and well 6-18 months (median 10 months) after transplantation.     

Pathological cell aggregates in bone marrow cultures from patients with various hematological diseases.

Non-clonal growth of macroscopic cell aggregates in methylcellulose cultures of abnormal marrow is described. They were seen in all patients with Graft-versus-Host Disease, graft rejection, and autoimmune disease presumably directed against hemopoietic cells, we found them in 35% of patients with primary hematological neoplasias and rarely in patients with solid tumors. They were never encountered in 80 healthy controls. The aggregates originated from small cell clumps which sedimented with the "buffy coat" in contrast to normal bone marrow particles. They contained tumor cells, grafted myeloid cells, or target cells of autoimmune disease in association with a widely varying amount of macrophages. Preliminary results suggest that the frequency of macrophages within the aggregates correlates inversely with the aggressiveness of the clinical condition. We propose that appearance of such aggregates in an indicator of immune activation; we expect that further quantitation of the phenomenon will reveal important clinical correlations and provide a model for the study of host defense to "foreign" cells.     

Risk of acquiring Creutzfeldt-Jakob disease from blood transfusions: systematic review of case-control studies

ObjectiveTo determine the strength of association between history of blood transfusion and development of Creutzfeldt-Jakob disease.ConclusionsCase-control studies do not suggest a risk of developing Creutzfeldt-Jakob disease from blood transfusion. Rather, a trend seems to exist towards a lower frequency of previous blood transfusion in patients with Creutzfeldt-Jakob disease than in controls. However, it is important to be aware of these studies'' methodological limitations—primarily the choice of control population and reliability of recall of transfusion status.     

自体CIK细胞联合化疗治疗老年急性白血病的临床疗效评估

目的:探讨自体细胞因子诱导杀伤(CIK)细胞联合化疗方案治疗老年急性白血病的临床疗效。方法:采集6例在我院进行化疗治疗的老年急性白血病患者的静脉血制备自体CIK细胞,成熟后回输入体内,持续注射10天为一个疗程。观察培养前和培养13天后白细胞各亚型细胞所占百分比,并比较CIK细胞回输前后患者白细胞亚群、感染次数及输血量的变化。结果:培养后CD3~+、CD8~+、CD3~+CD8~+、CD3~+CD56~+亚型细胞百分比均显著高于培养前(P0.05),CIK细胞回输后患者体内CD3~+、CD3~+CD8~+、CD3~+CD56~+亚群细胞百分比显著高于回输前(P0.05);CIK细胞回输后,患者感染次数和持续时间均显著少于回输前(P0.05),疾病稳定期输血量显著低于回输前(P0.05),疾病进展期输血量与回输前差异无显著性意义(P0.05)。结论:自体CIK细胞联合化疗治疗老年急性白血病患者有效且安全,可维持病情的稳定、提高机体细胞免疫功能和抗感染能力,值得临床推广。     

The immunomodulation effect of allogenic blood transfusion in colorectal cancer--a new approach

The total number of 542 patients with colorectal cancer surgery have been analyzed in order to estimate the effect of receiving transfusion local recurrences, and the disease free - survival. It should be examined whether there are changes in general immunity indicators which would be connected with perioperative transfusion. A significant connection has been found between local recurrences and blood transfusion (p<0.0001), the most noticeable being in Dukes A (p =0.045), localization on rectum (p=0.036). The receiving of blood transfusion is linked significantly with disease free - survival reduction (p =0.0068; log rank), the most significant being in Dukes A stage (p =0.0123; log rank) and with localization on rectum (p=0.0231). The analysis of general immunity indicators has shown significant immunocompromitation of patients just before the surgery and this could have effect on immunomodulation caused by transfusion and just as on the treatment prognosis of colorectal carcinoma.     

All clinically-relevant blood components transmit prion disease following a single blood transfusion: a sheep model of vCJD

Variant CJD (vCJD) is an incurable, infectious human disease, likely arising from the consumption of BSE-contaminated meat products. Whilst the epidemic appears to be waning, there is much concern that vCJD infection may be perpetuated in humans by the transfusion of contaminated blood products. Since 2004, several cases of transfusion-associated vCJD transmission have been reported and linked to blood collected from pre-clinically affected donors. Using an animal model in which the disease manifested resembles that of humans affected with vCJD, we examined which blood components used in human medicine are likely to pose the greatest risk of transmitting vCJD via transfusion. We collected two full units of blood from BSE-infected donor animals during the pre-clinical phase of infection. Using methods employed by transfusion services we prepared red cell concentrates, plasma and platelets units (including leucoreduced equivalents). Following transfusion, we showed that all components contain sufficient levels of infectivity to cause disease following only a single transfusion and also that leucoreduction did not prevent disease transmission. These data suggest that all blood components are vectors for prion disease transmission, and highlight the importance of multiple control measures to minimise the risk of human to human transmission of vCJD by blood transfusion.     

Ultrasound-guided fetal intravenous transfusion for severe rhesus haemolytic disease.

Intrauterine, intraperitoneal transfusion is associated with a poor survival rate in fetuses with hydrops and low gestational age. A method of direct fetal intravenous transfusion was used in two fetuses. One fetus with severe rhesus haemolytic disease was given transfusions in the 29th and 30th weeks of gestation, using an ultrasound-guided needle through the hepatic part of the umbilical vein without fetoscopy. In another fetus, an experimental cannulation of the umbilical vein succeeded in the 23rd week of gestation. Ultrasound-guided fetal intravenous transfusion avoids the use of fetoscopy, which has limitations, and may improve the prognosis for rhesus-sensitised fetuses.     

Highly Efficient Prion Transmission by Blood Transfusion

It is now clearly established that the transfusion of blood from variant CJD (v-CJD) infected individuals can transmit the disease. Since the number of asymptomatic infected donors remains unresolved, inter-individual v-CJD transmission through blood and blood derived products is a major public health concern. Current risk assessments for transmission of v-CJD by blood and blood derived products by transfusion rely on infectious titers measured in rodent models of Transmissible Spongiform Encephalopathies (TSE) using intra-cerebral (IC) inoculation of blood components. To address the biological relevance of this approach, we compared the efficiency of TSE transmission by blood and blood components when administrated either through transfusion in sheep or by intra-cerebral inoculation (IC) in transgenic mice (tg338) over-expressing ovine PrP. Transfusion of 200 µL of blood from asymptomatic infected donor sheep transmitted prion disease with 100% efficiency thereby displaying greater virulence than the transfusion of 200 mL of normal blood spiked with brain homogenate material containing 10³ID₅₀ as measured by intracerebral inoculation of tg338 mice (ID₅₀ IC in tg338). This was consistent with a whole blood titer greater than 10^3.6 ID₅₀ IC in tg338 per mL. However, when the same blood samples were assayed by IC inoculation into tg338 the infectious titers were less than 32 ID per mL. Whereas the transfusion of crude plasma to sheep transmitted the disease with limited efficacy, White Blood Cells (WBC) displayed a similar ability to whole blood to infect recipients. Strikingly, fixation of WBC with paraformaldehyde did not affect the infectivity titer as measured in tg338 but dramatically impaired disease transmission by transfusion in sheep. These results demonstrate that TSE transmission by blood transfusion can be highly efficient and that this efficiency is more dependent on the viability of transfused cells than the level of infectivity measured by IC inoculation.     

Transfusion strategies for acute upper gastrointestinal bleeding

This study aims to analyze the characteristics and influencing factors of intraoperative blood transfusion in children with congenital heart disease (CHD) and explore the preoperative blood preparation protocols and risk indicators for intraoperative blood transfusion. It retrospectively analyzed data from 243 patients under the age of 18 undergoing CHD surgery from December 2018 to March 2022. The patients were divided into four groups in terms of the following surgical methods: ventricular septal defect (VSD) repair (group A), atrial septal defect (ASD) repair (group B), VSD and ASD repair (group C), and others (group D). Influencing factors for intraoperative blood transfusion in different surgical methods and outcomes were assessed. (1) Among the 243 cases, 185 (76.13%) cases received intraoperative blood transfusion, 176 (72.43%) cases received red blood cell (RBC) transfusion, and 30 (12.35%) cases received plasma transfusion. The RBC transfusion rate of group C was 91.21%, which was significantly higher than those of the other three groups (P<0.05). The plasma transfusion rate of group D was 24.32%, which was significantly higher than those of the other three groups (P<0.05). (2) There was no significant difference in the volume of RBC preparation, intraoperative blood loss, intraoperative RBC transfusion, and postoperative hemoglobin (Hb) between the four groups (P>0.05). The preoperative weight and Hb of group C were lower than those of the other three groups; however, only the difference between group B and group C was statistically significant (P<0.05). (3) The influencing factors for intraoperative RBC transfusion, such as age, preoperative weight, and Hb, were negatively correlated in the four groups. (4) No adverse reactions of blood transfusion were found in the four groups. The postoperative infection rates of group C and group D were 31.33% and 29.73%, respectively, which were higher than those of group A and group B (9.72% and 16.28%, respectively) (P<0.05). The average duration of hospitalized days of group C and group D were higher than those of group A and group B (P<0.05). This study suggests that the individualized blood preparation should be achieved according to the characteristics of intraoperative blood transfusion in children with CHD and the evaluation of the risk of intraoperative blood transfusion.     

Depressed IL-1 production by chronic GVHD dermal fibroblasts

Chronic Graft-versus-Host disease (GVHD) is characterized by overt immunosuppression. In addition, the skin is a major anatomical site affected in chronic GVHD for reasons not yet known. Increased collagen deposition, a mononuclear cell infiltrate in the dermis as well as loss of fat and appendages, are observed in the skin. The inflammatory cytokine IL-1 was shown to affect fibroblast proliferation and secretory activities. In the present study, IL-1 generation by dermal fibroblasts, of chronic GVHD or control mice, was assessed. It was shown that two sequential signals are needed for IL-1 generation by dermal fibroblasts; priming by lymphokines/cytokines followed by a challenge with LPS. A variety of recombinant lymphokines and cytokines (G/M-CSF, IL-2, TNF, IL-1 beta and IFNs alpha, beta and gamma) were shown to be efficient in priming dermal fibroblasts for IL-1 generation. IL-1 activity in dermal fibroblasts, most probably of the IL-1 alpha species, was located in frozen-thawed cell lysates or associated to the cell membrane, though not secreted into the culture fluids. Dermal fibroblasts from chronic GVHD mice manifested a pronounced depression in IL-1 generation upon stimulation with exogenous lymphokines/cytokines and LPS. This was observed over a wide range of concentrations of lymphokines/cytokines and LPS. The depressed ability of chronic GVHD fibroblasts to generate IL-1 was pronounced even after few passages of the cells in vitro, and upon stimulation in culture outside the suppressive milieu of the animal.(ABSTRACT TRUNCATED AT 250 WORDS)     

International blood collection and storage: Clinical use of blood products

Human blood transfusion is the process of transferring blood or blood-based products from an individual into the circulatory system of another. From the theory of circulation of blood to the early practice of blood transfusion, transfusion medicine has been an important concept for many centuries. The practicality of transfusion, however, only became a possibility during and shortly after the Second World War. Today, blood and its derivatives play a critical role in worldwide health care systems, with blood components having direct clinical indications. Over the past several years worldwide organizations including the World Health Organization (WHO) have made a number of substantial improvements to the regulation of the worlds blood supply. This continuous supply plays a critical role throughout health care systems worldwide, with procedures for blood collection, processing, and storage now complex, standardised processes. As the areas of clinical validation of different disease states from blood-derived sources (i.e., disease biomarkers) move towards validation stages, the importance of controlled- and standardised-protocols is imperative.     

Epidemiology of hepatitis C virus in Europe

Abstract: Epidemiology of Hepatitis C virus (HCV) infection in Europe is changing very rapidly since the main source of contamination was blood transfusion and the use of surrogate markers allowed to diminish dramatically the number of patients contaminated through HCV post transfusion hepatitis. The recent descrition of several genotypes with different distributions over Europe and different pathogenicity will allow to explain various evolutive aspects of disease. At present, groups at risk are drug addicts (70%), hemophiliacs (contaminated with blood products before 1985), hemodialysis patients (20%) and patients with cirrhosis with or without hepatocellular carcinoma. The detection of HCV markers prior to blood transfusion allowed to detect asymptomatic carrirers of HCV, some of them with latent chronic hepatitis which can be predictedby the detection of HCV RNA in the serum. Vertical and sexual transmision are rare but possible event observed with certainty in patients co-infected with HIV and controversial in other situations.     

SUCCESSFUL AORTOCORONARY BYPASS SURGERY IN A PATIENT WITH CLASSICAL HEMOPHILIA A

A patient with documented Factor VIII deficiency (classical Hemophilia A) and a history of previous severe intra- and postoperative hemorrhage and transfusion reaction underwent myocardial revascularization for advanced triple vessel coronary artery occlusive disease. The coagulation status was investigated, and a replacement regimen was instituted. The surgical procedure and postoperative course were uneventful.     

The blast transformation capacity and karyotypic characteristics of the T-lymphocytes in hemolytic disease of the newborn]

The blood of 6 newborn boys with haemolytic disease of newborns and of 3 healthy newborn boys was examined. In all 949 metaphase plates were analysed. In all the investigated plates the karyotype was masculine, 46,XY [correction of 46HY]. The mitotic index is lowered considerably in sick children that suggests inhibition of their cellular immunity. In these conditions, the K and L lymphocytes of donor blood, introduced in substituting blood transfusion, can interact with the sensitized erythrocytes in accordance with the type of reaction "the transplant against the host" causing the increase in the level of bilirubin after the operation. It is expedient to study the possibility of realization of substituting blood transfusion using the leucocyte-free blood.     

Circulating microRNAs as Biomarkers for Detection of Autologous Blood Transfusion

MicroRNAs (miRNAs) are small non-coding RNAs that regulate various biological processes. Cell-free miRNAs measured in blood plasma have emerged as specific and sensitive markers of physiological processes and disease. In this study, we investigated whether circulating miRNAs can serve as biomarkers for the detection of autologous blood transfusion, a major doping technique that is still undetectable. Plasma miRNA levels were analyzed using high-throughput quantitative real-time PCR. Plasma samples were obtained before and at several time points after autologous blood transfusion (blood bag storage time 42 days) in 10 healthy subjects and 10 controls without transfusion. Other serum markers of erythropoiesis were determined in the same samples. Our results revealed a distinct change in the pattern of circulating miRNAs. Ten miRNAs were upregulated in transfusion samples compared with control samples. Among these, miR-30b, miR-30c, and miR-26b increased significantly and showed a 3.9-, 4.0-, and 3.0-fold change, respectively. The origin of these miRNAs was related to pulmonary and liver tissues. Erythropoietin (EPO) concentration decreased after blood reinfusion. A combination of miRNAs and EPO measurement in a mathematical model enhanced the efficiency of autologous transfusion detection through miRNA analysis. Therefore, our results lay the foundation for the development of miRNAs as novel blood-based biomarkers to detect autologous transfusion.     

Impact of Leucocyte Depletion and Prion Reduction Filters on TSE Blood Borne Transmission

The identification in the UK of 4 v-CJD infected patients thought to be due to the use of transfused Red Blood Cell units prepared from blood of donors incubating v-CJD raised major concerns in transfusion medicine. The demonstration of leucocyte associated infectivity using various animal models of TSE infection led to the implementation of systematic leuco-depletion (LD) of Red Blood cells concentrates (RBCs) in a number of countries. In the same models, plasma also demonstrated a significant level of infectivity which raised questions on the impact of LD on the v-CJD transmission risk. The recent development of filters combining LD and the capture of non-leucocyte associated prion infectivity meant a comparison of the benefits of LD alone versus LD/prion-reduction filters (LD/PR) on blood-borne TSE transmission could be made. Due to the similarity of blood/plasma volumes to human transfusion medicine an experimental TSE sheep model was used to characterize the abilities of whole blood, RBCs, plasma and buffy-coat to transmit the disease through the transfusion route. The impact of a standard RBCs LD filter and of two different RBCs LD/PR prototype filters on the disease transmission was then measured. Homologous recipients transfused with whole-blood, buffy-coat and RBCs developed the disease with 100% efficiency. Conversely, plasma, when intravenously administered resulted in an inconstant infection of the recipients and no disease transmission was observed in sheep that received cryo-precipitated fraction or supernatant obtained from infectious plasma. Despite their high efficacy, LD and LD/PR filtration of the Red Blood Cells concentrate did not provide absolute protection from infection. These results support the view that leuco-depletion strongly mitigates the v-CJD blood borne transmission risk and provide information about the relative benefits of prion reduction filters.     

Prospective study of post-transfusion hepatitis after cardiac surgery in a British centre.

A series of 248 consecutive patients undergoing cardiac surgery were examined in a prospective study of post-transfusion hepatitis in a single British centre. Patients received a total of 1796 units of blood or blood products (mean blood transfusion 6.28 units per patient). During five to 30 days after operation 38 of the patients showed an increase in serum transaminase activities. There was no serological evidence for fresh infection by hepatitis A or B virus, cytomegalovirus, Epstein-Barr virus, or herpes virus in any of these patients. The increase in transaminase activities was unexplained and reached over 100 IU/l (normal less than 40 IU/l) in six patients. The incidence of acute short incubation post-transfusion non-A, non-B hepatitis was therefore thought to be 2.4%. These six patients had normal liver function six months after transfusion but a further two of the surviving 228 patients had raised serum transaminase activities at six months. In one of these, liver biopsy disclosed chronic persistent hepatitis; in the other, alcoholic liver disease was suspected. The incidence of significant chronic liver disease after blood transfusion possibly attributable to a non-A, non-B hepatitis agent was therefore only 0.4%.     

A possible association between survival time and transfusion in cervical cancer

Some studies suggest that transfusion may be associated with an increased risk of recurrence of and death due to malignant human neoplasms. We examined retrospective data from patients with cervical cancer to see if any association between transfusion of blood at the time of initial treatment and the time interval to recurrence and death could be detected in this cancer. In 130 patients with cervical cancer, seen over a ten-year period at our institution, there was a trend toward earlier recurrence in transfused patients, but this trend did not achieve statistical significance. Death due to cervical cancer recurrence occurred after a median of Death due to cervical cancer recurrence occurred after a median of 12 months in the transfused patients and a median of 68 months in the non-transfused individuals, which was statistically significant. Transfused patients had, on average, more favorable prognostic factors than those not transfused, such as less advanced clinical stage of disease. Analysis using a proportional hazards risk model failed to demonstrate a significant association between transfusion and time to recurrence when other prognostic factors were considered, but a significant association between transfusion and time to cancer-related death (p less than 0.05) was found. While these results cannot be viewed as conclusive due to the small number and heterogeneity of the patients analyzed, our data support the possibility of an association between transfusion and cervical cancer survival. Further studies are warranted to confirm or refute this relationship.     

Hematologic and oncologic complications in the critically ill child

Admission of a patient to an intensive care unit for management of direct consequences of a hematologic or oncologic disease is occasionally necessary. Such problems included exchange transfusion, sepsis, compression of vital structures by malignant tumor, metabolic derangements, leukostasis, post-operative care, major sickling episodes in vital organs, and disseminated coagulopathy. More often, however, hematologic complications arise in the child critically ill from other causes, such as trauma or infections. The first two sections of this review address blood transfusion and hemostasis, topics likely to have wide application in the care of critically ill children. The last portion discusses problems unique to patients with sickling or malignant disease.     

An epidemiological model for the dynamics of Chagas' disease.

A model for the transmission dynamics of Chagas' disease is presented. The structure of the model is similar to that of the Ross-Macdonald model for malaria but includes an extra infectious compartment (chronically ill individuals) which is characteristic of Chagas' disease. In Chagas' disease there are two-main forms of transmission, by blood transfusion and by vector biting. The former is more common in urban environments and the latter is characteristic of rural settings. The characteristic long chronic (frequently asymptomatic) stage of Chagas' disease is potentially a risk factor that could enhance disease transmission by blood transfusion. The model evaluates the relative importance of both transmission modes in populations of constant size. The main results indicate that there is a strong tendency of the disease to reach an asymptotically stable endemic equilibrium point. Also, the magnitude of the basic reproductive number is very sensitive to the length of the chronic stage of the disease and hence it follows that early detection of cases (reducing the length of this stage) is important for the eventual eradication of the disease.