A case of immune complex type hemolytic anemia induced by initial micafungin administration.

We report the first case of immune complex type hemolytic anemia by initial micafungin administration that was given as prophylaxis to a 42-year-old Japanese man receiving chemotherapy for primary amyloidosis. The few cases found in the literature were associated with secondary administration causing immune hemolytic attacks. Despite its rarity, the present case calls for increased awareness of micafungin-induced hemolytic anemia upon initial administration.

CASE REPORT: Serial Cases of False-Positive Flow-Cytometry T Cell Crossmatch Associated With Anti-Blood Type Antibodies in Patients Undergoing ABO-Incompatible Kidney Transplantation.

Background: A positive flow-cytometry T cell crossmatch (FTXM) has important prognostic implications, even when the complement-dependent cytotoxicity crossmatch is negative. Recent studies have shown that ABO incompatibility is associated with positive FTXM, but the underlying mechanism remains poorly understood. Cases: In five ABO blood type O recipients of kidneys from wives with type B, FTXM was positive but complement-dependent cytotoxicity crossmatch was negative. Application of a solid-phase technique (LABScreen) revealed no case with antibodies to donor-specific human leukocyte antigen. After removal of type B antibodies from patient sera, FTXM was negative for all five patients. In one tested case, the eluate prepared from the donor's T lymphocyte agglutinated only type B red blood cells, implying the existence of blood type B substances on donor T lymphocytes. Discussion: False-positive FTXM reflects blood type B substrates bound to T lymphocytes. Repeat FTXM after incubation with donor-type red blood cells (to adsorb anti-ABO antibodies) was negative. This phenomenon explains the discrepancy between FTXM and solid-phase bead assays. Demonstration of type B substances on donor T lymphocytes is necessary before absolute test validity is confirmed. Conclusion: False-positive FTXM may be associated with type B antibodies bound to T lymphocytes when a blood type O recipient receives tissue from a type B donor. This phenomenon explains the false-positive FTXM observed in the setting of ABO-incompatible kidney transplantation.

Multiple HLA-matched platelet transfusions for a single patient with broad anti-HLA antibodies: a case report.

The efficacy of 30 platelet concentrate (PC) products transfused to a patient with myelodysplastic syndrome (MDS) was evaluated by calculating the 1-hour post-transfusion corrected count increment (1h-CCI). Of the 30 transfusions, all HLA-A/B-matched, the cross-match (CM) test was negative in 23 (CM(-)-PC) and weakly positive (CM(+)-PC) in 2, and the CM test was not conducted in 5 (non-CM-PC). The effective rate was higher with CM(-)-PC compared to non-CM-PC (82.6% vs 60%), but statistical significance was not achieved, which suggested that the CM test of PC may still be a not satisfactorily effective predictor of PC refractoriness. Studies are ongoing in Japan to confirm on the importance of CM test of PC.

Phase I/II trial of combination of temozolomide chemotherapy and immunotherapy with fusions of dendritic and glioma cells in patients with glioblastoma.

BACKGROUND: This trial was designed to evaluate the safety and clinical responses to a combination of temozolomide (TMZ) chemotherapy and immunotherapy with fusions of DCs and glioma cells in patients with glioblastoma (GBM). METHOD: GBM patients were assigned to two groups: a group of recurrent GBMs after failing TMZ-chemotherapy against the initially diagnosed glioma (Group-R) or a group of newly diagnosed GBMs (Group-N). Autologous cultured glioma cells obtained from surgical specimens were fused with autologous DCs using polyethylene glycol. The fusion cells (FC) were inoculated intradermally in the cervical region. Toxicity, progression-free survival (PFS), and overall survival (OS) of this trial were evaluated. Expressions of WT-1, gp-100, and MAGE-A3, recognized as chemoresistance-associated peptides (CAP), were confirmed by immunohistochemistry of paraffin-embedded tumor samples. Patient's PBMCs of pre- and post-vaccination were evaluated by tetramer and ELISPOT assays. RESULTS: FC-immunotherapy was well tolerated in all patients. Medians of PFS and OS of Group-R (n = 10) were 10.3 and 18.0 months, and those of Group-N (n = 22) were 18.3 and 30.5 months, respectively. Up-regulation and/or cytoplasmic accumulation of CAPs was observed in the recurrent tumors of Group-R patients compared with their initially excised tumors. Specific immune responses against CAPs were observed in the tetramer and ELISPOT assays. CONCLUSIONS: The combination of TMZ-treatment leading to up-regulation and/or cytoplasmic accumulation of CAPs, with FC-immunotherapy as a means of producing specific immunity against CAPs, may safely induce anti-tumor effects in patients with GBM.

Comprehensive technical and patient-care optimization in the management of pediatric apheresis for peripheral blood stem cell harvesting.

BACKGROUND: Pediatric apheresis for peripheral blood stem cell transplantation should be carried out with due concern for low corporeal blood volume and vulnerability to hypocalcemia-related complications, hypovolemic shock, and hypervolemic cardiac overload. STUDY DESIGN AND METHODS: We retrospectively investigated a total of 267 apheresis procedures from 1990 to 2013 on 93 children between 0 and 10 years old, including 89 patients and 4 healthy donors, with body weights of 6.3 to 44.0 kg. RESULTS: The median CD34+ cell yield per apheresis procedure was 2.3 × 106 CD34+ cells/kg (0.2-77.9 × 106 CD34+ cells/kg). Adverse events occurred in 11.6% of procedures (n = 31), including mild perivascular pain (n = 12), emesis (n = 9), hypotension (n = 3), urticaria (n = 2), numbness (n = 2), chest pain (n = 1), facial flush (n = 1), and abdominal pain (n = 1). Among hypotensive events, shock in a 9.6 kg one-year-old boy required emergency treatment in 1996. Thereafter, we adopted continuous injection of calcium gluconate, ionized calcium monitoring, central venous catheter access and circuit priming with albumin in addition to concentrated red cells. Since then we have had fewer complications: 16.4% per apheresis during 1990-1997 versus 5.8% during 1998-2013. No healthy pediatric donors suffered from any late-onset complications related to apheresis or G-CSF administration. CONCLUSION: By employing appropriate measures, peripheral blood stem cell apheresis for small children can have an improved safety profile, even for children weighing <10 kg.

Online reporting system for transfusion-related adverse events to enhance recipient haemovigilance in Japan: a pilot study.

BACKGROUND: A surveillance system for transfusion-related adverse reactions and infectious diseases in Japan was started at a national level in 1993, but current reporting of events in recipients is performed on a voluntary basis. A reporting system which can collect information on all transfusion-related events in recipients is required in Japan. METHODS: We have developed an online reporting system for transfusion-related events and performed a pilot study in 12 hospitals from 2007 to 2010. RESULTS: The overall incidence of adverse events per transfusion bag was 1.47%. Platelet concentrates gave rise to statistically more adverse events (4.16%) than red blood cells (0.66%) and fresh-frozen plasma (0.93%). In addition, we found that the incidence of adverse events varied between hospitals according to their size and patient characteristics. CONCLUSION: This online reporting system is useful for collection and analysis of actual adverse events in recipients of blood transfusions and may contribute to enhancement of the existing surveillance system for recipients in Japan.

The hematological and clinical effects of X-ray contrast medium contaminating autologous blood for transfusion purposes.

Little information is available regarding the influence of non-ionic low-osmolar iodinated contrast medium (CM) in stored blood on the quality of blood components. We sought to evaluate the quality of such CM-contaminated blood in terms of the degree of hemolysis, production of microaggregates, level of iodine concentration, and RBC shape, and to identify the pros and cons of autologous blood donation immediately after X-ray examination using CM. In conclusion, contamination by such CM in blood collected around 2h after the completion of X-ray examination appears unlikely to induce deleterious effects on blood components.

Guidelines for safety management of granulocyte transfusion in Japan.

Granulocyte transfusion (GTX) has recently been revived by the ability to stimulate granulocyte donors with granulocyte colony-stimulating factor (G-CSF), resulting in a greatly increased number of cells that can be collected. However, there is a paucity of guidelines for assessing the appropriateness and safety management of GTX. The objective of this study was to establish guidelines for the safety management of GTX appropriate for the clinical situation in Japan. The Japan Society of Transfusion Medicine and Cell Therapy, Granulocyte Transfusion Task Force issued the first version of guidelines for GTX considering the safety management of both granulocyte donors and patients who receive GTX therapy. The current guidelines cover issues concerning: (1) the appropriateness of medical institutions, (2) management of granulocyte donors, (3) quality assurance of granulocyte concentrates, (4) administration of granulocyte concentrates, (5) evaluation of the effectiveness of GTX therapy, and (6) complications of GTX therapy. The simple 'bag separation method' without apheresis may be recommended for granulocyte collection in pediatric patients. The first version of guidelines for GTX therapy has been established, which may be appropriate for the clinical situation in Japan. Care should be taken to perform the safety management of both granulocyte donors and patients who receive GTX therapy.

Accumulated cytokines in stored autologous blood do not cause febrile nonhemolytic transfusion reactions.

Accumulated inflammatory cytokines are considered to be a cause of febrile nonhemolytic transfusion reactions (FNHTRs) of platelet transfusions. Inflammatory cytokines have been found in red cell components stored at 4 degrees C; however, their relationship to FNHTRs has not been clearly demonstrated following red cell transfusions. We measured cytokine levels in stored blood, and determined whether inflammatory marker concentrations were elevated in subjects infused with autologous blood stored for 5 weeks. In conclusion, cytokines accumulated in blood stored at 4 degrees C, but their increases were small. No changes were seen in recipients' inflammatory markers after blood transfusion. Our results indicate that cytokines in stored autologous blood are not responsible for FNHTRs.

Nineteen years of experience with autotransfusion for elective surgery in children: more troublesome than we expected.

BACKGROUND: Under the rationale that children undergoing elective surgery are the best candidates for autologous blood donors because of their long life expectancy, aggressive donations of autologous blood, even from infants, have been reported. A number of problems are associated with the procedure, however, whereas the risks of homologous blood are very low. STUDY DESIGN AND METHODS: From 1987 through 2005, of 5792 patients referred to blood transfusion services at two Japanese university hospitals for autologous blood donations, 314 children younger than 16 years old served as subjects for assessment. RESULTS: Of 314 children, 7 were not suitable as autologous donors. In most cases this was due to uncooperative behavior. Over a follow-up period of 19 years, the authors encountered 53 cases (17.3%) of donation-related problems, and this rate was higher than the 6 percent rate recorded for adult cases (316/5305). Nine children suffered crucial complications such as vasovagal reactions, and one 14-year-old boy required a vasopressor drug. Important findings were that 6 of these were first-time donors, and the amount of blood drawn was under 10 percent of their estimated blood volume. CONCLUSION: Of 53 donation-related problems, 9 (17.0%) were accompanied by marked hypotension. Drawing autologous blood from children has become easier with advanced devices; however, lessening of anxiety and tension are essential for the safety of children's autologous blood donation programs. Aggressive donation should be avoided.

[Blood transfusion and consultation].

Many hospital staff, including doctors, nurses, pharmacists, etc., are engaged in blood transfusion practice, and various inquiries are referred to the blood transfusion services. In order to provide a prompt and proper reply, transfusionists must have a wealth of knowledge and experience concerning blood transfusion medicine. Q & A relating to blood transfusion can be found on the home page of the Japanese Society of Blood Transfusion, and these are useful staff resources to obtain simple information. However, we sometimes encounter difficult problems in the management of a patient's treatment. Three representative transfusion-related issues are described in this article: (1) blood transfusion to patients with a positive DAT; (2) emergency transfusion, especially in cases where unexpected antibodies are encountered; (3) management of platelet transfusion refractoriness. Minimum standards for the investigation of transfusion-related adverse reactions developed by SHOT (Serious Hazards of Transfusion) are also introduced in this article, and these have a highly practical value. Finally, the importance of education in transfusion medicine is described. The number of doctors in Japan who are engaged exclusively in transfusion medicine is small, but blood transfusions are performed in every hospital, regardless of whether such a specialist is present. We have recently had to deal with a wide range of transplantation-related issues. Therefore, there is a great need for special education in transfusion medicine for doctors in the transplantation and cell therapy age.

Pre-transfusion screening for platelet-reactive antibodies.

We retrospectively compared the cost of platelet concentrates (PCs) used for patients whose serum had already been screened for platelet-reactive antibodies with the cost for patients whose serum was examined after the commencement of treatment using platelets. On the basis of 774 patients' data, the mean cost of PCs for the latter group of patients ($5562) was higher than that for the former group ($2547). Screening beforehand ensured a prompt supply of specific PCs, and costs were suppressed by the avoidance of multiple transfusions. We conclude that screening for platelet-reactive antibodies followed by administration of crossmatch-negative PCs appears to be both clinically and economically advantageous.

Transfusion-related problems following major ABO-incompatible bone marrow transplantation.

A case of acute myelocytic leukemia has been reported in which the patient's surviving original B lymphocytes after pretransplant-conditioning chemotherapy probably reproduced hemagglutinins that reacted with red blood cells (RBCs) derived from engrafted donor marrow for a prolonged period of time. Although the direct antiglobulin test was negative and hemagglutinins were not detectable in the patient's sera but only in the eluate, the antibodies reappeared in the sera. Therefore, it is important to confirm that the eluate does not contain antibodies that would react with donor-derived RBCs when the type of red cell used for transfusion is switched from the patient's type to the donor's type in a major ABO-mismatched bone marrow transplantation (BMT). Testing of ABO subgroups using lectins is also recommended to avoid a delayed hemolytic transfusion reaction following BMT.