Allo-anti-M: Detection peaks around 2 years of age, but may be attenuated by red blood cell transfusion.

BACKGROUND: Anti-M is frequently observed as a naturally occurring antibody of little clinical significance. Naturally occurring anti-M is often found in children although the specific triggers of production, persistence, and evanescence of anti-M have yet to be elucidated. METHODS: In a retrospective, multicenter, nationwide cohort survey conducted from 2001 to 2015, alloantibody screening was performed before and after transfusion in 18,944 recipients younger than 20 years. Recipients were categorized into six cohorts based on their age at transfusion; within and among these cohorts, allo-anti-M was analyzed in regard to its production, persistence, and evanescence. RESULTS: In 44 patients, anti-M detected before and/or after transfusion was an age-related phenomenon, with a median age of 2 years and an interquartile range of 1-3 years; anti-M was most frequently detected in a cohort of children 1 to <5 years (0.77%, 31 of 4035). At least five patients were presumed to have concurrent infections. Among 1575 adolescents/young adults (15 to <20 years), no anti-M was detected. Of 29 patients with anti-M prior to transfusion, the antibody fell to undetectable levels in 17 recipients (89.5%, of whom at least 13 received only M-negative red cells) after anywhere from 5 days to 5.8 years; anti-M persisted in 2, and was not tested in 10. Only 15 recipients (0.08%) produced new anti-M after transfusion. CONCLUSION: Naturally occurring anti-M is a phenomenon of younger ages, predominantly between 1 and 3 years. After transfusion, it often falls to undetectable levels.

Effect of Cytokine Gene Polymorphisms on Eltrombopag Reactivity in Japanese Patients with Immune Thrombocytopenia.

BACKGROUND: Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by low platelet counts resulting from antiplatelet autoantibodies. Analysis of polymorphisms in cytokine-encoding genes is important for understanding the pathophysiology of ITP and selecting appropriate treatments. We investigated associations between polymorphisms in cytokine-encoding genes and responses to therapy in Japanese patients with ITP. METHODS: The participants in this study comprised 153 patients with ITP and 70 healthy controls. We extracted data on sex, age, platelet counts, bleeding symptoms, and therapeutic responses, including those to prednisolone (PSL) and eltrombopag. Genomic DNA was isolated from peripheral blood and polymorphisms in TNF-α, IL-10, TGF-ß1, and IFN-γ genes were analyzed using the PCR-SSP method. RESULTS: Our results showed that the TGF-ß1 +869 C/C genotype might be related to ITP in Japanese patients. The IL-10 -592 C/C and A/A, -819 C/C and T/T, and -1082, -819, -592 ATA/ATA genotypes might be associated with reactivity to PSL. Furthermore, the IL-10 -592 C/A -819 C/T genotypes, IL-10 ACC/ATA genotype, and TGF-ß1 +869 T/T and T/C genotypes might be linked to the response to eltrombopag. CONCLUSION: Our results indicate that analysis of polymorphisms in cytokine-encoding genes could aid in understanding PSL and eltrombopag responsiveness in Japanese patients with ITP.

Analysis of HLA haplotype and clinical factors during hematopoietic stem cell transplantation.

BACKGROUND: The human leukocyte antigen (HLA) haplotype of the recipient in hematopoietic stem cell transplantation (HSCT) is a key factor in its success or failure. We analyzed the relationship between HLA haplotype frequency and associated clinical factors in HSCT patients. METHODS: Patients who underwent allogeneic HSCT between 2000 and 2019 at our institution were enrolled in this study. The HSCT composition was 77 bone marrow transplantations (BMT), 38 peripheral blood stem cell transplantations (PBSCT), and 36 cord blood transplantations (CBT). Patients were classified into three groups according to their donor HLA haplotype frequency in the Japan Population: group A, top 1-10 haplotypes; group B, top 11-100 haplotypes; and group C, haplotype 101-. We then compared various items including clinical biomarkers with the HLA haplotype frequency. RESULTS: A significant negative correlation was identified between older persons and length of survival. There are also significant correlations between survival and levels of immunoglobulin G, D-dimer, and C-reactive protein, as well as the platelet-large cell ratio before transplantation. A total of 96, 30, and 25 patients were classified into groups A, B, and C, respectively. The HSCT match rate was significantly higher in group A patients than in those of groups B and C. In contrast, the death rate, D-dimer level, and length of time for engraftment were significantly higher in group B and C patients than in those of group A. CONCLUSION: An assessment of transplant-related complications is important in improving the performance of HSCT. The present data suggest that a special therapeutic strategy is necessary for HSCT using low-frequency HLA haplotypes.

A Japanese multi-institutional collaborative study of antigen-positive red blood cell (RBC) transfusions in patients with corresponding RBC antibodies.

BACKGROUND AND OBJECTIVES: It is sometimes difficult to obtain antigen-negative red blood cells (RBCs) for patients with antibodies against RBCs. However, the frequency and severity of the adverse reactions have not been well elucidated. Here, we conducted a multi-institutional collaborative study to clarify the background, frequency and clinical significance of antigen-positive RBC transfusions to patients with the respective antibodies. MATERIALS AND METHODS: The survey included the background of patients, antigens on RBCs transfused, total amount of antigen-positive RBCs transfused, results from antibody screen and direct antiglobulin tests, specificity of antibodies, adverse reactions and efficacies. All antibodies were surveyed regardless of their clinical significance. RESULTS: In all, 826 cases containing 878 antibodies were registered from 45 institutions. The main reasons for antigen-positive RBC transfusions included 'negative by indirect antiglobulin test' (39%) and 'detection of warm autoantibodies' (25%). In 23 cases (3% of total), some adverse reactions were observed after antigen-positive RBC transfusion, and 25 antibodies (9 of 119 clinically significant and 16 of 646 insignificant antibodies) were detected. Non-specific warm autoantibodies were detected in 9 cases, anti-E in 5 cases, 2 cases each of anti-Lea , anti-Jra or cold alloantibodies, and 1 case each of anti-Dib , anti-Leb or anti-P1. Other antibodies were detected in 2 further cases. Five (22%) of these 23 cases, who had anti-E (3 cases) or anti-Jra (2 cases), experienced clinically apparent haemolysis. CONCLUSIONS: Adverse reactions, especially haemolysis, were more frequently observed in cases with clinically significant antibodies than those with clinically insignificant antibodies (P < 0·001).

[Compliance with FOLFOX4 for Stage III colon cancer in the adjuvant setting].

AIMS: The usefulness of oxaliplatin(L-OHP)as adjuvant chemotherapy for Stage III colon cancer has been shown in clinical trials, such as the MOSAIC trial. The Leucovorin, fluorouracil, and oxaliplatin(FOLFOX)regimen has been recommended as adjuvant chemotherapy for colorectal cancer in Japan. In the MOSAIC trial, 74.7% of patients completed all planned treatment cycles. Neurological toxicity caused byL -OHP is one of the factors for discontinuing treatment. Therefore, we planned to administer FOLFOX4 as postoperative adjuvant chemotherapy and evaluated the safety and feasibility of this regimen. METHODS: From November 2009, 13 patients with Stage III colon cancer who had undergone complete resection of a primary tumor were enrolled. Patients received 4 cycles of FOLFOX4, followed by 4 cycles of the simplified fluorouracil and Leucovorin (LV5FU2)regimen and 4 additional cycles of FOLFOX4(12 cycles in total). RESULTS: Thirteen patients were treated with our FOLFOX4 regimen. In total, 11 patients(84.6%)completed all 12 planned treatment cycles. The median L-OHP dose per patient was 560mg/m / 2(compared with the per-protocol 12-cycle dose of 680 mg/m2). Grade 1 neurological toxicity during treatment was reported in 10 patients(76.9%). Neurological toxicity was reduced during the 4 cycles without L-OHP. CONCLUSION: Our FOLFOX4 regimen showed reduced neurological toxicity compared to other trials and can be used safely.