Treatment for pure red cell aplasia after major ABO-incompatible allogeneic stem cell transplantation: a multicentre study.

Pure red cell aplasia (PRCA) following allogeneic haematopoietic stem cell transplantation (aHSCT) with major ABO incompatibility is responsible for transfusion dependent anaemia, impaired quality of life and iron overload. We conducted a retrospective study, over a 10-year period, which included all consecutive patients who received a major ABO mismatched aHSCT, to assess the impact of specific treatment on PRCA. We did not observe any PRCA in the 57 aHSCT issued from cord blood. Among the remaining 631 patients, cumulative incidence of PRCA was 10·5% [range 8·2-13.0]. The median duration of resolved PRCA was 171 days [IQR 116; 261]. Pre-transplant high isohaemagglutinins titre was associated with an increased risk of PRCA (P < 10-4 ). PRCA did not affect overall survival (P = 0·95). Twenty-two patients (33·3%) received at least one specific treatment. The most commonly used treatments were rituximab (17 patients) and donor lymphocyte infusion (DLI; seven patients). Regarding PRCA resolution, we did not observe a significant difference between treated or untreated subjects (HR = 0·93, 95% confidence interval (CI) 0·48- 1·80; P = 0·82). Similar results were observed with erythropoietin treatment (22 patients, HR = 0·86 95% CI: [0·47-1·57] P = 0·62). Our data do not support the use of erythropoietin, rituximab or DLI for the treatment of PRCA.

Chronic Granulomatous Disease with the McLeod Phenotype: a French National Retrospective Case Series.

BACKGROUND: X-linked chronic granulomatous disease (CGD) is a primary immunodeficiency caused by mutations in the CYBB gene (located on Xp21.1). Patients with large deletions on chromosome Xp21.1 can present with the McLeod phenotype and also Duchenne muscular dystrophy or retinitis pigmentosa. The objective of the present study was to describe a series of French patients with CGD and the McLeod phenotype. METHODS: We retrospectively collected data from the medical records of 8 patients with CGD and the McLeod phenotype registered at the French National Reference Center for blood types. RESULTS: The median age at diagnosis of CGD was 1.2 years, the median age at diagnosis of the McLeod phenotype was 4.5 years, and the median length of follow-up was 15.2 years. Four patients displayed allo-immunization, with anti-KEL20 and anti-XK1 (formerly known as anti-KL) antibodies. Five of the 6 patients with available blood smears had acanthocytosis. Neuropsychiatric, muscle-related, and ocular manifestations were present in 4, 2, and 1 of the patients, respectively. Three of the 4 patients having undergone allogeneic hematopoietic stem cell transplantation (HSCT) are alive. Overall, 5 patients are alive, and 3 are alive and well. CONCLUSION: This is the largest yet descriptive study of a series of patients with X-linked CGD and the McLeod phenotype. Although this disease combination is rare, the timely, accurate diagnosis of the McLeod phenotype is critical because of the serious post-transfusion complications. However, HSCT can be considered in these patients.

Prevalence and risk factors for red blood cell alloimmunization in 175 children with sickle cell disease in a French university hospital reference centre.

Patients with sickle cell disease (SCD) show a high prevalence of red blood cell (RBC) alloimmunization, but few studies have focused on children. We aimed to study the prevalence and risk factors of RBC alloimmunization in SCD children. We retrospectively analysed the medical and transfusion files for 245 SCD children hospitalized in our centre in 2014 and included 175 patients who had received at least one RBC unit in their lifetime. The main clinical and immuno-haematological characteristics of alloimmunized and non-alloimmunized patients were compared. The prevalence of alloimmunization was 13·7% [95% confidence interval (CI) (8·6-18·6)], and 7·4% [95% CI (3·5-11·3)] after excluding the probable irregular natural antibodies (anti-M, anti-Lea , anti-Leb , anti-Lex ). Main risk factors for alloimmunization were increased number of RBC units received (median of 65 vs. 10 units per patient; P = 0·01) and the presence of one or more red cell autoantibodies (46·2% vs. 4·7%; P < 0·0001). The alloimmunization rate was higher for episodically transfused than chronically transfused patients (1·43 vs. 0·24/100 units received; P < 0·001). The presence of red cell autoantibodies appears to be a major risk factor for alloimmunization in SCD children and could justify specific transfusion guidelines.

Defective anti-polysaccharide response and splenic marginal zone disorganization in ALPS patients.

Autoimmune lymphoproliferative syndrome (ALPS) caused by impaired FAS-mediated apoptosis of lymphocytes is characterized by lymphoproliferation, autoimmunity, but also an increased risk of invasive bacterial infection, notably following splenectomy. We surveyed a cohort of 100 ALPS patients (including 33 splenectomized) and found that 12 (10 splenectomized) had experienced 23 invasive bacterial infections mainly caused by Streptococcus pneumoniae. This vulnerability was associated with evidence of defective B-cell function characterized by low serum immunoglobulin (Ig) M, low IgM antibody production in response to S pneumoniae following nonconjugated immunization, and low blood memory B-cells counts (including marginal zone [MZ] B-cell counts). This immunodeficiency strongly correlated with intensity of lymphoproliferation. Spleen sections from 9 ALPS patients revealed double-negative T-cell (DN-T) infiltration of the MZ, which was depleted of B cells. MZ in ALPS patients contained an abnormally thick layer of MAdCAM-1((+)) stromal cells and an excess of DN-Ts. DN-Ts were shown to express MAdCAM-1 ligand, the α4ß7 integrin. These observations suggest that accumulating DN-Ts are trapped within stromal cell meshwork and interfere with correct localization of MZ B cells. Similar observations were made in spleens of fas-deficient mice. Our data revealed an unexpected mechanism by which ALPS results in anti-polysaccharide IgM antibody production-specific defect. Splenectomy should be avoided.

Blood group genotyping by high-throughput DNA analysis applied to 356 reagent red blood cell samples.

BACKGROUND: DNA analysis for the prediction of blood group antigen expression has broad implications in transfusion medicine. It may be of particular interest especially to detect variants, when antigen expression is weak or altered. The use of high-throughput DNA analysis has never been applied to donors whose red blood cells (RBCs) are selected for reagent RBCs. The aim of this study was to analyze the concordance between the serologic phenotype and that predicted from DNA analysis in panel donors, to determine the benefit of the use of DNA analysis in reagent RBC selection strategy. STUDY DESIGN AND METHODS: The "Panel National de Référence du Centre National de Référence sur les Groupes Sanguins" is a reference reagent mainly used for antibody identification. DNA genotyping of 356 panel donors was performed with BeadChips (human erythrocyte antigen v1.2 BeadChips, BioArray Solutions). The comparison between serologic phenotype and that predicted from DNA analysis held on 8876 paired results obtained from 10 blood group systems and 25 antigens. RESULTS: A 99.95% concordance was observed. Discrepancies in four cases (RH, KEL, LU, and DO systems) were analyzed. Genotyping precisions on the Duffy system were of particular interest. No new rare blood group was observed. CONCLUSION: Systematic DNA analysis of panel donors should unquestionably change the management of reagent RBC selection. The notion of "antigens in double dose" should evolve regarding data obtained from DNA analysis, allowing an improved quality of reagent RBCs for antibody screening and identification.