Ross M. Fasano

Red blood cell alloimmunization is influenced by recipient inflammatory state at time of transfusion in patients with sickle cell disease.

Sickle cell disease (SCD) patients are at increased risk of red blood cell (RBC) alloimmunization. Recipient inflammatory state at time of transfusion has been shown to regulate alloimmunization in murine models, but evidence is lacking in SCD patients. We retrospectively studied a cohort of alloimmunized SCD patients to determine the influence of pro‐inflammatory SCD‐related complications at time of transfusion on alloimmunization. For each transfusion, the presence of pro‐inflammatory state, degree of RBC antigen matching, unit age, storage solution and alloantibody detection date were ascertained. Transfusion‐associated pro‐inflammatory events were compared between transfusions resulting and not resulting in new alloantibodies. Univariate analysis and multivariate logistic regression were performed. Fifty‐two patients received 3166 pre‐storage leuco‐reduced transfusions of which 128 resulted in alloantibodies. Transfusions during inflammatory events were associated with increased alloantibody risk on univariate and multivariate analysis; acute chest syndrome and vaso‐occlusive crisis showed strongest associations with alloimmunization. Increased antigen matching demonstrated a protective effect on alloimmunization (univariate and multivariate analysis). Although an association was seen between citrate‐phosphate‐dextrose (adenine) stored units and alloimmunization on univariate analysis, no effect was found on multivariate analysis. Identifying recipient pro‐inflammatory states at time of transfusion that promote alloimmunization can impact RBC unit selection decisions for SCD patients at risk for alloimmunization.

Blood component therapy.

Blood component transfusion is integral in the treatment of infants and children by pediatricians, surgeons, intensivists, and hematologists/oncologists. Technologic advances in blood collection, separation, anticoagulation, and preservation have resulted in component preparation of red blood cells, platelets, white blood cells, and plasma, which are superior to whole blood used in the past. Advances in donor selection, infectious disease testing, leukoreduction filters, and gamma irradiation have made products safer. Physicians prescribing blood components should have a basic understanding of indications (and contraindications) and be cognizant of methods of preparation, proper storage conditions, and requirements for modification of blood products to prevent potential adverse effects.

Severe Vaso-Occlusive Episodes Associated with Use of Systemic Corticosteroids in Patients with Sickle Cell Disease

Patients with sickle cell disease (SCD) are occasionally prescribed systemic corticosteroids to treat steroid-responsive conditions. Additionally, use of systemic corticosteroids for sickle cell pain episodes and acute chest syndrome is under investigation. We report 4 patients with SCD who developed severe vaso-occlusive events following the administration of systemic steroids. We also review similar cases from the literature and suggest measures for reducing the potential risk associated with use of systemic corticosteroids in this group of patients. We conclude that corticosteroids should be used with caution in patients with SCD.

Impact of red blood cell alloimmunization on sickle cell disease mortality: a case series.

Although red blood cell (RBC) transfusion represents an integral component of sickle cell disease (SCD) care, transfusion support for some patients can result in alloimmunization to RBC antigens. Alloimmunized patients with SCD appear to experience worse survival compared to nonalloimmunized patients. While this difference in mortality may in part be due to underlying immunologic differences related to disease severity, it may also reflect direct clinical consequences of RBC alloimmunization. Alloimmunized patients have an increased risk of serious hemolytic transfusion reactions (HTRs) and may not receive adequate RBC transfusion support due to lack of compatible RBC units.

HLA Associations with Nasopharyngeal Carcinoma

Several associations have been described between the frequency of human leukocyte antigen (HLA) class I genes in certain populations and the risk of developing nasopharyngeal carcinoma (NPC). Associations between ethnic background and geographic distribution, and relative disease incidence have been reported. Populations in geographical areas at higher risk of developing NPC display HLA distribution patterns different and sometimes opposite from areas of low incidence, whereas populations in areas with intermediate incidence display a totally independent pattern. Two main reasons may explain this association between HLA phenotype distribution and the risk of developing NPC in various populations. First, given the fact that expression of Epstein-Barr Virus (EBV) proteins by cancer cells is tightly linked with NPC development, HLA may influence the development of NPC by modulating the expression of EBV proteins. This explanation is, however, based primarily on theoretical assumptions given that no clear definition of HLA binding pattern of EBV epitopes has been directly shown to significantly alter the recognition of EBV proteins and the risk of developing the disease. Alternatively, HLA may represent a genetic marker flagging the presence of a NPC predisposition locus in close linkage disequilibrium with the HLA class I region. A critical review of known HLA associations in various geographical areas and their interpretation will be presented in this review.

Management of Patients with Sickle Cell Disease Using Transfusion Therapy: Guidelines and Complications

Red blood cell (RBC) transfusion therapy is a key component of comprehensive management of patients with sickle cell disease (SCD) and has increased over time as a means of primary and secondary stroke prevention. RBC transfusions also prove to be lifesaving for many acute sickle cell-related complications. Although episodic and chronic transfusion therapy has significantly improved the morbidity and mortality of patients with SCD, transfusions are not without adverse effects. This review addresses RBC transfusion methods, evidence-based and/or expert panel-based consensus on indications for chronic and episodic transfusion indications, and strategies to prevent and manage transfusion-related complications.

Accelerated lymphocyte reconstitution and long-term recovery after transplantation of lentiviral-transduced rhesus CD34+ cells mobilized by G-CSF and plerixafor.

OBJECTIVE Granulocyte colony-stimulating factor (G-CSF) in combination with plerixafor produces significant mobilization of CD34(+) cells in rhesus macaques. We sought to evaluate whether these CD34(+) cells can stably reconstitute blood cells with lentiviral gene marking. MATERIALS AND METHODS We performed hematopoietic stem cell transplantation using G-CSF and plerixafor-mobilized rhesus CD34(+) cells transduced with a lentiviral vector, and these data were compared with those of G-CSF and stem cell factor mobilization. RESULTS G-CSF and plerixafor mobilization resulted in CD34(+) cell yields that were twofold higher than yields with G-CSF and stem cell factor. CD123 (interleukin-3 receptor) expression was greater in G-CSF and plerixafor-mobilized CD34(+) cells when compared to G-CSF alone. Animals transplanted with G-CSF and plerixafor-mobilized cells showed engraftment of all lineages, similar to animals who received G-CSF and stem cell factor-mobilized grafts. Lymphocyte engraftment was accelerated in animals receiving the G-CSF and plerixafor-mobilized CD34(+) cells. One animal in the G-CSF and plerixafor group developed cold agglutinin-associated skin rash during the first 3 months of rapid lymphocyte recovery. One year after transplantation, all animals had 2% to 10% transgene expression in all blood cell lineages. CONCLUSIONS G-CSF and plerixafor-mobilized CD34(+) cells accelerate lymphocyte engraftment and contain hematopoietic stem cell capable of reconstituting multilineage blood cells. These findings indicate important differences to consider in plerixafor-based hematopoietic stem cell mobilization protocols in rhesus macaques.

Immunophenotypic parameters and RBC alloimmunization in children with sickle cell disease on chronic transfusion

Alloimmunization against red blood cell (RBC) antigens is a cause of morbidity and mortality in transfused patients with sickle cell disease (SCD). To investigate distinguishing characteristics of patients who develop RBC alloantibodies after transfusion (responders) versus those who do not (non‐responders), a cross‐sectional study of 90 children with SCD on chronic RBC transfusion therapy at a single institution was conducted in which 18 immune parameters (including T and B cell subsets) were tested via flow cytometry, and medical records were reviewed. RBC alloimmunization was present in 26/90 (29%) patients, with anti‐E, K, and C among the most commonly detected alloantibodies despite prophylactic matching for these antigens at the study institution. In addition, RBC autoantibodies had been detected in 18/26 (69%) of alloimmunized versus 7/64 (11%) of non‐alloimmunized patients (P < 0.0001). Alloimmunized patients were significantly older (median 13.0 years vs. 10.7 years, P = 0.010) and had more RBC unit exposures (median 148 U vs. 82 U, P = 0.020) than non‐alloimmunized patients. Sex, age at initiation of chronic transfusion, splenectomy, stroke, and transfusion outside of the study institution were not significantly associated with RBC alloimmunization. Alloimmunized patients had a significantly increased percentage of CD4+ T memory cells compared to non‐alloimmunized patients (57% vs. 49%, P = 0.0047), with no other significant differences in immune cell subsets or laboratory values detected between these groups. Additional research of RBC alloimmunization is needed to optimize transfusion therapy and to develop strategies to prevent alloimmunization. Am. J. Hematol. 90:1135–1141, 2015.

Daratumumab (anti-CD38) induces loss of CD38 on red blood cells

To the editor: The recently approved anti-CD38 monoclonal antibody daratumumab (DARA) provides a unique therapeutic strategy that more selectively targets plasma cells in patients with plasma cell myeloma.[1][1][⇓][2][⇓][3][⇓][4][⇓][5]-[6][6] While DARA recognizes and removes malignant

Cerebral vasculopathy in children with sickle cell anemia

Sickle cell anemia (SCA)-associated cerebral vasculopathy and moyamoya is a unique entity reflecting the abnormal interactions between sickled red blood cells (RBCs) and the cerebral arterial endothelium. Endothelial injury, coagulation activation, and the inflammatory response generated by sickled RBCs are implicated in the development of cerebral vasculopathy, but the pathophysiology remains incompletely understood. SCA-specific screening and treatment guidelines have successfully reduced the incidence of overt strokes in this high-risk population. However, despite aggressive hematological management, many children with cerebral vasculopathy due to SCA have progressive vasculopathy and recurrent strokes; therefore, more effective therapies, such as revascularization surgery and curative hematopoietic stem cell transplant, are urgently needed.