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BackgroundThe first step in manufacturing chimeric antigen receptor (CAR) T cells is to collect autologous CD3+ lymphocytes by apheresis. Patients, however, often have leukopenia or have other disease-related complications. We evaluated the feasibility of collecting adequate numbers of CD3+ cells, risk factors for inadequate collections, and the rate of adverse events.Study design and methodsApheresis lymphocyte collections from patients participating in three CAR T-cell clinical trials were reviewed. Collections were performed on the COBE Spectra by experienced nurses, with the goal of obtaining a minimum of 0.6 × 109 and a target of 2 × 109 CD3+ cells. Preapheresis peripheral blood counts, apheresis parameters, and product cell counts were analyzed.ResultsOf the 71 collections, 69 (97%) achieved the minimum and 55 (77%) achieved the target. Before apheresis, the 16 patients with yields below the target had significantly lower proportions and absolute numbers of circulating lymphocytes and CD3+ lymphocytes and higher proportions of circulating blasts and NK cells than those who achieved the target (470 × 106 lymphocytes/L vs. 1340 × 106 lymphocytes/L, p = 0.008; 349 × 106 CD3+ cells/L vs. 914 × 106 CD3+ cells/L, p = 0.001; 17.6% blasts vs. 4.55% blasts, p = 0.029). Enrichment of blasts in the product compared to the peripheral blood occurred in four patients, including the two patients whose collections did not yield the minimum number of CD3+ cells. Apheresis complications occurred in 11 patients (15%) and, with one exception, were easily managed in the apheresis clinic.ConclusionsIn most patients undergoing CAR T-cell therapy, leukapheresis is well tolerated, and adequate numbers of CD3+ lymphocytes are collected.

A substantial proportion of people infected with the hepatitis C virus (HCV) probably contracted the virus from exposure to infected blood. Among 248 blood donors who tested positive for HCV by two different tests, 27% had a history of blood transfusion, 68% snorted cocaine, 42% were intravenous drug addicts and 53% were sexually promiscuous. Sixty-nine percent had evidence of liver disease, but only 5 had severe liver disease. Nine of the sex partners of the HCV-positive donors were also HCV-positive but only one had no other risk factors.

Idiopathic membranous nephropathy is the most common cause of nephrotic syndrome in nondiabetic adults. The antibody most often implicated is the M‐type phospholipase A2 receptor (PLA2R) antibody, found in >70% of primary membranous nephropathy cases. First‐line therapy is immunosuppressive in nature, but for patients who are treatment‐resistant there is a significant risk of end‐stage renal disease and mortality. Hypercholesterolemia is not only a side effect of nephrotic syndrome, but also its presence may worsen renal function. A recent single‐arm observational study in Japan found that low‐density lipoprotein apheresis (LDL‐A) was able to ameliorate nephrotic syndrome in half of patients who were resistant to medication. We present a case of treatment resistant PLA2R negative membranous nephropathy who had significant improvement following two courses of LDL‐A. To our knowledge, this is the first such reported case in the United States. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions/Summary Pathogen reduction (PR) may be used as an alternative to gamma or x‐ray irradiation (I) to prevent transfusion associated graft versus host disease (TA‐GVHD) if the pathogen reduction technology has been shown to inactivate residual lymphocytes. However, as I is considered the gold standard for reducing the risk of TA‐GVHD, some centers continue to perform I in addition to PR. This study investigated the effect of concurrent pathogen reduction and irradiation (PR/I) on the biochemical characteristics of apheresis platelets at day 1, 5, and 7 of storage at room temperature.We compared in vitro characteristics of apheresis platelets (PLTs), PR PLTs, I PLTs, and PR/I PLTs at storage day 1, 5, and 7. PLTs from six healthy volunteers were suspended in 65% PAS‐3/35% plasma prior to splitting and treatment with PR, I, or PR/I. Parameters measured were: PLT loss, mean PLT volume (MPV), pH, glucose consumption, lactate production, CD62P, annexin V binding, PLT aggregation, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS).PR/I PLTs did not show significant changes in measured parameters when compared to PR PLTs. However, when compared to control PLTs, PR and PR/I PLTs showed significant declines in PLT content, pH, MMP, aggregation and significant increases in MPV, CD62P, annexin V binding, and ROS production, mostly on day 7 of storage. Irradiation did not cause significant changes in measured parameters in comparison to control PLTs.While PR impacts PLTs' biochemical characteristics and function, irradiation of PR PLTs did not cause additional significant changes. [ABSTRACT FROM AUTHOR]

Presents an analysis of hepatitis G virus (HGV) RNA, antibody to HGV envelope protein and risk factors for blood donors coinfected with HGV and hepatitis C virus (HCV). Enrollment of donors, initial evaluation and follow-up; Detection of HCV markers; Measurement of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and other biochemical markers; Detection of serum HGV RNA by nonradioisotopic for polymerase chain reaction (PCR).

Patients with severe aplastic anemia (SAA) are at high risk of morbidity and mortality due to severe infections. We aimed to characterize the role of granulocyte transfusions (GT) in SAA. Primary outcomes were survival after the first GT, including overall survival (OS) at last follow up, survival to discharge, and receipt of a hematopoietic stem cell transplant (HSCT) Secondary outcomes included evaluation of clinical response at 7 and 30 days after initiation of GT, using a clinical scoring system incorporating microbiological and radiographic response. Twenty-eight SAA patients underwent 30 GT courses with a per-dose median of 1.28x109 granulocytes/kilogram (range, 0.45-4.52x109). OS from initial GT to median last follow up (551 days) was 50%, with 39% (11/28) alive at last follow up. Sixty-four percent (18/28) of all patients survived to hospital discharge. Patients with a complete or partial response, or stable infection, at 30 days had significantly better OS compared to non-responders (P=0.0004). Eighty-six percent (18/21) of patients awaiting HSCT during GT underwent a transplant and 62% (13/21) survived to post-HSCT discharge. Sex, type of infection, and percentage of days with absolute neutrophil count >0.2x109/L during the course of GT were not predictive of survival (P=0.52, P=0.7 and P=0.28, respectively). Nine of 28 (32%) patients developed new or increased human leukocyte antigen alloimmunization during their GT course. GT in SAA may have an impact on survival in those patients with improvement or stabilization of their underlying infection. Alloimmunization can occur and OS in this population remains poor, but GT may be a useful tool to bridge patients to curative treatment with HSCT.