Safety of hypoxic red blood cell administration in patients with transfusion-dependent hematological malignancies: An interim analysis.

Anemia is a common symptom of hematological malignancies and red blood cell (RBC) transfusion is the primary supportive treatment, with many patients becoming transfusion dependent. Hemanext Inc. (Lexington, MA, United States) has developed a CE mark certified device to process and store RBCs hypoxically - citrate-phosphatedextrose (CPD)/phosphate-adenine-glucose-guanosine-saline-mannitol (PAGGSM) RBCs, leukocytes-reduced (LR), O2/CO2 reduced - with the aim of improving RBC quality for transfusion. This interim analysis describes the first patients to receive hypoxic RBCs, administered as part of a pilot post-marketing study in Norway. The primary outcome was adverse events (AEs) within 24 h of transfusion initiation and overall up to 7 days ( ± 1 day) post-transfusion. Secondary outcomes included changes in hemoglobin levels post-transfusion. Five patients with hematological malignancies were included (80 % male, mean age 69.8 [SD ± 19.3] years). Prior to the study, patients had been receiving conventional RBC transfusions every two weeks. Patients received 2 units of hypoxic RBCs over 2 h without complication. One mild AE (rhinovirus) was reported two days post-treatment and was deemed unrelated to treatment. The mean ± SD pre-transfusion hemoglobin level was 7.7 ± 0.5 g/dL, evolving to 9.0 ± 0.9 g/dL following administration of hypoxic RBCs; an increase of 17 %. This interim analysis showed that transfusion with hypoxic RBCs processed with the CPD/PAGGSM LR, O2/CO2 reduced system was effective and well tolerated in patients with hematologic malignancies. The overall clinical program will assess whether the use of hypoxic RBCs can reduce transfusion interval versus conventional RBCs in patients requiring acute and chronic transfusions.

HLA class I depletion by citric acid, and irradiation of apheresis platelets for transfusion of refractory patients.

BACKGROUND: Patients can form antibodies to foreign human leukocyte antigen (HLA) Class I antigens after exposure to allogeneic cells. These anti-HLA class I antibodies can bind transfused platelets (PLTs) and mediate their destruction, thus leading to PLT refractoriness. Patients with PLT refractoriness need HLA-matched PLTs, which require expensive HLA typing of donors, antibody analyses of patient sera and/or crossmatching. An alternative approach is to reduce PLT HLA Class I expression using a brief incubation in citric acid on ice at low pH. METHODS AND MATERIALS: Apheresis PLT concentrates were depleted of HLA Class I complexes by 5 minutes incubation in ice-cold citric acid, at pH 3.0. Surface expression of HLA Class I complexes, CD62P, CD63, phosphatidylserine, and complement factor C3c was analyzed by flow cytometry. PLT functionality was tested by thromboelastography (TEG). RESULTS: Acid treatment reduced the expression of HLA Class I complexes by 71% and potential for C3c binding by 11.5-fold compared to untreated PLTs. Acid-treated PLTs were significantly more activated than untreated PLTs, but irrespective of this increase in steady-state activation, CD62P and CD63 were strongly upregulated on both acid-treated and untreated PLTs after stimulation with thrombin receptor agonist peptide. Acid treatment did not induce apoptosis over time. X-ray irradiation did not significantly influence the expression of HLA Class I complexes, CD62P, CD63, and TEG variables on acid treated PLTs. CONCLUSION: The relatively simple acid stripping method can be used with irradiated apheresis PLTs and may prevent transfusion-associated HLA sensitization and overcome PLT refractoriness.

Evaluation of platelet activation and cytokine release during storage of platelet concentrates processed from buffy coats either manually or by the automated OrbiSac system.

BACKGROUND: This study aimed to compare platelet (PLT) quality during storage of buffy coat (BC) PLT concentrates (PCs), prepared either manually or by the automated OrbiSac system (Gambro BCT). STUDY DESIGN AND METHODS: Following overnight storage at 20 to 22 degrees C, five BCs were pooled with 300 mL of PLT additive solution. Twenty-one PCs were produced manually (M-PCs) and 21 by the automated OrbiSac system (A-PCs). Swirling, PLT count, mean PLT volume, blood gas analyses, potassium, glucose, and lactate were assessed. Expression of the activation markers CD42a, CD62P, and PAC-1 was analyzed by flow cytometry on resting PLTs and PLTs stimulated with thrombin receptor agonist peptide (TRAP). Levels of CCL5 and transforming growth factor-beta1 (TGF-beta1) were measured by enzyme-linked immunosorbent assay. RESULTS: The A-PCs had significantly larger volume and higher PLT yield, PLT recovery, and white blood cell concentration than the M-PCs, whereas the red blood cell content was significantly highest in the M-PCs. pH levels were between 6.9 and 7.2 in all PCs. Neither glucose consumption nor lactate production differed significantly over time. A-PCs had, compared to M-PCs, significantly higher expression of CD62P on resting PLTs, lower capacity for up regulating CD62P on TRAP-stimulated PLTs, and higher levels of CCL5 during storage. TRAP-stimulated A-PCs had a significantly higher potential for down regulation of CD42a than M-PCs. No difference was found in TGF-beta1 levels or TRAP-induced up regulation of PAC-1. CONCLUSION: The levels of CCL5 and the expression of CD62P in resting and stimulated PLTs indicate that PLTs in A-PCs are slightly more activated than in M-PCs, but the clinical importance of this finding is yet unknown.