Impact of the use of hydroxyethyl starch in granulocyte apheresis using Spectra Optia.

OBJECTIVES: To determine the impact of the use of hydroxyethyl starch (HES) in granulocyte apheresis using Spectra Optia. BACKGROUND: Granulocyte transfusion (GT) is a therapeutic option for neutropenic patients with severe bacterial or fungal infections. Recent studies in emergency medicine have shown the potential risk of using HES, which is routinely used in granulocyte apheresis to increase yield by sedimenting red blood cells. We hypothesized that the use of a newer device (Spectra Optia) would spare the need for HES. METHODS: We retrospectively compared granulocyte apheresis with HES (HES group, n = 89) and without HES (non-HES group, n = 36) using Spectra Optia. RESULTS: The granulocyte yield was significantly higher in the HES group (7.3 × 1010 vs. 2.0 × 10, p < 0.01) and was attributed to the difference in collection efficiency (36% vs. 7.7%, p < 0.01). The absolute neutrophil count on the following morning of GT was significantly higher in the HES group than in the non-HES group (2460/µl vs. 505/µl, p < 0.01). There were no significant differences in the occurrence of adverse events between the HES and non-HES groups. The renal function was unchanged in both groups after apheresis. CONCLUSIONS: We demonstrated that the advantage of using HES remained unchanged in granulocyte apheresis using Spectra Optia.

[Clinical experience of leukapheresis for CD19 CAR-T cell therapy].

To perform chimeric antigen receptor T (CAR-T) cell therapy in heavily pretreated patients with progressive disease and depleted lymphocytes, an optimized leukapheresis protocol must be established. To probe the effects of patient-related parameters on the collection efficiency of CD3+ cells, we retrospectively analyzed patients with relapsed/refractory diffuse large B-cell lymphoma who underwent leukapheresis for tisagenlecleucel at two centers. A total of 51 patients were analyzed, with a median age at apheresis of 59 years, and precollection hemoglobin levels, CD3+ cell counts, and platelet counts of 9.2 g/dl, 574/µl, and 15.8×104/µl, respectively. A median of 3.0×109 (0.7-8.4) CD3+ cells were harvested with 8.7 (4.0-15.7) l apheresis volume. The collection efficiency 2 (CE2) for CD3+ cells was 61.0% (21.0-127.3). One-day apheresis was sufficient to obtain the designated cell numbers in all cases. Lower hemoglobin levels, higher CD3+ cell counts, and higher platelet counts before apheresis were significantly associated with lower CE2 for CD3+ cells. These results suggest a need to increase the apheresis volume in anemic, lymphocyte- or platelet-rich patients due to an expected low CE2. Erythrocyte transfusions before or during apheresis may be a reasonable option for patients with anemia.

A Clinically Applicable Prediction Model to Improve T Cell Collection in Chimeric Antigen Receptor T Cell Therapy.

As chimeric antigen receptor (CAR) T cell therapy targeting CD19 has shown favorable outcomes in patients with relapsed or refractory (r/r) mature B cell lymphomas and B cell acute lymphoblastic leukemia (B-ALL), an increasing number of patients are waiting to receive these treatments. Optimized protocols for T cell collection by lymphapheresis for chimeric antigen receptor (CAR) T cell therapy are urgently needed to provide CAR T cell therapy for patients with refractory and progressive disease and/or a low number of lymphocytes owing to prior chemotherapy. The predicted efficiency of CD3+ cell collection in apheresis can guide protocols for apheresis, but a clinically applicable model to produce reliable estimates has not yet been established. In this study, we prospectively analyzed 108 lymphapheresis procedures for tisagenlecleucel therapy at 2 centers. The apheresis procedures included 20 procedures in patients with B cell acute lymphoblastic leukemia and 88 procedures in patients with diffuse large B cell lymphoma, with a median age at apheresis of 58 years (range, 1 to 71 years). After lymphapheresis with a median processing blood volume of 10 L (range, 3 to 16 L), a median of 3.2 × 109 CD3+ cells (range, .1 to 15.0 × 109 cells) were harvested. Collection efficiency 2 (CE2) for CD3+ cells was highly variable (median, 59.3%; range, 11.0% to 199.8%). Multivariate analyses revealed that lower hemoglobin levels, higher circulating CD3+ cell counts, and higher platelet counts before apheresis significantly decreased apheresis CE2. Based on multivariate analyses, we developed a novel formula that estimates CE2 from precollection parameters with high accuracy (r = .56; P < .01), which also suggests the necessary processing blood volume. Our strategy for lymphapheresis should help reduce collection failure, as well as achieve efficient utilization of medical resources in clinical practice, thereby allowing delivery of CAR T cell therapy to more patients in a timely manner.