Mobilized peripheral blood stem cell apheresis via Hickman catheter in pediatric patients

Abstract

BACKGROUND Autologous stem cell transplantation remains an integral treatment tool for certain childhood malignancies. In children, a central venous catheter is typically necessary to provide adequate flow rates for preparative apheresis. In this study, the feasibility and efficiency of collecting CD34+ cells via an indwelling Hickman catheter, preimplanted for chemotherapy, instead of placing an additional temporary central venous catheter was evaluated. STUDY DESIGN AND METHODS Forty‐eight pediatric leukaphereses for autologous hematopoietic stem cell transplantation using Spectra Optia MNC, Version 3.0 were reviewed. We compared preimplanted Hickman catheters with a temporary Shaldon catheter, inserted for apheresis. Apheresis was considered successful if a dose of 2 × 106 CD34+ peripheral blood stem cells/kg BW was achieved. RESULTS In 43 (89.6%) of the 48 patients, a Hickman catheter was used for leukapheresis. Only 5 patients (10.4%) received a temporary Shaldon catheter. In both groups, apheresis was performed without apparent adverse reactions. The dose of collected CD34+ peripheral blood stem cells was 12.7 × 106 (range, 2.3–70.7 × 106) cells/kg BW in the Hickman group and 16.2 × 106 (range, 3.8–48.4 × 106) cells/kg BW in the Shaldon group, showing no statistically significant difference (p = 0.58). In both groups, the primary endpoint of a minimal CD34+ cell concentration of 2 × 106 cells/kg BW was achieved at a maximum of two leukapheresis sessions. Apheresis efficacy was further confirmed by the collection efficiency of 40.2% in the Hickman group and 27.8% in the Shaldon group (p = 0.32). CONCLUSION These data indicate the reliable feasibility and efficacy of mobilized apheresis via an indwelling Hickman catheter. In light of this, the routine insertion of a dialysis catheter for the purpose of leukapheresis should be critically reconsidered.

Unstimulated apheresis for chimeric antigen receptor manufacturing in pediatric/adolescent acute lymphoblastic leukemia patients

“…Aphereses for CAR-T manufacturing in general were tolerated without severe or unexpected adverse effects. 22,[33][34][35] Tolerability of apheresis in our cohort was not unexpected, since both small children 12,15 and very sick and similarly pancytopenic as the patients here, namely patients with chronic graft-vs-host disease, routinely undergo uneventful leukaphereses at our center. Other centers report similar observations.…”

“…Specifically, we worked with a collection efficiency (CE2) of 40%, since we empirically established that at least 90% of leukaphereses will achieve a CE2 of 40% or greater (see below). Demonstration of feasibility and effectiveness 15 [27][28][29] Two apheresis systems were used, the continuous collection mode "Spectra Optia cMNC" and the intermittent collection mode "Spectra Optia MNC." We use the term "apheresis system" to encompass the totality of the respective software, filler, and tubing system.…”

“…10,11 As many groups including ourselves have shown, with some modifications apheresis can be successfully performed even in very small children. [10][11][12][13][14][15][16][17][18][19][20][21][22] The expectation, therefore, that unstimulated mononuclear cell (MNC) apheresis in children to generate a starting material for chimeric antigen receptor (CAR)-manufacturing should not only be feasible, but also safe and effective, seems at first glance reasonable yet is currently supported by a relatively small number of publications. 10,[23][24][25] Importantly, with the market authorization of Tisagenlecleucel, weight-adjusted WBC and T-cell apheresis target doses, as had been applied during the clinical trials, were abandoned.…”

A high-throughput microfluidic device based on controlled incremental filtration to enable centrifugation-free, low extracorporeal volume leukapheresis

“…The flow rate at which the CIF device operated with peak separation performance in our study (10 mL/min) is similar to clinical leukapheresis procedures, which are typically performed at 10–50 mL/min 1 , 17 , 54 . The observed decline in the separation efficiency at higher flow rates was likely due to the deformation (bulging) of the device channels at higher driving pressures, as we previously observed for similar devices 46 .…”

Peripheral blood stem and progenitor cell collection in pediatric candidates for ex vivo gene therapy: a 10-year series

“…Previous experience with mobilization was reported in healthy pediatric donors for allogeneic transplantation or autologous HSPC transplantation for malignancies. 9,12,[21][22][23] Our analysis focuses on a large cohort of pediatric subjects with nonmalignant diseases with various comorbidities related to the underlying disorder and include also infants <1 year of age and weighing less than 10 kg.…”