Initial Comparison Of 3 Apheresis Platforms For Supporting The .
Initial Comparison of 3 apheresis platforms for supporting the collection of CD3 cells for CAR-T production Watson D, Parrington J, Dowsing C, Harrison S, Evans A, Ross E, Smith N, Wall D ISCT, May 2016
Overview Cobe Spectra being “retired” Comparison of 3 different apheresis technologies (all Terumo platforms – two Optia; one Spectra) Collection of CD3 cells from steady state “healthy”/ “normal” donors Apheresis and cryopreservation at Peter MacCallum Cancer Centre, Melbourne 21 July 2016 Page 2
Terumo Apheresis systems Continuous flow Cell Separators Cobe Spectra – about to be retired! Optia MNC – dual stage, intermittent collection Optia cMNC 21 July 2016 Page 3
Literature Lisenko K et al, Journal of Clinical Apheresis 2016 epub Robitzsch JT et al, BMT 2015 Loaiza S et al, Transfusion & Apheresis Science 2013 Punzel M et al, BMT 2015: 50 (Supp 1)s348 Schulz M et al, Transfusion 2014: 54 (6) Del Fante et al, Transfusion 2013; 53(9) 2027 21 July 2016 Page 4
Method Ethics approval Panel of donors – medical and apheresis preassessment, screening and consent Mandatory IDM, biochemistry FBC & Flow (CD3 and subsets) on peripheral blood and product Assigned consecutively to Spectra, then Optia MNC, then Optia cMNC Initial processing target – 2 X TBV Data collected on Excel spreadsheet 21 July 2016 Page 5
Donor profile n 9 (male - 8; female - 1) Age range - median 40 - 45 TBV (range: 5537 - 7124mls) All used peripheral venous access All given calcium infusion (6 from start) 21 July 2016 Page 6
Collection summary Machine Median donor TBV (mls) Cobe Spectra Optia MNC Optia cMNC (n 3) (n 3) (n 3) 6180 (5510-7124) 6438 (5787-7008) 6124 (5537 -6766) Median run time (mins) Median TBV processed (mls) 210 (202 – 241) 259 (230 – 262) 227 (220 – 235) 12047 (11019 – 12355) 11050 (9911 – 12291) 11833 (11074 – 13533) Median TBV processed/ min (mls) Median BV ratio processed Median volume (apheresis bag) 54.6 (51.2 – 57.4) 46.9 (38.3 – 48.0) 53.8 (48.8 – 57.6) 21 July 2016 2.0 (1.7 – 2.0) 1.7 (1.7 – 1.8) 2.0 (1.9 – 2.0) 193 (181 – 205) 100 (64 – 100) 216 (181 – 228) Page 7
Key parameters Machine Cobe Spectra Optia MNC Median PB CD3 (106/ml) (range) 1.25 (0.80 – 1.34) 1.10 (0.70 – 1.5) 1.10 (1.0 – 1.11) Median TNC (range) x 109* 13.86 (12.87 – 22.62) 12.48 (11.80 – 17.20) Median CD3 (range) x 109* 8.04 (7.59 – 8.22) 3.50 (2.74 – 5.56) 7.80 (7.44 – 10.60) Median CE** 58 (58 – 76) 8.52 (6.30 – 10.14) 47 (27 – 59) Optia cMNC 76 (70 – 79) * Targets: TNC 7 x 109 (min 2 x 109); CD3 1 x 109 **cells collected (ml) x product volume (ml)/ CD3 pre-apheresis x vol processed 21 July 2016 Page 8
CD3 dose Total CD3 dose (109) 12 10 8 CD3 6 4 2 MNC cMNC 0 Machine 21 July 2016 Page 9 Spectra
Total TNC dose 9 (10 ) 25 Total TNC dose (109) 20 15 TNC dose 10 5 0 0 0.5 1 1.5 2 cMNC Machine 21 July 2016 Page 10 2.5 Spectra3 3.5
CD3 Collection Efficiency CD3 % CE 90 80 70 60 50 40 30 20 10 0 0 21 July 2016 0.5 1 1.5 2 Page 11 2.5 3 3.5
PB CD3 vs CD3 collected total CD3 10x9 total CD3 10x9 14 Linear (total CD3 10x9) 12 10 C D 3 8 6 4 2 0 0 21 July 2016 0.5 1 PB CD3 (10E6/ml) Page 12 1.5 2
PB WCC vs CD 3 collected total CD3 10x9 14 y 1.4307x - 2.5593 R² 0.5056 12 T 10 o t a 8 l C D total CD3 10x9 6 Linear (total CD3 10x9) 4 3 2 0 0 1 2 3 4 5 6 PB WCC x 10E9/ml 21 July 2016 Page 13 7 8 9 10
Summary cMNC significantly better than Optia MNC for collection efficiency (p 0.035) and total CD3 cells collected (p 0.011) Target of 2.5% Hct met for all Spectra and 2/3 cMNC collections All Optia MNC collections had Hct 2.5% Granulocyte contamination lower with cMNC cMNC quicker and more predictable 21 July 2016 Page 14
Conclusions Optia cMNC was quicker, more efficient and more predictable with a higher TBV processed minimised non- target cell collection compared to Optia MNC Intermittent collection of Optia MNC led to less certainty around both collection volumes & procedure durations Staff acceptance of cMNC – more “intuitive” Optia cMNC is the platform of choice to replace the Cobe Spectra for steady state MNC collections for CAR - T cell and other novel therapies 21 July 2016 Page 15
Considerations for CAR-T leukapheresis Donors vs. patients Venous access – peripheral vs. central Yield vs. purity Man (woman) vs. machine Uniformity vs. individualised treatment Data, sharing, presenting and publishing! 21 July 2016 Page 16
Acknowledgements Volunteers Apheresis Unit - Jack Parrington; Claire Dowsing; Annette Favorolo CT Cryo & processing – Alannah Evans; Elise Ross; Carmen Chong; Ayse Mouminoglu Lori Boren Simon Harrison Lunchtime tutorial – Friday 27th 1230hrs – Rm 335 21 July 2016 Page 17
LisenkoK et al, Journal of Clinical Apheresis 2016 epub RobitzschJT et al, BMT 2015 LoaizaS et al, Transfusion & Apheresis Science 2013 PunzelM et al, BMT 2015: 50 (Supp 1)s348 Schulz M et al, Transfusion 2014: 54 (6) Del Fanteet al, Transfusion 2013; 53(9) 2027 21 July 2016 Page 4
The decision to initiate therapeutic apheresis depends on multiple factors such as diagnosis and potential efficacy versus risk benefit ratio. The American Society for Apheresis (ASFA) publishes recommendations on the indications for therapeutic apheresis and uses categories from 1 to 4 depending on the evidence base and likely benefit. The 8th
99.79 Therapeutic apheresis, other 36522 Photopheresis, extracorporeal 99.88 Therapeutic photopheresis 38205 Blood-derived hematopoietic stem cell harvesting for transplantation, per collection; allogeneic 99.79 Apheresis (harvest) of stem cells 38206 autologous 99.79 Apheresis (harvest) of stem cells
Apheresis platelets are collected from a single donor by using an apheresis machine with an integrated leucoreduction system (removing 99% white cells). The machine draws blood from the donor, isolates the platelets and some plasma by centrifu
b) Donors may safely donate apheresis components without a prior whole blood donation. (Level B recommendation) However apheresis platelet donors should have a full set of mandatory infection screens performed at least 8 weeks prior to the first donation. 2.3 Implementation of this change of policy must be supported by monitoring and
Bard Access Systems, Inc. 3 Indications For Use Hickman* Hemodialysis/Apheresis Catheters are designed for long-term vascular access and for use in
4 What You Can Expect During the Collection You will be monitored by a specially trained nurse or technician throughout the collection The timing for the apheresis procedure varies, but it normally takes 2 to 6 hours If the veins in your arms are used for the collection, you will have a needle placed in each arm - Some patients may instead require the use of a catheter for
The apheresis team consists of: (1) Board certified transfusion medicine physicians, who are responsible for overseeing daily operations as well as managing all patients undergoing apheresis procedures; (2) A nurse manager and a nurse coordinator, who establish and update policies, processes and procedures, collect and
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