Cytotherapy, 2014; 16: 285e286

LETTER TO THE EDITOR

KENNY W. DOUGLAS, SHARON ROBERTSON, JOY E. SINCLAIR, SENGA TAYLOR &RACHEL H.A. GREEN

Scottish National Blood Transfusion Service, Glasgow, United Kingdom

To the Editor:

We note with interest a paper published last year by agroup from the University of Arkansas for MedicalSciences (1) and a prior abstract from the samegroup presented at the American Society for Hema-tology 2010 (2) describing the validation of a formulafor predicting daily CD34þ cell yields for peripheralblood stem cell (PBSC, otherwise known as HPC-A)products on the basis of the peripheral CD34þ counton the day of collection, the volume of the patient’sblood to be processed and an established “bench-mark” Collection Efficiency (CE) for the cell sepa-rator platform being used. The authors state in theirpaper that “to date this has not been published byother groups.”

This is incorrect because an essentially identicalmethod has been published previously by two othergroups. Pierelli et al. (3) first described the principleof CD34þ dose prediction on the basis of “bench-mark” CE in 2006. The principle described is thatif a “benchmark” CE can be established for CD34þcell apheresis, then this can be used for dose pre-diction by use of the following formula: PredictedCD34þ cell dose per kg ¼ (peripheral blood CD34þ cellcount on day of collection � volume of patient’s blood tobe processed � “benchmark” CE)/body weight in kg.Pierelli et al. chose a “benchmark” CE of 40% on thebasis of previously published CE figures for Frese-nius cell separator platforms and then validated theirformula on a series of 313 collection proceduresperformed either on Fresenius ComTec or on COBESpectra cell separator machines (“MNC” setting; seediscussion below regarding alternative collectionsettings on COBE Spectra). Our group subsequentlydescribed an essentially identical method in abstractform in 2008 (4), given as an oral presentation at theAmerican Society for Apheresis that year. Althoughthis was an abstract publication rather than a peer-reviewed paper, the method used was described infull: a “benchmark” CE was established for the cell

Correspondence to: Kenny W. Douglas, FRCP(UK), FRCPath, Clinical ApherRoad, Glasgow G12 0YN, UK. E-mail: kenneth.douglas@nhs.net

ISSN 1465-3249 Copyright � 2014, International Society for Cellular Therapy. Phttp://dx.doi.org/10.1016/j.jcyt.2013.12.001

separator platform and setting used (MNC setting onCOBE Spectra) by analysis of a training data set, andthe “benchmark” CE was then used prospectively fordose prediction. Rosenbaum et al. (1) subsequentlypublished their CD34þ dose prediction manuscriptin 2012. The formulas described in all three publi-cations are identical except that the actual valueused for “benchmark” CE is different: 40% forPierelli et al., 52% in our abstract, and 30% forRosenbaum et al. This is not unexpected because“benchmark” CE is likely to differ between centersas the result of technical differences in the apheresishardware and software protocols used, and eachcenter should ideally establish its own “benchmark”CE. Our group has subsequently published a furthervalidation of the CE-based dose prediction methodwith the use of our own “benchmark” CE as part ofa book chapter almost simultaneously with theRosenbaum et al. (5) paper and has also publishedin abstract form the successful use of CE-based doseprediction on a novel cell separator platform,Spectra Optia (6).

We understand that the three groups who havepublished on CE-based dose prediction (1,3,4)arrived at this method entirely independently andthat the University of Arkansas investigators wereunaware either of the Pierelli et al. paper or of ourabstract at the time of publication of their paper. Mygroup was unaware of the Pierelli et al. paper untilDecember 2013.

In their “Methods” section, Rosenbaum et al.state that cells were collected on COBE Spectra,software version 7.0, but they do not state whichactual collection setting was used for their pro-cedures. COBE Spectra software versions 6.0 andonward have offered two alternative collectionsettings, “MNC” and “autoPBSC,” which havedifferent CEs and also differ significantly in otherways (for instance, different disposable tubing setsand centrifuge fillers are used). The “benchmark”

esis Unit, Beatson West of Scotland Cancer Centre, 1053 Great Western

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286 K. W. Douglas et al.

CE reported by Rosenbaum et al. of 30% mightsuggest that the autoPBSC setting is used becausethe MNC setting has been reported to have a highermedian CE of 40e52% (3,4,7). However, Rose-nbaum et al. used an apheresis protocol with asomewhat higher than standard inlet flow rate(150 mL/min) and higher than standard inlet:ACratio (31:1) than are used by most centers for COBESpectra, and this may have resulted in lower“benchmark” CE. It would be of interest to haveconfirmation of whether the MNC or autoPBSCsetting was used.

Finally, we note the very recent publication of avalidation of the CE-based CD34þ dose predictionmethod by a large international consortium (8). CE-based CD34þ dose prediction was performedretrospectively for 1126 aphereses with the use of thePierelli et al. formula, with a “benchmark” CE of40%. However, although all procedures were per-formed on COBE Spectra, some centers used theMNC setting and some used the autoPBSC setting.Our experience would lead us to expect that the CE-based dose prediction method is likely to be mostaccurate when each individual center establishes itsown “benchmark” CE, based on the exact apheresishardware, the software protocol and the machinesettings used locally.

Disclosure of interests: KWD has receivedspeaker fees from TerumoBCT between 2010 and2012, total value less than $1000. The other authorshave no commercial, proprietary, or financial in-terest in the products or companies described in thisarticle.

References

1. Rosenbaum ER, O’Connell B, Cottler-Fox M. Validation of aformula for predicting daily CD34þ cell collection by leuka-pheresis. Cytotherapy. 2012;14:461e6.

2. RosenbaumER,O’Connell B, Cottler-FoxM.A successfulmodelfor predicting CD34þ cell collection by apheresis. (Abstract).Blood (ASHAnnualMeetingAbstracts). 2010;116:Abstract 1182.

3. Pierelli L, Maresca M, Piccirillo N, Pupella S, Gozzer M, et al.Accurate prediction of autologous stem cell apheresis yieldsusing a double variable-dependent method assures systematicefficiency control of continuous flow procedures. Vox Sang.2006;91:126e34.

4. Douglas KW, McGarvey M, Robertson S, Sinclair JE,Taylor S, Green RHA. “Will I have enough cells for a trans-plant, doctor?” Validation of a CD34þ dose prediction formulausing patient weight, peripheral CD34þ count and predictedend-run results in a series of 440 consecutive PBSC collectionprocedures using the MNC program on COBE Spectra.(Abstract). J Clin Apheresis. 2008;23:21e2.

5. Douglas KW. Experience with apheresis procedures after pler-ixafor mobilisation. How much blood to process? Dose predic-tion on the basis of peripheral CD34þ counts. In: Fruehauf S,Zeller WJ, Calandra G, editors. Novel Developments in StemCell Mobilisation. New York: Springer; 2012:137e8.

6. Nicholson F, Sinclair JE, Doig A, Alcorn M, Douglas KW.PBSC collection on the Optia cell separator platform: doseprediction based on a benchmark “CE2” collection efficiency issignificantly more accurate than “Collect Ratio”-based doseprediction using peripheral CD34þ count alone. (Abstract).Therapeut Apheresis Dialysis. 2011;15:A6.

7. Cooling L, Hoffmann S, Herrst M, Muck C, Armelagos H,Davenport R. A prospective randomized trial of two popularmononuclear cell collection sets for autologous peripheral bloodstem cell collection in multiple myeloma. Transfusion. 2010;50:100e19.

8. Hosing C, Saliba RM, Hamerschlak N, Kutner JM,Sakashita AM, et al. Peripheral blood stem cell yield calcu-lated using preapheresis absolute CD34þ cell count, periph-eral blood volume processed, and donor body weightaccurately predicts actual yield at multiple centers. Trans-fusion. 2013. http://dx.doi.org/10.1111/trf.12435.