Progenitor Cell Mobilisation Influence of Preapheresis Clinical Factors On
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Bone Marrow Transplantation (2003) 31, 851–855 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt Progenitor Cell Mobilisation Influence of preapheresis clinical factors on the efficiency of CD34+ cell collection by large-volume apheresis C Sarkodee-Adoo, I Taran, C Guo, F Buadi, R Murthy, E Cox, R Lopez, S Westphal, S Shope, B O’Connell, L Wethers and B Meisenberg University of Maryland School of Medicine, Greenebaum Cancer Center, Baltimore, MD, USA Summary: that transplants with peripheral blood HPC are associated with faster engraftment and lower costs than those We evaluated 120 leukapheresis procedures (93 patients), supported by steady-state bone marrow harvests.1 These in order to detect clinical factors that influence the advantages of peripheral blood stem cell transplantation efficiency of CD34+ collection using Cobe Spectrat cell (PBSCT) are partly dependent on the number of HPC separators. Hematocrit was 427% and platelet count infused, with CD34+ cell enumeration emerging as the 430 000/llin495% of patients. Platelet transfusions most usefulway of quantifying HPC dose. 2 The efficiency were given if the postprocedure count was o20 000/ll. of leukapheresis for CD34+ cell collection (EffCD34) has Multiple regression analysis was used to analyze putative been defined as the number of CD34+ cells collected per factors, and a predictive equation defined by stepwise volume processed at a given circulating CD34+ cell count.3 regression modeling. The mean efficiency was 0.59 (s.d. Thus, higher EffCD34 is valuable in enabling sufficient HPC 0.27). Sex (M4F; P ¼ 0.01), the volume processed (inver- to be collected in fewer procedures and over a shorter time, sely; P ¼ 0.01) and CD34+ cell count (inversely; P ¼ 0.04) minimizing the costs and risks of leukapheresis and graft were associated with efficiency, whereas hematocrit, processing, and potentially translating into safer ABMT. platelet or leukocyte count, catheter type and patient Yet, few studies have focused on identifying the determi- weight were not. The effect size for predictive factors was nants of EffCD34, and fewer still have involved Cobe small (R2 ¼ 0.21). Adverse events were limited to hypo- Spectrat apheresis machines, although they are frequently calcemia. We conclude that female sex, volume processed used for this purpose. In one study, focusing on the effects 4 and CD34+ cell count adversely influence the efficiency of hematocrit on EffCD34, Mehta et al did not find a of CD34+ cell leukapheresis. However, the impact of correlation, although the other existing study, reported by volume and CD34+ cell count is small, and likely to be Ford et al,3 suggested a correlation between hematocrit and offset by the influence of these same factors on overall EffCD34. In both of these studies, however, Fenwal3000 yield. Leukapheresis appears to be safe and efficient for (Plus) apheresis machines were used. In a more recent 5 autologous blood and marrow transplantation patients with study, Mehta et al did not find a relation between EffCD34 hematocrit 427% and platelet count 430 000/ll. of the Cobe Spectrat machine and the totalleukocyte Bone Marrow Transplantation (2003) 31, 851–855. count, and only a modest inverse relation with the doi:10.1038/sj.bmt.1704034 circulating CD34+ cell count. That study, however, was Keywords: leukapheresis; efficiency; CD 34; cobe not designed to identify other clinical factors that might influence EffCD34. Moreover, as observed by Mehta et al,4 many institutions (including ours) base leukapheresis eligibility on an Autologous blood and marrow transplantation (ABMT) is arbitrarily chosen preapheresis hematocrit, usually ranging useful in the treatment of selected patients with hematolo- from 25 to 30%. This may lead to delays in leukapheresis gic malignancies. In recent years, hematopoietic progenitor while blood transfusions are provided, since a substantial cell (HPC) mobilization followed by leukapheresis has number of patients mobilized with chemotherapy and almost supplanted bone marrow harvesting as a means of growth factors for ABMT are likely to be anemic. The obtaining HPC for ABMT, mainly because it obviates the determination of a threshold hematocrit above which use of generalor spinalanesthesia. At leastin theory, leukapheresis can be performed safely and with high peripheral blood HPC collections in patients with bone EffCD34 would likely reduce the impact of this problem. marrow diseases may also be less contaminated with tumor This is likely to be true for platelet counts also. cells than bone marrow harvests. Studies have also shown We analyzed data collected during leukapheresis with Cobe Spectrat apheresis machines in patients undergoing ABMT in our institution in order to identify preapheresis Correspondence: Dr C Sarkodee-Adoo, City of Hope Samaritan Bone clinical factors that influence Eff . We were particularly Marrow Transplant Unit, 1111 E McDowell Street, Phoenix, AZ 85006, CD34 USA interested in factors such as the catheter type, volume Received 21 October 2002; accepted 9 December 2002 processed, CD34+ cell or platelet count and hematocrit, Determinants of CD34+ cell leukapheresis efficiency C Sarkodee-Adoo et al 852 which could potentially be manipulated in the future as a manufacturer. Large-volume leukapheresis (up to 30 l at way to increase the yield of HPC collections. We also peak flow rates of 125 ml/min) was employed. Leukapher- sought to identify a threshold hematocrit and platelet count esis was repeated the next day if an insufficient number of above which large-volume leukapheresis could be consid- CD34+ cells was obtained. Conversely, in those patients ered safe. whose high CD34+ cell count predicted for adequate yields at smaller volumes, the duration of apheresis (rather than flow rates) was reduced. Anticoagulant consisted of Materials and methods ACDA (970 ml) plus heparin (10 000 ml), with an AC ratio of 30:1. Calcium supplements (oral or by central vein) were Patient selection given only if symptoms of hypocalcemia appeared. The type of centralvenous catheter used for leukapheresis, Between January and December 1999, 93 consecutive classified as having staggered (Bard-Hickman apheresis; patients underwent leukapheresis for collection of HPC as Bard, Salt Lake City, UT, USA) or nonstaggered (Neostar; part of University of Maryland at Baltimore Institutional Horizon MedicalProducts, Manchester, GA, USA) ports, Review Board approved treatment protocols. Informed was based on treating physician preference and was not consent was obtained from all patients. Men (n ¼ 57) decided by apheresis personnel. The EffCD34 was defined in outnumbered women (n ¼ 36). Baseline, preleukapheresis this study as laboratory results of the patients are shown in Table 1. The mean patient weight was 71.56 kg (s.d. 13.52). Staggered- Total# CD34 þ cells collected port catheters were used in 29 patients, and nonstaggered- Circulating CD34þ cell countÂnumber of liters processed port catheters in 60 patients, while peripheral veins or an unknown, previously placed catheter type was used in four All computations were based on complete blood counts patients. Two patients had platelet counts less than 20 000/ and circulating CD34+ cell counts obtained on the ml prior to leukapheresis, and were processed as planned morning of apheresis. Thrombocytopenia and anemia were deviations from our standard operating procedure. The not considered to be contraindications to leukapheresis mean volume processed was 22.8 l (s.d. 7.1 l). provided the platelet count and hematocrit were greater than 20 000/mland 25%, respectively.Instead, our standard Procedures operating procedure was to measure the complete blood count again after leukapheresis, and administer a platelet Mobilization consisted of treatment with cyclophospha- transfusion if the count was less than 20 000/ml. The mide with or without etoposide, followed by GCSF 10 mg/ CD34+ progenitor cell content of apheresis products was kg or GMCSF 250 mg/m2 administered subcutaneously measured using a dualplatformflow cytometric method once a day. Four patients, who failed to obtain enough (FACSCAN, Becton Dickinson, San Jose CA, USA) as circulating CD34+ cells to undergo leukapheresis, under- previously described.6 In order not to confound the analysis went a second attempt using a combination of GCSF 10 mg/ for patient-related (as distinct from procedure-related) kg and GMCSF 250 mg/m2 without chemotherapy, begin- factors, only the first apheresis procedure for each patient ning at least 3 weeks after the initial mobilization attempt. was included in the primary analysis. However, to gain Circulating CD34+ cell counts, determined by flow some independent measure of the variation in EffCD34 cytometry (ProCOUNT, Becton Dickinson, San Jose, between procedures rather than between patients, a CA, USA), were followed when the leukocyte count separate analysis was conducted using pairs of data sets recovered to 42000/ml after mobilization, and leukapher- obtained from patients who had more than one apheresis esis was begun when the CD34+ cell count exceeded 20– procedure. No interim analyses were performed, and the 40/ml or was felt to have peaked. Each patient’s transplant results of EffCD34 were not reported to apheresis staff until physician prescribed the target CD34+ cell number to be completion of the study. collected. Since ABMT protocols in our institution during this period were designed to deliver multiple cycles of post- Statistical methods transplant chemotherapy,