Japanese Journal of Clinical Oncology 30:153-158 (2000)
© 2000 Foundation for Promotion of Cancer Research
A Successful and Simplified Filgrastim Primed Single Apheresis Method Without Large Volume Apheresis for Peripheral Blood Stem Cell Collection
Departments of 1Medical Oncology, 2Internal Medicine, 3Immunology, 4Radiation Oncology, and 5Haematology, Gülhane Military Medical Academy, Ankara, Turkey
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Background: There is a tendency to use only one apheresis collection to reduce the morbidity and the cost of peripheral blood stem cell collection. We studied whether rapid and complete engraftment could be achieved by single apheresis by using only Filgrastim without large volume apheresis in previously treated patients.
Methods: Engraftment of single apheresis in 25 patients was compared with those of multiple apheresis in 26 patients; 52% of patients in the single apheresis group and 62% of patients in the multiple apheresis group were heavily pretreated. All patients received 10–15 µg/kg/day of Filgrastim starting on day 14 after 3–4 cycles of induction chemotherapy. Apheresis was performed using Cobe Spectra on day 4, 5 or 6 in the single apheresis group and every other day in the multiple apheresis group after day 3.
Results: The median collection volume was 250 ml (250–300 ml) in the single apheresis group and 750 ml (200–1500 ml) in the multiple apheresis group. The median CD34(+) cell number was not significantly different in the two groups (11.79 vs 9.38 x 106/kg). The median times to achieve leukocytes 
1 x 109/l and platelets 50 x 109/l counts were 10 days (8–21 days) and 15 days (9–38 days) in the single apheresis group vs 11 days (8–23 days) and 20 days (10–32 days) in the multiple apheresis group, respectively (p < 0.05). Antibiotic use was less in the single apheresis group than the multiple apheresis group (9 vs 12 days, p < 0.05).
Conclusion: Adequate numbers of peripheral stem cells were harvested by G-CSF in a single apheresis without large volume apheresis even in heavily pretreated patients. Rapid and complete engraftment occurred in all patients and it was faster in single than multiple apheresis.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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For the last decade, peripheral blood stem cell (PBSC) transplantation has been increasingly used for the treatment of haematological and oncological diseases. However, for autologous PBSC transplantation, an optimal mobilization technique has not yet been determined. However, mobilization techniques in which chemotherapy plus growth factors (GF) and multiple apheresis are used in order to collect an appropriate amount of CD 34(+) stem cells have often been used (1–3). On the other hand, this approach gives rise to an increase in morbidity and cost. Also, the apheresis procedure itself is a time- and cost-consuming attempt for both the patient and technician. Therefore, the clinical trials aiming for an optimization of leukapheresis and mobilization techniques, in which an appropriate amount of CD34(+) stem cell is obtained with a single apheresis have gained importance (4–6). Generally, obtaining an appropriate amount of CD34(+) stem cells requires a large volume leukapheresis (LVL) with a high flow-rate (>90 ml/min) in which at least three times the blood volume (15–35 l) is processed (6–9). Another uncertainty is the time for optimal apheresis. The time for optimal apheresis has been well determined for allogeneic conditions (10), whereas it has not been clearly defined for an autologous setting (11). For conditions combining chemotherapy with GF, GF is usually given one day after the termination of chemotherapy and apheresis is often started when the leukocyte count is
1 x 109/l (12,13), often leading to an unnecessary number of aphereses (14). In three clinical trials, however, a peak number of peripheral blood CD34(+) stem cells was achieved 2 days after reaching a leukocyte count of 2 x 109/l in the first (15), 1–2 days after that of 10 x 109/l in the second (16), and immediately after that of 5–10 x 109/l in the third (17). These numbers are normally obtained between 11 and 18 days after chemotherapy. In the light of these data, a clinical trial was conducted to decrease the cost and develop a more appropriate technique in our centre. In this study, whether an adequate number of stem cells could be obtained with a single apheresis using G-CSF administration 14 days after the induction chemotherapy was investigated and the findings of post-transplant engraftment and the requirements of supportive therapy were evaluated. |
MATERIALS AND METHODS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Patients
Fifty-one patients with various malignancies underwent autologous PBSC transplantation. Twenty-five patients had a single apheresis (SA) whereas 26 had a multiple apheresis (MA). Of the patients in the SA group, 11 were male (15 female) and the median age was 35 years (range, 19–67), whereas in the MA group 20 were male (six female) and the median age was 24 years (range, 20–53). The patients in the SA group consisted of 12 patients with breast cancer, six with non-Hodgkin’s lymphoma, one with Hodgkin’s disease, two with multiple myeloma, two with osteosarcoma, one with Ewing’s sarcoma and one with small cell lung carcinoma, whereas those in the MA group consisted of five patients with breast cancer, four with non-Hodgkin’s lymphoma, 11 with Hodgkin’s disease, three with testis tumour, one with small cell lung carcinoma, one with brain tumour and one with acute myelocytic leukaemia. Fifty-two percent (n = 13) of the patients in the SA group and 62% (n = 16) of those in the MA group had previously received chemotherapy, with a number of chemotherapy cycles
12. In addition to chemotherapy, radiotherapy had been administered to 48% of the patients (n = 12) in the SA group and 50% (n = 13) of those in the MA group. The median time from diagnosis to transplantation was 330 days (90–5110) in the SA group and 575 days (165–3160) in the MA group. Before the transplantation, all patients gave written consent. The distribution and characteristics of cases are shown in Table 1.
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PBSC Mobilization and Technique
The mobilization was performed after 3–4 cycles of induction chemotherapy in both groups. The drug combinations used as induction therapy included CAF (cyclophosphamide 500 mg/m2 day 1, doxorubicin 50 mg/m2 day 1, 5-fluorouracil 500 mg/m2 days 1 + 8) for patients with breast cancer, DHAP (dexamethasone 40 mg/day 4 days, ara-C 4 g/m2 day 2, cisplatin 30 mg/m2 3 days) for those with lymphoma, VAD (vincristine 0.4 mg/day 4 days, doxorubicin 9 mg/m2 4 days, dexamethasone 40 mg/day 12 days) for those with multiple myeloma, VIP (etoposide 75 mg/m2 5 days, ifosfamide 1200 mg/m2 5 days, cisplatin 20 mg/m2 5 days) for those with testis and brain tumours, IPA (ifosfamide 2000 mg/m2 3 days, cisplatin 30 mg/m2 3 days, doxorubicin 50 mg/m2 1 day) for those with osteosarcoma, VACA (vincristine 2 mg/day days 1, 8, 15, doxorubicin 30 mg/m2 2 days, cyclophosphamide 1200 mg/m2 1 day, dactinomycin 0.8 mg/day 3 days) for Ewing’s sarcoma and EP (etoposide 125 mg/m2 3 days, cisplatin 75 mg/m2 1 day) for those with small cell lung carcinoma. For the patient with AML the mobilization was performed after the intensification regimen (ara-C, etoposide). Fourteen days after the last cycle of induction therapy, rh G-CSF (Filgrastim, Roche) 10–15 µg/kg/day i.v. was given as a 2 h infusion. Using Cobe Spectra (Cobe Lakewood, USA), the leukapheresis procedure was performed with a three-way catheter 6–8 h after the last dose of G-CSF on the day 4, 5 or 6 in the SA group and on every other day after day 3 in the MA group. Harvested autologous plasma was mixed with dimethyl sulfoxide (DMSO) to a final DMSO concentration of 10%, frozen at –100°C using a computerized freezing device (R 201 Planar) and then stored at –197°C in liquid nitrogen until the day of use.
Immunofluorescence Analysis
1 x 106 MNC of the leukapheresis product were incubated for 30 min at 4°C with 10 ml of fluorescein isothiocyanate-conjugated anti-c antibody (HPCA-2) obtained from Becton Dickinson (Heidelberg, Germany). Isotype-identical antibodies served as controls. Immunofluorescence analysis was performed using FACScan (Becton Dickinson).
High-dose Chemotherapy Regimens
The conditioning regimens included ICE (ifosfamide 15 g/m2, carboplatin 1.5 g/m2, etoposide 1.5 g/m2 in 6 days in divided doses) for 17 cases in the SA group and 11 cases in the MA group; BEAM (BCNU 300 mg/m2/day, etoposide 200 mg/m2/day x 4 days, ara-C 400 mg/m2/day x 4 days, melphalan 140 mg/m2/day) for two cases in the SA group and three cases in the MA group; CyEAM (cyclophosphamide 1.5 g/m2/day, etoposide 200 mg/m2/day x 4 days, ara-C 400 mg/m2/day x 4 days, melphalan 140 mg/m2/day) for one case in the SA group and three cases in the MA group; BEAM + RT (involved field, 2400 cGy) for three cases in the MA group; CyEAM + RT for four cases in the MA group; Cy + TBI (cyclophosphamide 60 mg/kg/day x 2 days, TBI 1200 rad) for three cases in the SA group and one case in the MA group; melphalan 140 mg/m2/day for two cases in the SA group; and BECM (BCNU 300 mg/m2/day, etoposide 200 mg/m2/day x 4 days, carboplatin 1.5 g/m2/day, melphalan 140 mg/m2/day) for one case in the MA group (Table 1).
Infusion and Post-transplant Growth Factor
All patients who rested for 2 days following the conditioning regimens received the harvested product by infusion on the day when the product was thawed in a water bath at 37°C. Starting on the first (+1) day after the transplantation, all patients were administered G-CSF 5 µg/kg/day through i.v. infusion until the leukocyte count 1000/mm3 for three consecutive days.
Statistical Analysis
This study compared the results from two patient groups: first, patients for whom MA was done to collect an appropriate number of CD34(+) cells for a safe engraftment in early years; and second, those for whom SA was done in order to decrease the cost in recent years. Student’s t-test was used to compare the results obtained from both groups. The p value was considered statistically significant if <0.05. The correlation analyses were assessed using a linear regression method.
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RESULTS |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Leukapheresis Findings
The mean blood volume which was processed per minute was 40.20 ml/min (34.80–49.70) in the SA group and 47.40 ml/min (36.20–63.10) in the MA group (p = 0.0001), resulting in a total blood volume of 11.26 l (8.97–12.84) and 19.13 l (11.77–37.83), respectively (p = 0.0001). The mean number of aphereses and the product volume were 1 and 250 ml (250–300) in the SA group and 2.5 (2–7) and 700 ml (200–1500) in the MA group. Although the mean number of nucleated cells was higher in the SA group (9.06 x 108 vs 7.59 x 108/kg, p = 0.001), CD 34(+) cell number showed no statistical difference between the two groups (6.03 x 106 vs 8.78 x 106/kg) (Table 2). The correlation analyses indicated a positive correlation between CD34(+) cell number and the number of nucleated cells (r = 0.30, p = 0.036), whereas there was no relationship between CD34(+) cell number and the blood processing rate or processed blood volume.
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Side-effects
No serious side-effects were observed during the mobilization and harvesting in both groups. Side-effects such as fever (18%) and bone pain (24%) were simply controlled with antipyretic and analgesic drugs.
Engraftment Findings
A complete and persistent engraftment developed in all cases. The median time for leukocyte engraftment (1 x 109/l) was 10 days (8–21) in the SA group and 11 days (8–23) in the MA group (p = 0.012). Similarly, the platelet engraftment (50 x 109/l) developed earlier in the SA group [15 days (9–38) vs 20 days (10–32), p = 0.03] (Table 3). No correlation was found between CD34(+) cell number and the platelet or leukocyte engraftment.
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Post-transplant Supportive Therapy
The median period with fever was 2 days (0–6) in the SA group and 2 days (0–13) in the MA group; the median duration of hospitalization after transplantation was 11 days (8–49) in the SA group and 14 days (8–51) in the MA group; the median number of erythrocyte transfusions was 3 units (0–6) in the SA group and 3 units (0–10) in the MA group; the median number of platelets was 2 units (1–8) in the SA group and 2 units (0–10) in the MA group. There was no difference between the SA and MA groups in terms of the number of days with fever, the duration of hospitalization after transplantation and the number of erythrocyte and platelet transfusions, whereas the number of days that antibiotics were used was statistically less in the SA group (median 9 vs 12 days, p = 0.039) (Table 4). In correlation analysis, there was a negative correlation (r = –0.37, p = 0.019) only between CD34(+) cell number and the fact that antibiotics were used. The same correlation was more apparent in the SA group (r = –0.48, p = 0.015).
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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For autologous PBSC transplantation, an optimal mobilization time and technique have not been clearly defined. The mobilization techniques that could be used with autologous procedures include chemotherapy alone, CSF alone, chemotherapy + CSF, CSF combinations and monoclonal antibodies against the integrine receptors of stem cells. Owing to the potential to decrease the patient morbidity and the cost, there is a tendency towards collection procedures with single apheresis. Such procedures require LVL and a mobilization technique in which chemotherapy and CSFs are often combined. With the conditions in which chemotherapy and CSFs are combined, CSF is usually administered 1 day after the termination of chemotherapy and the leukapheresis procedure is often started when the leukocyte count is
1 x 109/l (12,13).
Accepting a leukocyte count 1 x 109/l to start to leukapheresis is possibly wrong as it subsequently will result in an inadequate number of aphereses. The most ideal method to determine the optimal time for apheresis is daily measurement of CD34(+) cell count in circulating blood (2,18). Hence apheresis must be started when the CD34(+) cell count reaches 0.1% of the number of nucleated cells (13,19). Recent studies have found a highest concentration of CD34(+) cells either 2 days after the leukocyte count reached 2 x 109/l (15) or 1–2 days after 10 x 109/l (16) or the day after reaching 5–10 x 109/l (17). Therefore, with the mobilization regimens in which CSFs and chemotherapy are combined, the best period for collecting is days 11–18 if the blood concentration of CD34(+) cells is not measured (14). Another study reported days 13–19 for the best collection period (15). On the other hand, the best collection time for the allogeneic mobilization technique, in which CSFs alone is used, has been well established as day +4, +5 or + 6 (10).
The pooled data from these two settings are the rationale of our study. We showed that an adequate number of stem cells could be obtained and a complete and permanent engraftment occurs with a single apheresis, which was performed on day 4, 5 or 6 following a 2 h G-CSF i.v. infusion of 10–15 µg/kg, 14 days after an induction therapy of 3–4 cycles. The measurement of the CD34(+) cell count on the day of leukapheresis showed that the number of CD34(+) cells is 0.1% of the number of nucleated cells in 90% of cases in the SA group (data not shown). It is well known that >2.5 x 106 CD34(+) cells/kg of can be collected by a single apheresis when the peripheral blood CD34(+) cell count is >4 x 104/ml (20). In a study in which Kanold et al. examined haematopoietic progenitor cell kinetics in children with solid tumours and leukaemia, who were treated with CSF alone (10 µg/kg/day), it was shown that peak peripheral blood levels of CD34(+) cells were achieved after the fourth and fifth doses of G-CSF and that, with a standard volume single apheresis in which one volume of blood is processed, 2 x 106 CD34(+) cells/kg could be collected (21).
Many studies have shown that there is a poor correlation between the collected number of CD34(+) cells and the baseline and pre-apheresis leukocyte count or MNC count in the product (4,11). Another study has suggested that the CD34+/CD71 cell concentration (>30/ml) of a steady-state bone marrow could be a good indicator of the CD34(+) cell content of a product which was mobilized by G-CSF (22). Other studies have reported that there is a positive correlation between pre-apheresis leukocyte count and the number of CD34(+) cells in the product and that the efficacy of CD34(+) cell collection could increase if the leukocyte count on the day of apheresis 30 000/mm3 (23,24). Among our cases, over 90% in the SA group had a leukocyte count 30 000/mm3 on the day of apheresis (data not shown). In our study, while there was a positive correlation between the CD34(+) cell content of the collected product and the number of nucleated cells (r = 0.30, p = 0.036), we observed no relationship between the blood flow-rate and the processed blood volume. So far, no study has reported an optimal blood flow-rate for Cobe Spectra to collect CD34(+) cells. By increasing the total volume of processed blood (15–35 l), single LVLs have been attempted to obtain an adequate number of stem cells (6–8). However, this requires an increased flow-rate (90 ml/min).
The fact that we observed no relationship between CD34(+) cell count and haematological improvement may be explained by our approach to give all patients stem cells at much higher levels than the limit CD34(+) levels. A study by Pettengell et al. came to the same conclusion (4). This study in which chemotherapy and G-CSF were combined for mobilization has shown that an adequate number of CD34(+) cells could be collected with a single apheresis between days 7 and 9, with a processed blood volume of 10–15 l. When the haematological engraftment findings of our study were compared with those in Pettengell et al.’s study, our results suggested a similarity in terms of leukocyte and platelet engraftments (10 vs 10 days and 15 vs 16 days). However, the median unit number of post-transplant platelet transfusions was two in our study and 24 in the other study. Jones et al. reported that the platelet requirement in the post-transplant period was 15 units (5). This can be explained by the fact that they had a higher number of intensely treated patients or that the mobilization procedure allowed the combination of G-CSF with chemotherapy regimens such as cyclophosphamide.
Our study has some important advantages since it offers a cost-effective use of an expensive drug such as G-CSF, requiring less supportive therapy. Further, an adequate number of CD34(+) progenitor cells can be mobilized by G-CSF only, which is given 14 days after an induction chemotherapy and collected with a single apheresis without LVL. Even a complete and permanent engraftment can occur among patients who were treated with an intense therapy. Using this effective and inexpensive method, randomized trials in which the effects of blood flow-rate, processed blood volume and other factors on the number of CD34(+) cells and engraftment process are examined may determine the optimal method.
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Acknowledgement |
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This study was presented at the 24th Annual Meeting of the European Group for Blood and Marrow Transplantation, Courmayeur, Italy, March 22–26, 1998, and was published in Bone Marrow Transplant 1998;21(Suppl 1):198 (Abstr 688).
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FOOTNOTES |
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+ For reprints and all correspondence: Fikret Arpaci, GATA Tibbi Onkoloji Bilim Dali, Etlik, 06018, Ankara, Turkey. E-mail: onkoloji@gata.edu.trAbbreviations: PBSC, peripheral blood stem cell; GF, growth factor; LVL, large volume leukapheresis; G-CSF, granulocte colony-stimulating factor; SA, single apheresis; MA, multiple apheresis; CAF, cyclophosphamide, doxorubicin, 5-fluorouracil; DHAP, dexamethasone, ara-C, cisplatin; VAD, vincristine, doxorubicin, dexamethasone; VIP, etoposide, ifosfamide, cisplatin; IPA, ifosfamide, cisplatin, doxorubicin; VACA, vincristine, doxorubicin, cyclophosphamide, dactinomycin; EP, etoposide, cisplatin; DMSO, dimethyl sulfoxide; MNC, mononuclear cell; HPCA-2, fluorescein isothiocyanate-conjugated anti-c antibody; ICE, ifosfamide, carboplatin, etoposide; BEAM, BCNU, etoposide, ara-C, melphalan; CyEAM, cyclophosphamide, etoposide, ara-C, melphalan; Cy, cyclophosphamide; TBI, total body irradiation; BECM, BCNU, etoposide, carboplatin, melphalan; RT, radiotherapy
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REFERENCES |
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TOPABSTRACTINTRODUCTIONMATERIALS AND METHODSRESULTSDISCUSSIONREFERENCES |
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1 Kessinger A, Bierman PJ, Vose JM, Armigate JO. High-dose cyclophosphamide, carmustine and etoposide followed by autologous peripheral stem cell transplantation for patients with relapsed Hodgkin’ s disease. Blood 1991;77:2322–5.
2 Hohaus S, Goldschmidt H, Ehrhardt R, Haas R. Successful autografting following myeloablative conditioning therapy with blood stem cells mobilized by chemotherapy plus rh G-CSF. Exp Hematol 1993;21:508–14.[ISI][Medline]
3 Bensinger W, Singer J, Appelbaum F, Lilleby K, Longin K, Rowley S. Autologous transplantation with peripheral blood mononuclear cells collected after administration of rh G-CSF. Blood 1993;81:3158–63.
4 Pettengell R, Morgenstern GR, Woll PJ, Chang J, Rowlands M, Young R. Peripheral blood progenitor cell transplantation in lymphoma and leukemia using a single apheresis. Blood 1993;82:3770–7.
5 Jones HM, Jones SA, Watts MJ, Khwaja A, Mills W, Fielding A. Development of a simplified single-apheresis approach for peripheral blood progenitor cell transplantation in previously treated patients with lymphoma. J Clin Oncol 1994;12:1693–1702.
6 Alegre A, Diaz MA, Madero L, Granda A, Vega A, Villa M. Large-volume leukapheresis for peripheral blood stem cell collection in children: a simplified single-apheresis approach. Bone Marrow Transplant 1996;17:923–7.[ISI][Medline]
7 Cull G, Ivey J, Chase P, Picciuto R, Hermann R, Cannell P. Collection and recruitment of CD34+ cells during large-volume leukapheresis. J Hematother 1997;6:309–14.[ISI][Medline]
8 Passos-Coelho JL, Machado MA, Lucio P, Leal-Da-Costa F, Silva MG, Pareira A. Large-volume leukaphereses may be more efficient than standard-volume leukaphereses for collection of peripheral blood progenitor cells. J Hematother 1997;6:465–74.[ISI][Medline]
9 Koumakis G, Vassilomanolakis M, Hatzichristou, Barbounis V, Filis J, Papanastasiov K. Predictive factors affecting mobilization and peripheral blood stem cell collection using single apheresis for rescuing patients after high-dose chemotherapy in various malignancies. Bone Marrow Transplant 1996;18:1065–72.[ISI][Medline]
10 Anderlini P, Körbling M. The use of mobilized peripheral blood stem cells from normal donors for allografting. Stem Cells 1997;15:9–17.
11 Gillespie TW, Hillyer CD. Peripheral blood progenitor cells for marrow reconstitution: mobilization and collection strategies. Transfusion 1996;36:611–24.[ISI][Medline]
12 Gianni AM, Siena S, Bregni M, Tarella C, Stern AC, Pileri A. GM-CSF to harvest circulating haemopoietic stem cells for autotransplantation. Lancet 1989;2:580–4.[ISI][Medline]
13 Siena S, Bregni M, Brando B, Belli N, Ravagnani F, Gandola L. Flow cytometry for clinical estimation of circulating hematopoietic progenitors for autologous transplantation in cancer patients. Blood 1991;77:400–9.
14 Leitman SF, Read EJ. Hematopoietic progenitor cells. Semin Hematol 1996;33:341–58.[ISI][Medline]
15 Ho AD, Glück S, Germand C, Sinoff C, Dietz G, Maruyama M. Optimal timing for collections of blood progenitor cells following induction chemotherapy and GM-CSF for autologous transplantation in advanced breast cancer. Leukemia 1993;7:1738–46.[ISI][Medline]
16 Dreger P, Marquardt P, Haferlach T, Jacobs S, Mulverstedt T, Eckstein V. Effective mobilization of peripheral blood progenitor cells with Dexa BEAM and G-CSF: Timing of harvesting and composition of the leukapheresis product. Br J Cancer 1993;68:950–7.[ISI][Medline]
17 Pettengel R, Testa NG, Crowther D, Dexter TM. Transplantation potential of hematopoietic cells released into the circulation during routine chemotherapy for non-Hodgkin’s lymphoma. Blood 1993;82:2239–48.
18 Bojko P, Stellberg W, Küdde C, Scharifi M, Hermann M, Mayer S. Kinetic study of CD34+ cells during large volume peripheral blood stem cell collections. Blood 1997;90(Suppl 1):210a (Abstr 924).
19 Dicke KA, Hood D, Hanks S. Peripheral blood stem cell collection after mobilization with intensive chemotherapy and growth factors. J Hematother 1994;3:141–4.[Medline]
20 Schwella N, Beyer J, Schwaner I, Heuft HG, Rick O, Huhn D. Impact of preleukapheresis cell counts on collection results and correlation of progenitor cell dose with engraftment after high-dose chemotherapy in patients with germ cell cancer. J Clin Oncol 1996;14:1114–21.
21 Kanold J, Berger M, Halle P, Rapatel C, Schoepfer C, Lumley L. Kinetics of hematopoietic progenitor cell release induced by G-CSF alone in children with solid tumors and leukemias. Bone Marrow Transplant 1998;21:59–63.[ISI][Medline]
22 Osma MM, Ortuno F, Arriba F, Lozano ML, Heras I, Moraleda JM. Bone marrow steady-state CD34+/CD71-cell content is a predictive value of r G-CSF mobilized CD34+ cells. Bone Marrow Transplant 1998;21:983–5.[ISI][Medline]
23 Bolwell B, Pohlman B, Overmoyer B, Andresen S, Goormastic M, Dannley R. The G-CSF primed WBC correlates with CD34+ cell yield. Blood 1997;90(Suppl 1):322b (Abstr 4202).
24 Kröger N, Zeller W, Hassan HT, Krüger W, Löliger C, Zander AR. Schedule-dependency of G-CSF in peripheral blood progenitor cell mobilization in breast cancer patients. Blood 1998;91:1828–30.
Received September 27, 1999; accepted December 14, 1999.
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