| | Factors influencing the collection of peripheral blood stem cells in patients with acute myeloblastic leukemia and non-myeloid malignanciesReceived 17 December 2001; accepted 9 April 2002. Abstract Factors influencing the collection of autologous peripheral blood stem cells (PBSCs) were studied in 182 mobilization procedures performed on 145 consecutive patients with acute myeloblastic leukemia (AML; n=67) and with various non-myeloid malignancies (NMM; n=78). PBSC were collected following mobilization with chemotherapy, treatment with granulocyte colony-stimulating factor (G-CSF) or chemotherapy plus G-CSF. Fewer colony-forming unit granulocyte-macrophages (CFU-GMs) were collected from patients with AML than from patients with NMM (P<0.0001), although there were no differences in the numbers of CD34+ cells collected between both groups. Multiple regression analysis showed that chemotherapy alone was predictive of a low CD34+ yield in patients with NMM (regression coefficient (RC)=−2.1; P=0.003). In addition, the interactions “diagnosis mutliple myeloma (MM)×mobilization with chemotherapy” (RC=2.9; P=0.004) and “diagnosis MM×mobilization with chemotherapy plus G-CSF” (RC=2.1; P=0.04) also remained in the model, both showing a favorable influence. In AML, mobilization with chemotherapy plus G-CSF was associated with higher CD34+ yields (P=0.003). In this subgroup of patients, multiple regression analysis identified the number of cycles of previous chemotherapy (≤2 cycles; RC=1.3; P=0.03) and peripheral blood counts (WBC ≥1.5×109/l and monocytes >20%; RC=0.8; P=0.02) as the factors most predictive of CD34+ cell yield. These findings emphasize the need to optimize harvesting technique to enhance safety and minimize morbidity and costs of this valuable procedure.
Abbreviations:
AML, acute myeloblastic leukemia,
BC, breast cancer,
CFU-GM, colony-forming unit granulocyte-macrophage,
HD, Hodgkin’s disease,
HGF, hemopoietic growth factor,
moAb, monoclonal antibody,
MM, multiple myeloma,
NHL, non-Hodgkin’s lymphoma,
NMM, non-myeloid malignancies,
PBSC, peripheral blood stem cell
1. Introduction  PBSCs are increasingly being used for autografting in patients with malignant diseases, because of the easier collection and faster engraftment compared with marrow stem cells [1]. Among the several procedures used for PBSC mobilization, the administration of HGF either alone or following chemotherapy is currently the most common [2], [3]. Several studies have reported data on factors influencing PBSC collection, especially in patients with NMM [4], [5], [6], [7], [8], [9], [10], [11]; however, data concerning patients with AML are very limited, with only a few series addressing this issue [12], [13]. The purpose of this study was to identify predictive factors of CFU-GM and CD34+ cell mobilization in a series of 182 procedures performed on 145 consecutive patients and to compare the data obtained in patients with AML and with NMM. 2. Patients and methods 2.1. Patients This study covers 182 mobilization procedures performed on 145 consecutive patients enrolled into the autologous PBSC transplant program at the University Hospital La Fe (Spain) between November 1989 and October 1996. Of these patients, 67 presented with AML and 78 with the following NMM: 22 with NHL, 24 with HD, 20 with MM and 12 with BC. Patient characteristics are listed in Table 1. |
a
NHL (n=22), HD (n=24), MM (n=20), BC (n=12).
b
Figures refer to number of cycles of mobilization.
c
Myelotoxic drugs: BCNU, melphalan and nitrogen mustard.
d
Mantle field (five patients), inverted-Y (one patient) and total nodal (one patient). |
Patients with NMM had been pre-treated with a variety of chemotherapy regimens, the most common being CHOP and ESHAP for NHL patients, ABVD and ESHAP for patients with HD, melphalan–prednisone and VAD in MM and FEC in BC. Before PBSC collection, patients had received a median of nine chemotherapy cycles (range: 1–32) of two different regimens (range: 1–4) and 36 received prior radiotherapy. The treatment protocols administered to patients with AML varied during the period of study, and have been reported elsewhere [14], [15]. Briefly, up to April 1992 the chemotherapy consisted of an induction and a consolidation course, both with DNR plus Ara-C (group A, 24 patients). The protocol employed thereafter consisted of an induction and a consolidation course with IDR and Ara-C, plus an additional intensification course with Ara-C (group B, 18 patients). Thirteen patients, diagnosed between November 1992 and October 1994, were included in a multicenter, randomized study to determine the efficacy and safety of G-CSF in AML (group C). This protocol consisted of an induction and a consolidation course using DNR, Ara-C, and VP-16 (DAV) with or without G-CSF, followed by an intensification course with Ara-C [16]. Eight patients received DAV with G-CSF and five received DAV without G-CSF. The last group includes a variety of protocols administered to patients referred from other centers, with resistant disease, older than 60 years or with acute promyelocytic leukemia (group D, 24 patients). 2.2. PBSC mobilization Mobilization characteristics are summarized in Table 2. The median number of leukaphereses per cycle was three (range: 1–6 in NMM and 2–7 in AML). Collections in patients with NMM were performed following administration of G-CSF alone (63%), chemotherapy alone (20%), or chemotherapy plus G-CSF (17%). The chemotherapy regimen administered for patients with lymphoma (NHL and HD) was ESHAP in all except two cases. All but one patient with MM received COAP (cyclophosphamide; 600 mg/m2 p.o. for 1 day; vincristine, 1.5mg/m2 i.v. for 1 day; Ara-C, 150mg/m2 per 12h s.c. for 5 days; and prednisone, 100mg/m2 p.o. for 5 days) as a mobilization regimen. When G-CSF was administered, the dose was 5–10μg/kg per day. In patients with NMM, only one mobilization cycle was planned, except for MM patients, in whom two mobilization cycles were performed until 1992. However, nine patients with low PBSC yields were mobilized twice (seven with lymphoma, one with MM and another with BC). In AML, most mobilizations (81%) were performed with chemotherapy alone; 13% of patients received chemotherapy followed by G-CSF and 6% received G-CSF alone. In group A, collections were performed after induction and consolidation chemotherapy and in groups B and C only after consolidation, as has been reported elsewhere [16]. In those cases in which the minimum number of CD34+ cells was not collected, an additional mobilization course with COAP was administered. 2.3. Leukapheresis procedure Methods of PBSC collection and cryopreservation have been described previously [17]. Harvesting was performed using continuous flow blood cell separators, either Fenwal CS3000 plus (Fenwal, Deerfield, IL, USA) or Cobe Spectra (Cobe, Lakewood, CO, USA). In patients receiving G-CSF alone, aphereses were started on the fifth day of G-CSF administration, while in those patients undergoing PBSC collections after chemotherapy, aphereses were initiated when the leukocyte (WBC) count was ≥1×109/l and there were 20–30% monocytes in the differential count. Finally, in patients mobilized with chemotherapy plus G-CSF, aphereses were started when the blood leukocyte count reached 10×109/l. After collection, cells were frozen in 10% dimethylsulfoxide to −120°C using a KRYO-10 series (Planer Products Ltd., Sunbury, UK) controlled freezer. Cells were stored in liquid nitrogen until use. 2.4. Progenitor evaluation For the enumeration of CFU-GM, samples were grown in a methylcellulose-based clonogenic assay [18], with human placental conditioned medium used as a source of colony-stimulating factors. A quantity of 2×105 cells were plated in triplicate and incubated at 37°C and 5% CO2 in humidified atmosphere. The formation of CFU-GM colonies was scored on day 10. CD34+ cells were quantified by flow cytometric analysis [19]. Briefly, 100μl aliquots of the sample, containing between 5×105 and 10×105 cells, were incubated for 30min at 4°C with phycoerythrin (PE; [HPCA-2])-conjugated moAb anti-CD34 and fluorescein isothiocyanate (FITC)-conjugated anti-CD45 moAb (Becton Dickinson, Mountain View, CA, USA). After incubation, the red cells were lysed and washed in phosphate-buffered saline. Cells were analyzed by fluorescence-activated cell sorting (FACScan, Becton Dickinson). For each sample, 50,000 cells were analyzed. 2.5. Statistical analysis Patients with NMM and AML were analyzed separately. For patients with NMM, the explanatory variables analyzed included patient age, sex, diagnosis, mobilization method, stage of disease, prior chemotherapy, prior radiotherapy, prior exposure to stem cell-toxic chemotherapy, marrow disease and diagnosis-to-PBSC harvest interval. The variables considered for AML patients were age, sex, mobilization method, stage of disease, prior chemotherapy, diagnosis-to-PBSC harvest interval and WBC count and monocyte count when initiating aphereses. On univariate analysis, for most numerical variables two groups were formed using the median as a cut-off value. The WBC and monocyte counts were categorized according to the most discriminating cut-off values. Categorical data were divided as appropriate into groups. To analyze prior chemotherapy, two groups were considered in patients with NMM, depending on whether they had received only one regimen and a maximum of eight cycles of chemotherapy before harvest, or whether they had been more intensively pre-treated. In AML, three groups were considered according to the number of previous chemotherapy cycles (≤2, 3 or >3). Finally, to evaluate the influence of myelotoxic drugs (BCNU, melphalan and nitrogen mustard), NMM patients were divided into two groups: low exposure (<7 cycles) and high exposure (≥7 cycles). On multivariate analysis, numerical variables were maintained as above with the exception of the WBC and monocyte counts and the amount of previous chemotherapy, which were coded as described for univariate analysis. Since most patients had PBSC collections performed using a target value rather than a fixed number of collections, it was not possible to use the total number of CD34+ cells/kg collected as the dependent variable. Therefore, following the method employed by other authors [4], the total number of CD34+ cells/kg body mass were divided by the number of collection days, to derive an average yield of CD34+ cells/kg per day. The non-parametric Mann–Whitney U and Kruskal–Wallis tests were applied for the comparison of leukapheresis yields between groups on univariate analysis. To separate the independent contributions of factors associated with progenitor cell yield, multivariate analysis was performed using the generalized lineal model. The logarithm of the number of CD34+ cells was used to make residual variance approximately constant, which permitted the use of linear regression. In patients with AML, we excluded from multivariate analysis 13 cycles in which mobilization was performed with G-CSF or with chemotherapy plus G-CSF, since the residual variances in all groups were not equal. Besides linear terms, the interaction term “diagnosis×mobilization” method was also included in the model in the group of patients with NMM. Pearson’s correlation was used to examine the relationship between CD34+ and CFU-GM yields. Analysis was performed using the BMDP statistical software 1990 edition. A significance level of P<0.05 was used. 3. Results 3.1. PBSC yields PBSC collection data are listed in Table 3. Patients with AML had fewer CFU-GM collected than did patients with NMM (median: 5.5×104/kg versus 11.7×104/kg; P<0.0001), although there were no differences in the amount of CD34+ cells collected between both groups. Regression analysis showed a close relationship between the counts of CD34+ cells and CFU-GM. For patients with AML and NMM the correlation coefficient was 0.9 and 0.7, respectively (P<0.001). |
a
CFU-GM counts not available in one mobilization cycle.
b
CD34+ counts not available in five mobilization cycles, CFU-GM in four cycles and neither of them in one cycle.
c
Total number of CD34+ cells/kg collected divided by the number of collection days. |
3.2. Variables affecting the yield of CD34+ cells 3.2.1. Non-myeloid malignancies None of the factors included in the univariate analysis significantly influenced CD34+ cell yields, although a trend to better yields was observed in patients mobilized with chemotherapy plus G-CSF, compared with patients mobilized with chemotherapy or with G-CSF alone (P=0.09). Furthermore, although the variable diagnosis was not significant, after grouping MM and BC versus lymphomas, yields in the first group were significantly better (P=0.03). On multiple regression analysis, the administration of chemotherapy alone was predictive of a low CD34+ yield in cells/kg per day. In addition, the interactions “diagnosis MM×mobilization with chemotherapy” and “diagnosis MM×mobilization with chemotherapy plus G-CSF” also remained significant in the model, both showing a favorable influence (Table 4). In other words and as shown in Fig. 1, the strong negative impact on CD34+ cells yields of mobilizing with chemotherapy alone in lymphomas was not evident in patients with MM. In contrast, mobilizing with chemotherapy plus G-CSF in patients with MM was associated with excellent yields that were not obtained in lymphomas with this combination therapy.  | Predictive variables | RC | CI 95% | P-value | |
| Mobilization with chemotherapy | −2.1 | [−3.5, −0.7] | 0.003 | |
| Diagnosis MM × mobilization with chemotherapy | 2.9 | [0.9, 4.8] | 0.004 | |
| Diagnosis MM × mobilization with chemotherapy + G-CSF | 2.1 | [0.08, 4.1] | 0.04 | | | | |
3.2.2. Acute myeloblastic leukemia In these patients, the mobilization method was also an important parameter determining PBSC yields. Patients who received chemotherapy plus G-CSF mobilized significantly more CD34+ cells/kg per day than those mobilized with chemotherapy or with G-CSF alone (median: 20×106/kg per day versus 0.8×106/kg per day versus 0.9×106/kg per day, respectively; P=0.003). Higher CFU-GM yields were also achieved in this group (median: 54.6×104/kg per day versus 1.4×104/kg per day versus 9.3×104/kg per day, respectively; P=0.01). As mentioned above, in patients with leukemia, the analysis of the influence of other factors on CD34+ cell yields was limited to the 73 mobilization cycles performed only with chemotherapy, because of statistical limitations. In this subgroup of patients, univariate analysis showed that more CD34+ cells/kg per day were collected from those who had received ≤2 cycles of chemotherapy prior to PBSC harvest, those who received transplants at the first remission, those who had a shorter interval between diagnosis and transplant, and those with whom collections were performed when the WBC was ≥1.5×109/l with monocytes >20%. Multiple regression analysis identified previous chemotherapy (≤2 cycles) and peripheral blood counts (WBC ≥1.5×109/l and monocytes >20%) as the factors most predictive of CD34+ cell yield (Table 5). |
a
Total number of CD34+ cells/kg collected divided by the number of collection days. |
4. Discussion Factors influencing mobilization of PBSC are being studied extensively in patients with NMM to improve the efficacy and safety of the procedure. However, the available data concerning patients with leukemia are scarce. In this study, we included patients with NMM and a large series of patients with AML, allowing for separate analysis of both groups. To our knowledge, this series is the largest reported in which factors affecting mobilization of PBSC in patients with AML have been specifically studied. With regard to the patients with NMM, the poorer yields obtained following mobilizing with chemotherapy alone confirm previous reports [6], [20] and currently this priming method has been replaced by the combination of chemotherapy plus HGF (the most common being G-CSF and GM-CSF) or by the administration of HGF alone. In our study, the mobilization method used had a different impact on the CD34+ cell yields, depending on the diagnosis. In patients with MM, yields were good with chemotherapy and excellent with chemotherapy and G-CSF. As opposed to this, lymphoma patients had poor yields with chemotherapy alone and somewhat better ones with the association of G-CSF. Chemotherapeutic regimens administered in both diagnostic groups were, however, different. Most patients with MM were treated with COAP and most lymphoma patients were given ESHAP. Since COAP is a more myelosuppressive treatment and there is some evidence that increasing the intensity of chemotherapy improves PBSC yields [6], [21], we believe this might have been the determining factor that explains this difference, even at the expense of increasing toxicity [22]. The low yields obtained with ESHAP in our series differ from those reported by other authors [23], a discrepancy that cannot be attributed to the timing of collections. Unfortunately, it is not possible to draw definitive conclusions about the reason for these differences, since relevant data such as the patients’ clinical situations or the amount of previous chemotherapy were not described in the other report [23]. PBSC yields obtained in patients with NMM receiving G-CSF alone were satisfactory and homogenous independently of the diagnosis, but lower than those obtained with the combination of COAP and G-CSF. This is in accord with previous reports suggesting better yields with chemotherapy plus G-CSF than with G-CSF alone [2], [3], [4], [7], [24]. It must be emphasized, however, that our patients received low to intermediate doses of G-CSF (5–10μg/kg per day) and several studies have suggested a relationship between the dose of G-CSF and mobilization capacity [25], [26], [27]. Extensive prior cytotoxic chemotherapy has been reported to adversely affect the yield of PBSC [4], [8], [9], [28], [29], [30]. In our series, as in others [5], [31], [32], we were unable to detect this negative effect. This may be due to the difficulty of measuring this variable appropriately, given the large number of agents administered at different doses and combinations. In addition, chemotherapeutic drugs widely differ in their toxicity to hematopoietic stem cells [33]. Furthermore, this general difficulty might have been amplified in our study because of the heterogeneity of the patient population. In fact, when we limited the analysis to patients with MM, we did observe a significant reduction of CD34+ cell counts in those patients who received ≥12 cycles of prior chemotherapy (data not shown). Finally, a score has been recently published in an attempt to better quantify this variable, and this should be evaluated in further studies [34]. Some reports have suggested that mobilization of PBSC in AML patients is poorer than that observed in patients with NMM. Recently, in a study in 152 patients with different diseases, the diagnosis of AML was predictive of an inferior CD34+ cell yield by multivariate analysis [21]. This finding was confirmed by other groups [13]. However, with the data currently available, a definitive answer to this question cannot be given, as reported values vary widely. In some reports, more than 12×106 CD34+ cells/kg have been collected in patients with AML [35], [36], whereas in others, patients with NMM did not achieve a CD34+ cell dose of 4×106/kg [5], [7], [32]. Furthermore, the comparison is biased, since both prior chemotherapy and the chemotherapy administered for mobilization differ completely between the two groups. Our results cannot give a definitive answer to this question, since previous chemotherapy regimens were different in NMM and AML groups and most patients with AML were mobilized with chemotherapy, whereas most patients with NMM received G-CSF. Nevertheless, the finding that CD34+ cell yields were similar in both groups, whereas CFU-GM yields were higher in NMM supports the concept of a lower mobilizing potential in leukemia. This lower cloning ability of PBSC in AML is consistent with experimental studies showing a significant clonogenic defect in this disease, [37], [38], [39] probably related to the inherent nature of the disease. As in other malignancies, in AML the harvest efficiency was determined largely by the mobilizing method employed [35], [40], [41]. The best results in both CD34+ cell and CFU-GM yields were observed in those patients receiving chemotherapy plus G-CSF, which in turn was associated with a more rapid engraftment after transplant (data not shown). In patients with AML, we did observe a detrimental effect of chemotherapy on PBSC yield. Two small early studies had already suggested an adverse effect of chemotherapy in AML [42], [43]. More recently, the Bordeaux group has noted that the number of chemotherapy courses administered significantly influences PBSC mobilization [35]. In addition, some studies have specifically addressed the potential adverse effect on PBSC yields of the administration of intermediate or high-dose Ara-C [44], [45], [46]. However, in other series, the total number of chemotherapy cycles received has not influenced the PBSC harvest content [13], [44]. It is interesting to note that PBSC values obtained in our series with chemotherapy plus G-CSF were higher than those reported in other series using this combination [13], [47]. This may be because our patients had received fewer cycles of chemotherapy before mobilization, and that high-dose Ara-C was not administered before mobilization. Taken together, our results and those previously published argue for a negative effect of chemotherapy on the hemopoietic reserve of patients with AML. Despite these considerations, the current general approach includes intensification of pre-harvest treatment with the intention of in vivo purging. Thus, additional studies evaluating PBSC yields, hemopoietic recovery and survival with different treatment strategies are required to improve definition of the optimum time for PBSC collection. Lastly, among the other pre-harvest variables tested, only the WBC and monocyte count at the time of harvesting emerged as independent factors affecting the CD34+ cell yields. Defining the timing of PBSC collection is crucial to optimize the yields and some reports have proposed WBC thresholds above which maximal mobilizations are observed [5]. However, this parameter is currently considered a less-efficient predictor of PBSC yields than is monitoring the CD34+ cell count in blood [12], [48], [49] and, in our department, this measurement has been recently incorporated. Because our study was retrospective and heterogeneous the conclusions must be tentative. Nevertheless our findings indicate that factors previously described to influence PBSC yields in patients with NMM are also important in AML. Therefore, it is necessary to minimize prior chemotherapy, select adequate mobilization methods and properly timing PBSC collections to optimize this procedure. Acknowledgements A. Carral concept and design; analysis of data; critical revision of the manuscript; collection of data. J. de la Rubia concept and design; analysis of data; critical revision of manuscript. G. Martin critical revision of manuscript. S. Mollá provision of study materials; drafting of the article. J. Martinez provision of study materials. G.F. Sanz statistical expertise and critical review of manuscript. M.A. Soler provision of study materials. I. Jarque provision of study materials and critical review of manuscript. C. Jimenez provision of study materials. M.A. Sanz concept and design; critical review of manuscript and gave final approval. References [1].
[1]
Gratwohl A, Passweg J, Baldomero H, Hermans J.
Blood and marrow transplantation activity in Europe 1997: European Group for Blood and Marrow Transplantation (EBMT).
Bone Marrow Transplant. 1999;24:231. MEDLINE [2].
[2]
Alegre A, Tomas JF, Martı́nez-Chamorro C, Gil-Fernandez JJ, Fernández-Villalta MJ, Arranz R, et al.
Comparison of peripheral blood progenitor cell mobilization in patients with multiple myeloma: high-dose cyclophosphamide plus GM-CSF versus G-CSF alone.
Bone Marrow Transplant. 1997;20:211. MEDLINE [3].
[3]
Desikan KR, Barlogie B, Jagannath S, Vesole DH, Siegel D, Fassas A, et al.
Comparable engraftment kinetics following peripheral blood stem cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma.
J. Clin. Oncol. 1998;16:1547. [4].
[4]
Bensinger W, Appelbaum F, Rowley S, Storb R, Sanders J, Lilleby K, et al.
Factors that influence collection and engraftment of autologous peripheral blood stem cells.
J. Clin. Oncol. 1995;13:2547. [5].
[5]
Watts MJ, Sullivan AM, Jamieson E, Pearce R, Fielding A, Devereux S, et al.
Progenitor cell mobilization after low-dose cyclophosphamide and granulocyte colony-stimulating factor: an analysis of progenitor cell quantity and quality and factors predictive for these parameters in 101 pre-treated patients with malignant lymphoma.
J. Clin. Oncol. 1997;15:535. [6].
[6]
Schwartzberg LS, 1993. Peripheral blood stem cell mobilization in the outpatient setting. In: Wunder EW, Hénon PR, editors. Peripheral blood stem cell autograft. Heidelberg: Springer, 1993. 177 p. [7].
[7]
Moskowitz CH, Glassman JR, Wuest D, Maslak P, Reich L, Gucciardo A, et al.
Factors affecting mobilization of peripheral blood progenitor cells in patients with lymphoma.
Clin. Cancer Res. 1998;4:311. MEDLINE [8].
[8]
Haas R, Möhle R, Frühauf S, Goldschmidt H, Witt B, Flentje M, et al.
Patient characteristics associated with successful mobilizing and autografting of peripheral blood progenitor cells in malignant lymphoma.
Blood. 1994;83:3787. MEDLINE [9].
[9]
Weaver CH, Schwartzberg LS, Birch R, Greco FA, Rhinehart S, Hainsworth J, et al.
Collection of peripheral blood progenitor cells after the administration of cyclophosphamide, etoposide and granulocyte colony-stimulating factor: an analysis of 497 patients.
Transfusion. 1997;37:896. MEDLINE [10].
[10]
Dreger P, Klöss M, Petersen B, Haferlach T, Löffler H, Loeffler M, et al.
Autologous progenitor cell transplantation: prior exposure to stem cell-toxic drugs determines yield and engraftment of peripheral blood progenitor cell but not of bone marrow grafts.
Blood. 1995;86:3970. MEDLINE [11].
[11]
Sautois B, Fraipont V, Baudoux E, Fassotte MF, Hermanne JP, Jérusalem G, et al.
Peripheral blood progenitor cell collections in cancer patients: analysis of factors affecting the yields.
Haematologica. 1999;84:342. MEDLINE [12].
[12]
Schlenk RF, Dohner H, Pforsich M, Benner A, Fischer K, Hartmann F, et al.
Successful collection of peripheral blood progenitor cells in patients with acute myeloid leukaemia following early consolidation therapy with granulocyte colony-stimulating factor-supported high-dose cytarabine and mitoxantrone.
Br. J. Haematol. 1997;99:386. MEDLINE [13].
[13]
Jowitt SN, Chang J, Morgenstern GR, Howe T, Ryder WD, Testa NG, et al.
Factors which affect the CFU-GM content of the peripheral blood haemopoietic progenitor cell harvests in patients with acute myeloid leukaemia.
Br. J. Haematol. 1998;100:688. MEDLINE |
CrossRef
[14].
[14]
Sanz MA, de la Rubia J, Sanz GF, Martı́n G, Martı́nez J, Jarque I, et al.
Busulfan plus cyclophosphamide followed by autologous blood stem cell transplantation for patients with acute myeloblastic leukemia in first complete remission: a report from a single institution.
J. Clin. Oncol. 1993;11:1661. [15].
[15]
de la Rubia J, Sanz GF, Martı́n G, Martı́nez J, Cervera J, Solves P, et al.
Autologous blood stem cell transplantation for acute myeloblastic leukemia in first complete remission: intensification therapy before transplantation does not prolong disease-free survival.
Haematologica. 1999;84:125. MEDLINE [16].
[16]
Heil G, Hoelzer D, Sanz MA, Lechner K, Liu Ying JA, Papa G, et al.
A randomized, double-blind, placebo-controlled, phase III study of filgrastim in remission induction and consolidation therapy for adults with de novo acute myeloid leukemia: The International Acute Myeloid Leukemia Study Group.
Blood. 1997;90:4710. MEDLINE [17].
[17]
de la Rubia J, Sanz MA.
Técnicas para la movilización y recolección de células hematopoyéticas.
Sangre. 1991;36:181. [18].
[18]
Iscove NN, Senn JS, Till JE, McCulloch EA.
Colony formation by normal and leukemic human marrow cells in culture: effect of conditioned medium from human leukocytes.
Blood. 1971;37:1. MEDLINE [19].
[19]
Sutherland DR, Anderson L, Keeney M, Nayar R, Chin-Yee I.
The ISHAGE guidelines for CD34+ cell determination by flow cytometry: International Society of Hematotherapy and Graft Engineering.
J. Hematother. 1996;5:213. MEDLINE [20].
[20]
Pettengell R, Testa NG, Swindell R, 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. MEDLINE [21].
[21]
Stewart DA, Guo D, Morris D, Poon MC, Ruether BA, Jones AR, et al.
Superior autologous blood stem cell mobilization from dose-intensive cyclophosphamide, etoposide, cisplatin plus G-CSF than from less intensive chemotherapy regimens.
Bone Marrow Transplant. 1999;23:111. MEDLINE [22].
[22]
Marit G, Thiessard F, Faberes C, Cony-Makhoul P, Boiron JM, Bernard P, et al.
Factors affecting both peripheral blood progenitor cell mobilization and hematopoietic recovery following autologous blood progenitor cell transplantation in multiple myeloma patients: a monocentric study.
Leukemia. 1998;12:1447. MEDLINE [23].
[23]
Watts MJ, Leverett D, Sullivan AM, Peniket AJ, Perry AR, MacMillan A.
A comparison of ESHAP + G-CSF versus cyclophosphamide (1.5 g/m2) + G-CSF for PBSC mobilization in pre-treated lymphoma patients: a matched pair analysis.
Blood. 1996;88:396a;
. [24].
[24]
Desikan KR, Barlogie B, Jagannath S, Vesole DH, Siegel D, Fassas A, et al.
Comparable engraftment kinetics following peripheral-blood stem cell infusion mobilized with granulocyte colony-stimulating factor with or without cyclophosphamide in multiple myeloma.
J. Clin. Oncol. 1998;16:1547. [25].
[25]
Zeller W, Guttensohn K, Stockschläder M, Dierlamm J, Kröger N, Koehne G, et al.
Increase of mobilized CD34-positive peripheral blood progenitor cells in patients with Hodgkin’s disease, non-Hodgkin’s lymphoma and cancer of the testis.
Bone Marrow Transplant. 1996;17:709. MEDLINE [26].
[26]
Kröger N, Zeller W, Fehse N, Hassan HT, Krüger W, Gutensohn K, et al.
Mobilizing peripheral blood stem cells with high-dose G-CSF alone is as effective as with Dexa-BEAM plus G-CSF in lymphoma patients.
Br. J. Haematol. 1998;102:1101. MEDLINE |
CrossRef
[27].
[27]
Weaver CH, Birch R, Greco FA, Schwartzberg L, McAneny B, Moore M, et al.
Mobilization and harvesting of peripheral blood stem cells: randomized evaluations of different doses of filgrastim.
Br. J. Haematol. 1998;100:338. MEDLINE |
CrossRef
[28].
[28]
Ketterer N, Salles G, Moullet I, Dumontet C, ElJaafari-Corbin A, Tremisi P, et al.
Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies.
Br. J. Haematol. 1998;103:235. MEDLINE |
CrossRef
[29].
[29]
Tricot G, Jagannath S, Vesole D, Nelson J, Tindle S, Miller L, et al.
Peripheral blood stem cell transplants for multiple myeloma: identification of favorable variables for rapid engraftment in 225 patients.
Blood. 1995;85:588. MEDLINE [30].
[30]
Gertz MA, Lacy MQ, Inwards DJ, Pineda AA, Chen MG, Gastineau DA, et al.
Factors influencing platelet recovery after blood cell transplantation in multiple myeloma.
Bone Marrow Transplant. 1997;20:375. MEDLINE [31].
[31]
Kotasek D, Shepherd KM, Sage RE, Dale BM, Norman JE, Charles P, et al.
Factors affecting blood stem cell collections following high-dose cyclophosphamide mobilization in lymphoma, myeloma and solid tumors.
Bone Marrow Transplant. 1992;9:11. MEDLINE [32].
[32]
McQuaker IG, Haynes AP, Stainer C, Anderson S, Russell NH.
Stem cell mobilization in resistant or relapsed lymphoma: superior yield of progenitor cells following a salvage regimen comprising ifosphamide, etoposide and epirubicin compared to intermediate-dose cyclophosphamide.
Br. J. Haematol. 1997;98:228. MEDLINE [33].
[33]
Mauch P, Constine L, Greenberger J, Knospe W, Sullivan J, Liesveld JL, et al.
Hematopoietic stem cell compartment: acute and late effects of radiation therapy and chemotherapy.
Int. J. Radiat. Oncol. Biol. Phys. 1995;31:1319. Abstract |
Full-Text PDF (3294 KB)
|
CrossRef
[34].
[34]
Drake M, Ranaghan L, Morris TC, Nolan L, Desai ZR, Irvine AE, et al.
Analysis of the effect of prior therapy on progenitor cell yield: use of a chemotherapy scoring system.
Br. J. Haematol. 1997;98:745. MEDLINE [35].
[35]
Reiffers J.
Peripheral blood stem cell transplantation in acute myeloid leukemia: the experience of the Bordeaux Group.
Stem Cells. 1995;13:19.
CrossRef
[36].
[36]
Linker CA, Ries CA, Damon LE, Sayre P, Navarro W, Rugo HS, et al.
Autologous stem cell transplantation for acute myeloid leukemia in first remission.
Biol. Blood Marrow Transplant. 2000;6:50. Abstract |
Full-Text PDF (87 KB)
|
CrossRef
[37].
[37]
Chang J, Geary CG, Testa NG.
Long-term bone marrow damage after chemotherapy for acute myeloid leukaemia does not improve with time.
Br. J. Haematol. 1990;75:68. MEDLINE |
CrossRef
[38].
[38]
Carlo-Stella C, Tabilio A, Regazzi E, Garau D, La Tagliata R, Trasarti S, et al.
Effect of chemotherapy for acute myelogenous leukemia on hematopoietic and fibroblast marrow progenitors.
Bone Marrow Transplant. 1997;20:465. MEDLINE [39].
[39]
Straetmans N, Herman P, Van Bockstaele DR, Michaux L, Hagemeijer A, Ferrant A.
Haemopoietic defect and decreased expansion potential of bone marrow autografts from patients with acute myeloid leukaemia in first remission.
Br. J. Haematol. 1998;101:571. MEDLINE |
CrossRef
[40].
[40]
Teshima T, Harada M, Takamatsu Y, Makino K, Taniguchi S, Inaba S, et al.
Cytotoxic drug and cytotoxic drug/G-CSF mobilization of peripheral blood stem cells and their use for autografting.
Bone Marrow Transplant. 1992;10:215. MEDLINE [41].
[41]
Marit G, Boiron JM, Reiffers J. Acute myeloid leukaemia. In: Reiffers J, Goldman JM, Armitage JM, editors. Blood stem cell transplantation. UK: Martin Dunitz Ltd., 1998. 91 p. [42].
[42]
To LB, Haylock DN, Kimber RJ, Juttner CA.
High levels of circulating haemopoietic stem cells in very early remission from acute non-lymphoblastic leukaemia and their collection and cryopreservation.
Br. J. Haematol. 1984;58:399. MEDLINE |
CrossRef
[43].
[43]
Reid CD, Kirk A, Muir J, Chanarin I.
The recovery of circulating progenitor cells after chemotherapy in AML and ALL and its relation to the rate of bone marrow regeneration after aplasia.
Br. J. Haematol. 1989;72:21. MEDLINE |
CrossRef
[44].
[44]
Cantin G, Marchand-Laroche D, Bouchard MM, Leblond PF.
Blood-derived stem cell collection in acute non-lymphoblastic leukemia: predictive factors for a good yield.
Exp. Hematol. 1989;17:991. [45].
[45]
Szer J, Juttner CA, To LB, Bradstock KF, Sage RE, Enno A, et al.
Post-remission therapy for acute myeloid leukemia with blood-derived stem cell transplantation: results of a collaborative phase II trial.
Int. J. Cell Clon. 1992;10:114. [46].
[46]
Martı́n C, Torres A, León A, Rubio V, Alvarez MA, Herrera C, et al.
Autologous peripheral blood stem cell transplantation (PBSCT) mobilized with G-CSF in AML in first complete remission: role of intensification therapy in outcome.
Bone Marrow Transplant. 1998;21:375. MEDLINE [47].
[47]
Reichle A, Hennermann B, Meidenbauer N, Zaiss M, Bross KJ, Andreesen R.
Peripheral blood stem cell transplantation (PBSCT) during consolidation treatment of the novo acute myelogenous leukemia.
Blood. 1996;88:287b;
. [48].
[48]
Armitage S, Hargreaves R, Samson D, Brennan M, Kanfer E, Navarrete C.
CD34 counts to predict the adequate collection of peripheral blood progenitor cells.
Bone Marrow Transplant. 1997;20:587. MEDLINE [49].
[49]
Yu J, Leisenring W, Bensinger WI, Holmberg LA, Rowley SD.
The predictive value of white cell or CD34+ cell count in the peripheral blood for timing apheresis and maximizing yield.
Transfusion. 1999;39:442. MEDLINE |
CrossRef
Bone Marrow Transplant Unit, Hematology Service, University Hospital La Fe, 46009 Valencia, Spain  Corresponding author. Tel.: +34-96-386-8757; fax: +34-96-386-8757.
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