Factors Affecting Mobilization of Peripheral Blood Progenitor Cells in Patients with Lymphoma’

Vol. 4, 311-316, February 1998 Clinical Cancer Research 311

Craig H. Moskowitz,2 Jill R. Glassman, (median, 13 versus 22 days; P 0.06). Patients who received 1l cycles of chemotherapy prior to PBPC mobilization David Wuest, Peter Maslak, Lilian Reich, tended to have delayed platelet recovery to >20,090/&l and Anthony Gucciardo, Nancy Coady-Lyons, to require more platelet transfusions than less extensively Andrew D. Zelenetz, and Stephen D. Nimer pretreated patients (median, 13.5 versus 23.5 days; P 0.15; Division of Hematologic Oncology, Department of Medicine median number of platelet transfusion episodes, 13 versus 9; [C. H. M., D. W., P. M., L. R., A. G., N. C-L., A. D. Z., S. D. N.] and P = 0.17). Department of Biostatistics [J. R. G.], Memorial Sloan-Kettering Cancer Center, New York, New York 10021 These data suggest that current strategies to mobilize PBPCs may be suboptimal in patients who have received either stem cell-toxic chemotherapy or 11 cycles of chem- ABSTRACT otherapy prior to PBPC mobilization. Alternative ap- The objective of this study was to identify factors asso- proaches, such as ex vivo expansion or the use of other ciated with poor mobilization of peripheral blood progenitor growth factors in addition to G-CSE, may improve mobili- cells (PBPCs) or delayed platelet engraftment after high- zation of progenitor cells for PBPC transplantation. dose therapy and autologous stem cell transplantation in patients with lymphoma. INTRODUCTION Fifty-eight patients with Hodgkin’s disease or non- The use of high-dose chemoradiotherapy supported by Hodgkin’s lymphoma underwent PBPC transplantation as cryopreserved autologous hematopoietic progenitor cells is ef- the “best available therapy” at Memorial Sloan-Kettering fective in treating relapsed HD3 and NHL; a high complete Cancer Center (New York, NY) between 1993 and 1995. response rate is seen and a significant fraction of patients appear PBPCs were mobilized with either granulocyte colony-stim- to be cured by this approach (1, 2). The preferred source of ulating factor (G-CSE) alone (n = 19) or G-CSE following progenitor cells has shifted from bone marrow to peripheral combination chemotherapy (n = 39). Forty-eight of these blood over the last several years, because of logistical and other patients underwent a PBPC transplant, receiving a condi- advantages of collecting PBPCs. PBPCs provide more rapid tioning regimen containing cyclophosphamide, etoposide, hematopoietic recovery than bone marrow-derived progenitors, and either total body irradiation, total lymphoid irradiation, if the PBPCs are collected following a strategy to mobilize or or carmustine increase the number of circulating progenitor cells (3). In con- A median number of 46 x 106 CD34+ cells/kg were trast, the rapidity of hematopoietic recovery using unmobilized obtained with a median of three leukapheresis procedures. PBPCs is not significantly different from that using bone mar- Mobilization of PBPCs using chemotherapy plus G-CSE was row cells (4). Since the initial demonstration that high-dose superior to G-CSE alone (6.7 x 106 versus 1.5 x 106 CD34+ cyclophosphamide, with or without GM-CSF, can mobilize cells/kg; P = 0.0002). Poorer mobilization of progenitor cells large numbers of progenitor cells into the peripheral blood (5, was observed in patients who had previously received stem 6), various combinations of chemotherapy, with or without cell-toxic chemotherapy, including (a) nitrogen mustard, cytokines, have been used to obtain sufficient numbers of pro- procarbazine, meiphalan, carmustine or >7.5 g of cytara- genitor cells for autologous transplant. The use of CSFs follow- bine chemotherapy premobilization (2.0 x 106 versus 6.0 x ing combination chemotherapy appropriate for the patient’s 106 CD34+ cells/kg; P 0.005), or (b) 11 cycles of any underlying disorder is currently the most common approach to previous chemotherapy (2.6 x 106 versus 6.7 x 106 CD34+ stem cell mobilization. cells/kg; P = 0M2). Platelet recovery to >20,000/id was Prior to the shift from bone marrow transplants to PBPCT delayed in patients who received <2.0 x 106 CD34+ cells for patients with lymphoma, some patients received both bone marrow progenitor cells and PBPCs because of concerns about the long-term engraftment potential of PBPCs. The amount or type of prior chemotherapy received has been reported to affect Received 3/21/97; revised 10/15/97; accepted 10/27/97. the mobilization of PBPCs as well as the long-term survival rate The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with I 8 U.S.C. Section 1 734 solely to indicate this fact. I This work was supported by National Cancer Institute Grant CA05826-34 from the United States Public Health Service and by The 3 The abbreviations used are: HD, Hodgkin’s disease: PBPC, peripheral Dewitt Wallace Foundation and the M. Lacher Research Foundation. blood progenitor cell; PBPCT, PBPC transplantation: CSF, colony- 2 To whom requests for reprints should be addressed, at Division of stimulating factor; GM-CSF, granulocyte-macrophage CSF; NHL, non- Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, 1275 Hodgkin’s lymphoma; IGL, intermediate-grade NHL; MNC, mononu- York Avenue, New York, NY 10021. Phone: (212) 639-2696; Fax: clear cell; TB!, total body irradiation; TLI, total lymphoid irradiation; (212) 717-3394; E-mail: [email protected]. ASCT, autologous stem cell transplantation.

Ta ble I Distribution of pa tient characteristics

-- -- All (%) LGL”-” IGL” HDd Total 58 8 39 11 No. that received SCTC’ 23 (40) 4 10 9 No. that received previous XRT 16 (28) 0 8 8 Male 35 (60) 1 26 6 Female 23 (40) 7 13 5 No. with bone marrow + 15 (26) 7 7 1 No. that received boost’ 18 (3 1 ) I 16 1 No. that received HDCYTX 15 (26) 2 12 1 G-CSF mobilization 19 (33) 4 9 6 Chemotherapy/G-CSF mobilization 39 (67) 4 30 5 BM infused 16(33) 6 5 5 No. that received TBITTLI 30 (63) 8 21 1 Chemotherapy only 18 (37) 0 9 9

ii LGL. low-grade lymphoma: SCTC. stem cell-toxic chemotherapy: XRT, radiotherapy: HDCYTX, high dose cyclophosphamide. I, Seven patients with follicular small cleaved cell and one patient with follicular mixed small- and large-cell lymphoma.

‘ Thirty-one patients with diffuse large-cell lymphoma, 5 patients with diffuse mixed lymphoma, and 3 patients with immunoblastic lymphoma. ,1 Nine patients with nodular sclerosis, one patient with mixed cellularity, and one patient with lymphocyte-predominant HD.

C. Two or more cycles of procarbazine, nitrogen mustard, melphalan, nitrosoureas, or >7.5 g cytarabine prior to PBPC mobilization. I Hyperfractionated radiotherapy given to 1-2 sites in BID fractions over a 1-2-week period (total dose, 1800-3600 cGy).

of patients with several different hematological malignancies. Transplant Regimens Used. Twenty-nine patients with Therefore, we analyzed the efficacy of progenitor cell collection NHL received TBI (1200-1375 cOy), 60 mg/kg/day cyclophos- and hematological recovery posttransplantation in patients with phamide for 2 days, and 250 or 350 mg/m’ etoposide for 3 days, lymphoma who received either a chemotherapy-only or a chemo- and 9 patients received 6000 mg/m2 cyclophosphamide, 1600 therapy- and radiotherapy-containing transplant conditioning mg/m2 etoposide, and 450 mg/m2 carmustine. One patient with regimen. Using univariate and multivariate analyses, we identi- HD who had not received extensive irradiation received TLI, fled several factors that were associated with successful PBPC 4500 mg/m2 cyclophosphamide, and 1000 mg/m2 etoposide. mobilization and rapid hematological recovery. We identified Nine patients with HD who had received extensive radiotherapy both patient-related and treatment-related factors that may aid in in the past were treated with 6000 mg/m2 cyclophosphamide, optimizing patient management and the design of clinical trials. 1600 mg/m2 etoposide, and 300 mg/m2 carmustine. Seventeen patients with NHL and 1 patient with HD had bulky disease PATIENTS AND METHODS prior to transplant and received hyperfractionated boost radio- Patient Information. Fifty-eight patients with HD or therapy ( 1800-3600 cGy) to the sites of bulky disease. NHL that was histologically confirmed at Memorial Hospital PBPC Mobilization. Patients underwent between one underwent PBPC mobilization between 1993 and 1995. This and eight leukapheresis procedures in an attempt to obtain at group represented all patients transplanted between 1993 and least 2 x 106 CD34+ cells/kg or 4 X l0 MNCs/kg. For each 1995 who were not eligible for cytokine trials or had not apheresis, 10 liters of blood were processed over a 2.5-3-h time received initial salvage chemotherapy at Memorial Hospital. period (representing a median number of blood volumes pro- Eleven patients had HD, and 47 patients had NHL. Forty-eight cessed per collection of 1 .9; range, I .4-3.4). Bone marrow ofthese patients ultimately received a PBPCT, of which 46 were harvests were performed for all patients, but the bone marrow evaluable for engraftment. Patients <65 years old with relapsed was kept as a back-up (i.e., should the patient not engraft) for all HD or NHL were offered PBPCT if their disease was responsive patients except the first six patients, who received bone marrow to salvage chemotherapy and they were HIV negative, had plus PBPCs regardless of the number of PBPCs obtained. A adequate pulmonary and cardiac function, and had a serum minimum of I x l0 MNCsIkg of bone marrow was collected. creatinine <2.0 mg/dl and a serum bilirubin <2.0 mg/dl. The If <2 x 106 CD34+ cell/kg were obtained, both PBPCs and autologous transplant was given as standard of care for the bone marrow cells were reinfused. Sixteen patients received treatment of chemosensitive relapsed or primary refractory lym- bone marrow and PBPCs: 1 1 patients with NHL and S with HD. phoma, and the conditioning regimen consisted of either cyclo- Patients with chemosensitive disease received disease- phosphamide, carmustine, etoposide (CBV); TBI, cyclophospha- specific chemotherapy and 10 p.g/kg/day G-CSF to mobilize mide, etoposide (TBI/Cy/Etop); or TLI, cyclophosphamide, PBPCs. Thirty patients received ifosfamide, carboplatin, and etoposide (TLI/Cy/Etop) conditioning regimens, as described etoposide; 5 patients received cyclophosphamide (3 g/m2); 2 previously by us (7, 8) and other centers (9, 10). The distribution patients received cyclophosphamide, doxorubicin, vincristine, of patient characteristics, including the number of cycles of prior and prednisone; 1 patient received etoposide, vinblastine, and chemotherapy, the presence or absence of bone marrow involve- doxorubicin; and I patient received methotrexate and cytara- ment, and the type of prior chemotherapy and radiotherapy bine. Patients whose disease was in second (or greater) remis-

received by the patients, is listed in Table 1 . The median age for sion received 10 p.g/kg/day G-CSF alone for mobilization. Leu- all patients was 45; the median ages for patients with low-grade kapheresis was initiated when the white blood count was 1000 NHL, IGL, and HD were 46, 50, and 31, respectively. WBCs4i.l and continued on a daily basis (except on Sunday) for

a median of 3 days in patients receiving chemotherapy and Table 2 Pro gnostic factors fo r CD34+ cells/kg collection G-CSF. In patients who had PBPCs mobilized with G-CSF CD34+ cells/kg alone, G-CSF was given for 7-9 days and PBPC collection was Factor n (median) P initiated on day S and continued on a daily basis (except on NHL 47 5.1 Saturday) for a median of 3 days. HD 11 1.6 0.06 Prior to cryopreservation, MNCs in each leukapheresis < 1 1 cycles 39 6.7 collection were analyzed for CD34 expression using flow cy- ll cycles 19 2.6 0.02 No SCTC 35 6.0 tometry. Briefly, 250 p.1 of the apheresis sample were incubated SCTC 23 2.0 0.005 with a FITC-conjugated CD34 monoclonal antibody (HPCA1, Chemotherapy/G-CSF 39 6.7 Becton Dickinson, Mountainview, CA) and a phycoerythrin- mobilization conjugated CD33 monoclonal antibody (MY9, Coulter, Hialeah, G-CSF mobilization 19 1.5 0.0002 No previous XRT 42 5.5 FL) for 30 mm at 4#{176}C.Erythrocytes were then lysed using a Previous XRT 16 3.7 0.25 commercially available lysing solution (Immunoprep Leukocyte a SCTC, stem cell-toxic chemotherapy; XRT, radiotherapy. Preparation System, Coulter), and the samples were immedi- ately analyzed using a EPICS Profile II (Coulter) flow cytom- eter equipped with a 488 nm laser. Approximately 100,000 events were measured for each sample, and forward and side scatter characteristics were used to discriminate between the similar but are not reported because median values were the populations of interest and erythrocytes/debris. The CD34+ preferred parameter for describing the results.) Subsequently, population was identified with a dual parameter histogram plot- multiple regression analyses were performed following log ting green fluorescence (Y axis) versus side scatter (X axis). transformation of the values for these same variables to identify Subsets within the CD34+ population were identified by low those variables that were most predictive of PBPC mobilization and intermediate side scatter patterns, as well as CD33 positiv- and platelet recovery. ity. The percentage of CD34+ cells was obtained by dividing the number of events in the CD34+ gate (both CD33+ and RESULTS

CD33 - fractions) by the total number of events analyzed and PBPC Mobilization. Forty-eight of the 58 patients who multiplying by 100. To obtain the total number of CD34+ underwent leukapheresis procedures underwent transplantation. cells/pA, the percentage of CD34+ cells was multiplied by the Four patients did not undergo immediate transplantation be-

WBC count. cause of either disease progression (n = 2) or marked deterio- All hematopoietic progenitor cell components (bone mar- ration in their performance status (n 2). Six patients had row, buffy coat, or leukapheresis product) were frozen within PBPCs collected prior to therapeutic whole-pelvis radiation as a 24 h of collection using 5% DMSO (Cryoserv, Research Indus- precaution, in case they needed cryopreserved stem cells to tries Corp., Salt Lake City, UT), 6% hydroxyethyl starch (Pen- support a future autologous transplant for relapsed disease. tastarch, McGaw Inc., Irvine, CA) and 4% serum albumin Although the quantity of CD34+ cells is now used to (Albuminar-25, Armour Pharmaceutical Co., Kankakee, IL) as define the adequacy of PBPC collection, initially the number of the cryopreservation solution (final concentrations). Compo- MNCs/kg was more reliable, and we used that number to define nents were placed in a -90#{176}Celectrical freezer overnight and what constituted an adequate collection. Nonetheless, CD34+ then transferred to a - 135#{176}Celectrical freezer for storage. cell counts were analyzed on all patients, and univariate Wilc- In-Hospital Management. All patients were cared for in oxon rank tests were performed to determine what factors af- single rooms once the absolute neutrophil count was <500/pA. fected the collection of CD34+ cells (Table 2). A median of Fever in the neutropenic patient was usually managed with 5.1 x 106 CD34+ cells/kg were obtained from patients with Timentin and Gentamicin, with the addition of Vancomycin NHL, and 1.6 x 106 CD34+ cells/kg were obtained from and/or Amphotericin B when necessary for continuing or recur- patients with HD (P = 0.06). Sixteen patients received bone rent fever. All patients received 5-10 pg/kg/day G-CSF s.c. marrow in addition to PBPCs. The median number of MNCsfkg posttransplantation. RBC transfusions were administered for a infused in patients who received both bone marrow and periph- hemoglobin concentration 7 g/dl. Platelet transfusions were eral blood was 4.2 X 108 (range, 0.7-14.0 X 108). Patients with administered prophylactically for a platelet count <20,000/pA NHL received a median of 4.7 X 108 MNCs/kg, and those with within 10 days of transplant, or a platelet count < 10,000/pA HD received 3.4 x 108 MNCs/kg. In addition, the median beyond that day, if the patient had no other risk factors for number of CD34+ cells/kg infused in these 16 patients was bleeding. All blood products were leukocyte depleted and irra- 0.6 X 106 (range, 0-6.0). Patients who received G-CSF alone diated prior to administration. mobilized significantly fewer PBPCs than those who received

Statistical Analysis. This was a retrospective study to G-CSF + chemotherapy (median CD34+ cells collected/kg = identify prognostic factors that predict for adequate PBPC mo- 1.5 X 106 versus 6.7 X 106; p 0.0002). Patients who received bilization and rapid hematological recovery. Univariate analyses previous treatment with nitrogen mustard, procarbazine, mel- were performed on 8 previously identified variables that might phalan, or nitrosoureas or >7.5 g of cytarabine chemotherapy affect CD34+ PBPC mobilization and on 10 variables that (referred to as stem cell-toxic chemotherapy; see Tables 1 and 2) might affect the speed of platelet recovery. For both analyses, a had significantly poorer mobilization (median, 2.0 X 106 versus

Wilcoxon rank test was used in stage one of the analysis to 6.0 X 106 CD34+ cells/kg; P = 0.005). In addition, patients screen the possible prognostic factors. (The t test results were who received 1 1 cycles of chemotherapy prior to PBPC mo-

Table 3 Correlation of days to platelet count of 20,000/pA versus the Transfusions. The 48 patients undergoing PBPCT re- number of CD34+ cells/kg infused in patients who received a TBI/ ceived a median of S units of packed RBCs posttransplantation TLI- versus non-TBITI’LI-containing transplant-conditioning regimen and had received nine platelet transfusion episodes before suf- No. of CD34+ Days to platelet count ficient endogenous hematopoietic recovery occurred to obviate cells/kg >20,0004,]” ii the need for transfusions. No TBI/TLI >2 million 12 12 Length of Hospital Stay. The median length of stay was <2 million 22 TBWTLI >2 million 15 21 29 days, which included the 7-1 1 days needed to administer the <2 million 24 6 conditioning regimen. Patients who received TBI required 7 31 days longer hospitalization than patients who received a che- All >2 million 13 <2 million 22 13 motherapy-only regimen (median, 31 versus 24 days; P = 0.008). ‘C p = 0.06 by Wilcoxon test (when all patients were analyzed).

DISCUSSION The efficacy of PBPCT versus autologous bone marrow bilization had fewer CD34+ cells collected (median, 2.6 X l0 transplantation for patients with lymphoma remains unclear, but

versus 6.7 x 106 CD34+ cells/kg; P = 0.02). Patients who had a randomized trial comparing G-CSF-mobilized PBPCT with received radiotherapy or had bone marrow involvement with autologous bone marrow transplantation in lymphoma patients lymphoma at any time prior to mobilization had median CD34+ determined that PBPC transplants significantly reduce the num- cell collections similar to those of patients with no prior radio- ber of platelet transfusions, the time to platelet and neutrophil

therapy or marrow involvement (P = 0.30 and 0.64, respec- recovery, and the length of hospital stay (1 1). Tumor cell tively; see Table 2). contamination of PBPCs appears to be less than bone marrow, Multiple regression analysis of log-transformed CD34+ but the reduction may not be clinically relevant. A survival cell counts identified mobilization regimen (G-CSF alone versus benefit for PBPCT was suggested by a retrospective analysis chemotherapy + G-CSF) and stem cell-toxic chemotherapy from the University of Nebraska; “good prognosis” patients (received or not received) as the factors most predictive of with relapsed IGL (defined by the following: a tumor mass 10 CD34+ cell yield after controlling for the other factors listed in cm, 2 prior chemotherapy treatment programs prior to PBPC Table 2 (P = 0.005 and 0.009, respectively). mobilization, and chemotherapy-sensitive disease) who re- Hematological Recovery. Forty-six of 48 patients had ceived PBPCs as the stem cell source had a superior event-free hematopoietic reconstitution posttransplantation with a median survival compared to patients who received bone marrow (12). time to absolute neutrophil count recovery of >500/pA of 9 days However, other retrospective studies have not suggested a ben- (range, 6-16 days), whereas 2 patients were not evaluable for efit. A prospective randomized trial is under way to determine neutrophil or platelet engraftment because of early mortality. whether PBPCT provides a therapeutic advantage over autolo- There was no difference in median time to neutrophil recovery gous bone marrow transplantation for patients with IGL. in patients who received G-CSF mobilized progenitor cells The mobilization of PBPCs using chemotherapy and/or versus those who received chemotherapy plus G-CSF mobilized hematopoietic growth factors is generally successful; however, progenitor cells (9 days in both subgroups). the optimal scheme for procuring progenitor cells, especially in Univariate Analysis. The median number of days to patients who have been heavily pretreated, has not been defined. reach a platelet count >20,000/pA was 16.5 (range, 6-47 days) Several studies have delineated parameters that may be associ- and was not significantly different in patients who received ated with poor mobilization of PBPCs, including slow recovery G-CSF versus chemotherapy plus G-CSF mobilized progenitor of monocytes and platelets at the time of PBPC collection, poor cells ( 15 versus 17 days). Patients who had received 1 1 cycles performance status, the use of <4 g/m of cyclophosphamide of chemotherapy prior to PBPC collection tended to have more for mobilization, prior radiation therapy, receiving 6 cycles of delayed platelet recovery than those who received < 1 1 cycles of chemotherapy prior to PBPC mobilization, cytotoxic chemo- chemotherapy prior to PBPC collection (median, 23.5 versus therapy within 2 months of PBPC mobilization, and increasing

13.5 days; P = 0. 15). Patients who received >2.0 X 106 age and bone marrow involvement ( 13-1 6). In addition, it was CD34+ cells/kg had faster platelet recovery to >20,000/pA than difficult to mobilize PBPCs in patients who had previously

those who received <2.0 X 106 CD34+ cells/kg (median, 13 received MOPP, Dexa-BEAM, or melphalan chemotherapy, and

versus 22 days; P 0.06). The observed effect ofcell dose upon significant delays in platelet recovery were seen in these patients platelet recovery was seen in patients who received a TBI- after high-dose therapy and ASCT ( 17, 1 8, 19). containing conditioning regimen (15 versus 24 days) and in We recently reported that in patients with IGL who re- those who received a chemotherapy-only conditioning regimen ceived hematopoietic growth factors as the sole mobilization (12 versus 22 days; see Table 3). strategy (20), prior therapy with specific stem cell-toxic chemo- Multiple regression analysis of log-transformed time to therapeutic agents (either 2 cycles of nitrogen mustard, pro- platelet count 20,000/p.l identified the number of CD34+ carbazine, nitrosoureas, or melphalan or 7.5 g of cytarabine) cells infused and whether or not a patient received a TBI- predicted for the collection of statistically fewer CD34+ cells, containing conditioning regimen as the factors most predictive burst-forming unit erythroid, MNCs, and granulocyte- of the speed of platelet recovery (P = 0.06 and 0.10, respec- macrophage colony-forming units per kg by repeated leuka- tively). phereses. This definition of stem cell-toxic chemotherapy also

predicted for delayed platelet count recovery to 20,000/p.l when can easily be applied to patients with advanced-stage HD. compared to patients who were not similarly treated. Chemotherapy programs, such as ABVD (the combination of In the current study, we examined PBPC mobilization and doxorubicin, vinblastine, bleomycin, and dacarabazine), have hematological recovery in patients with relapsed and primary been shown in randomized clinical trials to have efficacy equiv- refractory HD or NHL. G-CSF plus combination chemotherapy alent to the more toxic and leukemogenic nitrogen mustard- was more effective at mobilizing PBPCs than G-CSF alone, based chemotherapy programs for the initial treatment of ad- using both univariate and multivariate analysis, and the use of vanced-stage HD (22). Prognostic models have been developed combination chemotherapy plus G-CSF provided the added (23) that can reliably predict which patients with advanced-stage benefit of further cytoreduction of the lymphoma prior to my- HD have less than a 50% chance of long-term event-free sur- eloablative therapy. After evaluating all of the variables that vival; perhaps the use of doxorubicin, vinblastine, bleomycin, have previously been reported to adversely affect the collection and dacarabazine as initial treatment in these patients who may of CD34+ cells, we determined that patients who had received later require an ASCT for relapsed or primary refractory disease either stem cell-toxic chemotherapy (as defined above and in would be especially prudent. Ref. 20) or I 1 cycles of chemotherapy prior to PBPC mobi- Although earlier PBPC collection could result in more lization had a statistically significant poorer yield of CD34+ lymphoma cell contamination of the apheresis product, this cells, using univariate analysis. Multiple regression analysis speculation cannot be answered by available data. Various purg- determined that only a prior history of receiving stem cell-toxic ing strategies are being developed that may ultimately be useful chemotherapy (i.e. , being “extensively pretreated”) but not re- when more effective treatment regimens have been developed. ceiving II cycles of prior chemotherapy, and receiving G- Such approaches may be combined with ex vito expansion or CSF alone to mobilize PBPCs, predicted for a poor yield of the use of other growth factors in addition to G-CSF (such as CD34+ cells. stem cell factor or flt-3 ligand), which may increase the number Despite differences in the efficacy of PBPC mobilization, of PBPCs available for transplantation. rapid hematopoietic recovery was seen in nearly all patients infused with >2.0 X 106 CD34+ cells/kg, independent of REFERENCES whether they had received prior irradiation or stem cell-toxic 1. Philip. T.. Gugliemli, C., Hagenbeck, A.. Sommers. K.. Lelie, H.. chemotherapy. 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