A randomised study comparing peripheral blood progenitor mobilisation using intermediate-dose cyclophosphamide plus lenograstim with lenograstim alone

We conducted a prospective randomised study to compare the efficiency of out-patient progenitor cell mobilisation using either intermediate-dose cyclophosphamide (2 g/m(2)) and lenograstim at 5 micrograms/kg (Cyclo-G-CSF group, n=39) or lenograstim alone at 10 micrograms/kg (G-CSF group, n=40). The end points were to compare the impact of the two regimens on mobilisation efficiency, morbidity, time spent in hospital, the number of apheresis procedures required and engraftment kinetics. Successful mobilisation was achieved in 28/40 (70%) in the G-CSF group vs 22/39 (56.4%) for Cyclo-G-CSF (P=0.21). The median number of CD34+ cells mobilised was 2.3 x 10(6)/kg and 2.2 x 10(6)/kg for G-CSF and cyclo-G-CSF arms following a median of two apheresis procedures. Nausea and vomiting and total time spent in the hospital during mobilisation were significantly greater after Cyclo-G-CSF (P<0.05). Rapid neutrophil and platelet engraftment was achieved in all transplanted patients in both groups. In conclusion, G-CSF at 10 micrograms/kg was as efficient at mobilising progenitor cells as a combination of cyclophosphamide and G-CSF with reduced hospitalisation and side effects and prompt engraftment. When aggressive in-patient cytoreductive regimens are not required to both control disease and generate progenitor cells, the use of G-CSF alone appears preferable to combination with intermediate-dose cyclophosphamide.     

Mobilisation of tumour cells along with CD34+ cells to peripheral blood in multiple myeloma

BACKGROUND: Cells belonging to the malignant clone are found in the peripheral blood in myeloma patients. In order to minimise the content of tumour cells in the stem cell product it is crucial to perform stem cell harvest at a time when tumour cells in the peripheral blood are at a minimum. OBJECTIVE: The aim of the study was to compare the mobilisation kinetics of normal CD34+ cells and myeloma plasma cells during mobilisation with either G-CSF alone or high-dose cyclophosphamide (HDCy) plus G-CSF. DESIGN AND METHODS: Morning blood samples were drawn each day during mobilisation from start of G-CSF or HDCy and to the end of leukapheresis, and were analysed by flow cytometry for content of CD34+ cells and myeloma plasma cells (CD38+ + CD45-). Tumour cells were also estimated by a patient-specific real-time polymerase chain reaction (PCR) method based on the 5' nuclease TaqMan technology. RESULTS: Flow cytometry data from 16 patients showed concomitant mobilisation of CD34+ cells and myeloma plasma cells. Seven patients were mobilised twice; first with G-CSF alone and then with HDCy plus G-CSF. There was no difference between the two mobilisation regimens regarding tumour cell mobilisation kinetics. Real-time PCR was performed in one patient and confirmed the mobilisation of tumour cells at the time when CD34+ blood cells were at a maximum. CONCLUSIONS: Tumour cells are mobilised to the peripheral blood at the same time as CD34+ cells in multiple myeloma patients after priming with both G-CSF alone and HDCy in combination with G-CSF.     

Lymphoma cell contamination of PBSC: a murine model.

In P-388 bearing BDF1 mice stem cell mobilisation was tested on the survival of lethally irradiated isologous recipients. Contamination of the graft with lymphoma cells was evaluated by the number of clonogenic lymphoma cells (CFU-L) and the ability of the graft to induce lymphoma in non-irradiated recipients. A mobilisation protocol (200 mg/kg cyclophosphamide (CY) i.p. or 200 mg/kg CY followed by 125 microg/kg G-CSF administered every 12 h for 3 consecutive days, starting 14 days after lymphoma initiation) that resulted in a substantial stem cell mobilisation in normal mice, mobilised too few CFU-L to induce lymphoma in the recipients: 50 microl of blood obtained after mobilisation protected lethally irradiated mice but did not induce lymphoma in normal recipients. A minimum graft of bone marrow (2 x 105 cells, with 5580 CFU-L) from untreated P-388 bearing donors killed irradiated recipients presumably by lymphoma and not bone marrow failure. The mobilisation protocol reduced CFU-L so much that no lymphoma-associated death occurred even after the transplantation of 10 x 105 bone marrow cells. These data suggest that, although the PBSC mobilisation protocol may also mobilise some clonogenic lymphoma cells, with the minimum graft size no lymphoma transfer can be observed.     

Comparison of high-dose CY and growth factor with growth factor alone for mobilization of stem cells for transplantation in patients with multiple myeloma

We retrospectively analyzed outcomes of 716 patients with multiple myeloma who were mobilized using CY and growth factor (n=370) or growth factor alone (n=346) before SCT. Patients receiving CY had higher stem cell yields than the growth factor only group (median number of apheresis sessions needed to achieve stem cell collection goals, two vs four sessions, respectively (P=0.001)). However, patients treated with CY required more time for engraftment of platelets and neutrophils (P<0.001 for both). For patients receiving CY, 75% achieved engraftment (defined as a platelet count of 50 x 10(9)/l) by day 39, whereas 75% of patients not receiving CY achieved engraftment by day 18. Similar results were observed for neutrophil engraftment. These differences did not affect the duration of hospitalization, but patients treated with CY had a higher incidence of post transplant nonstaphylococcal bacteremia. For CY-mobilized patients, considerably faster platelet engraftment (5 fewer days) resulted if stem cell reinfusion occurred more than 30 days after the first apheresis session. Our data suggested that CY damaged the microenvironment and slowed engraftment. By lengthening the period between the completion of apheresis and stem cell reinfusion, the microenvironment may recover and result in faster engraftment.     

Is chemotherapy scoring useful to predict progenitor cell mobilisation in patients with non-Hodgkin's lymphoma?

About 10-30% of patients with non-Hodgkin's lymphoma (NHL) intended to receive high-dose therapy are difficult to mobilise. Damage to the stem cell pool caused by previous chemotherapy may be an important factor in predicting progenitor cell mobilisation. We have analysed associations between chemotherapy score and efficiency of progenitor cell mobilisation in 120 consecutive NHL patients mobilised with intermediate-dose cyclophosphamide (4 g/m(2)) plus G-CSF. The original chemotherapy scoring system proposed by Drake et al was applicable in only 27% of our patients and was not predictive for mobilisation outcome. Therefore we made an improved scoring system for previous chemotherapy by adding new drugs. Altogether, 111 patients (93%) could be scored. Our chemotherapy score showed an inverse correlation with the peak blood CD34(+) count measured after the mobilisation (r=-0.214, P=0.024) and with the number of CD34(+) cells collected (r=-0.234, P=0.02). However, in the receiver operating characteristics curve, no threshold value could be detected for chemotherapy score predicting mobilisation failure. Thus, both the original scoring system as well as our more widely applicable scoring system seem to be of limited value in predicting progenitor cell mobilisation in patients with NHL.     

Dexamethasone, paclitaxel, etoposide, cyclophosphamide (d-TEC) and G-CSF for stem cell mobilisation in multiple myeloma

Forty-one patients with multiple myeloma were treated with a novel stem cell mobilisation regimen. The primary end points were adequate stem cell mobilising ability (>1% circulating CD34-positive cells) and collection (> or = 4 x 10(6) CD34-positive cells/kg), and safety. The secondary end point was activity against myeloma. The regimen (d-TEC) consisted of dexamethasone, paclitaxel 200 mg/m(2) i.v., etoposide 60 mg/kg i.v., cyclophosphamide 3 g/m(2) i.v., and G-CSF 5-10 microg/kg/day i.v. A total of 84 cycles were administered to these 41 individuals. Patient characteristics included a median age of 53 years, a median of five prior chemotherapy cycles, and a median interval of 10 months from diagnosis of myeloma to first cycle of d-TEC. Seventy-five percent of the patients had stage II or III disease, 50% had received carmustine and/or melphalan previously, and 25% had received prior radiation therapy. Eighty-eight percent of patients mobilised adequately after the first cycle of d-TEC and 91% mobilized adequately after the second cycle. An adequate number of stem cells were collected in 32 patients. Of the remaining nine patients, three mobilised, but stem cells were not collected, two mobilised but stem cell collection was < 4 x 10(6) CD34-positive cells/kg, three did not mobilise, and one died of disease progression. Major toxicities included pancytopenia, alopecia, fever and stomatitis. One patient died from multi-organ failure and progressive disease. Fifty percent of evaluable patients demonstrated a partial response and 28.6% of patients had a minor response. This novel dose-intense regimen was safe, capable of stem cell mobilisation and collection, even in heavily pre-treated patients, and active against the underlying myeloma.     

Chemotherapy for mobilisation of Ph-negative progenitor cells from patients with CML: impact of different mobilisation regimens

Mobilised peripheral blood stem cells are widely used for autografting in patients with chronic myeloid leukaemia (CML) and it is generally thought that a high proportion of Ph-negative progenitor cells in the graft is desirable. We report here the results of 91 stem cell mobilisations performed with various chemotherapy regimens followed by G-CSF. We show that mobilisation of Ph-negative cells is possible after diagnosis as well as in advanced stages of the disease. The yield of Ph-negative cells is highly dependent on the chemotherapy regimen: while the combination of idarubicin and cytarabin for 3-5 days (IC3-5) mobilised Ph-negative cells in most patients, high-dose cyclophosphamide was ineffective. Mobilisation of Ph-negative progenitor cells after IC3 was at least as effective as after IC5; however, less apheresis sessions were required, and toxicity was much reduced after IC3. Compared to historical controls, IC was equally effective as the widely used ICE/miniICE (idarubicin, cytarabin, etoposide) protocol. No correlation was found between graft quality and the cytogenetic response to subsequent treatment with interferon-alpha. We conclude that IC3 is an effective and well-tolerated regimen for mobilising Ph-negative cells that compares well with more aggressive approaches such as IC5 and ICE/miniICE.     

Clonogenic potential and phenotypic analysis of CD34+ cells mobilized by different chemotherapy regimens.

BACKGROUND AND OBJECTIVE: Since limited data concerning quantitative and qualitative differences of CD34+ cells collected after different mobilization schedules are available, we investigated phenotype, proliferative capacity and primitive progenitor cell content of CD34+ cells mobilized with four different regimens. DESIGN AND METHODS: The number, phenotype, and progenitor cell content of CD34+ cells were investigated in 46 patients mobilized with cyclophosphamide (CY) 7 g/m(2) plus granulocyte colony-stimulating factor (G-CSF, 5 microg/kg) (CY7+G-CSF) (n=16), CY 4 g/m(2) plus G-CSF (CY4+G-CSF) (n=8), IVE [ifosphamide (2.5 g/m(2) for 3 d), etoposide (150 mg/m(2) for 3 d), epirubicin (100 mg/m(2) on day 1)] plus G-CSF (IVE+G-CSF) (n=9), or G-CSF (10 microg/kg) alone (n=13). RESULTS: The number of CD34+ cells collected per liter of processed blood was significantly higher in the CY7+G-CSF group than in the CY4+G-CSF and G-CSF groups (p 相似文献   

Etoposide (VP-16) plus G-CSF mobilizes different dendritic cell subsets than does G-CSF alone

Dendritic cells (DCs) are antigen-presenting cells that are critical to the generation of immunologic tumor responses. Myeloid DCs (DC1) express myeloid antigen CD11c; lymphoid DCs (DC2) express CD123(+) and are CD11c(-). Analysis of DC subsets from peripheral blood progenitor cells (PBPC) collected from normal donors mobilized with G-CSF shows a predominance of DC2 cells. Whether PBPCs mobilization by chemotherapy yields different subsets of DCs has not been studied. We analyzed DC subsets in apheresis products from 44 patients undergoing autologous stem cell transplantation from 6/00 to 5/01. Patients received either G-CSF alone (10 microg/kg per day, n=11) or etoposide (2 g/m(2)) plus G-CSF (n=33) for progenitor cell mobilization. The patients were apheresed for 2-10 days (median 3) to reach a minimum of 2.0 x 10(6) CD34(+) cells/kg. Patients receiving G-CSF alone mobilized significantly more total DC2s than did those receiving etoposide plus G-CSF (median 6.2 x 10(6)/kg vs 2.9 x 10(6)/kg, P=0.001). The DC2/DC1 ratio was also significantly different in the two groups, with the G-CSF group having a higher ratio (median 1.2 vs 0.4, P<0.001). We conclude that the combination of chemotherapy plus G-CSF yields different mobilized dendritic cell subsets than does G-CSF alone.     

Dose-intensive melphalan with stem cell support (CM regimen) is effective and well tolerated in elderly myeloma patients

BACKGROUND AND OBJECTIVE: Multiple myeloma (MM) typically afflicts elderly patients. High-dose therapy has recently been shown to lead to a better outcome than standard treatment, mainly in younger patients. The extent to which older subjects can benefit from intensified approaches without excessive toxicity is examined in this study. DESIGN AND METHODS: Between December 1994 and May 1997, 12 Italian Multiple Myeloma Study Group institutions entered 68 patients at diagnosis (median age 65) into an intensified chemotherapy regimen: cyclophosphamide (CY) 3 g/m(2) plus melphalan 60 mg/m(2) followed by peripheral blood progenitor cells (PBPC) and G-CSF (CM regimen). CY (day 0) and G-CSF were used to mobilize PBPC harvested by a single leukapheresis on day 10. Melphalan was infused on day 11. PBPC were kept unprocessed at 4 degrees C for 48 hours and reinfused on day 12. Three CM regimens were delivered at 6-month intervals. RESULTS: Sufficient PBPC to support the first CM cycle were available (median CD34(+) harvest: 4.9x10(6)/kg), but dropped significantly after the second (median CD34(+) harvest: 2x10(6)/kg) and the third (median CD34(+) harvest: 0.9x10(6)/kg). The median durations of severe neutropenia (absolute neutrophil count < 500 microL) were 3, 4, and 3 days, and those of severe thrombocytopenia (platelets < 25,000/microL) were 2.5, 2, and 1 days, after the first, second and third courses, respectively. The frequency of extramedullary toxicities was low. Treatment-related mortality (TRM) was 3% after the first CM, only. Complete remission (CR) was 14% after the first, 16% after the second and 27% after the third CM. After a median follow-up of 34 months (range 19-49 months), median event-free survival was 35.6 months. INTERPRETATION AND CONCLUSIONS: These results indicate that dose-intensity of melphalan can be increased by reinfusing PBPC with acceptable low toxicity. The combination of CY and melphalan followed by PBPC is an effective chemotherapy for elderly myeloma patients. Repeated melphalan infusion hampered subsequent CD34(+) harvests.     

Comparison of engraftment following different stem cell mobilization modalities in patients with multiple myeloma treated with a uniform induction regimen containing bortezomib,cyclophosphamide and dexamethasone

Bortezomib-based induction followed by autologous stem cell transplantation is a common treatment for multiple myeloma (MM). Stem cell (SC) mobilization with granulocyte-colony stimulating factor (G-CSF) alone has become an alternative to G-CSF combined with chemotherapeutic agents. This study aimed to compare the efficacy of the two mobilization modalities following induction with a uniform regimen containing bortezomib, cyclophosphamide and dexamethasone (VCD). We retrospectively evaluated results of SC mobilization using either G-CSF alone or combined with high-dose cyclophosphamide (HD-CY) in MM patients after VCD induction. The primary endpoints of the study were engraftment and mobilization-associated toxicity. Parameters of stem cell collection, transplantation and engraftment were assessed. Data of 92 patients were analyzed [56 (61%) mobilized with HD-CY + G-CSF and 36 (39%) with G-CSF only]. HD-CY + G-CSF provided a higher number of CD34 + cells (15.9 vs 8.1 × 10⁶/kg, p = 0.001) with fewer apheresis sessions. However, while no adverse events were observed in patients receiving G-CSF alone, nine patients (16%) receiving HD-CY + G-CSF developed neutropenic fever requiring hospitalization. Although a greater number of cells was transplanted following mobilization with HD-CY + G-CSF, neutrophil and platelet engraftment and duration of transplant-related hospitalization were similar in both cohorts. G-CSF alone provided a sufficient SC amount, without exposing patients to additional toxicity. While HD-CY + G-CSF resulted in a superior SC yield in MM patients induced with VCD, this advantage should be balanced against adverse effects of this mobilization regimen.     

High-dose melphalan (200 mg/m2) supported by autologous stem cell transplantation is safe and effective in elderly (>or=65 years) myeloma patients: comparison with younger patients treated on the same protocol

Limited information is available on the feasibility and efficacy of autologous stem cell transplantation (ASCT) in multiple myeloma (MM) patients >65 years of age. In 1995-2005, 22 myeloma patients >or=65 years (median 68, eight >or=70) and 79 patients <65 years (median 57) were included in an identical treatment protocol. The first progenitor cell mobilization with cyclophosphamide plus granulocyte-colony stimulating factor (G-CSF) was successful in 95 and 96% of the patients, respectively. To date, 92 patients have received MEL (melphalan) 200 mg/m2 supported by ASCT. No early treatment-related deaths were observed among 22 elderly patients, whereas one younger patient died early. Engraftment and the need for supportive care were comparable between groups. The elderly patients tended to have more WHO grade 3-4 oral or gastrointestinal toxicity when compared to the younger patients (45 vs 23%, P=0.06). After ASCT, a complete response was observed in 44% of the elderly patients and 36% of the younger patients, respectively. No difference was observed between these age groups in progression-free survival (23 vs 21 months) or overall survival (57 vs 66 months) after ASCT. We conclude that MEL200 is a safe and efficacious treatment in selected elderly myeloma patients.     

Mobilisation of peripheral blood stem cells with IVE and G-CSF improves CD34+ cell yields and engraftment in patients with non-Hodgkin's lymphomas and Hodgkin's disease.

The transplantation of mobilised peripheral blood stem cells is associated with more rapid engraftment than marrow transplantation. We have previously reported that G-IVE (G-CSF, ifosphamide, VP-16, epirubicin) improves the yield of CD34+ cells mobilised in patients with lymphoproliferative disorders compared with cyclophosphamide 3 g/m2 and G-CSF (G/CYCLO). In this study we have extended these observations to a larger series of patients including different lymphoma subtypes. Ninety-seven patients undergoing stem cell mobilisation were studied. Forty-two patients with lymphoproliferative disorders received G-IVE for mobilisation and 55 patients G/CYCLO. The median number of mobilised CD34+cells per leucapheresis was significantly higher for those patients receiving G-IVE: 5.82 x 106/kg (0.19-36) compared with 1.2 x 106/kg (0.04-17), P < 0.001 which resulted in a significantly reduced number of leucapheresis procedures performed in the G-IVE group. When patients were analysed dependent on underlying disease G-IVE mobilised significantly more CD34+cells per leucapheresis for all lymphoma types reaching 8.41 x 10(6)/kg (0.2-32) compared to 1.32 x 10(6)/kg (0. 06-17) for patients with high-grade NHL mobilised with G-IVE and C-GCSF respectively (P = 0.012). For patients with low-grade NHL 3. 12 x 10(6)/kg (0.10-24.39) compared to 1.08 x 10(6)/kg (0.04-9.74) were collected (P = 0.04) and for patients with Hodgkin's disease 3.02 x 10(6)/kg (1.48-36) and 1.04 x 10(6)/kg (0.1-12.3) (P = 0.001). Mobilisation with G-IVE resulted in the achievement of clinically significant CD34+ cell thresholds in a significantly higher proportion of patients compared to cyclophosphamide and G-CSF reaching >2.5 x 10(6)/kg CD34+ cells in 88% vs 62% (P = 0.004), >5 x 10(6)/kg in 67% vs18% (P = 0.001) and >10 x 10(6)/kg in 31% vs 14.5% (P = 0.05). Furthermore, an analysis of engraftment demonstrated that there was a significant reduction in the time to achieve platelet counts of >20 and >50 x 10(9)/l in patients receiving each incremental dose of CD34+ cells. We conclude that G-IVE mobilizes significantly more CD34+cells than G/CYCLO in patients with lymphoproliferative disorders. This effect is consistent in patients with high-grade NHL, low-grade NHL and HD and results in fewer failed stem collections and increased CD34+ cells available for transplantation which results in significantly accelerated platelet engraftment post transplant.     

Prediction of mobilisation failure in patients with non-Hodgkin's lymphoma

Factors affecting progenitor cell mobilisation in patients with non-Hodgkin's lymphoma (NHL) are incompletely understood. We have analysed factors predicting mobilisation failure in 97 consecutive patients with NHL (59 males, 38 females; median age 49 years) who received mobilisation with intermediate-dose CY (4 g/m(2)) followed by G-CSF. The histology included large cell B (N=50), mantle cell (N=16), follicular (N=16) and other NHL (N=15). The disease status was 1CR/PR/primary refractory in 66 patients and >1 CR/PR in 31 patients. The minimum criterion for successful mobilisation was the collection of >or=1.5 x 10(6)/kg CD34(+) cells. In all, 18 patients (19%) failed to reach this threshold. In univariate analysis, premobilisation factors associated with mobilisation failure included BM involvement at the time of diagnosis (P=0.001) or prior to mobilisation (P=0.001) and low platelet count just prior to mobilisation (P=0.001). In multivariate analysis, only BM involvement at diagnosis (P=0.004) and platelet count just prior to mobilisation (P=0.01) were associated with mobilisation failure. A mathematical model based on these two factors and presented in the form of a receiver operating characteristics curve showed a sensitivity of 0.71 and a specificity of 0.77 in the prediction of mobilisation failure. Patients at a high risk of mobilisation failure may benefit from novel approaches.     

Stem cell mobilization with G-CSF alone in breast cancer patients: higher progenitor cell yield by delivering divided doses (2 x 5 microg/kg) compared to a single dose (1 x 10 microg/kg)

We investigated the schedule dependency of G-CSF (10 microg/kg) alone in mobilizing peripheral blood progenitor cells (PBPC) in breast cancer patients. After a median of three cycles (range, 2-6) of anthracycline-based chemotherapy, 49 patients with breast cancer (stage II/III, > or = 10+ Ln n = 36; locally advanced/inflammatory n = 8, stage IV (NED) n = 5) underwent PBPC collection after steady-state mobilization either with 1 x 10 microg/kg (n = 27) or with 2 x 5 microg/kg (n = 22) G-CSF daily for 4 consecutive days until completion of apheresis. Apheresis was started on day 5. Priming with 2 x 5 microg/kg resulted in a higher median number of CD34+ cells (5.8 vs 1.9 x 10(6)/kg, P = 0.003), MNC (6.6 vs 2.6 x 10(8)/kg, P < 0.001) and CFU-GM (6.5 vs 1.3 x 10(4)/kg, P = 0.001) in the first apheresis than with 1 x 10 microg/kg. Also the overall number of collected BFU-E was higher in the 2 x 5 microg group (9.2 vs 3.1 x 10(4)/kg; P = 0.01). After high-dose chemotherapy with cyclophosphamide/thiotepa/mitoxantrone (n = 46) hematopoietic engraftment with leukocyte count > 1.0/nl was reached in both groups after a median of 10 days (range, 8-15) and with platelets count > 50/nl after 12 (range, 9-40) and 13 days (range, 12-41), respectively. A threshold of > 2.5 x 10(6)/kg reinfused CD34+ cells ensured rapid platelet engraftment (12 vs 17 days; P = 0.12). Therefore, the target of collecting > 2.5 x 10(6) CD34+ cells was achieved in 21/27 (80%) patients of the 1 x 10 microg group and in 21/22 (95%) patients of the 2 x 5 microg/kg group with a median of two aphereses (range, 1-4). None in the 10 microg/kg group, but 6/22 (28%) patients in the 2 x 5 microg/kg group required only one apheresis procedure, resulting in fewer apheresis procedures in the 2 x 5 microg/kg group (mean, 1.8 vs 2.3, P = 0.01). These results demonstrate that priming with 10 microg/kg G-CSF alone is well tolerated and effective in mobilizing sufficient numbers of CD34+ cells in breast cancer patients and provide prompt engraftment after CTM high-dose chemotherapy. G-CSF given 5 microg/kg twice daily (2 x 5 microg) leads to a higher harvest of CD34+ cells and required fewer apheresis procedures than when given 10 microg/kg once daily (1 x 10 microg).     

Plerixafor for PBSC mobilisation in myeloma patients with advanced renal failure: safety and efficacy data in a series of 21 patients from Europe and the USA

We describe 20 patients with myeloma and 1 with primary amyloidosis from 15 centres, all with advanced renal failure, most of whom had PBSC mobilised using plerixafor following previous failed mobilisation by conventional means (plerixafor used up-front for 4 patients). For 15 patients, the plerixafor dose was reduced to 0.16?mg/kg/day, with a subsequent dose increase in one case to 0.24?mg/kg/day. The remaining six patients received a standard plerixafor dosage at 0.24?mg/kg/day. Scheduling of plerixafor and apheresis around dialysis was generally straightforward. Following plerixafor administration, all patients underwent apheresis. A median CD34+ cell dose of 4.6 × 10(6) per kg was achieved after 1 (n=7), 2 (n=10), 3 (n=3) or 4 (n=1) aphereses. Only one patient failed to achieve a sufficient cell dose for transplant: she subsequently underwent delayed re-mobilisation using G-CSF with plerixafor 0.24?mg/kg/day, resulting in a CD34+ cell dose of 2.12 × 10(6)/kg. Sixteen patients experienced no plerixafor toxicities; five had mild-to-moderate gastrointestinal symptoms that did not prevent apheresis. Fifteen patients have progressed to autologous transplant, of whom 12 remain alive without disease progression. Two patients recovered endogenous renal function post autograft, and a third underwent successful renal transplantation. Plerixafor is highly effective in mobilising PBSC in this difficult patient group.     

Content of long-term culture-initiating cells, clonogenic progenitors and CD34 cells in apheresis harvests of normal donors for allogeneic transplantation, and in patients with acute myeloid leukaemia or multiple myeloma

Using a limiting dilution assay the frequency of long-term culture-initiating cells (LTC-IC) in the apheresis products following mobilization by granulocyte-colony stimulating factor (G-CSP) with or without chemotherapy from 14 normal donors (ND) for allogeneic bone marrow transplantation, 16 patients with multiple myeloma (MM) and 15 patients with acute myeloid leukaemia (AML), where the aphereses were intended for autologous transplantation, were compared. The estimated median incidences of LTC-IC in the first apheresis products from ND, MM and AML were 1/3289, 1/1775 and 1/13075 mononuclear cells (MNC) respectively. The patients with AML had a significantly lower incidence compared with the other two groups (P < 0.0001). There was a positive correlation between the incidence of LTC-IC and the number of CD34+ cells, the number of GM-CFC, and the number of BFU-E. The positive association with GM-CFC or BFU-E was weaker. In these experiments the percentage of CD34+ cells was the best predictor for the frequency of LTC-IC in the peripheral blood progenitor cells (PBPC). In eight cases of MM the LTC-IC assay was performed for both the first and second harvest. All cases had a lower LTC-IC frequency in the second harvest compared with the first, an average of 23% (13-42%, 95% confidence interval) and this reduction was statistically significant (P<0 001); CD34+ cells were also lower (P< 0.001).     

Superior autologous blood stem cell mobilization from dose-intensive cyclophosphamide, etoposide, cisplatin plus G-CSF than from less intensive chemotherapy regimens

The study purpose was to determine if G-CSF plus dose-intensive cyclophosphamide 5.25 g/m2, etoposide 1.05 g/m2 and cisplatin 105 mg/m2 (DICEP) results in superior autologous blood stem cell mobilization (BSCM) than less intensive chemotherapy. From January 1993 until May 1997, 152 consecutive patients with non-Hodgkin's lymphoma (n = 55), breast cancer (n = 47), Hodgkin's disease (n = 14), multiple myeloma (n = 9), AML (n = 9), or other cancers (n = 18) initially underwent BSCM by one of three methods: Group 1: G-CSF alone x 4 days (n = 30). Group 2: disease-oriented chemotherapy, dosed to avoid blood transfusions, followed by G-CSF starting day 7 or 8, and apheresis day 13 or 14 (n = 82). Group 3: DICEP days 1-3, G-CSF starting day 14, and apheresis planned day 19, 20 or 21 (n = 40). A multivariate analysis was performed to determine which factors independently predicted BSCM. The median peripheral blood CD34+ (PB CD34+) cell count the morning of apheresis linearly correlated with the number of CD34+ cells removed per litre of apheresis that day. The median PB CD34+ cell count and median CD34+ cells x 10(6) removed per litre of apheresis were highest for Group 3, intermediate for Group 2, and lowest for Group 1. By multivariate analysis, mobilization group (3 > 2 > 1), disease other than AML, no prior melphalan or mitomycin-C, and less than two prior chemotherapy regimens predicted better BSCM. Out of 15 Group 3 patients who had infiltrated marrows, 11 had no detectable cancer in marrow and apheresis products after DICEP. These data suggest that DICEP results in superior BSCM than less intensive chemotherapy regimens.     

Granulocyte-colony stimulating factor increases CD123hi blood dendritic cells with altered CD62L and CCR7 expression

Changes in blood dendritic cell (BDC) counts (CD123(hi)BDC and CD11c(+)BDC) and expression of CD62L, CCR7, and CD49d were analyzed in healthy donors, multiple myeloma (MM), and non-Hodgkin lymphoma (NHL) patients, who received granulocyte-colony stimulating factor (G-CSF) containing peripheral blood stem cell (PBSC) mobilization protocols. Low-dose G-CSF in healthy donors (8-10 microg/kg/d subcutaneously) and high-dose G-CSF in patients (30 microg/kg/d) increased CD123(hi)BDC (2- to 22-fold, mean 3.7 x 10(6)/L-17.7 x 10(6)/L and 1.9 x 10(6)/L-12.0 x 10(6)/L) in healthy donors and MM but decreased CD11c(+)BDC (2- to 10-fold, mean 5.7 x 10(6)/L-1.6 x 10(6)/L) in NHL patients, on the day of apheresis, compared with steady state. After apheresis, CD123(hi)BDC counts remained high, whereas low CD11c(+)BDC counts tended to recover in the following 2-5 days. Down-regulation of CD62L and up-regulation of CCR7 on CD123(hi)BDC were found in most healthy donors and MM patients. CD49d expression was unchanged. Thus, PBSC mobilization may change BDC counts by altering molecules necessary for BDC homing from blood into tissues.     

Etoposide plus G-CSF priming compared with G-CSF alone in patients with lymphoma improves mobilization without an increased risk of secondary myelodysplasia and leukemia

The use of etoposide (VP-16) for stem cell mobilization has been reported as a significant risk factor for the development of therapy-related myelodysplasia/therapy-related AML (tMDS/tAML) after transplantation. We compared the safety and effectiveness of VP-16+G-CSF (VP+G) to G-CSF alone for PBPC mobilization in patients with non-Hodgkin's lymphoma and Hodgkin's lymphoma who underwent autologous transplantation at the Cleveland Clinic and Ohio State University. In the VP+G group, median total CD34+ cells collected were 9.34 × 10(6) per kg (range 0.97-180.89), with 42% of all patients having adequate (2 × 10(6) cells per kg) CD 34+ collection after 2 days of apheresis compared with a median in the G-CSF group of 3.83 × 10(6) per kg (range, 0.72-50.38), with only 16% patients having adequate collection after 2 days (P<0.001). tMDS/tAML occurred in 15 patients (2.3%) in the VP+G and in 12 patients (3.8%) receiving G-CSF alone. (P=0.62). Increased number of days of apheresis was associated with the risk of tMDS/tAML (hazard ratio (HR) 1.19, 95% confidence interval (CI) 1.08-1.30, P<0.001). Priming regimen was not a significant variable for relapse-free survival or OS. The addition of etoposide significantly improves the effectiveness of mobilization at the cost of an increased incidence of neutropenic fever though with no mortalities. There is no evidence of increased incidence of tMDS/tAML in patients receiving VP+G compared with those mobilized with G-CSF alone.