Factors associated with successful mobilization of peripheral blood progenitor cells in 200 patients with lymphoid malignancies

Peripheral blood progenitor cells (PBPC) were mobilized and harvested in 200 patients treated for non-Hodgkin's lymphoma ( n  = 148), Hodgkin's disease ( n  = 22) and multiple myeloma ( n  = 30). The variables predicting the collection of a minimal (>2.5 × 10⁶/kg) or a high (>10 × 10⁶/kg) CD34⁺ cell count were analysed. Patients were mobilized with haemopoietic growth factors following either standard chemotherapy ( n  = 49) or high-dose cyclophosphamide, given alone ( n  = 55) or combined with high-dose VP16 ( n  = 86). 10 patients received haemopoietic growth factors only. The first mobilization resulted in a PBPC harvest with enough CD34⁺ cells in 179/200 patients (90%). High-dose cyclophosphamide, with or without VP16, did not mobilize a higher progenitor cell yield than standard chemotherapy. When performing multiple regression analysis in the 190 patients who received chemotherapy-containing mobilization, only the number of previous chemotherapy regimens and the exposure to fludarabine predicted for a failure to collect a minimal PBPC count ( P  = 0.06 and 0.0008 respectively). The target to collect a high CD34⁺ cell count was negatively associated with the number of previous chemotherapy regimens ( P  = 0.002). When only non-Hodgkin's lymphoma patients were considered for multivariate analysis, low-grade histology with fludarabine appeared to be associated with poor PBPC cell yield ( P  = 0.08 and 0.005 respectively). This data confirms that PBPC harvest should be planned early in the disease course in transplant candidates, and can be obtained after a standard course of chemotherapy.     

Peripheral blood stem cell mobilization using high-dose cyclophosphamide and G-CSF in pretreated patients with lymphoma

Summary. Peripheral blood stem cell (PBSC) mobilization for autologous transplantation is more difficult in treated patients and those with bone marrow involvement. In 17 pretreated lymphoma patients, cyclophosphamide (4 g/m²) and G-CSF mobilized a median circulating peak of 1959 CFU-GM/ml on day 12.5. PBSC harvesting commenced when WBC was 1×10⁹/l at day 10.5 collected a median of 21.2 × 10⁴/CFU-GM/kg. 13/17 (76%) patients exceeded the 10 × 10⁴ CFU-GM/kg threshold for engraftment. The CFU-GM yield was significantly higher in patients whose WBC recovered from 1–5 × 10⁹/1 in less than 3 days and correlated with the maximum WBC pre and post the cyclophospharnide induced nadir. This regime safely mobilized adequate PBSC in the majority of pretreated lymphoma patients.     

The dose of granulocyte colony-stimulating factor administered following cytotoxic chemotherapy is not related to the rebound level of circulating CD34+ haemopoietic progenitor cells during marrow recovery

We report on the RmetHuG-CSF (filgrastim)-related mobilization efficiency in 120 patients with multiple myeloma who received cytotoxic chemotherapy. Three schedules of G-CSF administration starting 24 h after the end of chemotherapy were used: (1) a standard dose of 300 μg/d until the completion of PBSC collection; (2) dose escalation from 300 to 600–1200 μg/d during marrow recovery; (3) 600 or 1200 μg/d starting 24 h after cytotoxic chemotherapy. As a result, the individual dose per kg bodyweight varied between 2.83 and 23.08 μg. No relationship was found between the dose of G-CSF administered and the peak level of circulating CD34⁺ cells or the CD34⁺ cell counts recorded over the entire collection period.     

Analysis of the effect of prior therapy on progenitor cell yield: use of a chemotherapy scoring system

A quantitative analysis of peripheral blood stem cell (PBSC) yield, measuring absolute numbers of CD34⁺ cells × 10⁶/kg and CFU-C × 10⁴/kg was performed in 74 consecutive patients. The interval or 'gap' from the end of previous chemotherapy to the date of priming was recorded in weeks.
Geometric mean CD34 and CFU-C values were significantly higher in patients with a score of ≤ 60 compared to those with score > 60 ( P  = 0.003 and 0.02, respectively) and a significant difference in CD34 values was also found when scores of ≤ 38 were compared with scores > 38 ( P  = 0.003), with the difference in CFU-C values approaching significance ( P  = 0.08). Patients exposed to toxicity factor 4 drugs had significant lowering of both CD34 and CFU-C values ( P  < 0.001 and P  = 0.038) and this emerged as the only independent factor when analysed using linear regression. No significant difference in the geometric mean CD34 or CFU-C values of patients was found in any of the gap categories analysed. Prior exposure to toxicity factor 4 drugs had a significant adverse effect on stem cell yield and should be avoided or minimized prior to stem cell harvesting.     

Early suppressive effects of chemotherapy and cytokine treatment on committed versus primitive haemopoietic progenitors in patient bone marrow

These studies investigated the effectiveness of in vivo administration of cytokines in ameliorating potential marrow damage induced by chemotherapy. Breast cancer patients received 5-fluorouracil, leucovorin, doxorubicin and cyclophosphamide (FLAC) followed by either GM-CSF, PIXY321, or no cytokine. Marrow was obtained before and after one or two cycles of FLAC once blood cell counts had recovered. Colony-forming units for granulocytes and macrophages (CFU-GM) were used to indicate the effect of therapy on recovery of committed progenitor cells responsible for early blood cell recovery. The frequency and number of CFU-GM in marrow obtained after FLAC + PIXY321 were significantly lower than in marrow obtained after FLAC + GM-CSF or FLAC without cytokine. CD34⁺ cell numbers were also reduced after FLAC + PIXY321. CFU-GM production in marrow long-term cultures (LTC) was used to assess the effect of therapy on primitive progenitors. After 5 weeks the number of CFU-GM in LTC of post-therapy marrow from all three treatment arms was < 15% of the number in pre-therapy LTC. Suppressive effects of FLAC on primitive progenitors were observed even when committed progenitors and CD34⁺ cells had recovered to pre-therapy levels. These results demonstrate that cytokine treatment did not ameliorate suppressive or toxic effects of FLAC on the functional integrity of the marrow.     

Collection of peripheral blood stem cells from normal donors 60 years of age or older

We report 14 normal peripheral blood stem cell (PBSC) donors ≥ 60 years of age who had cytokine mobilization followed by PBSC apheresis for allogeneic transplantation. Mobilization was achieved with filgrastim (6 μg/kg twice daily). Their median age was 63.5 years (range 60–77), and 43% had a positive medical history, mainly hypertension and/or cardiac problems. Their median pre-apheresis leucocyte count (×10⁹/l) was 38.6 (range 29.6–63.4). The median apheresis yield (×10⁶ CD34⁺ cells/litre blood processed, first apheresis) was 27.9 (range 1.6–54.8). The target cell dose (≥4& times; 10⁶ CD34⁺ cells/kg recipient) was reached with one procedure in eight (57%) donors. Filgrastim-related adverse events were acceptable and apheresis was well tolerated. When compared to younger donors (<60 years of age), a trend to a lower CD34⁺ apheresis yield and a requirement for more than one apheresis to achieve the collection target (≥4 ×10⁶ CD34⁺ cells/kg) was evident. Although older (≥60 years) donors seem to mobilize less effectively, these data suggest that PBSC collection from them is feasible and has an acceptable short-term safety profile.     

Flow cytometric detection of cytomegalovirus antigen in peripheral blood cells after bone marrow transplantation

We report 13 normal peripheral blood stem cell (PBSC) donors who had a second PBSC collection for allogeneic transplantation performed after the first. The median interval between the first and second collection was 5 months. Mobilization was achieved with filgrastim (12 μg/kg/d). No significant difference was found in the median pre-apheresis leucocyte count (×10⁹/l) between the two donations (40.2 v 38.5; P  = 0.91). The median apheresis yield (×10⁶ CD34⁺ cells/litre blood processed, first apheresis) was also similar (28 v 27.3; P  = 0.91). Filgrastim-related adverse events were comparable. These data suggest that second PBSC collections are feasible, similarly tolerated and provide comparable apheresis yields.     

Factors influencing collection of peripheral blood progenitor cells following high-dose cyclophosphamide and granulocyte colony-stimulating factor in patients with multiple myeloma

We treated 103 multiple myeloma (MM) patients with 7 g/m² cyclophosphamide (Cy) followed by 300 μg G-CSF/d to harvest peripheral blood progenitor cells (PBPC). PBPC autografts containing > 2.0 × 10⁶ CD34⁺ cells per kg body weight were obtained at the first attempt from 90/100 evaluable patients. The most significant factor predicting impairment of PBPC collection was the duration of previous melphalan treatment ( P  < 0.0001). In multivariate discriminate analysis, treatment with melphalan during the most recent chemotherapy cycles prior to mobilization ( P  = 0.0727) and previous radiotherapy ( P  = 0.0628) had a marginally significant negative influence on the efficacy of PBPC collection. We found no reduced functional capacity of CD34⁺ cells to restore haemopoiesis after myeloablative treatment related to the duration of melphalan exposure. At the time of best response to conventional treatment, a median paraprotein reduction of 21% was achieved following high-dose cyclophosphamide (HD-Cy). Two heavily pretreated patients died and one patient developed pulmonary toxicity W.H.O. grade IV following HD-Cy. Potential transplant candidates should undergo mobilization and harvesting of PBPC before melphalan-containing treatment. Combinations of haemopoietic growth factors and their dose modifications should be investigated to improve PBPC collection, to allow a dosage reduction of the mobilization chemotherapy.     

Feasibility of peripheral blood progenitor cell harvest and transplantation in patients with poor-risk myelodysplastic syndromes

Myelodysplastic syndromes (MDS) are a group of clonal haematological disorders with a highly unfavourable prognosis. Allogeneic bone marrow transplantation offers the sole possibility for cure and prolonged survival, but is only available for a minority of patients. Therefore, we investigated the feasibility of PBPC collection and transplantation in 11 patients with high-risk myelodysplasia who were not eligible for allogeneic bone marrow transplantation. In six patients, PBPC were harvested after mobilization with G-CSF alone. Five patients were harvested during the recovery phase of intensive chemotherapy combined with G-CSF. This resulted in seven patients in an adequate CD34 progenitor yield >1 × 10⁶/kg. Six patients obtained a CFU-GM content of the PBPC harvest >10 ×10⁴/kg. Five patients were subsequently transplanted following a standard BuCy4 regimen. The median to ANC (absolute neutrophil count) ≥0.5 and 1.0 × 10⁹/l was respectively 14 d (range 10–18) and 16 d (range 11–25). Platelets were self-supporting ≥20 × 10⁹/l after a median of 41 d (range 8–144). One patient had a persistent lack of platelet engraftment unresponsive to infusion of back-up bone marrow.
These data demonstrate that in selected patients with high-risk MDS, adequate PBPC collection appears feasible, enabling the harvest of sufficient cell numbers required for rapid and stable engraftment after reinfusion. Improvement in mobilization efficiency may enable the collection of higher CD34⁺ progenitor cell numbers required for more rapid platelet engraftment. PBPC transplantation may be an alternative treatment option for patients who lack an allogeneic marrow donor. Follow-up is, however, still too limited to draw any conclusion regarding the long-term cure rate.     

Duration of filgrastim mobilization and apheresis yield of CD34+ progenitor cells and lymphoid subsets in normal donors for allogeneic transplantation

Seventy-seven normal donors underwent leukapheresis for peripheral blood progenitor cell collection beginning on day 4 ( n  = 45) or day 5 ( n  = 32) of filgrastim mobilization (12 μg/kg/d). The two groups were comparable for age, weight, blood volumes processed during leukapheresis and target CD34⁺ cell dose to be collected. The day 5 schedule allowed a more consistent achievement of the target cell dose with one apheresis ( P  = 0.005) and resulted in the initial collection of a significantly larger number of CD34⁺ cells ( P  = 0.009). There was no statistically significant difference in the leukapheresis yield of lymphoid subsets and natural killer cells.     

STEM CELL MOBILIzATION IN NORMAL DONORS FOR ALLOGENEIC TRANSPLANTATION: ANALYSIS OF SAFETY AND FACTORS AFFECTING EFFICACY

The use of peripheral blood stem cells instead of bone marrow as the source of haemopoietic cells for allogeneic transplantation is being increasingly explored. We have analysed data from 17 normal donors who underwent stem cell mobilization for allogeneic transplantation with an identical protocol using G-CSF at a dose of 10 μg/kg/d, with the first leukapheresis (LP) on the day following the fourth dose of G-CSF. Both G-CSF administration and leukapheresis were well tolerated. Donors underwent a median of two leukaphereses (range one to three) and a median of 6.80 × 10⁶ CD34⁺ cells/kg recipient weight (range 2.4–15.6 × 10⁶) were collected. The median number of CD34⁺ cells per kg donor weight was 6.05 × 10⁶, when corrected for a 12 litre leukapheresis, this gave a median total of 3.89 × 10⁶ CD34⁺ cells/kg donor weight. When analysed with respect to factors which might influence the efficacy of mobilization, male donors were associated with a superior yield. The median number of CD34⁺ cells/kg/LP harvested was 4.96 × 10⁶ in males and 2.79 × 10⁶ in females ( P <0.05). The results suggested that, given a recipient of 75 kg, in a male donor a single 12 litre leukapheresis should yield sufficient CD34⁺ cells (4 × 10⁶/kg), whereas a female donor would be likely to need two leukaphereses. Age was not found to affect donor yield. In summary, these data confirm that leukapheresis is a safe procedure in normal donors and suggest that males may be more efficient mobilizers of stem cells than females.     

G-CSF alone mobilizes sufficient peripheral blood CD34+ cells for positive selection in newly diagnosed patients with myeloma and lymphoma

We have evaluated CD34⁺ cell positive selection from granulocyte-colony stimulating factor (G-CSF)-mobilized peripheral blood progenitor cells (PBPC) in 26 patients with either multiple myeloma (MM, n  = 18) or follicular non-Hodgkin's lymphoma (NHL, n  = 8). 26 PBPC were collected with two leukaphereses: 16 contained sufficient numbers of CD34⁺ cells and were selected. The absolute number of CD34⁺ cells in the leukapheresis products was found to be significantly related to the duration of underlying disease and exposure to prior treatment. CD34⁺ cell positive selection allowed recovery of a median of 35% of CD34⁺ cells, the selected fraction containing a median number of 1.43 × 10⁶/kg CD34⁺ cells/kg (range 0.48–41.5). 10 patients were transplanted and received a median dose of 1.51 × 10⁶ CD34⁺ cells (range 0.48–4.2). The median time to granulocyte (>0.5 × 10⁹/l) and platelet (>20 × 10⁹/l) engraftment was 12 and 13 d respectively (ranges 10–13 and 0–95). Lymphoma cells were found by a sensitive polymerase chain reaction technique in four out of five CD34⁺ cell fractions tested.     

G-CSF after peripheral blood stem cell transplantation in lymphoma patients significantly accelerated neutrophil recovery and shortened time in hospital: results of a randomized BNLI trial

We have undertaken a prospective randomized study in 90 patients with relapsed or resistant lymphomas to assess the value of G-CSF (lenograstim) in the acceleration of myeloid recovery after peripheral blood stem cell transplantation (PBSCT). A common regimen of cyclophosphamide 1.5 g/m² on day 1 and lenograstim 263 μg s.c. on days 2–10 with two aphereses on days 10 and 11 was used for stem cell mobilization. 77% of patients achieved an adequate PBSC collection in two harvests (>2 × 10⁸ MNC/kg or >2 × 10⁶ CD34⁺ cells/kg). 65 patients went on to receive high-dose BEAM chemotherapy and engraftment data was available for 62. 34 patients had been randomized to receive lenograstim 263 μg/d s.c. and 28 to no growth factor. The median time to ANC > 0.5 × 10⁹/l was 9 d in the lenograstim arm versus 12.5 d in the no-lenograstim arm ( P  = 0.0001). This was associated with a median duration of time in hospital post PBSCT of 13 d in the lenograstim arm versus 15.5 d in the no-lenograstim arm ( P  = 0.0002). Median days to platelet independence, platelet transfusions, incidence of infection and red cell transfusion were the same in both arms. These data indicate that lenograstim significantly accelerated myeloid recovery after PBSCT and shortened the duration of hospital stay.     

Intensive chemotherapy with blood progenitor transplantation for primary resistant multiple myeloma

Summary. This study assessed the feasibility and effect of blood progenitors as the only source of haemopoietic support for myeloablative therapy for patients with primary resistant multiple myeloma and markedly infiltrated bone marrow. 17 patients with advanced, primary resistant myeloma received a priming regimen of cyclophosphamide (3 g/m²) and etoposide (900 mg/m²) with GM-CSF. During haematological recovery, at least 2 × 10⁶ CD34⁺ mononuclear cells/kg were collected from each patient with 4-12 leukaphereses. High-dose chemotherapy was then given which consisted of thiotepa (750 mg/m²), busulfan (10 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of the blood progenitors. Haemopoietic reconstitution was rapid with recovery of granulocytes to >1.0 × 10⁹/1 after a median of 10 d and of platelets to 50 × 10⁹/1 after a median of 29 d. The myeloma responded in 10/17 patients for a projected median duration of at least 12 months. Survival was prolonged significantly in comparison with the outcome of control patients who did not receive intensive treatment. Blood progenitors, assessed from the number of CD34⁺ cells, produced early haemopoietic recovery after myeloablative therapy that induced sustained control of advanced and resistant multiple myeloma.     

Effective in vivo purging with rituximab and autologous peripheral blood stem cell transplantation in a woman with CD5 positive primary cutaneous diffuse large B-cell lymphoma

Abstract:  Generalized subcutaneous tumors developed without any other sites of the disease in a Japanese woman. Skin biopsy revealed CD5⁺ and CD20⁺ atypical diffuse large cells infiltrating subcutaneous tissues. The diagnosis was CD5⁺ primary cutaneous diffuse large B-cell lymphoma. Tumor-specific PCR showed the existence of malignant cells in the peripheral blood and bone marrow. After three cycles of chemotherapy, she was remained in partial remission. Peripheral blood stem cells (PBSC) were harvested after the fourth cycles of chemotherapy combined with rituximab for in vivo purging. The contamination of tumor cells in PBSC was negative with PCR. She then underwent autologous peripheral blood stem cell transplantation using purged PBSC and has remained in complete remission for the past 24 month.     

Recombinant human megakaryocyte growth and development factor increases levels of circulating haemopoietic progenitor cells post chemotherapy in patients with acute myeloid leukaemia

By participating in a randomized safety and efficacy study of pegylated-recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) post induction and consolidation chemotherapy for de novo acute myeloid leukaemia, serial determinations of circulating haemopoietic progenitor cells were performed during 18 chemotherapy courses in eight patients (three receiving placebo; one, 2.5; and four, 5.0 μg/kg/d MGDF, respectively). Whereas failure to achieve complete remission (CR) was generally associated with poor progenitor cell increments following chemotherapy, substantial progenitor cell mobilization consistently occurred during haemopoietic recovery in patients entering, or in CR, with significantly higher peak values in patients receiving 5 μg/kg/d of MGDF as compared to controls. The median increases of progenitor cell numbers by chemotherapy alone and chemotherapy plus 5.0 μg/kg/d MGDF over that in normal individuals with steady-state haemopoiesis were 10- and 45-fold for CFU-GM, 3- and 17-fold for BFU-E, and 2- and 18-fold for CFU-mix. CFU-Mk levels were not increased above normal by chemotherapy alone but were 15-fold enhanced by chemotherapy plus MGDF. Recruitment of CD34⁺ cells post chemotherapy was also potentiated by MGDF. Our results suggest MGDF as a potent agent to augment progenitor cell mobilization after successful induction or consolidation chemotherapy in patients with AML.     

HIGH-DOSE THERAPY WITH PERIPHERAL BLOOD STEM CELL TRANSPLANTATION RESULTS IN A SIGNIFICANT REDUCTION OF THE HaEMOPOIETIC PROGENITOR CELL COMPARTMENT

In order to study the effect of high-dose therapy with peripheral blood stem cell transplantation (PBSCT) on the haemopoietic reserve in man, the number and composition of bone marrow (BM) and peripheral blood (PB)-derived progenitor cells were examined in 137 cancer patients. In 45 patients, paired samples from BM and PB were obtained before PBSC mobilization and 6–27 months after transplantation. Following PBSCT, the proportion of CD34⁺ cells was significantly smaller than before mobilization (BM 1.99±0.24 versus 0.8±0.09, P <0.001), and no change was observed at several follow-up visits thereafter.
The reduction was most pronounced for the primitive BM progenitor subsets such as the CD34⁺/DR⁻ and CD34⁺/Thy-1⁺ cells. The impairment of hematopoiesis was also reflected by a significant reduction in the plating efficiency of BM and PB samples.
No relationship was found between the decrease in the proportion of CD34⁺ cells and any particular patient characteristics, kind of high-dose therapy or the CD34⁺ cell content in the autograft.
In conclusion, high-dose therapy with PBSC transplantation is associated with a long-term impairment of the haemopoietic system. The reduction in the number of haemopoietic progenitor cells is not associated with a functional deficit, as peripheral blood counts post-transplantation were normal in the majority of patients.     

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

We analysed the factors influencing the efficacy of peripheral blood stem cell (PBSC) collection in patients with lymphoma. Sixty-six patients underwent initial PBSC collection following mobilization with chemotherapy plus recombinant granulocyte colony-stimulating factor (300 μg/d). Patients were mobilized with one of two chemotherapy regimens, either cyclophophamide (3 g/m² or 4 g/m²) (n=50) or ifosphamide, etoposide and epirubicin (IVE; n=16). The target of collecting >2.0×10⁶ CD34⁺ cells/kg was achieved in 43/66 (65%) patients with a median of two apheresis procedures. The IVE plus G-CSF mobilization regimen gave a significantly higher median yield of CD34⁺ cells (8.62 × 10⁶/kg) compared with cyclophosphamide plus G-CSF (3.59 × 10⁶/kg) (P=0.045). The median yield of CD34⁺ cells per leukapheresis was almost twice as high in patients receiving IVE (1.94 × 10⁶/kg) compared to cyclophosphamide (1.03 ×10⁶/kg) (P= 0.035). In a univariate analysis of the factors affecting mobilization, the subtype of lymphoma (high-grade NHL) and the mobilization regimen were the only factors associated with high CD34⁺ cell yield. However, in a multivariate analysis of factors affecting mobilization including age, lymphoma subtype, previous chemotherapy and radiotherapy, only the use of the IVE protocol was predictive of a high yield of CD34⁺ cells. In 13 patients undergoing a second mobilization procedure the use of IVE was associated with a significantly higher yield of CD34⁺ cells compared to cyclophosphamide; three patients who failed cyclophosphamide plus G-CSF mobilization were able to proceed to transplantation following success-ful mobilization with IVE + G-CSF. These results demon-strate that IVE is a highly effective mobilization regimen which is superior to cyclophophamide and has the benefit of being effective salvage therapy for lymphoma patients.     

Granulocyte colony-stimulating factor given in addition to interferon-α to mobilize peripheral blood stem cells for autologous transplantation in chronic myeloid leukaemia

In order to potentially mobilize and harvest the Ph⁻ cells observed in most patients with chronic myeloid leukaemia (CML) during interferon-α (IF-α) therapy, G-CSF (filgrastim), 5 μg/kg/d, was administered subcutaneously together with IF-α to 30 CML patients in haematological remission but with various degrees of cytogenetic remission, after IF-α therapy. Peripheral blood stem cells (PBSC ) were harvested using standard aphereses from day 5 of G-CSF. Patients underwent one to four (median three) aphereses. Median total yields/kg were 7.6 (range 3.8–25) × 10⁸ MNC, 3.4 (0–140) × 10⁶ CD34⁺ cells, and 17 (1.1–107) × 10⁴ CFU-GM. No patient had a significant increase in the percentage of Ph⁺ cells in the bone marrow under G-CSF therapy. The percentage of Ph⁺ cells in apheresis products tended to decrease between the first and the last apheresis ( P  = 0.05). 14 patients who were not responsive to IF-α were transplanted after conditioning with busulphan 16 mg/kg and melphalan 140 mg/m². Median time to neutrophils > 0.5 × 10⁹/l was 20 d (16–114 d) and to platelets > 50 × 10⁹/l 18 d (12–149 d). Nine patients had a major cytogenetic response post graft, which correlated with the amount of Ph⁺ cells reinfused with the graft ( P  = 0.02). We conclude that this procedure is feasible, allowing the harvest of enough PBSC, some of them Ph⁻ in patients who responded to IF-α, to allow autologous transplantation.     

Comparative study of peripheral blood progenitor cell collection in patients with multiple myeloma after single-dose cyclophosphamide combined with rhGM-CSF or rhG-CSF

Summary. Patients suffering from high-risk multiple myeloma (MM) were randomized to receive single high-dose cyclophosphamide followed by either rhGM-CSF or rhG-CSF in order to harvest circulating peripheral blood progenitor cells. The safety of the procedure, the mobilization kinetics, the relative efficacy of rhGM-CSF and rhG-CSF to mobilize progenitor cells and their relative toxicity were studied. Special attention was paid to the antigenic profile of CD34⁺ progenitor cells.
Group I patients (n=ll) were treated with cyclophosphamide 4 g/m² i.v. followed by rhGM-CSF at 10 /ig/kg/d by subcutaneous administration. Group II (n=ll) patients received rhG-CSF s.c. at 10/zg/kg/d after the same dose cyclophosphamide. Both mobilization regimens appeared to be equally effective. No significant differences in absolute numbers of circulating progenitors, determined by CD34 expression or in yields of MNC, CFU-GM, BFU-E and CD34 subsets were observed. rhGM-CSF administration resulted however in delayed haemopoietic recovery and an increased complication rate.
We conclude that rhG-CSF may be preferred because of its markedly lower toxicity and lower in-hospital costs.