A comparison of peripheral blood stem cell mobilisation after chemotherapy with cyclophosphamide as a single agent in doses of 4 g/m or 7 g/m2 in patients with advanced cancer

Summary:We aimed to assess the effectiveness of cyclophosphamide, etoposide and G-CSF (C+E) to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma. A matched cohort study was performed comparing patients mobilized with C+E to patients mobilized with cyclophosphamide and G-CSF (C alone). Patients were matched for disease, prior radiotherapy and a chemotherapy score reflecting the amount and type of prior chemotherapy. Thirty-eight consecutive patients mobilized with C+E were compared with 38 matched controls. C+E was equivalent to C alone in terms of numbers of patients achieving a minimum threshold of у2 ؋ 10 6 /kg CD34 + cells (82% vs 79%, P = 0.74). C+E was superior, however, in terms of total CD34 + yield (6.35 vs 3.3 ؋ 10 6 /kg, P Ͻ 0.01), achieving a target graft of у5 ؋ 10 6 /kg (55% vs 34%, P = 0.04) and obtaining both a minimum (61% vs 32%, P Ͻ 0.01) and target (45% vs 13%, P Ͻ 0.01) graft in one apheresis. This superiority was largely confined to patients with lower chemotherapy scores. There was no difference in neutrophil and platelet recovery or transfusion requirements for those who subsequently received high-dose therapy and stem cell transplantation. Thus, C+E improves the efficiency of peripheral blood stem cell collection, but does not increase the number of patients who can proceed to transplantation. Most of the benefit of the regimen was confined to patients who had not received extensive prior therapy. Novel strategies are required to increase the collection efficiency of 'hard to mobilize' patients. in patients with lymphoma. Engraftment following transplantation of PBSCs is more rapid than with bone marrow 1 and has been demonstrated to correlate best with the number of CD34 + cells in the graft. With standardization of CD34 + enumeration, 2 у5 ϫ 10 6 /kg CD34 + cells has been suggested as a reasonable target for PBSC collection, as this allows optimal engraftment in nearly all patients. [3][4][5] Alternatively, transplantation of Ͻ1 to 2 ϫ 10 6 /kg CD34 + cells has been associated with delayed and failed engraftment, 6-10 leading to the concept of a minimum threshold CD34 + count in order to safely proceed with ASCT.Optimizing PBSC collection remains an important goal for several reasons: to increase the proportion of patients who can proceed to ASCT; to reduce the time to hematopoietic recovery post transplant; to maximize the efficiency of the PBSC collection process given the morbidity and costs of apheresis; and to reduce the need for second mobilizations and bone marrow harvests. Several studies 5,11-14 have described factors influencing the yield of PBSCs, including age, diagnosis, marrow involvement, prior radiation and time from prior chemotherapy therapy, but amount of previous chemotherapy seems to be the most consistent. The prior use of stem cell toxic regimens or agents such as nitrogen mustard, procarbazine, melphalan, carmustine, high-dose cytarabine, 15 Dexa-BEAM 16 and mini-BEAM 17,18 result in poor and unpredictable mob...

Section: C+e C (Matched Controls)mentioning

confidence: 99%

Cyclophosphamide, etoposide and G-CSF to mobilize peripheral blood stem cells for autologous stem cell transplantation in patients with lymphoma

Mollee

Pereira

Nagy

et al. 2002

“…1,5,14 Several reports suggest that the intensity (measured as a total dose) of chemotherapy (eg, 7 g/m 2 vs 4 g/m 2 of cyclophosphamide or combination chemotherapy) is superior to single-agent chemotherapy with cytokines. 5,14 Data from centers using the combined modality approach that appear to include significant numbers of hard-to-mobilize patients suggest that there may be an advantage to chemotherapy plus cytokines. No comparative trials of various mobilization regimens have been performed, however, in groups consisting only of hard-to-mobilize patients.…”

Section: Mobilization With Cytokines and Chemotherapymentioning

confidence: 99%

Management strategies for the hard-to-mobilize patient

Stiff

1999

Summary:Delayed hematopoietic engraftment, particularly of platelets, is seen in 5-35% of patients undergoing high-dose chemotherapy with autologous stem cell transplantation. Studies indicate that delayed engraftment is related to low CD34 + cell dose, and that risk factors for poor mobilization of CD34 + cells relate primarily to the type and extent of prior therapy. Data indicating an appropriate strategy to ensure that 'hardto-mobilize' patients will achieve adequate CD34 + cell numbers are limited. It is clear, however, that marrow harvesting (performed frequently by a number of centers), is of limited value. Remobilization, best accomplished with a regimen of high-dose chemotherapy and cytokines, is of benefit in selected patients, but has substantial costs and morbidity. Instead of ad hoc treatment of patients who have a poor first mobilization, high-risk groups should be identified prospectively, and strategies should be developed to ensure adequate mobilization in all high-risk patients. The first randomized trial utilizing this approach has recently been reported. In this trial, stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) alone was compared to mobilization with G-CSF combined with stem cell factor (SCF) in heavily pretreated patients with Hodgkin's and non-Hodgkin's lymphoma. The combination of G-CSF and SCF led to collection of a higher total CD34 + cell dose compared to G-CSF alone. Further, more patients in the combination group were able to mobilize an optimal CD34 + cell dose (ie 5 × 10 6 /kg). Additional trials are needed to determine long-term outcomes and the economic impact of achieving optimal stem cell mobilization in these patients, who would otherwise not be candidates for high-dose chemotherapy.

“…21 Although from these studies high-dose cyclophosphamide appears to be more effective at PBSC mobilisation than intermediate or low doses, its use has been associated with a longer duration of cytopenia and a high rate of nonhaematological morbidity including haemorrhagic cystitis. 18,22 These risks have led many groups to explore the use of lower doses of cyclophosphamide (Ͻ4 g/m 2 ) with the aim of reducing the procedural morbidity. Cyclophosphamide at doses of 1.5 g/m 2 to 3 g/m 2 have now been reported with low toxicity and minimal requirements for hospitalisation.…”

Section: Pbsc Mobilisation With Cyclophosphamide and Growth Factorsmentioning

confidence: 99%

Stem cell mobilisation in lymphoproliferative diseases

Russell

McQuaker

Stainer

et al. 1998

Summary:A number of different regimens have evolved for the mobilisation of peripheral blood stem cells for autologous transplantation in patients with lymphoma or myeloma. A successful regimen could be defined as one which consistently resulted in the collection of an optimal number of CD34 ؉ cells with a minimum number of apheresis procedures with minimal toxicity. Initial protocols, which used chemotherapy alone as a mobilising agent, have now been replaced by regimens involving the use of haematopoietic growth factors either alone or in combination with variable doses of cyclophosphamide. Although there is good evidence that highdose cyclophosphamide (6-7 g/m 2 ) is an effective mobilising agent it is associated with significant toxicity and many groups have now utilised lower doses of cyclophosphamide with reduced toxicity which have still proven to be effective in the majority of patients. More recently a number of 'second generation' combined salvage chemotherapy and mobilisation regimens have been reported for use in the lymphomas which have the advantage of avoiding a specific stem cell mobilisation step and at the same time appear more consistently effective at mobilising stem cells than cyclophosphamide and G-CSF. These regimens are associated with fewer 'poor-mobilisers' and indeed some patients who have failed previous mobilisation with cyclophosphamide and G-CSF have been successfully re-mobilised. It is clear that in both lymphoma and myeloma patients the success of PBSC mobilisation is affected by the amount and type of previous chemotherapy and radiotherapy and probably other pre-treatment factors as exemplified by variability seen in normal donors mobilised with G-CSF alone. In myeloma most groups have utilised cyclophosphamide in variable doses in combination with G-CSF or GM-CSF. However, recent randomised studies have confirmed that G-CSF alone is an effective and nontoxic alternative although it appears that the efficacy of G-CSF as a single agent is related to the dosage used with daily doses of 16 g/kg/day or greater being most effective. Thus, disease-specific mobilisation strategies appear to be emerging and these will undoubtedly be Correspondence: Prof NH Russell, Department of Haematology, Nottingham City Hospital, Nottingham, NG5 1PB, UK Received 14 July 1998; accepted 19 July 1998 modified further as more is understood concerning the biology of blood stem cell mobilisation.