Impact of Mobilization and Remobilization Strategies on Achieving Sufficient Stem Cell Yields for Autologous Transplantation

Abstract

The purpose of this article was to examine historic institutional autologous stem cell mobilization practices and evaluate factors influencing mobilization failure and kinetics. In this retrospective study we analyzed clinical records of 1834 patients who underwent stem cell mobilization for autologous transplantation from November 1995 to October 2006 at the Washington University in St. Louis. Successful mobilization was defined as collection of > or =2 x 10(6) CD34(+) cells/kg. From 1834 consecutive patients, 1040 met our inclusion criteria (502 non-Hodgkin's lymphoma [NHL], 137 Hodgkin's lymphoma, and 401 multiple myeloma [MM]). A total of 976 patients received granulocyte colony-stimulating factor (G-CSF) and 64 received G-CSF plus chemotherapy (G/C) for the initial mobilization. Although the median CD34(+) cell yield was higher in G/C group than in G-CSF alone group, the failure rates were similar: 18.8% and 18.6%, respectively. Overall, 53% of patients collected > or =2 x 10(6) CD34(+) cells/kg during the first apheresis with either mobilization regimen. Regardless of mobilization regimen used, MM patients had the highest total CD34(+) cell yield and required less aphereses to collect > or =2 x 10(6) CD34(+) cells/kg. Mobilized, preapheresis, peripheral blood CD34(+) count correlated with first day apheresis yield (r = .877, P < .001) and 20 cells/microL was the minimum threshold needed for a successful day 1 collection. For the remobilization analysis we included patients from the whole database. A total of 269 of 1834 patients underwent remobilization using G/C, G-CSF, and/or GM-CSF, and G-CSF plus plerixafor. Only 23% of remobilized patients achieved > or =2 x 10(6) CD34(+) cells/kg and 29.7% failed to pool sufficient number of stem cells from both collections. Patients receiving G-CSF plus plerixafor had lowest failure rates, P = .03. NHL patients remobilized with G-CSF who waited > or =25 days before remobilization had lower CD34(+) cell yield than those who waited < or =16 days, P = .023. Current mobilization regimens are associated with a substantial failure rate irrespective of underlying disease. Patients who fail initial mobilization are more likely to fail remobilization. These findings suggest that there is a need for more effective first-line mobilization agents.

Identification of prognostic factors for plerixafor‐based hematopoietic stem cell mobilization

“…Overall, the patients were characterized by features that are known to affect standard stem cell mobilization negatively, including advanced age, a diagnosis of NHL, previous radiotherapy, extensive treatment with chemotherapy, treatment with lenalidomide or purine analogues, previous autoSCT, or failure of at least one previous attempt at mobilization [7][8][9][10][11][12][13][14][15]. We observed that, despite these unfavorable characteristics, mobilization with plerixafor and G-CSF enabled the required number of stem cells to be collected in 67.5% of patients.…”

“…A number of factors are known to affect the outcome of stem cell mobilization negatively in the context of traditional mobilization regimens that are based on the administration of G-CSF with or without chemotherapy. These factors include advanced age, a diagnosis of non-Hodgkin's lymphoma (NHL), previous radiotherapy, extensive treatment with chemotherapy, treatment with lenalidomide or purine analogues, and the failure of at least one previous attempt at mobilization [7][8][9][10]. In this study, we decided to investigate whether the above-mentioned factors might allow the prediction of a suboptimal outcome for stem cell mobilization with plerixafor and G-CSF.…”

Improving stem cell mobilization strategies: future directions

“…However, the combination of G-CSF and GM-CSF is used as a salvage mobilization regimen when mobilization with G-CSF alone has been unsuccessful. 23,47,99 Boeve et al 23 remobilized stem cells in 86 patients in whom a previous mobilization attempt with G-CSF alone had failed. Nineteen patients received a daily regimen of G-CSF 10 mg/kg plus GM-CSF 5 mg/kg from 4 days before apheresis until the end of PBSC collection, and the remaining 67 patients received high-dose G-CSF (16 mg/kg twice daily).…”

“…43,44 The utility of all current mobilization regimens is limited by their high failure rates, which are estimated to be from 5 to 30%, regardless of the approach. 26,[45][46][47] The question of whether failure rates after chemomobilization are lower than failure rates after cytokine-only mobilization has not been adequately studied. There remains a significant controversy over the question of which method of PBSC mobilization is the safest and most predictable.…”

Ancestim (r-metHuSCF) plus filgrastim and/or chemotherapy for mobilization of blood progenitors in 513 poorly mobilizing cancer patients: the French compassionate experience

“…Recently, plerixafor, formerly known as AMD-3100, was shown to be useful in association with G-CSF for a proportion of poorly mobilizing patients. [9][10][11][12] Recombinant human SCF (rhSCF) or ancestim has also been used in this patient subset.…”