Blood graft cellular composition and posttransplant outcomes in myeloma patients mobilized with or without low‐dose cyclophosphamide: a randomized comparison

Valtola, Jaakko; Silvennoinen, Raija; Ropponen, Antti; Siitonen, Timo; Säily, Marjaana; Sankelo, Marja; Terävä, Venla; Putkonen, Matti; Kuittinen, Taru; Pelkonen, Jukka; Mäntymaa, Pentti; Remes, Kari; Varmavuo, Ville; Jantunen, Esa

doi:10.1111/trf.13574

Cited by 18 publications

(24 citation statements)

References 39 publications

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“…We observed a significantly higher number of late granulocyte and monocyte forming myeloid progenitors in grafts collected in the CGP‐group whereas GP mobilized patients collected more CD19 + B‐cells and NK cells. Except for CD19 + B‐cells our results are comparable to other reports . The higher amount of late granulocyte precursors in grafts obtained after chemotherapy and plerixafor mobilization could lead to a more rapid ANC engraftment in these patients.…”

Section: Discussionsupporting

confidence: 87%

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Worel

Fritsch

Agis

et al. 2016

J of Clinical Apheresis

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Plerixafor in combination with granulocyte-colony stimulating factor (G-CSF) is approved for autologous stem cell mobilization in poor mobilizing patients with multiple myeloma or malignant lymphoma. The purpose of this study was to evaluate efficacy and safety of plerixafor in an immediate rescue approach, administrated subsequently to G-CSF alone or chemotherapy and G-CSF in patients at risk for mobilization failure. Eighty-five patients mobilized with G-CSF alone or chemotherapy were included. Primary endpoint was the efficacy of the immediate rescue approach of plerixafor to achieve ≥2.0 × 10 CD34 cells/kg for a single or ≥5 × 10 CD34 cells/kg for a double transplantation and potential differences between G-CSF and chemotherapy-based mobilization. Secondary objectives included comparison of stem cell graft composition including CD34 cell and lymphocyte subsets with regard to the mobilization regimen applied. No significant adverse events were recorded. A median 3.9-fold increase in CD34 cells following plerixafor was observed, resulting in 97% patients achieving at least ≥2 × 10 CD34+ cells/kg. Significantly more differentiated granulocyte and monocyte forming myeloid progenitors were collected after chemomobilization whereas more CD19 and natural killer cells were collected after G-CSF. Fifty-two patients underwent transplantation showing rapid and durable engraftment, irrespectively of the stem cell mobilization regimen used. The addition of plerixafor in an immediate rescue model is efficient and safe after both, G-CSF and chemomobilization and results in extremely high success rates. Whether the differences in graft composition have a clinical impact on engraftment kinetics, immunologic recovery, and graft durability have to be analysed in larger prospective studies.

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Section: Discussionsupporting

confidence: 87%

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Worel

Fritsch

Agis

et al. 2016

J of Clinical Apheresis

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“…Most of the other authors did not provide information about gating strategies but also reported higher proportions of CD38-/CD341 cells after plerixafor compared to G-CSF alone. [8][9][10]12,13 In addition, Taubert and coworkers 14 found increased proportions of CD38-cells after plerixafor mobilization and reported higher CD133 mRNA levels in CD341/ALDH bright cells. Based on recent studies describing a revision of the hematopoietic tree, 15,16 we established a multicolor single-platform analysis to enumerate CD34 subtypes of stem cell grafts.…”

Section: Discussionmentioning

confidence: 98%

“…Subsequent reports showed similar results. However, none of these groups described their gating strategies or showed figures depicting how “CD38 dim ” “CD38 low ” or “CD38 negative ” cells had been defined . Various groups have developed the model of a hematopoietic tree, describing the differentiation from the earliest CD34+ MPPs to lineage‐committed CD34+ precursors giving rise to defined blood cells.…”

Section: Discussionmentioning

confidence: 99%

“…[3][4][5][6] Several authors investigated the composition of PBSC grafts after various mobilization methods. [7][8][9][10] However, preanalytic methods including the use of fluorochromes and antibody combinations to characterize PBSC by flow cytometry and analysis techniques reported are different. Fruehauf and colleagues 11 described a higher frequency of "CD38-primitive stem cells" after plerixafor administration showing also CD38 dot plots.…”

Section: Discussionmentioning

confidence: 99%

“…To enhance CD34+ cell release from the BM, plerixafor, a chemokine receptor Type 4 (CXCR4) antagonist, can be given in addition to G‐CSF with or without chemotherapy . Several authors investigated the composition of PBSC grafts after various mobilization methods . However, preanalytic methods including the use of fluorochromes and antibody combinations to characterize PBSC by flow cytometry and analysis techniques reported are different.…”

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confidence: 99%

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Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes

Worel¹,

Frank

Frech

et al. 2017

Transfusion

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In contrast to the findings of other authors, our study shows a clear shift toward more committed CD34+ subsets after plerixafor in poor mobilizers and elucidates the importance of informative surface markers like CD45RA and CD133 in addition to CD38 to discriminate earlier from more committed CD34+ cells. Further studies are needed to analyze whether these findings have an impact on clinical outcome.

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Cost analysis of a randomized stem cell mobilization study in multiple myeloma

et al. 2016

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Upfront autologous stem cell transplantation (ASCT) is the standard therapy for younger multiple myeloma (MM) patients. MM patients usually undergo stem cell mobilization with cyclophosphamide (CY) followed by granulocyte colony-stimulating factor (G-CSF), or with G-CSF alone. A limited number of randomized studies are available comparing costs of different mobilization strategies. Eighty transplant-eligible patients aged up to 70 years with untreated MM were included in this prospective study. The patients were treated with RVD induction for three 21-day cycles and randomized 1:1 at inclusion into one of the two mobilization arms CY 2 g/m(2) + G-CSF [arm A] vs. G-CSF alone [arm B]. Plerixafor was given according to a specific algorithm if needed. Sixty-nine patients who received mobilization followed by blood graft collection were included in the cost analysis. The median total costs of the mobilization phase were significantly higher in arm A than in arm B (3855 € vs. 772 €, p ≤ 0.001). The cumulative median cost of the mobilization and collection phases was significantly lower in arm B than in arm A (8524 € vs. 11,622 €, p = 0.012). There was no significant difference between the arms in the total median costs of ASCT (n = 59) (34,997 € in arm A vs. 31,981 € in arm B, p = 0.118). Mobilization with G-CSF alone seems to be a preferable mobilization method for MM patients in terms of mobilization and apheresis costs. In addition, it requires less hospital resource utilization.

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Blood graft cellular composition and posttransplant outcomes in myeloma patients mobilized with or without low‐dose cyclophosphamide: a randomized comparison

Abstract: CY plus G-GSF yields more CD34+ cells but seems to diminish lymphocyte and NK cell counts in the grafts and hampers immune recovery after transplantation. Thus G-CSF alone might be a preferred mobilization method due to more rapid immune recovery posttransplant.

Cited by 18 publications

References 39 publications

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Plerixafor as preemptive strategy results in high success rates in autologous stem cell mobilization failure

Influence of plerixafor on the mobilization of CD34+ cell subpopulations and lymphocyte subtypes

Cost analysis of a randomized stem cell mobilization study in multiple myeloma

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