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Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma

Leukemia volume 22, pages 1282–1284 (2008)Cite this article

High-dose melphalan followed by autologous stem cell transplant (ASCT) has been a cornerstone of therapy for multiple myeloma (MM) since landmark articles demonstrating clinical benefit were published over 10 years ago.1 As adequate stem cell collection is a prerequisite for successful ASCT, it was quickly appreciated that prior use of the alkylating agent melphalan resulted in an inability to collect stem cells in approximately 60% of patients who had received more than five cycles of therapy.2 As a consequence of this observation, the use of lower dose melphalan was abandoned as an induction therapy in patients in whom stem cell transplant was later being considered and was replaced with dexamethasone-based induction regimens. Following the use of dexamethasone alone or in combination with adriamycin and vincristine-based (VAD) chemotherapy, stem cell collection is successful in the vast majority of patients.3 However, recent positive clinical trial results have prompted a shift in the choice of induction therapy to regimens combining an immunomodulatory drug such as thalidomide, or more recently, lenalidomide with dexamethasone in preference to VAD chemotherapy.4, 5 Thalidomide is not generally myelosuppressive and in large studies, stem cell collection numbers were only modestly lower than that seen with VAD chemotherapy, with 84% of patients collecting sufficient stem cells for tandem transplant.6 Promising results on the use of lenalidomide and dexamethasone have resulted in a recommendation for the use of this combination in newly diagnosed patients heading for transplant.7 However, one recent analysis of stem cell collection following lenalidomide induction indicated that stem cell collection yields are compromised in some patients.8 We read with interest the paper by Mazumder et al. on the effect of lenalidomide on stem cell mobilization.9 We report here further evidence for a detrimental effect of lenalidomide on the ability to mobilize stem cells successfully. Specifically, in 9 of 20 (45%) patients who received lenalidomide at our center as induction therapy, a successful stem cell collection (>2 × 106 CD34-positive cells kg−1) following granulocyte colony-stimulating factor (G-CSF) 10 μg kg−1 alone could not be obtained or was severely comprised at first collection attempt by prior lenalidomide use.

We performed a retrospective chart review after the clinical observation of difficulty in mobilizing stem cells in patients treated with lenalidomide and dexamethasone was made. MM patients undergoing stem cell collection between January 2005 and October 2007 were analyzed for type and duration of induction therapy, collection efficacy and engraftment in patients who went to transplant. All data were extracted from patient medical records and from our transplant database. The study was approved by the Mayo Foundation Institutional Review Board.

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References

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Authors and Affiliations

  1. Department of Hematology and Oncology, Mayo Clinic Arizona, Scottsdale, AZ, USA

    H Paripati, A K Stewart, S Cabou, A Dueck, V J Zepeda, N Pirooz, C Ehlenbeck, C Reeder, J Slack, J F Leis, J Boesiger, A S Torloni, R Fonseca & P L Bergsagel

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  1. H Paripati
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  2. A K Stewart
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  3. S Cabou
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  13. R Fonseca
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Correspondence to H Paripati.

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Supplementary Information accompanies the paper on the Leukemia website (http://www.nature.com/leu)

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Paripati, H., Stewart, A., Cabou, S. et al. Compromised stem cell mobilization following induction therapy with lenalidomide in myeloma. Leukemia 22, 1282–1284 (2008). https://doi.org/10.1038/sj.leu.2405100

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