Myeloma cell contamination of peripheral blood stem-cell grafts can predict the outcome in multiple myeloma patients after high-dose chemotherapy and autologous stem-cell transplantation

Vogel, Wichard; Kopp, Hans‐Georg; Kanz, Lothar; Einsele, Hermann

doi:10.1007/s00432-004-0635-y

Cited by 49 publications

(48 citation statements)

References 18 publications

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“…Of the four MM cell lines that were tested for reovirus purging efficacy, one demonstrated complete purging, whereas the others showed a significant tumor reduction. As less tumor burden in an autograft could lead to an advantage in PFS, 8 reovirus purging may be considered as an option for many MM patients. In an era where a personalized approach to medicine is sought, one might even envision that MM represents a malignancy where BM aspirates could easily be withdrawn from patients and tested for reovirus sensitivity before initiating either a treatment regimen or purging strategy.…”

Section: Discussionmentioning

confidence: 99%

“…8 In addition, syngeneic twin transplantation has shown significantly lower relapse risk than autotransplantation for MM, again suggesting that graft contamination may impact outcome following ASCT. 9,10 Although CD34 þ cell selection has been used as a purging modality in the clinic, several studies have demonstrated that even after CD34 þ cell selection, MRD could still be detected in MM patient autografts.…”

Section: Introductionmentioning

confidence: 99%

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Reovirus as a successful ex vivo purging modality for multiple myeloma

Thirukkumaran

Zhong

Luider

et al. 2013

Bone Marrow Transplant

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Autologous stem cell rescue (ASCT) following high-dose myeloablative chemotherapy is considered to be a therapeutic option for many multiple myeloma (MM) patients; however relapse post ASCT presents a major challenge. The oncolytic potential of reovirus has been previously demonstrated and is currently undergoing phase I monotherapy clinical trials for MM and phase II/III clinical trials for solid tumors. Here we tested the hypothesis that reovirus can successfully purge MM in a murine model that partially recapitulates human MM. RPMI 8226, MM1S, H929 and U266 human myeloma cell lines were exposed to reovirus and oncolysis was assessed. Apheresis product admixed with MM cells was purged with live reovirus (LV) or dead virus (DV) and purging efficacy was monitored via flow cytometry, reverse transcribed-PCR (RT-PCR) and disease relapse in non obese diabetic/severe combined immune deficient (NOD/SCID) mice. Significant LV purging was seen with MM1S, H929 and U266 and the complete ex vivo purging achieved with RPMI 8226 was confirmed by flow cytometry, RT-PCR and absence of disease relapse in vivo. Mice that received LV-purged autografts exhibited 100% survival in comparison to mice that received DV-purged controls. Reovirus's unique ability to kill MM while sparing hematopoietic stem cells places it as an attractive purging agent for MM during ASCT.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reovirus as a successful ex vivo purging modality for multiple myeloma

Thirukkumaran

Zhong

Luider

et al. 2013

Bone Marrow Transplant

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“…27,28 Various methods have been used to reduce tumor cell contamination in the apheresis product for autologous transplantation, but these methods failed to improve disease-free or overall survival. 29,30 To date, there is no evidence of tumor cell mobilization in plerixafor-treated patients in phase 2 studies.…”

Section: Discussionmentioning

confidence: 99%

Plerixafor and G-CSF versus placebo and G-CSF to mobilize hematopoietic stem cells for autologous stem cell transplantation in patients with multiple myeloma

DiPersio

Stadtmauer

Nademanee

et al. 2009

Blood

713

756

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This phase 3, multicenter, randomized (1:1), double-blind, placebo-controlled study evaluated the safety and efficacy of plerixafor with granulocyte colonystimulating factor (G-CSF) in mobilizing hematopoietic stem cells in patients with multiple myeloma. Patients received G-CSF (10 g/kg) subcutaneously daily for up to 8 days. Beginning on day 4 and continuing daily for up to 4 days, patients received either plerixafor (240 g/kg) or placebo subcutaneously. Starting on day 5, patients began daily apheresis for up to 4 days or until more than or equal to 6 ؋ 10 6 CD34 ؉ cells/kg were collected. The primary endpoint was the percentage of patients who collected more than or equal to 6 ؋ 10 6 CD34 ؉ cells/kg in less than or equal to 2 aphereses. A total of 106 of 148 (71.6%) patients in the plerixafor group and 53 of 154 (34.4%) patients in the placebo group met the primary endpoint (P < .001). A total of 54% of plerixafor-treated patients reached target after one apheresis, whereas 56% of the placebo-treated patients required 4 aphereses to reach target. The most common adverse events related to plerixafor were gastrointestinal disorders and injection site reactions. Plerixafor and G-CSF were well tolerated, and significantly more patients collected the optimal CD34 ؉ cell/kg target for transplantation earlier compared with G-CSF alone. This study is registered at www. clinicaltrials.gov as #NCT00103662. (Blood. 2009;113:5720-5726)

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“…Tumor cell contamination does occur and there is no consensus on the acceptable and safe limit of tumor cells in the apheresis product. [4][5][6][7][8][9][10][11] There are various assays to quantify tumor cell contamination with sensitivities ranging from 1/100 cells using flow cytometry to 1/100 000 cells using PCR. 12 Although PCR testing is the superior method in terms of sensitivity, it is impractical for clinical practice as it is expensive, time consuming and requires patient-specific primers to be produced from myeloma cell samples.…”

Section: Introductionmentioning

confidence: 99%