Radiosensitivity of human clonogenic myeloma cells and normal bone marrow precursors: Effect of different dose rates and fractionation

Glück, Stefan; Dyk, Jake Van; Messner, Hans A.

doi:10.1016/0360-3016(94)90107-4

Cited by 18 publications

(10 citation statements)

References 17 publications

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“…Based on the whole body BLI measurements we calculated that an approximate 2 log tumor reduction was achieved by radiotherapy, which is in agreement with the radiosensitivity of the clonogenic MM cells. 38 While for small individual lesions radiotherapy seemed to be sufficient for tumor eradication (there was no reappearance of the tumor), this was clearly not the case for the larger tumor foci. Tumors in these latter foci eventually progressed at the same pace, with the radio-therapy providing only a 6-week prolongation in overall survival.…”

Section: Discussionmentioning

confidence: 99%

A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect

Rozemuller¹,

Spek²,

Bogers-Boer³

et al. 2008

Haematologica

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Section: Discussionmentioning

confidence: 99%

A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect

Rozemuller¹,

Spek²,

Bogers-Boer³

et al. 2008

Haematologica

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“…In this regard in vitro evidence of a dose-response of myeloma cells to the effects of radiation 17 together with clinical evidence of the efficacy of escalating melphalan guided our decision to utilize escalated doses of these agents in an attempt to increase the proportion of malignant cells killed during the transplant induction therapy. Furthermore, it was reasoned at the time of study initiation that etoposide 18,19 may help eliminate the putative germinal center B cells potentially contributing to the malignant plasma cell clone on an ongoing basis.…”

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confidence: 99%

Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma

Abraham

Chen

Tsang

et al. 1999

Bone Marrow Transplant

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Summary:Randomized trials conducted by the Intergroupe Française du Myelome (IFM) demonstrate that the use of high-dose chemotherapy (HDCT) and stem cell transplantation (SCT) improves event-free (EFS) and overall survival (OS) in younger patients with multiple myeloma (MM). Nevertheless, current HDCT regimens remain inadequate as all patients ultimately relapse following SCT. In an attempt to improve the OS of MM patients post-SCT we used an escalated HDCT regimen incorporating both intensified melphalan (160 mg/m 2 ) and fractionated total body irradiation (12 Gy) to maximize the dose response of myeloma cells to these agents and included infusional etoposide 60 mg/kg in an attempt to eradicate clonal B cells potentially contributing to the myeloma clone. One hundred patients with MM received this intensified SCT regimen. The 100-day treatment-related mortality was 12% predominantly reflecting the development of interstitial pneumonitis (IP) in 28% of patients of whom 7/28 (25%) died. The predicted 5-year OS and EFS following the diagnosis of MM were 60% and 35%, respectively. The median OS from the time of transplant is 41 months and the median EFS is 28 months. More than two prior chemotherapy regimens, previous radiation therapy (RT) and the presence of an abnormal karyotype involving chromosomes 11 or 13 were significantly predictive of poor outcome. Interferon maintenance was not associated with improved outcome. Intensification of the HDCT regimen utilizing etoposide together with escalated melphalan and TBI increases morbidity and mortality without increasing OS beyond that reported with less toxic regimens. Keywords: myeloma; autologous; stem cell; transplant; radiation Despite therapeutic advances over the past decade, multiple myeloma (MM) remains an incurable disease. Following conventional-dose melphalan-based chemotherapy, objective responses are observed in 50-60% of patients, although these are rarely durable and the median overall survival (OS) is less than 3 years. 1 Using higher dose melphalan 2,3 responses can be obtained even in patients previously refractory to this drug, however severe but reversible myelosuppression is observed, with toxic death rates of 10-20%. [4][5][6][7][8] With the advent of autologous bone marrow (ABMT) and peripheral blood stem cell transplantation (SCT), melphalan-based myeloablative regimens have been tested in selected younger patients. Toxic death rates related to high-dose melphalan have subsequently fallen to between 2 and 11%. [9][10][11] Reported response rates in single center phase II trials of SCT incorporating high-dose melphalan range between 25-80% (reflecting the variable response criteria employed), however the median duration of response from the time of transplant generally fails to exceed 2-3 years. [12][13][14][15] In the only published randomized controlled trial (RCT) of intensive therapy, the Intergroupe Français du Myelome (IFM) demonstrated the superiority of high-dose melphalan and total body irradiation (TBI) with ABMT support over conve...

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“…2 Multiple myeloma remains incurable causing more than 10 000 deaths each year in the United States. 3 Although cultured myeloma cells are relatively resistant to radiotherapy in vitro, 4,5 the malignancy is highly radiosensitive and radiation therapy is routinely used for palliation of pain, neurologic compromise, or structural instability from focal myeloma deposits. Efforts to use radiation as a systemic modality for definitive therapy of myeloma, however, have been problematic because of collateral toxicity to normal tissues especially the bone marrow progenitor cells.…”

Section: Introductionmentioning

confidence: 99%

Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV(Δ51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene

Goel¹,

Carlson²,

Classic

et al. 2007

Blood

118

117

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Multiple myeloma is a radiosensitive malignancy that is currently incurable. Here, we generated a novel recombinant vesicular stomatitis virus [VSV(⌬51) - IntroductionMultiple myeloma is a malignancy of antibody-secreting plasma cells that reside predominantly in bone and bone marrow and secrete a monoclonal immunoglobulin. 1 The disease responds initially to alkylating agents, corticosteroids, and thalidomide, but eventually becomes refractory. 2 Multiple myeloma remains incurable causing more than 10 000 deaths each year in the United States. 3 Although cultured myeloma cells are relatively resistant to radiotherapy in vitro, 4,5 the malignancy is highly radiosensitive and radiation therapy is routinely used for palliation of pain, neurologic compromise, or structural instability from focal myeloma deposits. Efforts to use radiation as a systemic modality for definitive therapy of myeloma, however, have been problematic because of collateral toxicity to normal tissues especially the bone marrow progenitor cells. 6,7 Developing novel therapies for multiple myeloma based on the targeted delivery of radioisotopes to sites of active disease may have important clinical implications for myeloma therapy.Gene transfer using the thyroidal sodium iodide symporter (NIS) gene offers a novel strategy for delivery of radionuclides to disseminated cancer cells. 8 NIS is a transmembrane protein in thyroid follicular cells that actively mediates iodide uptake to a concentration gradient more than 20 to 40-fold. 9 Cloning the human NIS cDNA has aided in imaging and therapy of dedifferentiated thyroid cancer and nonthyroid cancers such as glioma, neuroblastoma, melanoma, multiple myeloma, and ovarian, breast, cervix, lung, liver, and colon carcinoma. 10 Tissue-specific NIS expression has been achieved in various cancer xenografts with minimal toxicity to normal organs by using promoters and enhancers from genes encoding immunoglobulins, prostate-specific antigen, probasin, and mucin-1. [11][12][13][14][15][16] Cancer therapy using oncolytic viruses (oncolytic virotherapy) requires agents that amplify efficiently through replication and spread causing rapid tumor lysis, yet are safe causing minimal toxicity to normal tissue enabling systemic inoculations to treat metastatic cancers. 17,18 We previously engineered the NIS gene into a lymphotropic, replication-competent attenuated strain of measles virus (MV-NIS) 19 that was subsequently used for oncolytic virotherapy of myeloma xenografts. Intratumoral spread of MV-NIS could be monitored noninvasively by radioiodine imaging and virus-resistant tumors were ablated after administration of 131 I. 20 A phase I clinical trial to evaluate the targeting properties of MV-NIS in patients with recurrent or refractory myeloma is ongoing at our institution. Several RNA viruses other than measles virus, including reovirus, Newcastle disease virus, mumps virus, and vesicular stomatitis virus (VSV), are being developed as systemic oncolytic agents for cancer therapy. 18,21 Each of these viruses ...

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Radiosensitivity of human clonogenic myeloma cells and normal bone marrow precursors: Effect of different dose rates and fractionation

Cited by 18 publications

References 17 publications

A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect

A bioluminescence imaging based in vivo model for preclinical testing of novel cellular immunotherapy strategies to improve the graft-versus-myeloma effect

Intensification of the stem cell transplant induction regimen results in increased treatment-related mortality without improved outcome in multiple myeloma

Radioiodide imaging and radiovirotherapy of multiple myeloma using VSV(Δ51)-NIS, an attenuated vesicular stomatitis virus encoding the sodium iodide symporter gene

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