Joint HOVON-50/GMMG-HD3 randomized trial on the effect of thalidomide as part of a high-dose therapy regimen and as maintenance treatment for newly diagnosed myeloma patients

Goldschmidt, Hartmut; Sonneveld, Pieter; Cremer, FW; Holt, Bronno van der; Westveer, Petra H. M.; Breitkreutz, Iris; Benner, Axel; Glasmacher, Axel; Schmidt-Wolf, I.; Martin, Hans; Hoelzer, Dieter; Ho, A. D.; Lokhorst, Henk M.

doi:10.1007/s00277-003-0685-2

Cited by 41 publications

(29 citation statements)

References 28 publications

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“…These 206 patients were treated with vincristine, adriamicyne and dexamethasone (VAD), high-dose melphalan (HDM) and autologous stem cell transplantation (ASCT) 27 and were included in the following Heidelberg-Montpellier (HM) series. The .CEL files and MAS5 files have been deposited in the ArrayExpress public database under accession number E-MTAB-362.…”

Section: Primary Myeloma Cellsmentioning

confidence: 99%

A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines

Moreaux¹,

Klein²,

Bataille³

et al. 2010

Haematologica

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Section: Primary Myeloma Cellsmentioning

confidence: 99%

A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines

Moreaux¹,

Klein²,

Bataille³

et al. 2010

Haematologica

Self Cite

140

200

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“…For clinical parameters, see Supplementary Table S3. According or in analogy to the GMMG-HD3 trial (Goldschmidt et al, 2003), 168 patients underwent frontline high-dose chemotherapy with 200 mg/m 2 melphalan and autologous stem cell transplantation. Survival data were validated by an independent cohort of 345 patients treated within the total therapy 2 protocol (Barlogie et al, 2006).…”

Section: Patients and Healthy Donorsmentioning

confidence: 99%

Bone morphogenic protein 6: a member of a novel class of prognostic factors expressed by normal and malignant plasma cells inhibiting proliferation and angiogenesis

et al. 2009

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Pathogenesis of multiple myeloma is associated with an aberrant expression of pro-proliferative, pro-angiogenic and bone-metabolism-modifying factors by malignant plasma cells. Given the frequently long time span from diagnosis of early-stage plasma cell dyscrasias to overt myeloma and the mostly low proliferation rate of malignant plasma cells, we hypothesize these to similarly express a novel class of inhibitory factors of potential prognostic relevance. Bone morphogenic proteins (BMPs) represent possible candidates as they inhibit proliferation, stimulate bone formation and have an effect on the survival of cancer patients. We assessed the expression of BMPs and their receptors by Affymetrix DNA microarrays (n ¼ 779) including CD138-purified primary myeloma cell samples (n ¼ 635) of previously untreated patients. BMP6 is the only BMP expressed by malignant and normal plasma cells. Its expression is significantly lower in proliferating myeloma cells, myeloma cell lines or plasmablasts. BMP6 significantly inhibits the proliferation of myeloma cell lines, survival of primary myeloma cells and in vitro angiogenesis. A high BMP6 expression in primary myeloma cell samples delineates significantly superior overall survival for patients undergoing high-dose chemotherapy independent of conventional prognostic factors (International Staging System (ISS) stage, b 2 microglobulin).

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“…2,6 The protocol of the German-speaking Myeloma-Multicenter Group (GMMG-HD3) and of the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON-50) investigates in a multicenter phase 3 trial the effect of Thal on survival and outcome of MM patients in a high-dose chemotherapy therapy setting with maintenance therapy. 7 As successful peripheral blood stem cell (PBSC) collection remains a key factor for a high-dose chemotherapy strategy, we here investigate the influence of Thal on PBSC collection analyzing the data of 398 MM patients enrolled in the GMMG-HD3-and HOVON-50 trial, respectively.…”

Section: Introductionmentioning

confidence: 99%

Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield

et al. 2007

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In a phase III randomized, multicenter study, the Germanspeaking Myeloma-Multicenter Group (GMMG) and the DutchBelgian Hemato-Oncology Cooperative Group (HOVON) group investigated the influence of thalidomide (Thal) on the outcome of peripheral blood stem cell (PBSC) collection in multiple myeloma (MM) before peripheral autologous blood stem cell transplantation (ABSCT). We analyzed the data of 398 myeloma patients after induction with Thal, doxorubicin and dexamethasone (TAD) in comparison with vincristine, doxorubicin and dexamethasone (VAD) followed by mobilization with cyclophosphamide, doxorubicin, dexamethasone (CAD) and PBSC collection. Within both the study groups, patients treated with TAD showed to collect significantly fewer CD34 þ cells compared with VAD (GMMG, TAD: median 9.8 Â 10 6 /kg; range 2.0-33.6; VAD: median 10.9 Â 10 6 /kg range 3.0-36.0; P ¼ 0.02) (HOVON, TAD: median 7.4 Â 10 6 /kg; range 2.0-33.0; VAD: median 9.4 Â 10 6 /kg; range 0.0-48.7; P ¼ 0.009). However, engraftment after peripheral autologous stem cell transplantation showed no difference between Thal and VAD groups. We conclude that Thal as a part of induction regimen is associated with better response rates (GMMG-HD3: CR/PR 79%, VAD: CR/PR 58%; HOVON-50: TAD: CR/PR 81%, VAD: CR/PR 61%), but significantly affects the yield of PBSC collection. Nevertheless, the number of total CD34 þ cells collected was sufficient for double autologous transplantation in 82% of the Thal patients, with at least 2.5 Â 10 6 /kg CD34 þ cells.

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Joint HOVON-50/GMMG-HD3 randomized trial on the effect of thalidomide as part of a high-dose therapy regimen and as maintenance treatment for newly diagnosed myeloma patients

Cited by 41 publications

References 28 publications

A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines

A high-risk signature for patients with multiple myeloma established from the molecular classification of human myeloma cell lines

Bone morphogenic protein 6: a member of a novel class of prognostic factors expressed by normal and malignant plasma cells inhibiting proliferation and angiogenesis

Thalidomide in newly diagnosed multiple myeloma: influence of thalidomide treatment on peripheral blood stem cell collection yield

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