Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study

Segeren, Christine M.; Sonneveld, Pieter; Holt, Bronno van der; Vellenga, Edo; Croockewit, Alexandra J.; Verhoef, Gregor; Cornelissen, Jan J.; Schaafsma, M; Oers, Marinus H. J. van; Wijermans, Pierre W.; Fibbe, W. E.; Wittebol, Shulamit; Schouten, Harry C.; Kooy, Marinus van Marwijk; Biesma, Douwe H.; Baars, Joke W.; Slater, Rosalyn; Steijaert, Monique; Buijt, I.; Lokhorst, Henk M.

doi:10.1182/blood-2002-03-0889

Cited by 139 publications

(72 citation statements)

References 35 publications

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“…13,14 In MM, the upper age limit in randomized trials has shifted from 60 15,16 to 65 years. [17][18][19] For the purpose of this review, ASCT recipients X60 years are regarded elderly, as most randomized data on the feasibility and efficacy of ASCT in comparison to conventional therapy comes from studies performed in younger patients.…”

Section: Who Is Elderly?mentioning

confidence: 99%

“…Based on randomized studies performed in younger myeloma patients 15,17 as well as matched-pair comparisons, 29,30 ASCT is considered the standard care in younger myeloma patients although not all studies have confirmed the superiority of ASCT. 18 Based on a randomized French trial, 31 melphalan 200 mg/m 2 (MEL200) has become the standard high-dose regimen.…”

Section: Experiences Of Asct In Patients With MMmentioning

confidence: 99%

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Autologous stem cell transplantation beyond 60 years of age

Jantunen

2006

Bone Marrow Transplant

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Along with improved supportive care and thus reduced treatment-related mortality, an increasing number of elderly patients (460 years) with haematological malignancies are now considered for high-dose therapy (HDT) supported by autologous stem cell transplantation (ASCT). ASCT is feasible in selected elderly patients with multiple myeloma and those with non-Hodgkin's lymphoma. As elderly patients have generally been excluded from randomized studies evaluating efficacy of ASCT in comparison with non-transplant approaches, limited data are available on the efficacy of ASCT in this patient population. Recent developments in supportive care including amifostine and palifermin may increase feasibility of ASCT in elderly patients. Prospective studies are needed to evaluate feasibility and efficacy of ASCT in patients over 60 years of age. Also, further studies are needed in order to decrease toxicity of high-dose regimens in this patient group where co-morbid conditions may modify the toxicity of HDT in a clinically significant manner.

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Section: Who Is Elderly?mentioning

confidence: 99%

Section: Experiences Of Asct In Patients With MMmentioning

confidence: 99%

Autologous stem cell transplantation beyond 60 years of age

Jantunen

2006

Bone Marrow Transplant

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“…3,4 Furthermore, clinical outcomes of patients with MM are extremely heterogeneous, with survival ranging from only a few months to more than 15 years. [4][5][6] Increasing evidence suggests that genetic heterogeneity in MM cells largely accounts for the divergent clinical outcomes. 6 We have been pursuing the genetic characteristics of MM for nearly 10 years, which has contributed to the classification of MM diseases.…”

Section: Introductionmentioning

confidence: 99%

RARα2 expression is associated with disease progression and plays a crucial role in efficacy of ATRA treatment in myeloma

Wang

Tricot

Shi

et al. 2009

Blood

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IntroductionMultiple myeloma (MM) is a plasma cell malignancy. 1,2 Although high-dose therapy and tandem bone marrow autotransplantation can produce higher response rates and longer survival than standard chemotherapy, MM remains largely incurable by current therapeutic strategies. 3,4 Furthermore, clinical outcomes of patients with MM are extremely heterogeneous, with survival ranging from only a few months to more than 15 years. [4][5][6] Increasing evidence suggests that genetic heterogeneity in MM cells largely accounts for the divergent clinical outcomes. 6 We have been pursuing the genetic characteristics of MM for nearly 10 years, which has contributed to the classification of MM diseases. [7][8][9][10][11] However, it remains unknown how to transform MM into a curable disease. Therefore, identification of new targets and genetic alterations, especially those for which there are available drugs, is important.All-trans retinoic acid (ATRA)-based regimens have been used in the therapy of acute promyelocytic leukemia (APL) for more than 20 years and have dramatically raised the 5-year disease-free survival to more than 70%. Furthermore, the toxicity of ATRA has been limited compared with conventional cytotoxic chemotherapy. 12 The high efficacy of retinoic acid (RA)-based therapy in APL and its well-documented safety profile have stimulated considerable interests in the treatment of other malignancies, [13][14][15] including myeloma. 16,17 Despite many efforts, however, clinical benefits of ATRA treatment in other tumors have been minor. RAR␣ has 2 major isoforms, RAR␣1 and RAR␣2, which differ in their expression patterns and N-terminal AF-1 functional domains. 18 Both RAR␣1 and RAR␣2 are considered specific receptors for RA-based reagents. However, the specific cellular roles of RAR␣1 and RAR␣2 are still unclear. In this study, we found that RAR␣2 plays a crucial role in myeloma progression, and more importantly, in mediating RA-based therapy of RAR␣2 ϩ MM diseases. Methods Study subjectsCD138 ϩ myeloma cell samples were obtained from patients who were enrolled on the National Institutes of Health (NIH)-sponsored clinical trials UARK 98-026 (Total Therapy 2 [TT2]) and UARK 03-033 (TT3). The Institutional Review Board of the University of Arkansas for Medical Sciences approved the research studies, and all subjects provided written informed consent in accordance with the Declaration of Helsinki.We have an inventory of more than 30 myeloma cell lines in our laboratory. Cells from these cell lines were cultured in RPMI 1640 containing 10% heat-inactivated fetal calf serum (FCS), 2 mM L-glutamine (Gibco), penicillin (100 U/mL), and streptomycin (100 g/mL) in a humidified incubator at 37°C in 5% CO 2 . Gene expression profilingPlasma cell purifications and gene expression profiling, using the Affymetrix U133Plus2.0 microarray, were performed as previously described. 9,11 Signal intensities were preprocessed and normalized by GCOS1.1 software (Affymetrix). 9,11 Myeloma cell samples from 80 newly diagnosed patien...

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“…3 The CYP3A4 genotype was assessed in 197 patients. A CYP3A5 genotype was successfully assigned to 205 patients.…”

mentioning

confidence: 99%

Influence of genetic polymorphisms in CYP3A4, CYP3A5, GSTP1, GSTM1, GSTT1 and MDR1 genes on survival and therapy-related toxicity in multiple myeloma

Schilthuizen¹,

Broyl²,

Holt³

et al. 2007

Haematologica

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We investigated the role of single nucleotide polymorphisms in genes encoding for drug-metabolizing enzymes in 209 newly diagnosed multiple myeloma patients included in a clinical trial comparing single with double intensive therapy. We observed no significant association between polymorphisms in CYP3A4, CYP3A5, MDR1, GSTM1 and GSTT1 and outcome either after treatment with induction chemotherapy or after high-dose therapy.

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Overall and event-free survival are not improved by the use of myeloablative therapy following intensified chemotherapy in previously untreated patients with multiple myeloma: a prospective randomized phase 3 study

Cited by 139 publications

References 35 publications

Autologous stem cell transplantation beyond 60 years of age

Autologous stem cell transplantation beyond 60 years of age

RARα2 expression is associated with disease progression and plays a crucial role in efficacy of ATRA treatment in myeloma

Influence of genetic polymorphisms in CYP3A4, CYP3A5, GSTP1, GSTM1, GSTT1 and MDR1 genes on survival and therapy-related toxicity in multiple myeloma

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