Bortezomib and high-dose melphalan as conditioning regimen before autologous stem cell transplantation in patients with de novo multiple myeloma: a phase 2 study of the Intergroupe Francophone du Myelome (IFM).

Autologous stem cell transplantation (ASCT) is recommended for younger patients with newly diagnosed multiple myeloma. Achieving complete response (CR) or at least very good partial response (VGPR) is a major prognostic factor for survival with 20% to 30% of patients achieving CR after ASCT. Bortezomib has shown synergistic effects with melphalan and no prolonged hematologic toxicity.

Achievement of at least very good partial response is a simple and robust prognostic factor in patients with multiple myeloma treated with high-dose therapy: long-term analysis of the IFM 99-02 and 99-04 Trials.

Purpose: The prognostic impact of complete response (CR) achievement in multiple myeloma (MM) has been shown mostly in the context of autologous stem-cell transplantation. Other levels of response have been defined because, even with high-dose therapy, CR is a relatively rare event. The purpose of this study was to analyze the prognostic impact of very good partial response (VGPR) in patients treated with high-dose therapy.

International Myeloma Working Group molecular classification of multiple myeloma: spotlight review.

Myeloma is a malignant proliferation of monoclonal plasma cells. Although morphologically similar, several subtypes of the disease have been identified at the genetic and molecular level. These genetic subtypes are associated with unique clinicopathological features and dissimilar outcome.

Prognostic significance of copy-number alterations in multiple myeloma.

Purpose: Chromosomal aberrations are a hallmark of multiple myeloma but their global prognostic impact is largely unknown.

Patients And Methods: We performed a genome-wide analysis of malignant plasma cells from 192 newly diagnosed patients with myeloma using high-density, single-nucleotide polymorphism (SNP) arrays to identify genetic lesions associated with prognosis.

Results: Our analyses revealed deletions and amplifications in 98% of patients.

The role of complete response in multiple myeloma.

In multiple myeloma (MM), the impact of complete response (CR) could be shown only after introduction of high-dose therapy plus autologous stem cell transplantation (ASCT). In the context of ASCT, achieving CR (negative immunofixation and normal bone marrow) or at least very good partial response is associated with longer progression-free survival and in most studies longer survival. With novel agents, high CR rates are achieved and this prognostic impact of CR is being shown as well, both in relapsed and in newly diagnosed MM.

Loss of the SMRT/NCoR2 corepressor correlates with JAG2 overexpression in multiple myeloma.

Multiple myeloma (MM) is a clonal B-cell neoplasm that accounts for 10% of all malignant hematologic neoplasms and that affects terminally differentiated B cells (i.e., plasma cells).

Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33(+) primary resistant or relapsed acute myeloid leukemia.

Purpose: To determine the antitumor activity and safety of a combination of gemtuzumab ozogamicin (GO), intermediate-dose cytarabine, and mitoxantrone (MIDAM) in patients with refractory or relapsed CD33(+) acute myeloid leukemia (AML).

Patients And Methods: We treated 62 patients with refractory (n = 18) or relapsed (n = 44) CD33(+) AML. Median age was 55.

Prediction of survival in multiple myeloma based on gene expression profiles reveals cell cycle and chromosomal instability signatures in high-risk patients and hyperdiploid signatures in low-risk patients: a study of the Intergroupe Francophone du Myélome.

Purpose: Survival of patients with multiple myeloma is highly heterogeneous, from periods of a few weeks to more than 10 years. We used gene expression profiles of myeloma cells obtained at diagnosis to identify broadly applicable prognostic markers.

Patients And Methods: In a training set of 182 patients, we used supervised methods to identify individual genes associated with length of survival.

Role of genetics in prognostication in myeloma.

As in other hematological malignancies, cytogenetics is becoming a major prognostic parameter in myeloma. Myeloma differs from other hemopathies particularly in technical aspects related to low proliferation and partial infiltrates. Thus, fluorescence in-situ hybridization (FISH) is probably the best method for cytogenetic assessment in myeloma, but it requires the identification of the malignant cells (morphologically, immunologically or through sorting).

Stem cell transplantation in multiple myeloma.

Multiple myeloma (MM) is one of the key hematologic malignancies in which the impact of dose intensity has been demonstrated. Consequently, in 2005, MM was the most common disease for which autologous stem cell transplantation (ASCT) was indicated both in Europe and in the U.S.

The clinical presentation and prognosis of diffuse large B-cell lymphoma with t(14;18) and 8q24/c-MYC rearrangement.

Background And Objectives: Diffuse large B-cell lymphomas (DLBCL) are common lymphomas that have been classified into three subgroups on the basis of their patterns of gene expression. The aim of this study was to characterize the clinical, biological, immunophenotypic and cytogenetic features of DLBCL with concurrent t(14;18) and 8q24/c-MYC rearrangement.

Design And Methods: Sixteen cases of DLBCL with the dual translocation were identified between 1998 and January 2006.

Melphalan and prednisone plus thalidomide versus melphalan and prednisone alone or reduced-intensity autologous stem cell transplantation in elderly patients with multiple myeloma (IFM 99-06): a randomised trial.

Background: In multiple myeloma, combination chemotherapy with melphalan plus prednisone is still regarded as the standard of care in elderly patients. We assessed whether the addition of thalidomide to this combination, or reduced-intensity stem cell transplantation, would improve survival.

Methods: Between May 22, 2000, and Aug 8, 2005, 447 previously untreated patients with multiple myeloma, who were aged between 65 and 75 years, were randomly assigned to receive either melphalan and prednisone (MP; n=196), melphalan and prednisone plus thalidomide (MPT; n=125), or reduced-intensity stem cell transplantation using melphalan 100 mg/m2 (MEL100; n=126).

Anti-CS1 humanized monoclonal antibody HuLuc63 inhibits myeloma cell adhesion and induces antibody-dependent cellular cytotoxicity in the bone marrow milieu.

Currently, no approved monoclonal antibody (mAb) therapies exist for human multiple myeloma (MM). Here we characterized cell surface CS1 as a novel MM antigen and further investigated the potential therapeutic utility of HuLuc63, a humanized anti-CS1 mAb, for treating human MM. CS1 mRNA and protein was highly expressed in CD138-purified primary tumor cells from the majority of MM patients (more than 97%) with low levels of circulating CS1 detectable in MM patient sera, but not in healthy donors.

CD117 (c-kit) is aberrantly expressed in a subset of MGUS and multiple myeloma with unexpectedly good prognosis.

CD117 (c-kit) was evaluated on normal plasma cells (PC) (n=10), PC of individuals with monoclonal gammopathy of undetermined significance (MGUS, n=12), malignant PC from patients with multiple myeloma (MM) either at diagnosis (n=83) or relapse (n=38) and on 23 human myeloma cell lines (HMCL). Whereas CD117 is never expressed in normal PC, it is expressed in 50% of MGUS (p=0.015).

Heterogeneity of t(4;14) in multiple myeloma. Long-term follow-up of 100 cases treated with tandem transplantation in IFM99 trials.

One hundred de novo multiple myeloma patients with t(4;14) treated with double intensive therapy according to IFM99 protocols were retrospectively analyzed. The median overall survival (OS) and event-free survival (EFS) were 41.4 and 21 months, respectively, as compared to 65 and 37 for patients included in the IFM99 trials without t(4;14) (P<10(-7)).

[Genetic abnormalities in multiple myeloma: role in oncogenesis and impact on survival].

Purpose: Recent development of interphase fluorescence in situ hybridization (FISH) allows analysis on non-proliferant plasma cells. We describe the most frequent genetic abnormalities in multiple myeloma and their prognostic value.

Current Knowledge And Key Points: Most frequent genetic abnormalities are illegitimate rearrangements involving the IGH gene at 14q32 (60% of patients), hyperdiploidy (50 to 60% of patients), chromosome 13 deletion (40 to -50% of patients), chromosome 1q gain (30 to -40% of patients) chromosome 17 deletion (10% of patients).

[Malignant transformation of monoclonal gammopathy of undetermined significance].

Monoclonal gammopathy of undetermined significance (MGUS) is found in approximately 3% of the general population aged 50 years or older. MGUS is a premalignant state. The risk of malignant transformation is about 1% per year.

Bortezomib plus dexamethasone as induction treatment prior to autologous stem cell transplantation in patients with newly diagnosed multiple myeloma: results of an IFM phase II study.

Background And Objectives: Induction regimens prior to autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma patients usually result in complete remission (CR) rates of <10%. The use of novel agents may increase the CR rate before ASCT, which may improve post-transplantation response and survival.

Design And Methods: This was a phase II, open-label trial of bortezomib (1.