The Molecular Characterization of Multiple Myeloma at Relapse
The Molecular Characterization of Multiple Myeloma at Relapse
Observational study investigating prognostic factors in newly diagnosed and relapsed multiple
 myeloma patients by use of clinical data, biochemical markers (blood samples), cytogenetic
 markers and gene expression profiling (myeloma cells from fresh bone marrow samples).
 Enabling future genetic studies by establishing a biobank of bone marrow and peripheral blood
 samples.
Multiple myeloma (MM) is an incurable cancer. The disease can often be brought to a halt with
 chemotherapy which in younger patients is accompanied by stem cell transplantation. But the
 disease relapses almost invariably. Cytogenetic changes in the myeloma cells can serve as
 prognostic markers. Accordingly, 25% of the patients show changes associated with a prognosis
 so poor that they should probably receive experimental treatment right from the start.
 Nevertheless, a part of these patients survive much longer than expected. Thus, the prognosis
 must depend on additional genetic events.

 The aim of this project is to widen the investigators knowledge of the nature, chronology and
 prognostic value of the genetic events in MM in order to improve the risk stratification of
 the patients and hence the choice of treatment. Using cytogenetics (interphase FISH) and
 molecular biological analyses (SNP, GEP, miRNA) the investigators will study the changes in
 the myeloma cells. The investigators will search for genetic and clinical differences between
 patients within the same cytogenetic group and between patients at diagnosis and at relapse.
 The study population will consist of 100 newly diagnosed patients and 100 relapse patients
 included prospectively over a 2-year period in a cooperation between the four departments of
 hematology in Zealand, Denmark.

 Hypotheses:

 1. Early relapse depends on a) molecular defects in the myeloma cells detectable with FISH,
 GEP, SNP and/or miRNA analyses, and b) the acquisition of new mutations resulting in
 chemotherapy resistance and increased prolific capacity.

 2. The progressive reduction of event free survival seen with every relapse until the
 disease turns refractory can be explained by selection of critical mutations.

 3. The cytogenetic changes associated with poor prognosis represent a heterogenous group of
 patients in whom the responsible genetic events remain unknown.
Inclusion Criteria:

 -  patients newly diagnosed with multiple myeloma and at the same time eligible for high
 dose chemotherapy and autologous stem cell transplantation

 -  patients with multiple myeloma experiencing relapse after high dose chemotherapy and
 autologous stem cell transplantation

 Exclusion Criteria:

 -  for newly diagnosed patients: age or comorbidity preventing high dose chemotherapy and
 autologous stem cell transplantation,

 -  for all patients: age below 18, physical or psychological incapability to give an
 informed consent.