Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma

Hillengaß, Jens; Zechmann, Christian M.; Nadler, Andreas; Hose, Dirk; Cremer, Friedrich W.; Jauch, Anna; Heiß, Christian; Benner, Axel; Ho, Anthony D.; Bartram, Claus R.; Kauczor, Hans‐Ulrich; Delorme, Stefan; Goldschmidt, Hartmut; Michel, Thomas

doi:10.1002/ijc.23455

Cited by 19 publications

(11 citation statements)

References 22 publications

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“…We found that patients with a diffuse MRI pattern had a higher incidence of high risk cytogenetic features, including del17p, add1q21, and del 13q compared to patients with focal or normal MRI patterns. This result is described for the first time and is in accordance with a recent observation of the Heidelberg group in 87 untreated myeloma patients where the gain of 1q21 and the deletions of 17p and 13q significantly correlated with at least one abnormal finding in bone marrow dynamic contrastenhanced MRI, that is, aberrant ''focal'' microcirculation pattern, increase in median microcirculation parameter amplitude A or exchange rate constant kep, suggesting that these chromosomal abnormalities trigger the angiogenic cascade in MM [14]. Indeed, our group has described that patients with diffuse MRI pattern have increased microvessel density in their trephine biopsies and adverse myeloma features [5].…”

Section: Mri Patterns and Cytogenetic Abnormalitiessupporting

confidence: 91%

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

et al. 2012

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Magnetic Resonance Imaging (MRI) and specific cytogenetic abnormalities offer important prognostic information for myeloma patients. However, limited data are available about the association between cytogenetic abnormalities and MRI patterns of marrow infiltration. To address this issue, we analyzed 228 consecutive newly diagnosed, symptomatic patients who were diagnosed and treated in a single center. On bone marrow MR images, 95 (41%) patients had diffuse, 94 (41%) had focal, 35 (15%) were normal, and 4 (1.7%) patients had variegated pattern of marrow infiltration. High risk cytogenetics were more commonly observed with diffuse MRI pattern (50% vs. 31% in focal and normal patterns). Patients with diffuse MRI pattern had poorer survival compared to others and responded better to novel agent-based therapies than to conventional chemotherapy (objective response: 88% vs. 46%, P < 0.001). There was a significant improvement of patients' survival with a diffuse MRI pattern when treated upfront with novel agents compared to conventional chemotherapy (47 vs. 24 months; P < 0.001). Diffuse MRI pattern along with ISS-3 and high risk cytogenetics could identify a very high risk group of patients with extremely poor median survival (21 months) and an only 35% probability of 3-year OS. Our study shows that symptomatic myeloma patients with a diffuse MRI pattern at diagnosis very often show high risk cytogenetic abnormalities and are benefiting from upfront novel agent-based therapies. Diffuse MRI pattern in combination with high risk cytogenetics and ISS-3 can identify a subset of myeloma patients with very poor prognosis who may need innovative treatment strategies and possibly more aggressive therapies. Am. J. Hematol. 87:861-864, 2012. V

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Section: Mri Patterns and Cytogenetic Abnormalitiessupporting

confidence: 91%

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

et al. 2012

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“…Different patterns of bone marrow involvement of MM in conventional as well as DCE-MRI have been described concordantly by different authors (14,23,29,30). Diffuse distribution of microcirculation was found in healthy controls as well as in all stages of plasma cell disease.…”

Section: Discussionsupporting

confidence: 56%

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Hillengaß

Zechmann

Bäuerle

et al. 2009

Clinical Cancer Research

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Purpose: The aim of our study was to investigate whether dynamic contrast^enhanced magnetic resonance imaging (DCE-MRI) allows visualization of changes in microcirculation between healthy controls on the one side and early/advanced stages of plasma cell disease on the other. Experimental Design: We examined a group of 222 individuals consisting of 60 patients with monoclonal gammopathy of undetermined significance (MGUS), 65 patients with asymptomatic multiple myeloma (aMM), 75 patients with newly diagnosed symptomatic MM (sMM), and 22 healthy controls with DCE-MRI of the lumbar spine. Results: A continuous increase in microcirculation parameters amplitude A and exchange rate constant kep reflecting vascular volume and permeability, respectively, was detected from normal controls over MGUS and aMM to sMM. For A and kep, significant differences were found between controls and aMM (P = 0.03 and P = 0.004, respectively) as well as controls and sMM (P = 0.001and P < 0.001, respectively). Although diffuse microcirculation patterns were found in healthy controls as well as MGUS and MM, a pattern with focal hotspots was exclusively detected in 42.6% of sMM and in 3 MGUS and 3 aMM patients. MGUS and aMM patients with increased microcirculation patterns showed significantly higher bone marrow plasmocytosis compared with patients with a low microcirculation pattern. Conclusions: Our investigations substantiate the concept of an angiogenic switch from early plasma cell disorders to sMM. Pathologic DCE-MRI findings correlate with adverse prognostic factors and DCE-MRI identifies a distinct group of patients with increased microcirculation parameters in aMM and MGUS patients.

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“…33 Two model variables are used to describe the tissue-specific information of the signal intensity-time curves: amplitude A (arbitrary units) is proportional to the relative signal enhancement as a surrogate for MVD and perfusion, the exchange rate constant kep (minutes) reflects the contrast agent transit between the extravascular and intravascular compartment.…”

Section: In Vivo Assessment Of Angiogenesis By Dynamic Contrast-enhanmentioning

confidence: 99%

Induction of angiogenesis by normal and malignant plasma cells

Hose

Moreaux

Meißner

et al. 2009

Blood

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Gain of 1q21 and distinct adverse cytogenetic abnormalities correlate with increased microcirculation in multiple myeloma

Cited by 19 publications

References 22 publications

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: A single center experience on 228 patients

Dynamic Contrast-Enhanced Magnetic Resonance Imaging Identifies a Subgroup of Patients with Asymptomatic Monoclonal Plasma Cell Disease and Pathologic Microcirculation

Induction of angiogenesis by normal and malignant plasma cells

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