Leukemia (2009), 1­12
& 2009 Macmillan Publishers Limited All rights reserved 0887-6924/09 $32.00
www.nature.com/leu
REVIEW
International myeloma working group consensus statement and guidelines regarding the
current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma
M Dimopoulos1, E Terpos1, RL Comenzo2, P Tosi3, M Beksac4, O Sezer5, D Siegel6, H Lokhorst7, S Kumar8, SV Rajkumar8,
R Niesvizky9, LA Moulopoulos10 and BGM Durie11 On behalf of the IMWG
1Department of Therapeutics, Alexandra Hospital, Athens, Greece; 2Blood Bank and Stem Cell Processing Laboratory, Tufts
Medical Center, Boston, MA, USA; 3Institute of Hematology and Medical Oncology, University of Bologna, Bologna, Italy;
4Ankara University, Cebeci Yerles¸kesi, Ankara, Turkey; 5Department of Hematology/Oncology, Charite´-University Hospital,
Berlin, Germany; 6Division of Multiple Myeloma, Hackensack University Medical Center, Hackensack, NJ, USA;
7Department of Hematology, University Hospital Utrecht, Utrecht, The Netherlands; 8Department of Hematology,
Mayo Clinic, Rochester, MN, USA; 9Center for Lymphoma and Myeloma, Weill Medical College of Cornell University,
New York, NY, USA; 10Department of Radiology, Alexandra Hospital, Athens, Greece and 11Aptium Oncology Inc.,
Cedars-Sinai Outpatient Cancer Center at the Samuel Oschin Comprehensive Cancer Institute, Los Angeles, CA, USA
Several imaging technologies are used for the diagnosis and
the arms and legs.2 Furthermore, almost 10% of the patients
management of patients with multiple myeloma (MM). Conven-
present with diffuse osteopenia or osteoporosis at diagnosis.3
tional radiography, computed tomography (CT), magnetic reso-
Myeloma bone destruction represents a major cause of
nance imaging (MRI) and nuclear medicine imaging are all used
in an attempt to better clarify the extent of bone disease and soft
morbidity and mortality. Progression of skeletal disease is often
tissue disease in MM. This review summarizes all available data
not affected by chemotherapy even in responding patients.4 The
in the literature and provides recommendations for the use of
mechanisms of bone destruction are related to increased
each of the technologies. Conventional radiography still remains
osteoclastic bone resorption, which is accompanied by an
the `gold standard' of the staging procedure of newly diagnosed
exhausted osteoblast function and reduced bone formation.5­7
and relapsed myeloma patients. MRI gives information comple-
Thus, a characteristic feature of myeloma bone disease is that
mentary to skeletal survey and is recommended in MM patients
with normal conventional radiography and in all patients with an
the lesions rarely heal even when the patients are in complete
apparently solitary plasmacytoma of bone. Urgent MRI or CT
remission.3,8 This finding is in keeping with the observation that
(if MRI is not available) is the diagnostic procedure of choice to
bone scans are often negative in myeloma patients who have
assess suspected cord compression. Bone scintigraphy has no
extensive lytic lesions, and offer very little in the follow-up of
place in the routine staging of myeloma, whereas sequential
bone disease in these patients.9 Appropriate use of imaging
dual-energy X-ray absorptiometry scans are not recommended.
techniques is essential in the identification and characterization
Positron emission tomography/CT or MIBI imaging are also not
recommended for routine use in the management of myeloma
of the skeletal complications resulting from MM and in
patients, although both techniques may be useful in selected
determination of the extent of intramedullary bone disease.
cases that warrant clarification of previous imaging findings, but
Imaging also is critical for detection of extramedullary foci,
such an approach should ideally be made within the context of a
identification and characterization of infectious and other
clinical trial.
complications and evaluation of progression of the disease.
Leukemia advance online publication, 7 May 2009;
However, we lack a consensual and standardized imaging
doi:10.1038/leu.2009.89
Keywords: multiple myeloma; conventional radiography; computed
protocol for both newly diagnosed myeloma patients or for
tomography; magnetic resonance imaging; nuclear medicine
following patients in the course of treatment and disease
imaging
progression.10
Lytic lesions are generally diagnosed by radiographic
analysis. One weakness of radiographic detection is that it
may reveal lytic disease only when over 30% of the trabecular
bone has been lost.11 This results in suboptimal assessment of
generalized osteopenia, which affects MM patients and corre-
lates with an increased risk of early vertebral collapse.12 The
Introduction
morbidity of vertebral collapse is significant. Chronic pain,
functional limitations and respiratory compromise, which
Multiple myeloma (MM) is a plasma-cell malignancy and is
increase the risk of pulmonary infections are typical clinical
characterized by the presence of lytic bone disease causing
sequelae of vertebral compression fractures. Due to the
severe bone pain, pathological fractures, spinal cord compres-
limitations of standard radiographic analysis, computed tomo-
sion and hypercalcemia. Up to 90% of myeloma patients
graphy (CT) or magnetic resonance imaging (MRI) have been
develop osteolytic lesions during the course of their disease.1
used to increase the sensitivity and specificity of early detection
These lesions occur predominantly in the axial skeleton, that is,
of myeloma-associated bone destruction. CT and MRI also allow
skull, spine, rib cage and pelvis, as well as the proximal areas of
discrimination of malignant and benign compression fractures,
visualization of soft tissue involvement and spinal cord and/or
Correspondence: Dr M Dimopoulos, Department of Clinical Ther-
nerve root compression or jeopardy.
apeutics, University of Athens School of Medicine, 80 Vas. Sofias,
In recent years, positron emission tomography (PET) has also
Athens, 11528, Greece.
been used in MM imaging. 18F-fluorodeoxyglucose (FDG) is
E-mail: mdimop@med.uoa.gr
taken up by metabolically active cells, which can then be
Submitted on behalf of the International Myeloma Working Group
Received 2 March 2009; accepted 5 March 2009
imaged using PET. High uptake by tumor cells is visible on PET
Role of imaging techniques in multiple myeloma
M Dimopoulos et al
2
imaging, as they have increased metabolic rates. This review
reproducibility of the results is very low between different
summarizes all available data for the role of imaging in MM and
centers and in a recent study an expert radiological review of
aims to provide practical information for the usage of these
skeletal surveys was able to detect additional abnormalities in
techniques by clinicians who manage myeloma patients.
23% of the studied cases.22 A major disadvantage of conven-
tional X-rays is that almost 20 separate films/exposures are
needed, requiring a lengthy period on the radiographic table.
Conventional radiology
The patient's ability to tolerate the standard bone survey is an
important issue because myeloma patients can experience
Since 1903, when Weber first observed that myeloma lesions
severe pain when they are rotated and positioned for multiple
are evident on radiographs, X-rays have been extensively used
individual radiographic exposures. To override this problem,
to identify myeloma-related bone lesions both at diagnosis and
some centers have introduced a whole-body conventional
during disease course. Lytic lesions on plain X-rays are typically
radiographic skeletal survey, the low-dose whole-body radio-
holes ­ that is, punched-out lesions with absent reactive
graphic system (Statscan) for the detection of focal metastatic
sclerosis of the surrounding bone ­ in the flat bones of the skull
deposits in cancer and myeloma patients, which can give a high
and pelvis.13 In the long bones, there is a range of appearances
quality imaging of the bones in less than 5 min.23 In a study of
from endosteal scalloping, to discrete small (o1 cm) lytic
30 patients with solid tumors metastatic to the skeleton and MM,
lesions, to mottled areas of multiple small lesions, to large
the whole-body radiography was found as effective as CT or MRI
destructive lesions.14 These lesions correspond to nodular
in revealing focal lesions,23 a result that has not yet been
replacement of marrow by plasma cells with entire bone
confirmed by others.10 Furthermore, plain X-rays cannot be used
destruction.15 Conventional radiography may also reveal diffuse
for the assessment of response to therapy as the lytic bone
osteoporosis, which is best recognized in the spine.16
lesions seldom show evidence of healing,8 whereas new
The presence of lytic lesions is a criterion for myeloma
compression vertebral fractures do not always indicate disease
diagnosis, whereas the extent of lytic disease is included in
progression and may occur due to ongoing bone loss or
Durie­Salmon staging system.17 Therefore, it is important to
reduction of tumor mass that supports the bony cortex.24 For
include in a `complete skeletal survey' all areas of possible
all these reasons, although conventional X-rays are considered
myeloma involvement, such as the cervical, thoracic and
as a `gold standard' for the determination of the extent of
lumbar spine, skull, chest, pelvis, humeri and femora. Almost
myeloma bone disease at diagnosis, further imaging is needed
80% of patients with myeloma will have radiological evidence
during follow-up mainly in the absence of the detection of lytic
of skeletal involvement on the skeletal survey, most commonly
lesions or the presence of diffuse osteoporosis only.
affecting the following sites: vertebrae in 65% of patients, ribs in
45%, skull in 40%, shoulders in 40%, pelvis in 30% and long
bones in 25%. However, radiologically detectable lesions distal
to the elbows and knees are exceptional.18 Patients who are
Computed tomography
asymptomatic but have radiological evidence of bone disease
(at least one lytic lesion) are at high risk of progression with a
CT scanning allows the detection of small osteolytic lesions in
median time to progression of 8 months.19,20 The importance of
MM, which are not revealed by plain radiography. CT imaging is
the presence of lytic lesions is further supported by the notion
much faster then standard radiographic procedures and allows
that in the International Myeloma Working Group Classification
excellent 3D reconstruction of images. In a few institutions, CT
for plasma cell dyscrasias, patients with bone disease are
scanning has replaced conventional radiography as the initial
classified as `symptomatic' and require treatment even in the
imaging tool used in patients with trauma to the spine25 or
absence of clinical symptoms.21
pelvis.26 Furthermore, CT can accurately depict the extent of
However, even with complete radiographic surveys 10­20%
associated soft tissue masses and can direct needle biopsy for
of the patients have normal results.18 This may be due to some
histological diagnosis.27 The advantages of CT vs conventional
important disadvantages of conventional radiology, as suggested
X-rays: (1) the duration of the examination is practically three
in Table 1. In plain X-rays some areas are not well visualized; for
times less than that necessary to perform standard radiography;
this reason both lateral and anteroposterior views of the spine
therefore, there is significant economy in the work time of
are needed for the better visualization of the vertebral bodies.
technicians; (2) CT scanning allows the complete diagnostic
Furthermore, conventional X-rays have limited sensitivity as
evaluation in a single examination without having to reposition
they cannot detect early lytic lesions and limited specificity as
the patients, a procedure that is necessary in conventional
they fail to distinguish myeloma-related osteoporosis from
studies; this is certainly an important point to consider when
osteoporosis due to other reasons, such as steroid-induced or
examining a patient in pain; (3) the diagnostic sensitivity of CT
postmenopausal osteoporosis.18 The observer and technology
imaging is superior to that of standard radiography and reveals
dependence of conventional X-rays have also the risk of
more lesions as compared with conventional radiology, mainly
underdiagnosis of lytic disease. It has also reported that the
in areas that cannot be accurately visualized by plain radio-
graphy, for example, scapulae, rib or sternum;28,29 (4) CT has
proven to be superior in estimating fracture risk and instabil-
ity;30,31 (5) CT scanning can demonstrate other unsuspected
Table 1
Conventional radiology: limitations
pathological processes, especially those involving the lungs,
although the percentage is not significant;32 (6) it is superior in
K
Some areas not well visualized
planning the radiation therapy or the surgical intervention as it
K
Limited sensitivity: 10­20% of lesions/abnormalities missed
K
Reduced specificity vs benign causes of osteopenia
depicts the anatomic area very accurately (Table 2). Further-
(e.g., steroids/postmenopausal)
more, a novel CT technique, the multidetector row computed
K
Observer dependent
tomography (MDCT) was found to be very sensitive in detecting
K
Time/tolerance for standard survey not ideal
small osteolytic lesions (o5 mm) in the spine, as compared with
K
Usual fail to show response to treatment
MRI and PET.33
Leukemia
Role of imaging techniques in multiple myeloma
M Dimopoulos et al
3
Table 2
Advantages of computed tomography (CT)
Table 3
Role of magnetic resonance imaging (MRI)
K
Detects small osteolytic lesions
K
More sensitive than standard radiography
K
Faster than standard radiographic survey
K
Excellent imaging of axial skeleton
K
Provides 3D reconstruction of images
K
Discriminates myeloma vs normal marrow
K
Shows associated soft tissue disease
K
Excellent diagnostic discrimination for spinal cord/nerve
K
Greater sensitivity and specificity versus standard radiography
compression issues, as well as soft tissue disease
K
Allows estimation of fracture risk
K
Can detect avascular necrosis of the femoral head
K
Excellent for radiotherapy planning and for surgical intervention
K
Can detect amyloid/light chain deposits in the heart
and other sites
K
Can be used to assess disease status in monoclonal
One of the negative points advanced against CT scanning is
gammopathy of undetermined significance (MGUS),
the radiation dose delivered to patients. The amount of radiation
asymptomatic myeloma and for solitary plasmacytomata
of bone
is 1.3­3 times higher than that delivered during standard
K
Can be used to monitor response (although improvements
radiography.31,34 In summary, conventional or low-dose CT
can be delayed)
scanning of the spine is considered to be a realistic alternative to
standard radiography in MM patients presenting with painful
symptoms because it allows for obtaining an exhaustive
head that may result from high-dose steroid therapy or radio-
evaluation of the skeletal lesions in a short period. Furthermore,
therapy, and is demonstrated by the presence of the character-
CT is helpful as a basis for radiation therapy planning, for the
istic double-line sign on T2-weighted MR images.42 Early
preparation for surgical intervention to delineate the anatomic
recognition of avascular necrosis before the development of a
architecture as precisely as possible and for a CT-guided needle
subchondral fracture is extremely important for the success of
biopsy. Finally, CT may identify lesions that are negative on
conservative management.
plain radiography, and should be considered in patients who
In general, the advantages of MRI over conventional radio-
remain symptomatic despite having no evidence of osteolysis on
graphy and CT scan include: (1) the excellent imaging of
the skeletal survey.
the axial skeleton due to the greater sensitivity of the method, (2)
the discrimination of myeloma from normal marrow, (3) the
accurate illustration of spinal cord and/or nerve root compres-
Magnetic resonance imaging
sion, soft tissue extension, head and neck plasmacytomas,
avascular necrosis of the femoral head and (4) better evaluation
MRI has been widely available for the evaluation of MM during
of cardiac amyloidosis and/or soft tissue amyloid deposits
the last two decades and is used by several myeloma centers of
(see Table 3).
excellence for the management of myeloma patients. MRI
allows visualization of the medullary cavity and a direct
assessment of the degree of MM cell infiltration before bone
MRI sequences in myeloma
destruction becomes visible on plain radiographs, in the
Several MRI techniques have been developed to aid in the
absence of radiation exposure.35,36 Furthermore, in the event
assessment of the bone marrow in hematological malignan-
of suspected cord compression, MRI is the technique of
cies.43.The MRI sequences that are most informative are the
choice.37 It provides an accurate assessment of the level and
T1-weighted, the T2-weighted with fat suppression, the short
extent of cord or nerve root compression, the size of the tumor
time inversion recovery (STIR) and the gadolinium T1-weighted
mass and the degree to which it has extended into the epidural
with fat suppression. Typical myeloma lesions have a low
space. MRI can also be used to predict the risk for vertebral
signal intensity on T1-weighted images and a high signal
fracture. Patients with advanced myeloma who had more than
intensity on T2-weighted and STIR images44 and generally show
10 lesions on spinal MRI had a 6- to 10-fold higher risk of
enhancement on gadolinium enhanced images. In a recent
fracture than patients who had normal appearance or fewer than
study, three MRI sequences were evaluated to reveal the method
10 lesions on MRI.38 However, MRI does not predict the risk of
which provides the highest confidence level in depicting the
fracture by level.39
MM lesions.45 The authors compared a precontrast T1w-TSE
MRI can assist in the distinction between benign from
sequence (TR: 700 ms, TE: 10 ms), a T2w-TIRM sequence (TR:
malignant compression fractures. A benign osteoporotic fracture
8000 ms, TE: 80 ms) and a contrast-enhanced T1w-TSE se-
is suggested when a retropulsed bone fragment is seen, when fat
quence with fat saturation (TR: 700 ms, TE: 10 ms). The turbo
signal is preserved on T1-weighted images throughout the body
inversion recovery magnitude (TIRM) sequence is a turbo ­spin-
and there is no high signal on T2-weighted images, when there
echo sequence (TSE) with an inversion recovery pulse (IR) in
is only a thin (o1 cm) surrounding soft tissue component and
combination with the calculation of the magnitude signal
when horizontal band-like areas representing the fracture plane
intensity (M). Studying 59 MRI examinations of 23 consecutive
are seen following gadolinium administration. A malignant
patients, the authors found that the T2w-TIRM sequences
etiology of collapse is suggested when the posterior cortex is
achieved the highest level of sensitivity and best reliability.
convex toward the spinal canal, epidural mass is seen, when the
However, they suggest that for an exact staging and grading the
entire vertebral body or pedicles are replaced by low signal on
examination protocol should encompass unenhanced and
T1-weighted images, and high or heterogeneous signal is seen
enhanced T1w-MRI sequences, in addition to T2w-TIRM.45
within the body following gadolinium injection or on T2-
weighted images.10 MRI can be also used for the accurate
illustration of the vertebral fractures or the percentage loss of
MRI patterns in myeloma
vertebral height before the performance of percutaneous
Five MR imaging patterns of marrow involvement in myeloma
vertebroplasty and kyphoplasty.40,41
have been recognized: (1) normal appearance of bone marrow
MR imaging is the most sensitive and specific imaging
despite minor microscopic plasma cell infiltration, (2) focal
modality for the diagnosis of avascular necrosis of the femoral
involvement, (3) homogeneous diffuse infiltration, (4) combined
Leukemia
Role of imaging techniques in multiple myeloma
M Dimopoulos et al
4
diffuse and focal infiltration, (5) `salt-and-pepper'-pattern
41 foci with abnormal signal intensity were detected by MRI in
with inhomogeneous bone marrow with interposition of fat
192 thoracic and lumbar vertebrae from 18 myeloma patients,
islands.35,46 In almost 30% of MM patients a normal-looking
compared to X-ray films that showed osteolytic lesions in 4
bone marrow signal is found in all sequences with high signal on
vertebral bodies and bone scanning, which was positive in 2
T1-weighted and intermediate signal intensity on T2-weighted
cases only.52 Ghanem et al reported that the whole-body MRI
spin-echo images as well as low signal in fat-saturated
detected bone marrow infiltration in 20% of myeloma patients
sequences, such as STIR.35 More specifically, a normal marrow
(10/54) who had negative skeletal X-rays. Furthermore, MRI
appearance is present at diagnosis in 50­75% of untreated
revealed bone involvement more extensively than conventional
Durie­Salmon stage I myeloma and in 20% of untreated Durie­
radiography in 90% (27/30) of patients with concordant positive
Salmon stage III disease.47,48 In histology, this corresponds to a
imaging findings.53 MRI was found to be superior to radiographs
slight interstitial plasma cell infiltration (o20 vol% in bone
for the detection of osteolytic lesions in the pelvis (75% vs 46%
marrow biopsy).
of patients) and the spine (76% vs 42% of patients),54 especially
The focal pattern consists of localized areas of abnormal
in the lumbar spine.55 A recent study in 41 newly diagnosed
marrow and is found in approximately 30% of myeloma cases.
MM showed that whole-body MRI is also superior to whole-
On T1-weighted images, focal lesions are darker that yellow
body MDCT, a very sensitive CT methodology, in detecting
marrow and slightly darker or isointense to red marrow. On
bone lesions in the skeleton.56 In the largest series of patients
T2-weighted images they are brighter than both red and yellow
published to date, Walker et al compared MRI and conventional
marrow, and on enhanced T1-weighted images they enhance to
radiography in 611 patients who were treated uniformly with a
various degrees depending on the vascularity of the underlying
tandem autologous transplantation. MRI and conventional
myeloma. STIR and fat-saturation T2-weighted images provide
radiography detected focal lesions in 74 and 56% of imaged
contrast between focal lesions and uninvolved marrow.35,47
anatomic sites, respectively. Furthermore, 52% of 267 patients
In the diffuse MR pattern of abnormal marrow, the normal
with normal skeletal survey had focal lesions on MRI. More
bone marrow is completely replaced by the abnormal process.
specifically, significantly higher proportions of patients had
The intervertebral discs appear brighter or isointense to the
focal lesions on MRI than on conventional radiography in spine
diseased marrow. On T1-weighted images, there is a diffuse
(78 vs 16%; Po0.001), pelvis (64 vs 28%; Po0.001) and
decrease in the signal intensity of the marrow. On T2-weighted
sternum (24 vs 3%; Po0.001); similar percentages were noted
images, a variable increase in the signal intensity of the
with both techniques in skull and shoulders, and lower fractions
abnormal marrow is observed. After the administration of
were seen on MRI than on conventional radiography in ribs (10
intravenous contrast, the abnormal marrow enhances. The
vs 43%; Po0.001) and long bones (that is, humeri and femora;
intervertebral discs appear darker than the enhanced spine.35,47
37 vs 48%; P ¼ 0.006).57
A combined focal and diffuse infiltration pattern can be found
in about 10% of myeloma patients. On T1-weighted SE images
the bone marrow signal intensity is diffusely decreased with
MRI findings in MGUS
additional foci interspersed. Those foci are often better
Monoclonal gammopathy of undetermined significance (MGUS)
demarked on fat-saturated or gradient-echo images.
is defined by a monoclonal immunoglobulin concentration in
Finally in about 3­5% of the patients the so-called `salt-and-
serum of 3 g/100 ml or less, the absence of lytic bone lesions,
pepper'-pattern can be found. On T1-weighted SE images, and
anemia, hypercalcemia and renal insufficiency related to the
also on gradient-echo and T2-weighted SE sequences, the bone
proliferation of monoclonal plasma cells, and a proportion of
marrow presents a very inhomogeneous patchy pattern. How-
plasma cells in the bone marrow of 10% or less. In large referral
ever, no hyperintense areas are demarcated in fat-saturated
centers, half the patients with a monoclonal gammopathy have
sequences. This imaging corresponds to bone marrow with
MGUS, whereas only 15% to 20% have MM.58 Although, lytic
circumscribed fat islands beside normal bone marrow with a
lesions are not found in MGUS by definition, osteoporosis is a
minor infiltration of plasma cells (o20%).35,47
common finding among MGUS patients who have a higher
Low tumor burden is usually associated with a normal MRI
incidence of vertebral fractures compared to normal popula-
pattern, but a high tumor burden is usually suspected when there
tion.59 Therefore, sometimes it is difficult to differentiate MGUS
is diffuse hypointense change on T1-weighted images, diffuse
from early myeloma. MRI studies have been performed in
hyperintensity on T2-weighted images and enhancement with
patients with MGUS. Bellaiche et al found that the MRI of the
gadolinium injection. In general, patients with normal or `salt-and-
thoracolumbar spine was normal in all tested patients with
pepper' MRI pattern tend to have signs of lower tumor burden
MGUS (n ¼ 24) compared with only 6 out of 44 (13.6%) with
than those with diffuse or focal marrow involvement patterns.47­49
newly diagnosed MM.60 In another study, bone marrow
Furthermore, a significant correlation between diffuse and focal
abnormalities were detected with MRI imaging in 7 out of 37
MRI patterns of marrow involvement with low serum hemoglobin
patients (19%) with MGUS or monoclonal gammopathy of
values and high percentage of marrow plasmacytosis has been
borderline significance (all MGUS criteria but plasma cell
reported, supporting that diffuse or focal marrow involvement
infiltration of between 10 and 30%). All patients with a normal
patterns correlate with high tumor burden.47
MRI investigation had not required treatment after a median
The main methodological consideration with MRI imaging is
follow-up of 30 months, whereas time to progression to MM was
the lack of specificity of the findings. Focal or diffuse changes
significantly higher for patients with abnormal MRI.61
may exist at diagnosis, may be variations of the normal, or reflect
an alternative pathological or physiological process such as iron
loading,50 amyloid deposition 51 or reactive marrow hyperplasia.
MRI and solitary plasmacytoma of the bone
Approximately 2% of patients with plasma cell dyscrasias have
solitary bone plasmacytoma (SBP). The diagnosis of SBP requires
MRI vs conventional radiography and CT
a solitary bone lesion, a biopsy of which shows infiltration by
MRI is more sensitive than conventional radiography in
plasma cells, negative results on a skeletal survey, absence of
detecting lytic lesions in the skeleton. Ludwig et al showed that
clonal plasma cells in a random sample of bone marrow and no
Leukemia
Role of imaging techniques in multiple myeloma
M Dimopoulos et al
5
evidence of anemia, hypercalcemia or renal involvement
response to treatment include a reduction in signal intensity on
suggesting systemic myeloma. Although definitive radiotherapy
T2-weighted spin-echo images and the absence of contrast-
usually eradicates the local disease, the majority of patients will
induced rim-enhancement that was previously present.35 Focal
develop MM because of the growth of previously occult lesions
lesions may shrink or remain unchanged in size after effective
which have not been detected by conventional radiography.62
antimyeloma therapy 72 or they may remain hyperintense in
MRI imaging is the preferred imaging modality for the initial
both responders and nonresponders to treatment due to
assessment and for the follow-up of the osseous and extraossous
treatment-induced necrosis and inflammation.73 Therefore,
extent of an SBP. Moulopoulos et al showed that MRI of the
post-antimyeloma therapy MRI of the bone marrow may provide
thoracic and lumbosacral spine showed additional foci of
important information for patients with equivocal clinical and
marrow replacement in four of 12 patients with SBP; thus some
laboratory results as well as for patients with nonsecretory
patients who have an SBP diagnosed by standard criteria may be
myeloma. In a study by the Arkansas group, focal lesions were
understaged if an MRI is not performed. After treatment with
present on MRI in 27 of 30 patients with nonsecretory MM. After
definitive radiotherapy to the painful lesion, three patients
treatment, bone marrow-defined CR occurred in 22 (81%) of
developed systemic disease within 18 months from diagnosis.63
these 27 patients, and MRI-CR was documented in 41% of
Furthermore, Liebross et al reported that among SBP patients
patients at 36 months.57
with thoracolumbar spine disease, seven of eight staged with
Autologous stem cell transplantation (ASCT) is considered the
plain radiographs alone developed MM in comparison with only
treatment of choice for younger myeloma patients. Lecouvet
one of seven patients who also had MRI studies of the spine.64
et al developed an index for the assessment of changes
These results suggest that MRI should be part of the staging
occurring in the spine after transplant.74 The index numerically
procedures in patients with SBP, to better assess both the extent
combines findings related to the number of lesions, lesion size,
of the local tumor and the revealing of occult lesions elsewhere.
contrast enhancement and marrow background. A score of 0, 1
Coronal images of the central skeleton may increase the
or 2 is given for each parameter depending on whether there is
incidence of unsuspected lesions.
improvement, stability or worsening. Patients with an index
below 4 had a better treatment response than those with an
index of 4 or more. In this point, it is crucial to mention that MRI
MRI in smoldering multiple myeloma
evaluation post-ASCT has to be performed at least 1 month after
Asymptomatic patients with paraprotein level in the serum of
G-CSF administration. There can be diffuse or focal marrow
X30 g/l and/or bone marrow clonal plasma cells of X10%, and
changes after treatment with G-CSF that cannot be easily
no myeloma-related organ or tissue impairment, are considered
distinguished by active disease.75
to have smoldering multiple myeloma (SMM), according to the
International Myeloma Working Group.21 These patients
account for about 15­20% of myeloma patients, and have a
MRI findings and prognosis in symptomatic myeloma
median time to disease progression of 2­3 years. According to
The prognostic value of MRI findings in symptomatic myeloma
current practice, patients with SMM may remain stable for years
has been evaluated in different studies. Patients with a single
without therapy and thus should be followed without treatment
lytic lesion on plain radiography, who are found to have further
until there is evidence of imminent disease progression.65,66
lesions on MRI have a shorter time to progression and shorter
Asymptomatic patients with at least one lytic lesion in
time to starting therapy compared to those with a normal MRI
conventional X-rays have a median time to progression of 10
study.20,68,70,76 Patients with advanced disease who have
months; therefore, they should be treated at diagnosis.67 MRI
normal MR findings and receive conventional dose chemother-
reveals abnormal marrow appearance in 30­50% of the
apy have a longer survival compared to those with diffuse or
patients.35,47 Moulopoulos et al reported that patients with
focal abnormalities on MR imaging.77 The pattern of MR bone
abnormal MRI studies required therapy after a median of 16
marrow involvement in myeloma also has prognostic signifi-
months vs 43 months for those with normal MRI studies
cance, with both focal and diffuse patterns being associated with
(Po0.01).68 Moreover, Mariette et al showed that during a
a higher tumor burden.47­49,77 In 142 symptomatic myeloma
median follow-up of 25 months, 10 out of 53 SMM patients
patients, Moulopoulos et al showed that the median survival
developed disease progression; of those, 8 out of 17 had
was 24 months for patients with the diffuse pattern, 51 months
abnormal MRI and 2 out of 38 patients had normal MRI. In that
for those with the focal pattern, 52 months for those with the
study, abnormal MRI independently predicted for time to
variegated pattern and 56 months for patients with the normal
progression.69 This result has not been confirmed by other
pattern (P ¼ 0.001). The presence or absence of a diffuse MRI
studies. However, MRI may be particularly useful in patients
pattern separated patients with ISS stages I and II into two
with asymptomatic myeloma who have an intermediate risk for
subgroups with significantly different survival times of 28
disease progression.70
months and 61 months, respectively (P ¼ 0.01). Furthermore, a
diffuse MRI pattern predicted inferior outcome regardless of
whether or not patients had received high-dose therapy with
MRI and assessment of response
ASCT.46
MRI can be used to assess the effects of antimyeloma therapy,
The largest study in the literature, which reported on the
although the response rates to conventional chemotherapy are
prognostic value of MRI in myeloma patients was published by
similar among patients with different MRI patterns 46 and the
the Arkansas group. In 611 myeloma patients who were treated
time to complete response (CR) is similar among patients with
uniformly with a tandem autologous transplantation-based
different number of focal lesions on MRI (47vs p7).57 A
protocol, MRI, but not conventional radiography, defined that
change in MRI pattern may correlate with response to therapy.
focal lesions independently affected survival. In particular,
Moulopoulos et al reported that CR is characterized by complete
cytogenetic abnormalities and more than seven focal lesions on
resolution of the preceding marrow abnormality, and partial
MRI distinguished three risk groups: 5-year survival was 76% in
response is demonstrated by conversion of a diffuse to a
the absence of both more than seven focal lesions on MRI and
variegated or focal pattern.71 Features suggestive of an objective
cytogenetic abnormality (n ¼ 276), 61% in the presence of one
Leukemia
Role of imaging techniques in multiple myeloma
M Dimopoulos et al
6
of these adverse features (n ¼ 262) and 37% in the presence of
and serum b2-microglobulin.88,94 Furthermore, MIBI washout
both unfavorable parameters (n ¼ 67). High number of MRI focal
may predict for response to conventional or high-dose
lesions (47) correlated with low albumin and elevated levels of
chemotherapy.95,96 MIBI scan added no relevant prognostic
C-reactive protein, lactate dehydrogenase and creatinine, but
information to the ISS in patients with stages I and III MM, but
did not correlate with age, b2-microglobulin and cytogenetic
the MIBI scan was of prognostic value in stage II MM patients.88
abnormalities. Resolution of the focal lesions on MRI post-
MIBI scan cannot detect the necrotic lesions of osteonecrosis of
antimyeloma therapy that occurred in 60% of the patients
the jaw in myeloma patients.97
identified a subgroup with superior survival. Furthermore, at
disease progression after CR, according to clinical criteria, MRI
focal lesions were present in 70% of the patients, including 26%
with new focal lesions outside of the areas of initial involve-
Positron emission tomography
ment, 28% focal lesions that were larger than the original
PET is a tomographic nuclear imaging procedure that uses
lesions and 15% with both an increase in original size and new
positrons as radiolabels and positron­electron annihilation
MRI focal lesions.57
reaction g-rays to locate the radiolabels. A low dose of a
radiopharmaceutical labeled with a positron emitter, such as 18-
fluorine-fluoro-deoxyglucose (FDG), is injected into the patient,
Nuclear medicine imaging
who is scanned by a tomographic system. The main limitation of
PET scanning is limited spatial resolution; thus subcentimeter
Traditional technetium bone scintigraphy has high sensitivity for
lytic lesions seen on plain radiographs may not be detectable
the detection of solid tumors metastatic to the skeleton but its
on PET scanning.98 The advent of fusion scanning combining
sensitivity in MM and solitary plasmacytoma is very low.
both PET and CT addresses the issue of limited spatial resolution.
Technetium bone scintigraphy scanning may detect lytic lesions
In PET/CT fusion scanning, the patient receives an injection of
in 35­60% of MM patients, but its specificity and sensitivity at
FDG about 1 h before image acquisition. After the patient is
the time of the initial diagnosis, in follow-up studies and in the
positioned on the scanner bed, an initial topogram is acquired to
evaluation of bone pain is lower compared to conventional
define the examination range for the PET/CT image acquisition
radiography.78­80 In myeloma patients, the skull, the extremi-
(usually from the ears to the hips). A spiral CT is then performed
ties, the iliac and pubic bones are better assessed with plain
after which the scanner bed is moved back to the starting
radiography, whereas for new vertebral lesions and for lesions in
position and the PET scan commenced. Reconstruction of the
the ribs and sternum, bone scintigraphy seems to be superior
image, incorporating PET and CT data are completed soon after
and for sacrum both methods are equal.81 The inferiority of bone
PET image acquisition. The actual scanning time is shorter for
scans vs conventional radiography is primarily due to the
PET/CT (approximately 30 min) than a PET scan alone (approxi-
osteoblast dysfunction in myeloma,1,6,7 as skeletal uptake of
mately 1 h) because CT data are used to perform attenuation
99Tcm-diphosphonate is related mainly to osteoblastic process.
correction.99
Therefore, newer techniques have been developed in an effort to
Several studies have shown PET/CT is reliable for most bone
improve the sensitivity of detection of myeloma bone disease.
lesions that are at least 1 cm in diameter using a standard SUV
cutoff of 2.5 to indicate the presence of disease.100 For lesions
smaller than 5 mm in diameter, it has been suggested that any
99mTc-sestamibi
amount of FDG uptake should be considered positive regardless
99mTc-labeled hexakis-2-methoxyisobutylisonitrile (99mTc-sesta-
of SUV. Lesions between 5 and 10 mm are considered
mibi) is a lipophilic cationic g-emitting radiopharmaceutical
indeterminate if the SUV is less than 2.5. The patient's weight
originally introduced as a myocardial perfusion imaging tracer.
and body mass are additional factors that affect the SUV.101 The
Because of its biochemical characteristics, which favor accu-
sensitivity of FDG PET in detecting myelomatous involvement is
mulation in tissues with high cell density and mitochondrial
approximately 85% and its specificity is 92%.98 The first
activation, 99mTc-sestamibi (MIBI) is actively concentrated in a
assessment FDG PET in myeloma, a study of 66 patients
variety of malignant tumors such as sarcomas, breast, brain, lung
followed serially, showed that FDG PET allows identification of
and thyroid cancers.82 MIBI imaging closely reflects myeloma
high-risk myeloma and can be used to monitor nonsecretory
disease activity in bone marrow with very high sensitivity and
myeloma as well as patients in CR without measurable
specificity.83,84 Additionally, bone marrow MIBI uptake is
M-component.102 This led to the inclusion of myeloma into
linearly related to bone marrow biopsy results and MIBI was
larger studies of PET/CT in the United States.103,104 The National
reported to be localized inside the plasma cells infiltrating the
Oncologic PET Registry (NOPR), a large prospective program,
bone marrow.85­87
enrolled 22 975 cancer patients in the first year and revealed
In MGUS patients, MIBI is always negative83,88,89 and it
that 36.5% of the time treating physicians changed the intended
cannot be used to predict MGUS transformation; thus it is not
management of the basis of PET/CT results. The registry has thus
useful in MGUS work-up.88 MIBI imaging can detect soft and
far included over 1300 myeloma patients. PET/CT has been
skeletal lesions in MM patients and is more sensitive than
included as an option in the diagnosis and monitoring of
conventional radiography.90 Its overall sensitivity is approxi-
myeloma patients within NCCN guidelines.105 Further targeted
mately 92% and it specificity is 96%.89 However, MIBI imaging
studies in myeloma are required to further clarify aspects of the
has inferior value compared to FDG-PET/CT,91 and found to
specific utility in myeloma patients. In addition to demonstrating
underestimate the extent of myelomatous bone marrow infiltra-
persistent or recurrent osseous disease, PET/CT studies are
tion in the spine, especially in patients with low disease stage,
more sensitive than other imaging modalities for localizing
compared to MRI.92 The pattern of MIBI uptake is significantly
extramedullary sites of disease, where they reveal additional
different in MM patients. Focal uptake reflects active myeloma
lesions in almost 30% of the patients who had been diagnosed
sites, whereas diffuse uptake without the presence of focal
with solitary plasmacytoma by MRI.10,106,107 In two recent
uptake does not indicate active myeloma.93 MIBI score was
studies in patients with SBP, PET/CT allowed detection of other
significantly related to ISS, bone marrow biopsy infiltration rate
unsuspected sites of bone involvement, upstaging the extent of
Leukemia
Role of imaging techniques in multiple myeloma
M Dimopoulos et al
7
the disease and significantly affect the therapeutic deci-
increased risk for early vertebral fractures.12 This makes DEXA a
sions.108,109
valuable test to consider, as it may also influence the decision to
In a prospective comparison among 18F-FDG PET/CT, MRI
begin bisphosphonate treatment, which can produce a 5­10%
and conventional radiography (whole-body X-rays) in 46 newly
improvement over a 6-month period.10 Another advantage of
diagnosed myeloma patients, PET/CT was superior to plain
DEXA is that the technique, which involves assessment of bone
radiographs in 46% of patients, including 19% with negative
mineral density (BMD) in the lumbar spine, hip and distal
X-rays. However, in 30% of patients, PET/CT scans of the spine
radius, is a quick, noninvasive investigation that uses a small
and pelvis failed to show abnormal findings in areas in which
dose (o1 lSV) of radiation.122 Disadvantages of the method
MRI revealed an abnormal pattern of bone marrow involvement,
includes its influence by spondylosis, spinal osteophytes 123 and
more frequently of diffuse type. In contrast, in 35% of patients,
the presence of vertebral collapse, and its difficulty to recognize
PET/CT enabled the detection of myelomatous lesions in areas
myeloma osteoporosis from malignant osteoporosis. Further-
which were out of the field of view of MRI. By combining MRI of
more, sequential DEXA-scans show heterogeneous local BMD
the spine/ pelvis and PET/CT the ability to detect sites of active
changes, and cannot predict disease progression.12
MM, both medullary and extramedullary, was as high as 92%.
Following ASCT, 15 out of 23 patients had negative PET/CT
scans (including 13 with a very good partial response or at least
Conclusions
a near CR), but only 8 had normal MRI.110
There are several small studies supporting that either 18F-
Various imaging technologies have been used for the diagnosis
FDG PET/CT was comparable to MRI in the detection of focal
and management of myeloma patients. As part of the staging
lesions in the spine and pelvis, but it was superior for an
procedure of newly diagnosed myeloma, the skeletal survey is
accurate whole-body evaluation,111 or MRI is superior to FDG-
mandatory and should include a posteroanterior view of the
PET in detecting bone marrow involvement in the spine of
chest, anteroposterior and lateral views of the cervical spine
patients with advanced MM.112 In summary, although all
(including an open mouth view), thoracic spine, lumbar spine,
reported studies have confirmed the superiority of PET/CT
humeri and femora, anteroposterior and lateral views of the skull
over conventional radiography, they have also revealed that if
and anteroposterior view of the pelvis. In addition, symptomatic
PET/CT was the sole imaging study done, it would miss many
areas should also be specifically visualized. Whole-body, low-
additional small lytic skeletal lesions and could miss diffuse
dose MDCT has substituted conventional radiography in some
spine involvement compared to MRI.113,114 Another disadvan-
centers for both diagnosis and follow-up of MM patients and the
tage of PET/CT is the false-positive results it has especially in
clinicians have to take this method into consideration if it is
areas of inflammation or infection, deposits of brown fat
available. Whole-body MRI can give complementary informa-
(especially in the mediastinum and neck), postsurgical changes,
tion to skeletal survey and is recommended in patients with
vertebroplasty changes and occasionally other benign or
normal conventional radiography. MRI of the whole spine
malignant processes, such as renal, pancreatic, uterine and
should be performed in addition to the skeletal survey as part of
prostate cancer.115­117
staging in all patients with an apparently solitary plasmacytoma
FDG PET/CT was found more sensitive than MRI for making
of bone irrespective of site of index lesion. Urgent MRI is the
the diagnosis of mandibular osteonecrosis,97,118 although it is
diagnostic procedure of choice to assess suspected cord
not an accurate method for the detection of femoral head
compression in myeloma patients even in the absence of
osteonecrosis.119 To override these problems, novel radiola-
vertebral collapse. Urgent CT may be used to establish the
beled agents have also been used in PET/CT. The use of the
presence of suspected cord compression in cases where MR
radiolabeled amino-acid carbon 11 (11C) methionine with PET/
imaging is unavailable, impossible due to patient intolerance or
CT showed 11C-methionine-positive lesions in normal cancel-
contraindicated, for example, intraorbital metallic foreign
lous bone in the majority of 19 MM patients, and in all patients
bodies or cardiac pacemakers. CT of the spine or other areas
with extramedullary diseases.120
of the skeleton may be considered to clarify the presence or
In general, MIBI and PET/CT are useful additional diagnostic
absence of bone destruction in cases of clinical concern.
tools for detecting otherwise occult sites of myeloma. A recent
Furthermore, CT is indicated to clarify the nature and extent of
large study of NOPR on the relative impact of PET on patients
soft tissue disease and, where appropriate, to guide tissue
with 18 different types of known cancers for three distinct
biopsy. MRI should be used to clarify the significance of
indications (initial staging, restaging and detection of suspected
ambiguous CT findings, as these two imaging techniques can
recurrence) revealed that when intended management was
give complementary information, whereas both can be used
classified as treatment or nontreatment, physicians changed
before vertebroplasty or kyphoplasty. Bone scintigraphy has no
their intended management for almost 49% of myeloma
place in the routine staging of myeloma, although sequential
cases.121 This result depicts the change of management of MM
DEXA scans are not recommended. Based on the currently
patients with the broad use of PET in myeloma. However,
available evidence, neither PET nor MIBI imaging can be
further studies are needed before the recommendation of using
recommended for routine use in the management of myeloma
PET as a standard tool in both diagnosis and follow-up of MM
patients, although both techniques may be useful in selected
patients. Finally, the use of MIBI PET should particularly be
cases that warrant clarification of previous imaging findings, but
considered in the evaluation of a patient with an early-stage MM
such an approach should ideally be made within the context of a
to exclude the presence of more extensive disease.9
clinical trial.
In the event of disease progression, the skeletal survey should
be repeated as part of the restaging process. Any newly
Dual-energy X-ray absorptiometry
symptomatic areas of the skeleton should be specifically
targeted. MRI should be performed in all patients with negative
Osteoporosis in the general population is currently diagnosed
skeletal survey. MRI or CT can be used for monitoring the
using dual-energy X-ray absorptiometry (DEXA). In MM patients,
response of soft tissue masses to therapy. The usefulness of
reduced lumbar spine bone mineral density correlates with
PET/CT and MIBI on the follow-up of myeloma has not been
Leukemia
Role of imaging techniques in multiple myeloma
M Dimopoulos et al
8
confirmed and further trials are needed. Treating physicians
Jean-Luc Harousseau, Institute de Biologie, Nantes, France
must keep foremost in mind that myeloma bone disease is often
Hiroyuki Hata, Kumamoto University Hospital, Kumamoto, Japan
the cause of the most disabling problems that patients face and,
Yutaka Hattori, Keio University School of Medicine, Tokyo, Japan
therefore, careful baseline and serial radiographic assessments
Joy Ho, Royal Prince Alfred Hospital, Sydney, Australia
are essential to maintaining and improving their patients' quality
Vania Hungria, Clinica San Germano, Sao Paolo, Brazil
of life.
Shinsuke Ida, Nagoya City University Medical School,
Nagoya, Japan
Conflict of interest
Peter Jacobs, Constantiaberg Medi-Clinic, Plumstead, South
Africa
The authors declare no conflict of interest.
Sundar Jagannath, St Vincent's Comprehensive Cancer
Center, New York, NY, USA
Submitted on behalf of the International Myeloma Working
Hou Jian, Shanghai Chang Zheng Hospital, Shanghai, China
Group:
Douglas Joshua, Royal Prince Alfred Hospital, Sydney,
Australia
Rafat Abonour, Indiana University School of Medicine,
Michio Kawano, Yamaguchi University, Ube, Japan
Indianapolis, IN, USA
Nicolaus Kro¨ger, University Hospital Hamburg, Hamburg,
Ray Alexanian, MD Anderson, Houston, TX, USA
Germany
Kenneth Anderson, Dana Farber Cancer Institute, Boston,
Shaji Kumar, Department of Hematology, Mayo Clinic, MN, USA
MA, USA
Robert Kyle, Department of Laboratory Med and Pathology,
Michael Attal, Purpan Hospital, Toulouse, France
Mayo Clinic, MN, USA
Herve Avet-Loiseau, Institute de Biologie, Nantes, France
Juan Lahuerta, Grupo Espanol di Mieloma, Hospital
Ashraf Badros, University of Maryland, Baltimore, Md, USA
Universitario, Madrid, Spain
Leif Bergsagel, Mayo Clinic Scottsdale, Scottsdale, AZ, USA
Jae Hoon Lee, Gachon University Gil Hospital, Incheon, Korea
Joan Blade´, Hospital Clinica, Barcelona, Spain
Xavier LeLeu, Hospital Huriez, CHRU Lille, France
Bart Barlogie, MIRT UAMS Little Rock, AR, USA
Suzanne Lentzsch, University of Pittsburgh, Pittsburgh, PA, USA
Regis Batille, Institute de Biologie, Nantes, France
Henk Lokhorst, University Medical CenterUtrecht, Utrecht,
Meral Beksac, Ankara University, Ankara, Turkey
The Netherlands
Andrew Belch, Cross Cancer Institute, Alberta,Canada
Sagar Lonial, Emory University Medical School, Atlanta,
Bill Bensinger, Fred Hutchinson Cancer Center, Seattle, WA, USA
GA, USA
Mario Boccadoro, University of Torino, Torino, Italy
Heinz Ludwig, Wilhelminenspital Der Stat Wien, Vienna, Austria
Michele Cavo, Universita di Bologna, Bologna, Italy
Angelo Maiolino, Rua fonte da Saudade, Rio de Janeiro, Brazil
Wen Ming Chen, MM Research Center of Beijing, Beijing, China
Maria Mateos, University of Salamanca, Salamanca, Spain
Tony Child, Leeds General Hospital, Leeds, United Kingdom
Jayesh Mehta, Northwestern University, Chicago, IL, USA
James Chim, Department of Medicine, Queen Mary Hospital,
GianPaolo Merlini, University of Pavia, Pavia, Italy
Hong Kong
Joseph Mikhael, Mayo Clinic Arizona, Scottsdale, AZ, USA
Ray Comenzo, Tufts Medical Center, Boston, MA, USA
Philippe Moreau, University Hospital, Nantes, France
John Crowley, Cancer Research and Biostatistics, Seattle,
Gareth Morgan, Royal Marsden Hospital, London, England
WA, USA
Nikhil Munshi, Diane Farber Cancer Institute, Boston, MA, USA
William Dalton, H Lee Moffitt, Tampa, FL, USA
Ruben Niesvizky, Weill Medical College of Cornell
Faith Davies, Royal Marsden Hospital, London, England
University, New York, NY, USA
Ca´rmino de Souza, Univeridade de Campinas, Caminas, Brazil
Yana Novis, Hospital Si´rioLibane^s, Bela Vista, Brazil
Michel Delforge, University Hospital Gasthuisberg, Leuven,
Amara Nouel, Hospital Rutz y Paez, Bolivar, Venezuela
Belgium
Robert Orlowski, MD Anderson Cancer Center, Houston, TX,
Meletios Dimopoulos, Alexandra Hospital, Athens, Greece
USA
Angela Dispenzieri, Mayo Clinic, Rochester, MN, USA
Antonio Palumbo, Cathedra Ematologia, Torino, Italy
Brian GM Durie, Cedars-Sinai Outpatient Cancer Center, Los
Santiago Pavlovsky, Fundaleu, Buenos Aires, Argentina
Angeles, CA, USA
Linda Pilarski, University of Alberta, Alberta, Canada
Hermann Einsele, Universita¨tsklinik Wu¨rzburg, Wu¨rzburg,
Raymond Powles, Leukaemia & Myeloma, Wimbledon, England
Germany
S Vincent Rajkumar, Mayo Clinic, Rochester, MN, USA
Theirry Facon, Centre Hospitalier Regional Universitaire de
Donna Reece, Princess Margaret Hospital, Toronto, Canada
Lille, Lille, France
Tony Reiman, Cross Cancer Institute, Alberta, Canada
Dorotea Fantl, Socieded Argentinade Hematolgia, Buenos
Paul Richardson, Dana Farber Cancer Institute, Boston, MA,
Aires, Argentina
USA
Jean-Paul Fermand, Hopitaux de Paris, Paris, France
Angelina Rodriquez Morales, Bonco Metro Politano de
Rafael Fonseca, Mayo Clinic Arizona, Scottsdale, AZ, USA
Sangre, Caracas, Venezuela
Gosta Gahrton, Karolinska Institute for Medicine, Huddinge,
Orhan Sezer, Department of Hem/Onc, Universitatsklinikum
Sweden
Charite, Berlin, Germany
Morie Gertz, Mayo Clinic, Rochester, MN, USA
John Shaughnessy, MIRT UAMS, Little Rock, AR, USA
John Gibson, Royal Prince Alfred Hospital, Sydney, Australia
Kazuyuki Shimizu, Nagoya City Midori General Hospital,
Sergio Giralt, MD Anderson Cancer Center, Houston, TX, USA
Nagoya, Japan
Hartmut Goldschmidt, University Hospital Heidelberg, Hei-
David Siegel, Hackensack, Cancer Center, Hackensack, NJ, USA
delberg, Germany
Jesus San Miguel, University of Salamanca, Salamanca, Spain
Philip Greipp, Mayo Clinic, Rochester, MN, USA
Chaim Shustik, McGill University, Montreal, Canada
Roman Hajek, Brno University, Brno, Czech Republic
Seema Singhal, Northwestern University, Chicago, IL, USA
Izhar Hardan, Tel Aviv University, Tel Aviv, Israel
Pieter Sonneveld, Erasmus MC, Rotterdam, The Netherlands
Leukemia
Role of imaging techniques in multiple myeloma
M Dimopoulos et al
9
Andrew Spencer, The Alfred Hospital, Melbourne, Australia
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Keith Stewart, Mayo Clinic Arizona, Scottsdale, AZ, USA
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