Australian Doctor Australian Doctor 15th September 2017 | Page 25

involves metaphase karyotyping
and relies on actively proliferat-
ing cells, so the yield is low in
multiple myeloma. The preferred
method for detection of cytoge-
netic abnormalities is interphase
fluorescent in-situ hydridisation
(iFISH). Here fluorescent probes
are used to detect genetic abnor-
malities commonly associated
with multiple myeloma. 13
Normal cytogenetics is associ-
ated with a low risk of smoulder-
ing multiple myeloma progression,
and with a good prognosis for
multiple myeloma. Hyperdiploidy
is associated with intermediate risk
of smouldering multiple myeloma
progression, but a good progno-
sis in patients with symptomatic
multiple myeloma. Cytogenetic
abnormalities including del(17p),
t(4;14) and t(4;16) portend a poor
prognosis in multiple myeloma. 14
Prognostic scores
The prognosis at diagnosis of mul-
tiple myeloma varies enormously
with predicted survival estimated
from months to over a decade.
Figure 7.
Micrograph of a
plasmacytoma.
Source: Nephron
http://bit.ly/2uAQYk3
tem (R-ISS) (see table 5).
The R-ISS was developed ret-
rospectively by analysing patients
presenting from 2005 to 2012.
Compared with previous analyses
it has found improved survival of
all stages of the disease correlat-
ing with the significant increase
in treatment options over the past
decade. 14
The International Staging System
(ISS) has been used since its devel-
opment in 2005 to stratify risk
and predict survival. With the
identification of genetic prognos-
tic markers, a revised system has
been developed to incorporate
classic genetic with biochemi-
cal markers of prognosis — the
Revised International Staging Sys-
Table 5. Revised International Staging System (R-ISS) for
Multiple Myeloma
Stage by
R-ISS Criteria Five year
overall
survival Median
overall
survival
I Stage I by ISS:
• serum albumin ≥ 35g/L
• serum beta-2-microglobulin
<3.5mg/L
• normal serum lactate
dehydrogenase (LDH) 82% More than 46
months
AND
Figure 8. Plasma
cells in a marrow
film from a patient
with myeloma.
Source: Dr Osaro
Erhabor http://bit.
ly/2vAv25O
Standard risk chromosomal
abnormalities by interphase
fluorescence in-situ
hybridisation (iFISH) or high
LDH
II • not fitting R-ISS I or III 62% 83 months
III Stage III by ISS:
• serum beta-2-microglobulin
>5.5mg/L
• high risk cytogenetics -
t(4;14), t(4;16), del(17p) or
elevated LDH 40% 43 months
AND
High risk chromosomal
abnormalities by iFISH or high
LDH
Adapted from Palumbo, et al. Journal of Clinical Oncology, 2015. 12
Treatment
AS noted, there has been a sig-
nificant increase in the number of
treatment options for myeloma in
recent years. At present, all thera-
peutic strategies still have the aim
of ‘control’, as myeloma remains an
incurable disease. Monoclonal gam-
mopathy of uncertain significance
and smouldering multiple myeloma
do not require treatment, but are
monitored over time, with the fre-
quency of monitoring depending on
the risk of progression. No interven-
tion has been shown to prevent the
progression of MGUS to