ARTIKEL PENELITIAN

76 Indonesian Journal of Cancer Vol. 5, No. 2 April - June 2011

ABSTRACT
Aim: to overview the clinical characteristics of multiple myeloma patients in Indonesia. Methods: We conducted
descriptive method, crosssectional multicentre study on November 2008 until November 2009. Data of seventy
multiple myeloma patients was taken from Indonesias Multiple Myeloma Study Group.
Results: Over sixty percent of MM patients were at the age of more than fifty years old (65.71%), gender approximately
equal between male and female. Approximately half of the patients were Javanese, senior high school educational
background, and unemployeed.
Fifty-three percent patients have less then 30% plasma cells in the bone marrow with seventy percent patients had
negative Bence Jones proteinuria and positive monoclonal gammopathy serum in more than eighty percent patients.
The percentage of plasma cells in the bone marrow were more frequent among younger patients (34.05% vs 24.24%
vs 7.5%).
We reported that almost half of the patients had IIIA stage based on Durie-Salmon staging system. A higher stage
associated with older patients according to International Myeloma Working Group System classification.
Melphalan/prednisone was the most chemotherapy regimen that used for the treatment (59.7%) while forty five
percent patients had a partial response as the most frequent best response to primary chemotherapy.
Conclusion: Multiple myeloma patients characteristics in Indonesia predominantly Javanese ethnicity, senior high
school background and unemployeed status. Based on clinical characteristics, most of the patients had less than 30%
palsma cells in the bone marrow with negative Bence Jones proteinuria and positive monoclonal gammopathy serum.
Almost half of the patients had IIIA stage with melphalan/prednisone as the most chemotherapy regimen used with a
result of partial response as the most frequent best response found.
Keyword : Multiple myeloma, clinical characteristics, Indonesia
ABSTRAK
Tujuan: Melihat karakteristik klinis pasien mieloma multipel di Indonesia.
Metode: studi deskriptif, potong lintang, multisenter, dilakukan pada November 2008 sampai dengan November 2009.
Tujuh puluh data pasien mieloma multipel diambil dari seluruh Indonesia, dari kelompok studi mieloma multipel di
Indonesia.
Hasil: Lebih dari enam puluh persen pasien mieloma multipel di Indonesia berusia lebih dari 50 tahun (65,71%) dengan
perbadingan jenis kelamin yang kurang lebih sama antara pria dan wanita. Kurang lebih lima puluh persen pasien
bersuku Jawa, dengan tingkat pendidikan Sekolah Menengah Atas (SMA) dan tidak bekerja.
Lima puluh tiga persen pasien memiliki kurang dari 30% sel plasma di sumsum tulangnya dengan 70% pasien tidak
memiliki proteinuria Bence Jones dan 80% pasien memiliki serum monoclonal gammopathy yang positif. Persentase sel
plasma di sumsum tulang lebih banyak ditemukan pada pasien yang berusia lebih muda (34,05% vs. 24,24% vs. 7,5%).
Dilaporkan bahwa hampir lima puluh persen pasien memiliki stadium IIIA berdasarkan klasifikasi Durie Salmon Staging
system. Stadium penyakit yang lebih tinggi berkaitan dengan usia yang lebih tua berdasarkan klasifikasi International
Myeloma Working Group. Melphalan/prednisone merupakan pilihan kemoterapi yang paling banyak digunakan (59,7%)
dengan hasil pengobatan terbanyak adalah respons parsial.
Kesimpulan: karakteristik pasien mieloma multipel di Indonesia didominasi oleh suku Jawa, dengan tingkat pendidikan
SMA dan tidak bekerja. Sebagian besar pasien memiliki sel plasma kurang dari 30% di sumsum tulang, proteinuria
Bence Jones yang negatif, dan serum monoclonal gammopathy yang positif. Hampir lima puluh persen pasien memiliki
stadium IIIA dengan melphalan/prednison sebagai jenis kemoterapi terbanyak yang diberikan dengan hasil terbaik
sebagian besar adalah respon parsial.
Kata kunci : mieloma multipel, karakteristik klinis, Indonesia
KORESPONDENSI:
dr. Hilman Tadjoedin, Sp
PD KHOM,
SMF Hematologi-
Onkologi RS. Kanker
Dharmais
Multiple Myeloma in Indonesia
HILMAN TADJOEDIN, ARRY HARRYANTO REKSODIPUTRO, TOMAN TORUAN, ABDULMUTHALIB,
AGUS KOSASIH, IMAN SUPANDIMAN, RACHMAT SUMANTRI, HERI FADJARI, PANDJI I FIANZA, C
SUHARTI, JOHAN KURNIANDA, IBNU PURWANTO, AMY AZHARIATI, UGROSENO, MADE P SEDANA,
BUDI DARMAWAN, I MADE BAKTA, AZMI S KAR, DAIRION GATOT, NOEZIRWAN ACANG, MEDIARTY
SYAHRIR, ANDI F BENYAMIN, TUTIK H, HARLINDA KUMAAT
RS. Kanker Dharmais, Divisi HematologiOnkologi FKUI/RS. Cipto Mangunkusumo
Diterima tanggal, 16 Maret 2011, Disetujui 11 April 2011
Indonesian Journal of Cancer Vol. 5, No. 2 April - June 2011 77
HILMAN TADJOEDIN, ARRY HARRYANTO REKSODIPUTRO, TOMAN TORUAN, ABDULMUTHALIB, AGUS KOSASIH, IMAN SUPANDIMAN, RACHMAT SUMANTRI,
HERI FADJARI, PANDJI I FIANZA, C SUHARTI, JOHAN KURNIANDA, IBNU PURWANTO, AMY AZHARIATI, UGROSENO, MADE P SEDANA, BUDI DARMAWAN, I
MADE BAKTA, AZMI S KAR, DAIRION GATOT, NOEZIRWAN ACANG, MEDIARTY SYAHRIR, ANDI F BENYAMIN, TUTIK H, HARLINDA KUMAAT. 7681
INTRODUCTION
M
ultiple myeloma is characterized by malignant
plasma cells infiltrating the bone marrow, and some
patients a malignant plasma cells infiltrate other organs
and extramedullary tissues. Based on a laboratory view,
plasma cells neoplasma are distinguished by an idiotypic
rearrangement of the immunoglobulin gene, which occurs
prior to the malignant transformation of an early plasma
cell precursor. The clone that develops must increase to
about 5 x 10
9
cells before it produces enough of the
i di otypi c i mmunogl obul i n to be recogni zed as a
monoclonal spike (M protein or paraprotein) in a serum
electrophoresis pattern. Most subjects with a serum M-
protein can be ruled out, they are labeled as monoclonal
gammopathies of undermined significance (MGUS). By
definition, the monoclone in MGUS is stable and the
serum M-protein concentration remains more or less at
the same level for many years. However, prolonged follow
up of a large group of MGUS subjects at the Majo Clinic
has shown that about 2% of these patients progress per
year to develop symptomatic multiple myeloma (MM),
macroglobulinemia, malignant lymphoma, chronic lym-
phocytic leukemia or amyloidosis. Almost all the genetic
aberrations identified in MM (aneuplody, monosomy 13,
14q13 chromosome translocations) are also present in
MGUS. Additional neoplastic changes are required to
convert this large stable clone into MM, a progressively
expanding tumor with malignant characteristics.
1-3
In most cases, monoclonal immunoglobulin molecules
or immunoglobulin light chains can be measured in the
serum or urine and used as a specific marker for diagnosis
and follow up. Presenting symptoms depend on tumor
burden and individual complications induced by each
myeloma plasma cells clone. The clone may produce and
secrete monoclonal immunoglobulin, different cytokines,
and less defined biological and physically active factors,
which interfere with bone metabolism, renal function,
hematopoeisis, immune mechanisms, and other organ
systems. Different patterns of such complications
contribute to the heterogeneity of MM patients in terms
of symptoms, treatment strategy, and prognosis.
1,4,5
Epidemiologic approaches can be used to track the
occurrence of disease, to characterize natural history, and
to identify determinants of disease. These evidences are
needed as foundation to develop better therapy inspites
all the limitations of current therapy in the treatment of
the disease. The objectives of the study is to overview the
clinical characteristics of multiple myeloma patients in
Indonesia.
MATERIAL AND METHODS
We conducted descriptive method, crosssectional
multicentre study on November 2008 until November
2009. Data of seventy multiple myeloma patients was
taken from Indonesias Multiple Myeloma Study Group.
Basic characteristics data was taken from patients
including: age, gender, ethnicity, educational background
and employment status. Clinical characteristicss data that
evaluated including : percentage of plasma cells in bone
marrow, Bence Jones proteinuria, monoclonal gammo-
pathy serum frequency and multiple myeloma staging.
This study also evaluated the type of chemotherapy that
used for treatment and the best response to treatment.
The data collected were analyzed by SPSS programme.
RESULTS
Basic Characteristics
The multiple myeloma demographic data in Indonesia
is presented in table 1. It is acknowledged that over sixty
percent MM patients were at the age of more than fifty
years old and the gender approximately equal between
male and female. Approximately half of the patients were
Javanese, senior high school educational background,
and unemployeed.
Clinical Characteristics
We also collected the percentage of plasma cells in
bone marrow. More than fifty percent of the Indonesian
MM patients have less than thirty percent of plasma cells
in bone marrow, and only fifteen percents have plasma
cells more than forty percents in the bone marrow.
Table 1: Basic characteristics of multiple myeloma in Indonesia
CHARACTERISTICS FREQUENCY (%)
Age
< 30 years 2.86
30 50 years 31.43
> 50 years 65.71
Gender
Male 52.86
Female 47.14
Ethnicity
Balinese 37.14
Buginese 28.6
Chinese 2.86
Gorontalo 5.71
Javanese 51.42
Educational background
Elementary school 26.67
Senior high school 57.78
University 15.56
Employment status
Unemployeed 56.0
Employeed, part time 12.0
Employeed, full time 30.0
78 Indonesian Journal of Cancer Vol. 5, No. 2 April - June 2011
Multiple Myeloma in Indonesia. 7681
Based on plasmacytoma examination (10 patients), we
found positive results in 8 patients (80%) and negative
results in 2 patients (20%).
Based on age classification (table 3), we found that the
percentage of plasma cells in bone marrow is more
frequent among younger patients. Based on gender
classification, it seems that female tendency have fewer
percentage plasma cell than male.
We found that over seventy percent of MM patients
have negative Bence Jones proteinuria and more than
eighty percent have positive monoclonal gammopathy
serum, reversely (table 4).
Stage of multiple myeloma as initial diagnosis can be
assessed by two types of staging system which are Durie-
Salmon staging system and International Myeloma
Working Group Staging (IMWG) System.
4,13
Based on
Durie-Salmon staging system, we found that almost half of
patients have IIIA stage at first diagnosis and that result
was similar if we used International Myeloma Working
Group system (table 6).
According to International Myeloma Working Group
system classification (table 7), we found that a higher
stage associated with older and female MM patients.
Table 2: Percentage of plasma cells in bone marrow
Percentage of plasma cells in bone marrow Frequency (%)
< 30% 35 (53.03)
30 - 40 % 21 (31.82)
> 40% 10 (15.15)
Table 5: Percentage of Bence Jones proteinuria and monoclonal gam-
mopathy serum based on age and gender classification
Variables % of plasma cells in Monoclonal
bone marrow gammopathy (%)
Negative Positive Unknown Positive
Age classification
< 30 years 0 0 0 2.86
30 50 years 26.09 4.35 0 31.43
> 50 years 47.83 21.74 15.71 50.00
Gender
Male 39.13 15.22 7.14 45.71
Female 34.78 10.87 8.57 38.57
Table 6: Multiple myeloma stage based on Durie-Salmon staging system
and International Working Group staging system
Multiple myeloma stage Frequency (%)
Durie-Salmon Staging System
IA 1 (1.47)
IB 1 (1.47)
IIA 10 (14.71)
IIB 6 (8.82)
IIIA 32 (47.06)
IIIB 18 (26.47)
International Myeloma Working Group Staging System
Unknown 2 (8.33)
I 2 (8.33)
II 5 (20.83)
III 15 (62.50)
Table 3: Percentage of plasma cells in bone marrow based on age and
gender classification
Variables Percentage of plasma cells in the bone marrow
< 30 30 40 >40
Age classification
< 30 years 1.52 16.67 34.05
30 50 years 0 7.5 24.24
> 50 years 0 7.5 7.5
Gender
Male 22.73 19.7 10.61
Female 30.30 12.12 4.55
Table 4: Frequency of Bence Jones proteinuria and monoclonal gam-
mopathy serum
Variables Frequency (%)
Bence Jones proteinuria
Negative 34 (73.91)
Positive 12 (26.09)
Serum protein electrophoresis (monoclonal gammopathy)
Negative 11 (15.71)
Positive 59 (84.29)
Table 7: Distribution of Durie-Salmon staging system of multiple
myeloma by age and gender classification
Variables Stage of multiple myeloma based on international
myeloma working group staging system (%)
I II III
Age classification
< 30 years 0 0 4.17
30 50 years 4.17 0 29.17
> 50 years 4.17 20.38 29.17
Gender
Male 4.17 4.17 25.00
Female 4.17 16.67 37.50
Indonesian Journal of Cancer Vol. 5, No. 2 April - June 2011 79
HILMAN TADJOEDIN, ARRY HARRYANTO REKSODIPUTRO, TOMAN TORUAN, ABDULMUTHALIB, AGUS KOSASIH, IMAN SUPANDIMAN, RACHMAT SUMANTRI,
HERI FADJARI, PANDJI I FIANZA, C SUHARTI, JOHAN KURNIANDA, IBNU PURWANTO, AMY AZHARIATI, UGROSENO, MADE P SEDANA, BUDI DARMAWAN, I
MADE BAKTA, AZMI S KAR, DAIRION GATOT, NOEZIRWAN ACANG, MEDIARTY SYAHRIR, ANDI F BENYAMIN, TUTIK H, HARLINDA KUMAAT. 7681
Based on type of chemotherapy that used for the
treatment, we found the most frequent regiment for
chemotherapy was melphalan/prednisone (59.70%), the
others were VAD, VBMC, thalidomide/dexametasone.
Forty five percent patients had a partial response as the
most frequent best response to primary chemotherapy
(table 8).
DISCUSSION
Cytomorphology of Peripheral Blood and Bone Marrow
The finding of plasma cells which produce a mass
effect indicates displacement of normal tissue through
plasma cells infiltration, evidencing the uncontrolled
growth of a malignant clone. This pathologic micro-
anatomic property contrasts with the usual randomly
dispersed, non-aggregated plasma cells in a benign
reactive plasmacytosis. Beyond a mass effect, addi-
tional cytologic properties favor a neoplastic process.
Specifically, these include the findings of multinucleated
plasma cells and plasma cell immaturity or anaplasia.
Since 1-5% of reactive plasma cells may be binucleate or,
rarely, trinucleate, it is the finding of bizzare multinucleate
(greater than trinucleate) forms that is mostly considered
pathologic. The findings of immaturity include dispersed
nuclear chromatin, high nuclear/cytoplasmic ratio and
prominent nucleoli, giving a blastic appearance
indicative of plasmablasts. Since nuclear-cytoplasmic
asynchrony and immaturity rarely occur in reactive
circumstances, they are realiable indicators of atypical
or pl eomorphi c pl asmacytosi s greatl y favori ng a
diagnosis of neoplasia.
6
In this study, we found that over
fifty percent of the Indonesian MM patients have less than
thirty percent of plasma cells in bone marrow, and only
fifteen percents have plasma cells more than forty
percents in the bone marrow (table 2).
Biochemical and Immunological Investigations
Biochemical investigations play an important role in
the diagnosis, prognosis and monitoring of Multiple
Myeloma. The monoclonal immunoglobulin resulting
from the clonal proliferation of the B cells is an important
tumor marker and rel i abl e detecti on, typi ng and
quantification of the monoclonal protein (M protein or
paraprotein) is vital. Measures of proteins related to B-cell
function or turnover, e.g. the polyclonal background
immunoglobulins or 2-microglobulin, can give indica-
tions of tumor burden and prognosis.
7
Additionally, in the
investigation of patients with B-cell dyscrasiasis, a wide
range of biochemical markers are useful to monitor renal
function, bone and calcium metabolism, infection and the
effects of treatments. Monoclonal proteins may be
present at very high concentrations and often show
mani festati ons not seen wi th normal pol ycl onal
immunoglobulins, such as hyperviscosity, protein
precipitation, or interference in analytical systems, where
their presence can influence a variety of analyzes and
methods.
In this study, we found that over seventy percent MM
patients have negative Bence Jones proteinuria and more
than ei ghty percent have posi ti ve monocl onal
gammopathy serum (table 4). Although we found that
over seventy MM patients have negative Bence Jones
proteinuria, there are more than eighty percents have
positive monoclonal gammopathy serum, reversely. This
has fulfill one of the all 3 required of MM diagnostic
criteria according to the Durie-Salmon staging system.
Yet, to confirm the diagnosis, the Durie Salmon criteria
requires the presence of monoclonal plasma cells in the
bone marrow 10% and/or presence of a biopsy-proven
plasmacytoma and one or more of myeloma-related
organ dysfunction.
Cytogenetics
In recent years, considerable progress has also been
made in cytogenetic and molecular genetic investigation
of lymphoproliferative disorders, and most investigators
believe that almost every case is characterized by
chromosomally abnormal clones. This is also true for
multiple myeloma (MM), but cytogenetic studies of MM
cells are often hampered by the low mitotic rate of the
myelomatous clone. For this reason, use of molecular
cytogenetic techniques, which do not necessarily depend
on dividing cells, has greatly enhanced our possibilities to
i nvesti gate MM and monocl onal gammopathy of
undetermined significance (MGUS) at the cytogenetic
level and to derive clinically relevant information from
these studies.
The ability to obtain karyotypic information in MM is
greatl y i nfl uenced by the aggresi veness and the
Table 8: Type of chemotherapy and response on first line chemotherapy
Variables Frequency (%)
Chemothrapy protocols
Melphalan/prednison 40 (59.70)
VAD 15 (22.39)
VBMPC 2 (2.99)
Thalidomide/dexametasone 3 (4.48)
Other protocols 7 (10.45)
Best respons on first line treatment with primary chemotherapy
Complete response 3 (8.57)
Partial response 16 (45.71)
Minimal response 4 (11.43)
Stable disease 3 (8.57)
Progressive disease 9 (25.71)
80 Indonesian Journal of Cancer Vol. 5, No. 2 April - June 2011
Multiple Myeloma in Indonesia. 7681
proliferative capacity of the malignant clone. Abnormal
karyotypes are, therefore, almost never observed in
MGUS; in MM, chromosomally abnormal clones can be
found in 30-40% of patients with newly diagnosed
disease, in up to 60% of patients with relapsed disease,
and in up to 80% of patients with plasma cell leukemia.
8
Karyotypes in MM typically exhibit a complex set of
numerical and structural abnormalities. Cytogenetic
studies performed in large patient population have
reproducibly shown that two main groups of MM patients
can be di sti ngui shed based on the number of
chromosomes in the abnormal metaphases. One group is
characterized by the presence of a hyperdiploid clone
(with mean chromosome numbers between 50 and 53)
with frequent occurrence of trisomies of chromosomes 3,
5, 7, 9, 11, 15 and 19. Strucutural abnormalities may or
may not be present along with these numerical gains.
9,10
The second group is defined by hypodiploid and pseudo-
diploid karyotypes which are invariably associated with
structural abberations. This pattern of chromosomal
changes obviously represents distinct MM entities, which
is also reflected by the different clinical course of these
patient populations. In our study, cytogenetics evaluation
is not routinely performed.
11,12
Stage and Prognostic Factors
The tumor burden can be assessed by means of the
Durie and Salmon classification, which was specifically
obtained from mathematical models for the evaluation of
tumor mass.
13
Other prognostic factors that reflect the
tumor burden are the proportion plasma cells (PC). A high
number of PC in BM as well as a diffuse pattern of infiltra-
tion are generally associated with a poor prognosis.
However, these are not consistent prognostic factors,
probably owing to the heterogenous distribution of PC in
BM (these areas with bone tenderness or lytic lesions are
usually more heavily infiltrated). The detection of
circulating PC, identified either by morphology or
immunophenotyping, is associated with advanced
disease, and it has been reported that the presence of
high levels of circulating PC (> 4% PC) is an independent
adverse prognostic factor.
12,14
Based on Durie-Salmon and International Myeloma
Working Group staging system classification, we found
that almost half of patients have III stage as first diagnosis
and also showed that a higher stage associated with older
and female MM patients (table 6 and 7).
Treatment of Myeloma
During the past decade there has been an enormous
increase in knowledge of multiple myeloma and related
di sorders. Much of thi s has come about as new
technologies and have made it possible to refine studies
on chromosomes and genes, to gain information about
gene expression. Multiple Myeloma continues to present
a theurapetic challenge.
Multiple Myeloma (MM) continues to present a
therapeutic challenge. Attempts have been made to
utilize the new knowledge to develop targeted therapy
and, although results are still modest, improvements have
been obtained with thalidomide and analogues, as well as
proteasome inhibitors.
In spite of new approaches to treatment, MM at
present remains incurable, with a median survival of
between 3 and 4 years. Treatment produces a response in
approximately two-thirds of patients, with a fall in
paraprotein and improvement of resolution of clinical
symptoms. However, complete remission (CR) is very rare,
except after high-dose therapy, and in most patients the
paraprotein falls but reaches a plateau after a few months
of treatment. At this stage, the patient is said to be in
plateau phase. Sooner or later the paraprotein starts to
rise again, indicating relapse, or there may be a recurence
of symptoms. Further treatment at this stage, perhaps
with a different drug or drug combination, may again
produce a response, but the duration of response is
ussually shorter than that of the initial remission.
Eventually, the disease becomes refractory to treatment
and the patient succumbs to infection, renal failure, or
other disease complication. High-dose therapy with
autologous stem cell support prolongs remission and
survival, but it is not curative and, at present, the only
potential curative treatment approach is allogeneic
transplantation, which is an option for only minority of
patients. The most important aims of treatment are,
therefore, to relieve symptoms and to prolong life without
the treatment causing unacceptable side effects.
15
In thi s study, we found that the most type of
chemotherapy that used for the treatment was
melphalan/prednisone with the most patients had a
partial response as the best response to primary
chemotherapy. Actually, multiple myeloma can be treated
with several categories of medications. Principally, the
treatment of choice for MM is based on the patients age
and prognostic factors. According to the literature, the
first-line treatment for MM is bone marrow transplan-
tation. Yet, because of several limitations in our country,
we preferred Melphalan-Prednison (MP) as the first-line
treatment. More research, which can give benefit as
preliminary reports, is needed to enrich the multiple
myeloma management modalities in Indonesia.
CONCLUSION
A summary of the frequency of MM in our population
is presented in table 1, it showed a strongly influenced
and increases with age. In our population, the frequency
Indonesian Journal of Cancer Vol. 5, No. 2 April - June 2011 81
HILMAN TADJOEDIN, ARRY HARRYANTO REKSODIPUTRO, TOMAN TORUAN, ABDULMUTHALIB, AGUS KOSASIH, IMAN SUPANDIMAN, RACHMAT SUMANTRI,
HERI FADJARI, PANDJI I FIANZA, C SUHARTI, JOHAN KURNIANDA, IBNU PURWANTO, AMY AZHARIATI, UGROSENO, MADE P SEDANA, BUDI DARMAWAN, I
MADE BAKTA, AZMI S KAR, DAIRION GATOT, NOEZIRWAN ACANG, MEDIARTY SYAHRIR, ANDI F BENYAMIN, TUTIK H, HARLINDA KUMAAT. 7681
of multiple myeloma is rare below 30 years old with the
median age is more than 50 years old.
One of the modalities of MM diagnostic investigation
is hematologic investigation by cytomorphology of
peripheral blood and bone marrow. It is conducted that
just over fifty percent of the Indonesian MM patients have
less than thirty percent of plasma cells in bone marrow,
and only fifteen percents have plasma cells more than
forty percents in the bone marrow.
Based on age classification, we also found that
percentage of plasma cells in bone marrow is more
frequent among younger patients. Meanwhile, based on
gender classification, it seems that female tendency have
fewer percentage plasma cell than male.
Biochemical investigations play an important role in
the diagnosis, prognosis and monitoring of multiple
myeloma. Although we found that over seventy MM
patients have negative Bence Jones proteinuria, there are
more than eighty percents have positive monoclonal
gammopathy serum.
In this study, we found that the most frequent cases in
our population were at least stage IIIA with the most type
of chemotherapy that used for the treatment was
melphalan/prednisone and a partial response as the best
response to primary chemotherapy. As consequences:
early detection, recognition of potentially treatable
condition and assessment of functional reserve should
be improved. Because of several limitations in our
country, we preferred Melphalan-Prednison (MP) as the
first-line treatment.
Cytogenetic and molecular genetic investigations of
l ymphoprol i ferati ve di sorders are not routi nel y
performed. So, for further research we need elaboration
that associated of genetic involvements and molecular
findings. Improvement of these investigations is essential
because it contribute in determining prognostic factors
that eventually will be useful for effective treatment
choice. More research, which giving benefit as preli-
minary report, is needed to enrich the multiple myeloma
management modalities in Indonesia. v
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