M y e lo d y s p la s tic s y n d ro m e s (M D S ): p ro g n o s tic
fa c to rs a n d s c o rin g s y s te m s
D e p a r t m e n t o f H e m a t o l o g y , D e p a ~ t m e n t o f B i o s t a t i s ~ c s a n d D e p a r t m e n t o f P a t h o l o g y ,
D e p a r t m e n t o f H e m a t o l o g y , F a c u l d a d e d e M e d i c i n a d e B o t u c a t u , E s c o l a
P a u l i s t a d e M e d i c i n a l U N I F E S P - S ã a P a u l o , B ~ a z i l
O b je ctive : T o e va lu a te th e sco re syste m s o f C a ssa n o a n d S a n z a n d su g g e st a n e w o n e . D e sig n : C a se se rie s. L o ca tio n : T e a ch in g h o sp ita is: E P M U N IF E S P a n d F a cu ld a d e d e M e d icin a d e B o tu ca tu . P a rticip a n ts: 5 9 p a tie n ts d ia g n o se d fro m 1 9 7 9 to 1 9 9 2 .ln te rve n tio n : E va lu a tio n ' o f clin ica i-la b o ra to ria l d a ta . M e a su re m e n t: S ta tistica l co m p a riso n , u n i a n d m u ltiva ria te a n a lysis a n d a ctu a ria l su rviva l cu rve s. R e su lts: C a ssa n o 's syste m d ivid e d th e p a tie n ts in to h ig h a n d lo w risk (p = 0 .0 9 6 6 ) w h ile . S a n z's g é ive h ig h , in te rm e d ia te a n d lo \y risk (p = 0 .0 1 0 8 ). T h e u n iva ria te a n a lysis sh o w e d h e m o g lo b in , W B C co u n t, E /M ra tio , live r size a n d b la st p e rce n ta g e in B M a s sta tistica lly sig n ifica n t. T h e m u ltiva ria te a n a lysis sh o w e d b la st p e rce n ta g e in B M (p = 0 .0 0 4 ) a n d H b (p = 0 .0 5 0 ) a s sig n ifica n t. O u r syste m , co n sid e rin g th e m u ltiva ria te a n a lysis d a ta , d ivid e d th e p a tie n ts in to h ig h , in te rm e d ia te a n d lo w risk (p = 0 .0 0 3 8 ). C o n clu sio n s: S a n z's syste m w a s m o re fu n ctio n a l th a n C a ssa n o 's, w h ile o u rs sh o w e d p re d ictive su rviva l va lu e a n d e a se o f u se in clin ica i p ra ctice .
U N IT E R M S : M ye lo d ysp la stic syn d ro m e s. P ro g n o sis. S u rviva l.
IN T R O D U C T IO N
M
g r o u py e l O d Y S P l a s t i cs y n d r o m e so f h e m a t o l o g i c a l d i s o r d e t s( M D S ) a r e a c o m p l e xc h a r a c t e r i z e d 'b y h y p e r c e l l u l a r b o n e m a r r o w w i t h
d y s h e m a t o p o i e s i s i n v o l v i n g o n e o r m o r e c e l l l i n e a g e s a n d
p e r i p h e r a l b l o o d c y t o p e n i a s t h a t f r e q u e n t l y t r a n s f o r m i n t o
a c u t e l e u k e m i a1,2 ,3 .
D i f f e r e n t a u t h o r s h a v e s t r e s s e d t h a t t h e M D S c l a s s i f i c a t i o n ,
p r o p o s e d b y t h e F r e n c h - A m e r i c a n - B r i t i s h ( F A B )
c o o p e r a t i v e g r o u p i n 1 9 8 23 i s o n l y a b l e t o s e p a r a t e p a t i e n t s i n t o t w o r i s k g r o u p s : r e f r a c t o r y a n e m i a ( R A ) p l u s r e f r a c t o r y
A d re s s fo r c o rre s p o n d e n c e :
M a ria d e L o u rd e s L . F . C h a u ffa il/e R u a B o tu c a tu 7 4 0 , 3 º a n d a r
S ã o P a u lo /S P - B ra s il - C E P 0 4 0 2 3 -0 6 2
a n e m i a w i t h r i n g e d s i d e r o b l a s t s ( R A R S ) ( l o w r i s k ) a n d
r e f r a c t o r y a n e m i a w i t h e x c e s s o f b l a s t s ( R A E B ) p l u s
r e f r a c t o r y a n e m i a w i t h e x c e s s o f b l a s t s i n t r a n s f o r m a t i o n
( R A E B - t ) ( h i g h r i s k ) 4 , 5 , 6 ,7 ,8 ,9 ,1 0 ,1 1 . T h e c h r o n i c
m y e l o m o n o c y t i c l e u k e m i a ( C M M o L ) g r o u p l a c k s a c l e a r l y
-d e f i n e -d r i s k c l a s s i f i c a t i o n6 , 7 , 9 ,1 0 ,1 2 , 1 3 • .
D u r i n g t h e l a s t 1 0 y e a r s t h e r e h a s b e e n a g r o w i n g
i n t e r e s t i n t h e a n a l y s i s o f v a r i a b l e s o f p r o g n o s t i c v a l u e i n
M D S , e s p e c i a l l y b a c a u s e o f c a s e s w i t h u n e x p e c t e d c l i n i c a I
e v o l u t i o n o r u n c l a s s i f i e d a c c o r d i n g t o F A B . c r i t e r i a l 4 .
P r o g n o s t i c s t u d i e s h a v e r e c e n t l y b e e n p r o p o s e d u s i n g
v a r i a b l e s s e l e c t e d b y u n i v a r i a t e a n d m u l t i v a r i a t e r e g r e s s i o n
a n a l y s i s . T h e r e f o r e , m a n y s c o r i n g s y s t e m s f o r p r e d i c t i n g
s u r v i v a l a n d l e u k e m i c t r a n s f o r m a t i o n , a s w e l l a s f o r
s e l e c t i n g a d e q u a t e t h e r a p e u t i c a p p r o a c h e s f o r e a c h
i n d i v i d u a l c a s e , h a v e b e e n p r o p o s e d9 ,1 1 ,1 5 ,1 6 ,1 7 ,1 8 .
T h e a i m s o f t h i s s t u d y w e r e : 1 ) T o e v a l u a t e t h e
e s t a b l i s h e d s c o r i n g s y s t e m s p u b l i s h e d b y C a s s a n o .15 a n d
S O U T O , E . X .; C H A U F F A IL E , M .L .L .F .; M O N C A U , J.E .C .; N IE R O -M E L O , L .; B R A G A , G .W .; S IL V A , M .R .R .; K E R B A U Y , J. - M ye lo d ysp la stic syn d ro m e s (M D S ): p ro g n o stic fa cto rs a n d sco rin g syste m s
Sanz
l7in our group of patients, 2) To access variables of
prognostic value and 3) To propose a new, simplified scoring
system easy to use in clinicaI practice.
M A T E R I A L S A N D M E T H O D S :
We studied 59 patients with MDS that were diagnosed
at two different teaching hospitaIs in the state of São Paulo
(Escola Paulista de MedicinalUNIFESP and Hospital da
Faculdade de Medicina de Botucatu - Hospital da UNESP)
from 1979 to 1992.
AlI patients
were classified
according
to the
estabilished scoring systems of Cassano
l5(Table 1) and
Sanz
1 7(Table 2).
Only patients with primary MDS were analyzed, and
therefore those with poor prognosis (secondary and/or
therapy-related MDS) were excluded. Patients who had
more than 30% of blast cells in bone marrow were also
excluded
2•ClinicaI,
laboratorial
and
bone
marrow
cytohistological
data were collected from all patients
according to FAB criteria
3•Peripheral blood and bone marrow smears were dyed"
with Leishman's
stain.
Hemoglobin
leveI (g/dl),
reticulocytes
(%), WBC (x10
9/1), neutrophils
(%),
monocytes (%), lymphocytes (%), blast cells (%) and
platelet count ( xl 0
9/1) were determined.
Bone marrow aspiration and biopsy materiaIs were
dyed with hematoxilin-eosin (HE) and Giemsa stains and
stained for reticulin by the Gomori method and were
examined
for:
1) cellularity
(BM/fat ratio < 1/3 =
hypocellular
= grade O; BM fat ratio
1/3 - 1/1 =
normocellular = grade 1; BM/fat ratio >1/1 = grade 2; 2)
erythro/myeloid ratio (>0.53 or < 0.53); 3) BM blast cell
percentage; 4) dyserythropoiesis (proerythroblast excess,
erythoblasts
arrested
at the same stage, scattered
erythroblasts); 5) dysgranulopoiesis (dysplastic changes,
Pelger
Huet abnormality,
degranulation
of mature
neutrophils);
6) dysmegakaryocytopoiesis
(dystrophy,
abnormal size and nuclear lobulations): grade
O -2+ =
0-30% abnormal cells, grade 3+ - 4+ = 31 - 60% abnormal
cells, grade 5+ - 6+ = 61 - 100% abnormal cells; 7) BM
fibrosis
(O -
1+ = absent, 2+ = moderate, 3+ = significant);
8) ALIP - abnormallocalization
of immature precursors,
according to the criteria of Tricot et aI. Criteria: grade 0+
= <3 clusters, 1+ = 3 - 4 clusters, 2+ = >4 clusters; 9) BM
sideroblasts «15%
or >15%). Differential counts were
performed on at least 500 marrow cells. All cases were
reviewed by tw~ hematologists independently (EXS and
MLLFC) and were allocated to the appropriate
FAB
subgroup.
ClinicaI features such as sex, race, age, interval
between first symptoms and diagnosis, liver and spleen
enlargement, and survival time were also examined.
In addition, cases were classified according to a
scoring system using the significant variables of univariate
and multivariate analysis.
Statistica/ Ana/ysis
Actuarial survival probability "curves were plotted
according to the method of Kaplan and Meyer
1 9•
Different
curves were compared statistically using the Cox-Mantel
(log rank) or the generalized Wilcoxon test
20•For univariate
analysis, the cut-offlevel of each quantitative variable was
established based on data in the literature. In some cases,
the cut-off was established by trial and error, until "p" values
were found close to 5%. For qualitative variables, the
different categories were compared to each other. After
prognostic features were selected by univariate analysis,"
multivariate analysis was performed according to Cox's
modeFI. Variableswhich remained significant were included
in the equation, the relative risk for each patient was
estimated, and ~hepopulation was divided into three risk
groups: low, intermediate and high.
R E S U L T S
The 59 patients were followed up from 0.4 to 103
months. There were 31 men (52.6%) and 28 (47.4%)
women. 51 of the patients (86.5%) were white and .8
(13.5%) were black. The median age was 56 years (range
16 - 86), and 33 (55.9%) were younger and 26 (44%)
were older than 60 years of age, with a median survival of
35.30 and 46.20 months, respectively (p=0.5013).
The
general median survival was 35.50 months.
Univariate analysis indicated six variables associated
with poor prognosis
(p<0.05):
liver enlargement
(p=0.0070), WBC 2.0 x 10
9/1 (p=0.0214), BM blast cell
percentage when comparing the groups: <5%, 5%-10% and
>10% (p= 0.0025), erythroid/myeloid (E/M) ratio 0.40
(p=0.0456), FA~ classification
(RAEB plus RAEB-t,
p=0.3670), and hemoglobin leveI 6 g/dl (p=0.0526) (Table.
1). Twenty patients had RA (33.9%), 12 (20.3%) RARS,
16 (27.1 %) RAEB, 2 (3.4%) RAEB-t,5 (8.5%) LMMoC
and 4 (6.8%) were unclassified. The median survivals were:
88.7,57.4,24.2,3.4,31.1
and 17.0 months respectively.
S O U T O , E . X . ; C H A U F F A I L E , M . L . L . F . ; M O N C A U , J . E . C . ; N I E R O - M E L O , L . ; B R A G A , G . W . ; S I L V A , M . R . R . ; K E R B A U Y , J . - M y e l o d y s p l a s t i c s y n d r o m e s ( M O S ) : p r o g n o s t i c f a c t o r s a n d s c o r i n g s y s t e m s
Isolated com parison am ong all groups w as not significant
(p= 0.1404) , but in grouping betw een R A plus R A R S versus
R A E B plus R A E B -t, statistical significance w as found
(p= 0.0367)), w ith m edian survivals of 84.7 m onths versus
19.3, respectively. T he variables of sex, race, age, interval
betw een first sym ptom s and diagnosis, spleen enlargem ent,
platelet counts, B M cellularity, erythroid/m yeloid ratio
«0.53 or > 0.53), dyserythropoiesis, dysm yelopoiesis,
dysm egakaryocytopoiesis, B M fibrosis and presence of
A L IP s w ere not significant at the different cut -off leveIs
exam ined. .
M ultivariate analysis show rrl2 variables of prognostic
im portance: B M blast cell percentage (p= 0.0040) and
hem oglobin leveIs (p= 0.0050). T he equation derived from
m ultivariate analysis w as: R R = E xp 1(0.09163 x % B M
blast cells) - (0.2336 x H b)l, w here R R = relative risk.
T he patients w ere then divided into 3 risk groups: low
(R R 0.04 - 0.15), interm ediate (R R 0.18 - 0.33) and high
(R R 0.36 - 2.57). T he W ilcoxon test show ed a siginificant
difference in survival w hen low versus high (p= 0.0346)
and low versus interm ediate risk groups (F igure 1) w ere
com pared.
A pplying C assano's scoring system to our population
there w ere 11 patients (26.8% ) w ith score 5 and survival
above 50% in the period of study period and 30 patients
(73.1 % ) w ith score 5 and m edian survival of31.10 m onths
(p= 0.0966) (F igure 1). A pplying S anz's scoring'system
there w ere 27 patients (49.10% ) w ith score 0-1 and a
m edian survival of84.7 m onths; 23 patients (41.18% ) w ith
score 2-3 and a m edian survival of 16.1 m onths; 5 patients
(9.10% ) w ith score 4- 5 and m edian survi vaI of 7 .2 m onths.
S ignificant statistical difference w as seen am ong the
survival curves (p= O .O 108) (F igure 2).
C onsidering the significant variables of univariate and
m ultivariate analysis a new scoring system w as elaborated:
o
2B M b la st ce lls (%) < 5 5 -1 0 > 1 0
H b (g /d l) > 6 ~ 6
W B C
(x10
9/1)
> 2 .0 ~ 2 .0E /M ra tio > 0 .4 0 ~ 0 .4 0
T his scoring system divides the patients into three risk
groups: group O (low risk) - 19 patients (32.2% ) w ith
survival above 80% in the study period; group 1
(interm ediate risk) - 21 patients (35.5% ) w ith m edian
survival of 31.10 m onths and group 2+ 3 (high risk) - 19
patients (32.2% ), w ith m edian survivaI of 12.80 m onths.
W hen com paring the survivaI curves of Iow versus
interm ediate (p= 0.00056) and Iow versus high groups (p=
0.0006), there w as a significant difference, but not w hen
interm ediate versus high risk groups w ere com pered
(p= 0.0869) (F igure 5)
D IS C U S S IO N
T he general m edian survival in the present group of
patients w as 35.50 m onths, longer than seen in m ost studies.
T he m edian age w as 56 years, a num ber low er than seen in
published papers9,1O ,17.
A lthough observed in m any studies4,1O ,13,17,22,old age
is not significant in the B razilian population (m ean age of
21,7 years). O n dividing the patients into tw o groups, above
and below 60 years old, as S anzl7 proposed, w e observed
m edian survivals of 46.2 and 35.3 m onths (p= 0.5013).
U sing univariate analysis, liver size w as a significant
variable. P atients w ith an enlarged li ver had a survi vaI of
19.30 m onths versus 84.70 m onths in those w ith unpalpable
liver (p= 0.0070). T his w as probably associated w ith m ore
aggressive F A B groups and w ith the liver infiltration seen
in m ore "aggressive" F A B subgroups (R A E B , R A E B -t and
C M M oL ).
H em oglobin values w ere analyzed in the sam e ~ anner
as in S anz'sl7 w ork, com paring the survival curves ofthree
groups: as proposed by S anz et aI. (1989): < 8 g% , 8-10
g% and > 10 g% , but w as not significant. W hen the patients
w ere divided into tw o groups, w ith H b 6
g/dl
(m edian survival of 24.40 m onths) and w ith H b > 6g/dl
(m edian survival of 49.60 m onths), univariate and m ultivariateanalysis show ed statistically significant difference. T hese
results confirm that hem oglobin leveIs are an im portant
prognostic indicator, agreeing w ith other
au th ors4,9,13,17,22,23,24,25,26.
U nivariate analysis show ed that W B C count w as
significant (p= 0.0214) w hen the survivaI curves of groups
w ith W B C counts of2.0 x 109
1
1 (m edian survivaI of 16.10m onths) and > 2.0 x 109
I
I (m edian survivaI of 46.20m onths) w ere com pared (p= 0.0214), confirm ing the
im portance of peripheraI cytopenias as observed by others 17.
In contrast to the Iiterature, in this study platelet counts
did not appear to be a significant prognostic factor in this
population. S anz et aI. (1989) observed significant
difference am ong survivaI curves of groups w ith 50 x
10
91
1, 50-100 x 109
1
I and 100 x 109
1
I platelet counts, and
V arela et alI 1show ed that groups w ith <20 x 109
1
I plateletcounts had a poor prognosis.
B one m arrow cellularity w as not significant, but the
. '.m edian survival in the group w ith norm ocellularity w as
higher (84.70 m onths) than that of the hypercellular and
. n m :lm ! ..
S O U T O , E . X .; C H A U F F A IL E , M .L .L .F .; M O N C A U , J.E .C .; N IE R O -M E L O , L .; B R A G A , G .W .; S IL V A , M .R .R .; K E R B A U Y , J. - M ye lo d ysp la stic syn d ro m e s (M D S ): p ro g n o stic fa cto rs a n d sco rin a ~ vste m s
hypocellular groups (35.50 and 31.10 m onths
respectively). S om e authors have stressed that B M
hypercellularity is an indicator of poor prognosis Ii,22,27.B M qualitative variables such as dyserythropoiesis,
dysgranulopoiesis and dysm etakaryiocytopoiesis w ere not
statistically significant.
B M fibrosis w as present to som e extent in 40% of
patients, but w as not significant.
T he presence of A L IP s in B M biopsies has been
dem onstrated I0,25,28,29,30,31as a significant prognostic factor, but not in the present population.
C om parisons of erythro/m yeloid ratio w ere significant
(p= 0.0456) in univariate analysis w hen com paring the
survival curves of groups w ith R E /M < 0.40 versus > 0.40,
w ith m edian survival of 19.60 and 84.70 m onths
respectively (p= 0.0456). T his w as aIs o observed by
C assanol5, w hen com paring the survival curves of groups
w ith R E /M < 0.53 versus > 0.53. T he significance of this
variable m ay be related to the increase in m yeloid lineage
and B M blast cells.
T he B M blast cells percentage w as the m ost significant
prognostic factor in seen in this population, as already stressed by m any other authors4,9, 10,13,23,24,26.S tatistical
significance w as seen in univariate and m ultivariate analysis
(p= 0.0025 and p= 0.0040, respectively), w hen the follow ing
survival curves w ere com pared:
• < 5% B M blast cells: m edian survival of 84.70
m onthsnths.
• 5 - 10% B M blast cells: m edian survival of 35.30
m onths.
• > 10% B M blast cells: m edian survival of 7.20
m onths.
B M blast cell percentage, com bined w ith the
cytogenetics abnorm alities, are considered to be the m ost
im portant prognostic factors for survival ofM D S patients.
S coring system "A " of C assano et aI (1990) divided
the patients into tw o risk groups: score < 5 (low risk) w ith
survival > 50% in the period analyzed, and score > 5 (high
risk) w ith survival of 31.10 m onths, but w as not statistically
significant despite the difference in survival tim e. T his is
very interesting scoring because it included B M biopsy
and qualitative data (dysm egakaryopoiesis, fibrosis and
presence of A L IP s). T his population show ed a long
survival rate in the high risk group (31.10 m onths), in
concordance w ith the original w ork.
U sing S anz's scoring system (S anz et aI, 1989),
patients w ere divided into three risk groups: score 0-1,
w ith m edian survival of 84.70 m onths; score 2-3, w ith
m edian survival of 16.10 m onths; score 4-5 m onths, w ith
m edian survival of 7.20 m onths. T he com parison of alI
survi vaI curves w as significant using the W ilcoxon test
(p= 0.0108) and also using C ox M antel: 0-1 versus 2-3
(p= 0.0027), 0-1 versus 4-5 (p= 0.0027) and 2-3 versus 4-5
(p= 0.0080). S anz's system seem s to be m ore appropriate
and m ore easily applicable for clinicaI practice than
C assano's.
T he population could be separated into three risk
groups using C ox's relative risk rnodel: 0.004-0.15 - low
risk, w ith > 50% survival during the period studied;
0.18-0.33 - interm ediate risk, w ith > 50% survival during the
period studied; and 0.36-2.57 - high risk, w ith survival of
16.10 m onths. T he difference am ong the survival curves
w as significant (p= O .O 165).
U sing our proposed scoring systern, w hich includes
variables derived from univariate analysis, ie W B C count
and R E /M , patients w ere divided into three risk groups: O
(low ) w ith survival above 80% during the study period; 1
(interm ediate) w ith m edian survival of 31.10 m onths and
2+ 3 (high) w ith m edian survival of 12.80 m onths
(p= 0.0038).
W e conclude that the new scoring system presented
here is easier to apply than S anz's and C assano's because
it includes variables that are easily accessible to clinicians.
C ytogenetics abnorm alities have been considered an
im portant prognostic factor for survival of M D S patients.
H ow ever, as it is not yet a test available to all patients, w e
consider that future studies in our country should include
cytogenetic analysis. .
O bjetivo: Avaliar utilidades dos sistem as de escore de C assa no e Sanz e propor outro. D esenho: Serie de C asos. Local: H ospitais universitários: EPM -U N IFESP e Faculdade de M edicina de Botucatu. P articipantes: 59 pacientes diagnosticados entre 1979 e 1992. Intervenção: Avaliação de parâm etros çlínico-Iaboratoriais. M ensuração: C om paração estatística, análise uni e m ultivariada e curva de sobrevida atuarial. R esultados: O sistem a de C assano dividiu os pacientes em alto e baixo risco (p=0.0966) enquanto o de Sanz em alto, interm ediário e baixo risco (p=0.0108). A análise univariada dem onstrou que hem oglobina, contagem de G B, relação EM , aum ento do fígado e % de blastos na m edula (M O ) eram estatisticarrente
significantes. A regressão m ultivariada dem onstrou com o sendo significantes a% de blastos da M O (p=0.004) e os níveis de
H b (p=0.050). O nosso sistem a, considerando os parâm etros da análise univariada, dividiu os pacientes em alto, interm ediário e baixo risco (p=0.0038). C onclusões: O sistem a de Sanz foi m ais prático que o de C assa no enquanto o nosso, dem onstrou valor preditivo de sobrevida e uso fácil na prática clínica.
SO U TO , E. X.; C H AU FFAILE, M .L.L.F.; M O N C AU , J.E.C .; N IER O -M ELO , L.; BR AG A, G .W .; São Paulo M edicai Journal/R PM 115(5): 1537-1541, 1997 SILVA, M .R .R .; KER BAU Y, J. - M yelodysplastic syndrom es (M O S): prognostic factors and
REFERENCES
1. A ksoy M , Erden S. Follow ing study on the m ortality and developm ent of leukem ia in 44 pancytopenic patients, w ith chronic exposure to benzene. Blood 1978; 52:285-292. 2. Bennet JM , Catovsky D , D aniel M T, Flandrin G , G alton
D A G , G ralnick H R, Sultan C. Proposals for the classification of acute m yeloid leukem ia. Br J H aem atol1976; 3:451-458. 3. Bennet JM , Catovsky D , D aniel M T, Flandrin G , G alton D A G , G ralnick H R, Sultan C. Proposal for the classification of the m yelodysplastic syndrom es. Br J H aem atol 1982; 51:189-199.
4. Coiffier B, A deleine P, G entilhom m e O , Felm an P, Treille-Ritquet D , Bryon P. M yelodysplastic syndrom es: A m ultiparam etric study of prognostic factors in 336 patients. Cancer 1987; 60: 3029-3032.
5. Fenaux P, Estienne M H , Lepelley P, Zandecki M , Lai JL, Beuscart R, Jouet Jp, Cosson A , Beuters F. Refractory anaem ia according to the FA B classification: a report of 69 cases. Eur J H aem atol 1988; 40:318-325.
6. Foucar K , Langdon RM , O lson D B, Carroll TJ. M yelodysplastic Syndrom es: a clinicaI and pathologic analysis of 109 cases. Cancer 1985; 56: 553-561.
7. G arcia S, Sanz M A , A m igo V , Colom ina P, Carrera M D , Lourenzo JI, Sanz G F. Prognostic factors in chronic m yelodysplastic syndrom es: a m ultivariate analysis in 107 cases. A m J H em ato 1988; 27:163-168.
8. J acobs A . M yelodysplastic syndrom es: pathogenesis, functional abnorm alites and clinicaI im plications. J Clin Pathol 1985; 38: 1201-1217.
9. M ufti G J, Stevens JR, O scier D G , H am blin TJ, M achin D . m yelodysplastic syndrom es: a scoring system w ith prognostic significance. Br J H aem atol 1985; 59:425-433. 10. Tricot G , V lietnickR, Boogaerts M A , H endrickx B, D e W
olf-Peeters C, V an D en Berghe H , V erw ilghes RL. Prognostic factors in the m yelodysplastic syndrom es: im portance of initial data on peripheral blood counts, bone m arrow cytology, tephrine biopsy and chrom osom al analysis. Br J H aem atol 1985; 60: 19-32.
11. V arela BL, Chuang C, W oll JE, Bennett JM . M odifications in the classification of prim ary m yelodysplastic syndrom es: the addition of a scoring system . H em atol O nco11985; 3:55-63.
12. Fenaux P, Beuscart R, Lai JL, J ouet Jp, Bauters F. Prognostic factors in adult chronic m yelom onocytic leukem ia: an anlysis of 107 cases. J Clin O nco11988; 6:1417-1424.
13. K erkhofs H , H erm ans J, H aak H L, Leeksm a CH W . U tility of the FA B classification for m yelodysplastic syndrom es: investigation of prognostic factors in 237 cases. Br J H aem atol 1987; 65:73-81.
14. H oelzer D , G anser A , H eim pl H . A typical leukem ias: preleukem ia, sm ouldering leukem ia and hypoplastic leukem ia. Cancer Res 1984; 93:69-101.
15. Cassano E, G iordano M , Riccardi A , Coci A , Cazzola M . M yelodysplastic syndrom es: m ultiparam etric sutdy of prognostic factors and a proposed scoring system . H aem atologica 1990; 75: 141-145.
16. Rubio-Félix D , G iraldo M P, Perella M , G im eno J, Franco E, G iralt M . A nálisis de cuatro sistem as de puntuoación e£l 197 síndrom es m ielodisplásicos. Sangre 1991; 36(supll.l):463-469.
17. Sanz G F, Sanz M A , V allespi T, CafíÍzo M C, Torrabadella M , G arcía S, Irreguible D , Sanz M iguel JF. Tw o regression m odels and a scoring system for predicting survi vaI and planning treatm ent in m yelodysplastic syndrom es: A m ultivariate analysis of prognostic factors in 370 patients. Blood 1989; 74(suppl.l): 395-408.
18. W orsley A , O scier D G , Stevens J, D arlow S, Figes A , M ufti G , H am blin TJ .. Prognostic features of chronic m yelom onocytic leukaem ia: a m odified Bournem outh score gives the best prediction of survival. Br J H aem atol 1988; 68: 17-21.
19. K aplan EL; M eier P. N onparam etric stim ulation from incom plete observations. J A m Stat A ssoc. 1958; 53:457-481.
20. Lee BS. Statistical m ethods for survival data analysis. Belm ont Publication Lifetim e Learning. 1980,pp 551 p. 21. Cox D R. Regression m odels and life tables. J R Stat Soe
(B). 1972; 34: 187-202.
22. Riccardi A , G iordano M , G iordano P, Cassano E, G irino M , Cazzola M , Scivetti P, D anova M , U cci G . Prognostic param eters in m yelodysplastic syndrom es: a m ultiple regression analysis. Eur J H aem atol 1988; 40: 158-162. 23. Coiffer B, A deleine P, V iala JJ, Bryon PA , Fiere D ,
G entilhom m e O , V uvan H . D ysm yelopoietic syndrom es: A m ultiparam etric study of prognostic factors in 336 patients. Cancer 1987; 60: 3029-3032.
24. G oasguen JE, G arand R, Bizet M , Brem ond JL, G ardais J, Callat M P, A ccard F, Chaperon J. Prognostic factors of m yelodysplastic syndrom es: a sim plified 3-D scoring system . Leukem ia Res 1990; 14:255-262.
25. Tricot G , V lietnick R, V erw ilghen RL. Prognostic factors in m yelodysplastic syndrom es: a review . Scand J H aem atol
1986; 36(suppI45):107-113.
26. V an D er W eide M , Sizoo W , N auta JJp, K refft J, Langenhuijsen M M A C. M yelodysplastic syndrom es: analysis of clinicaI and prognostic features in 96 patients. Eur J H aem atol 1988;41: 115-122.
27. Ríos A , Caõizo M C, Sanz M A , V allespi T, Sanz G , Torrabadella M , G om is F, Ruiz C, San M iguel JF. bone m arrow biopsy in m yelodysplastic syndrom es: m orphological characteristics and contribuition to the study of prognostic factors. Br J H aem atol 1990; 75:26-33. 28. M elo LN , Franco M , G ushiken T, G uilherm e EL, M achado
PEA . Síndrom es m ielodisplásicas: avaliação clínica, hem atológica e histopatológica da m edula óssea em 23 casos. Rev A ss M ed Brasil 1987;33(3/4):53-56.
29. Tricot G , D e W olf-Peeters C, H endrickx B, V erw ilghen RL. Bone m arrow histology in m yelodysplastic syndrom es: histological findings in m yelodysplastic syndrom es and com parison w ith bone m arrO Wsm ears. Br J H aem atol 1984; 57:423-430.
30. Tricot G , D e W olf-Peeters C, V lietnick R, V erw ilghen RL. Bone m arrow histology in m yelodysplastic syndrom es: prognostic value of abnorm al localization of im m ature precursors in M D S. Br J H aem atol 1984; 58:217-225.
SO UTO , E. X.; CHAUFFAILE, M .L.L.F.; M O NCAU, J.E.C.; NIERO -M ELO , L..; BRAG A, G .W .;
SILVA, M .R.R.; KERBAUY, J. - M yelodysplastic syndrom es (M O S): prognostlc factors and
scoring system s
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