Research Article
Partial and total monosomal karyotypes in myelodysplastic syndromes:
Comparative prognostic relevance among 421 patients
Carolina B. Belli,1*y Raquel Bengió,1 Pedro Negri Aranguren,2 Francisco Sakamoto,2 Marı́a G. Flores,3y
Nora Watman,4 Elsa Nucifora,5y Marı́a V. Prates,6y Jorge Arbelbide,5 and Irene Larripa1
Myelodysplastic syndromes (MDS) include a group of heterogeneous hematological disorders with a variable risk of leukemic evolution and short survival. Around 40–50% of patients show abnormal karyotypes
that are mostly characterized by monosomies or deletions. Cytogenetic findings are an independent prognostic factor and the International prognostic scoring system (IPSS) differentiates three cytogenetic categories, despite the Intermediate one being heterogeneous. The aim of this study, including 421 Argentinean
patients with primary MDS, is to characterize the cytogenetic profile, to test its prognostic value and to
compare partial and monosomal karyotypes against other cytogenetic findings. An abnormal karyotype
(median survival: 26 months) was observed in 176 patients. The presence of complex karyotypes, number
of alterations, and the IPSS cytogenetic groups showed significant differences for predicting outcome.
Behavior of patients with isolated deletions (median survival: 49 months) did not differ from those with normal karyotype (56 months, P 5 0.654) or Good prognostic findings (43 months, P 5 0.371). However, a
worse prognosis was observed when another alteration was added (31 months, P 5 0.043). Karyotypes with
autosomal monosomies (median survival: 16 months) had a prognostic impact similar to other Poor cytogenetic findings (17 months, P 5 0.626). In our population classified according to French-American-British
(FAB) or World Health Organization (WHO), this new categorization of cytogenetic abnormalities, recognizing three different risk groups, showed an independent prognostic impact and a better discriminating power
than the IPSS categories. It can be concluded that all isolate deletions (excluding 7q-) are good prognostic
findings and all monosomies (excluding Y chromosome loss) are bad indicators. Am. J. Hematol. 00:000–
C 2011 Wiley-Liss, Inc.
000, 2011. V
some particular cytogenetic alterations. This categorization
was later adopted by the WHO classification-based prognostic scoring system (WPSS) [10]. However, the Intermediate group, including trisomy 8 and other chromosome
alterations not specified, is heterogeneous and is matter of
debate [3,7,11,12].
Recently, some deletions, which are usually found in a
low frequency, have been related with a favorable outcome
in MDS, such us deletion 9q, 11q, and 12p [3,13,14]. Also,
monosomal karyotypes have been proposed as a better indicator of poor prognosis in AML, which refers to or more
Introduction
Myelodysplastic syndromes (MDS) comprise a heterogeneous group of bone marrow (BM) clonal disorders characterized by ineffective hematopoiesis leading to pancytopenia and variable risk of evolution to acute myeloid leukemia
(AML) [1–3]. Although MDS has been recognized for more
than 50 years, the first criteria for a systematic classification of MDS into five subgroups were defined in 1982 by
the French–American–British (FAB) cooperative group on
the basis of morphologic characteristics, percentage of BM
blasts and peripheral monocyte count [4]. In 1999, the
World Health Organization (WHO) proposed a revised classification distinguishing nine categories, placing chronic myelomonocytic leukemia (CMML) and refractory anemia with
excess of blast in transformation (RAEBt) among ‘‘myelodysplastic/myeloproliferative disorders’’ and AML, respectively [5]. This last classification has been recently reviewed
redefining two additional categories [6].
Abnormal karyotypes are usually found in 26–56% of
MDS [1–3,7,8]. They are not associated with any particular
chromosomal alterations and are most often characterized
by total or partial losses of chromosome material from
chromosomes 5, 7, 13, 17, 20 or a sex chromosome, as
well as a relatively high incidence of genetic gains such as
trisomy 8, 19, and 21, while recurrent translocations or
other structural abnormalities are rare.
The great variability in the natural history of MDS complicates decision-making regarding therapies. During the last
25 years, since the development of the Bournemouth index
[9], different scores have been proposed for the prediction
of the clinical outcome in these patients. The karyotype has
been recognized as an independent predictor since 1993
when Lille system [1] confirmed that the presence of complex karyotypes (CK) was associated with poor prognosis.
In 1997, the International prognostic scoring system (IPSS)
[2] recognized three cytogenetic categories of risk including
Additional Supporting Information may be found in the online version of this
article.
Conflict of interest: Nothing to report.
All authors gave significant contributions to draft the article, critically revise
the content of the manuscript, approve the final version to be submitted and
declare no conflict of interest.
y
On behalf of the Argentinean MDS Study Group sponsored by the Argentinean Society of Hematology, Argentina
1
Instituto de Investigaciones Hematológicas (IIHEMA), Academia Nacional
de Medicina, Buenos Aires, Argentina; 2Instituto Privado de Hematologı́a y
Hemoterapia, Paraná, Argentina; 3Servicio de Hematologı́a, Hospital General de Agudos ‘‘C. Durand,’’ Buenos Aires, Argentina; 4Servicio de Hematologı́a, Hospital General de Agudos ‘‘J. M. Ramos Mejı́a,’’ Buenos Aires, Argentina; 5Servicio de Hematologı́a, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina; 6Servicio de Hematologı́a, Hospital Italiano de La
Plata, Argentina
*Correspondence to: Dr. Carolina B. Belli, PhD; Instituto de Investigaciones
Hematológicas, Pacheco de Melo 3081, 1425, Buenos Aires, Argentina.
E-mail: [email protected]
Contract grant sponsors: Argentinean grants from the Consejo Nacional de
Investigaciones Cientı́ficas y Técnicas (CONICET), the Agencia Nacional de Promoción Cientı́fica y Tecnológica (ANPCyT), and Fundación ‘‘A. J. Roemmers’’.
Received for publication 13 January 2011; Revised 11 March 2011; Accepted
14 March 2011
Am. J. Hematol. 00:000–000, 2011.
Published online in Wiley Online Library (wileyonlinelibrary.com).
DOI: 10.1002/ajh.22034
C 2011 Wiley-Liss, Inc.
V
American Journal of Hematology
1
http://wileyonlinelibrary.com/cgi-bin/jhome/35105
research article
distinct autosomal chromosome monosomies or one single
autosomal monosomy in the presence of structural abnormalities [15]. Therefore, the aim of this study was to characterize the cytogenetic profile, to test its prognostic value
and to compare partial and monosomal karyotypes against
the rest of the cytogenetic findings characterized by the
IPSS in the Argentinean MDS patients.
Methods
Patients. This is a multicenter retrospective analysis of 421 patients
with available cytogenetic data at diagnosis evaluated from 1982 to
2010. Of these, 168 patients belong to the pilot study for MDS registry
promoted by the Argentinean Society of Hematology. Patients without
cytogenetic analysis (n 5 20) or with failure of cytogenetic analysis (n
5 47) were not included in this study. Hematologists from the participating institutions completed a standard registration form for each
patient describing the clinical and hematological features at presentation and during the follow-up. Patients included in this study had a confirmed diagnosis of primary MDS, without documented previous radioor chemotherapy, and fulfilled prerequisite criteria according to Valent
et al., 2007 [16]. Refractory cytopenia was defined as a hemoglobin
level of less than 10 g/dL, an absolute neutrophil count of less than 1.5
3 109/L, or a platelet count of less than 100 3 109/L [16]. Initially, all
patients were categorized according to FAB [4] and 401 patients were
also evaluated according to WHO [5]. Most patients received supportive care; chemotherapy was administered once the leukemic phase of
the disease was diagnosed (62 patients) or for stem cell transplant (14
patients); 44 patients received hypomethylating agents and 8 lenalidomide. Infections, bleeding and leukemic evolution were considered as
MDS-related causes of death. BM transplanted patients were excluded
from survival analysis.
Cytogenetic analysis. Unstimulated BM cells were short term cultured and G-banding analyses were performed following standard procedures. Whenever possible, 20 metaphases were analyzed and 11 of
them karyotyped according to the International system for chromosome
nomenclature (ISCN) [17]. The following abnormalities were scored for
each chromosome: loss of a chromosome (monosomy), partial loss of
a chromosome (deletion), partial or total extra copy of a chromosome
(partial or total trisomy), other structural cytogenetic abnormalities
(inversion, translocation, addition of chromosomal material, derivative
chromosomes from translocations -that frequently also encompassed
partial losses and/or trisomies-, dicentrics, isochromosomes, and duplications), marker chromosomes, ring chromosomes and double minutes.
Aberrations were counted following the International Working Group on
MDS Cytogenetic Study (IWGMC) consensus guidelines [18].
Statistical analysis. The Kaplan-Meier estimates of survival were
calculated from the day of diagnosis for each variable and compared
using the log-rank test (Mantel-Cox) provided by SPSS software version 15.00 (SPSS, Chicago) and curves were plotted using GraphPad
Prism version 4.00 (GraphPad Software, San Diego). The Cox proportional hazards model was applied to multivariate analysis using the
enter method provided by SPSS software. The level of statistical significance was fixed at 0.05.
Results
Description of the population and clinical data
Table I provides a summary of the 421 patients demographic and clinical data at diagnosis: age, sex, % BM
blast, number of cytopenias, FAB and WHO classification,
IPSS and WPSS prognostic systems. The median age was
69 (17–93) years with a gender ratio of 1.3 (M/F: 238/183).
During the follow-up (mean: 28 months, range: 1–266
months), 101 (24.1%) evolved to AML and 193 (45.8%)
died, including 89 who evolved to AML.
Cytogenetic analysis
Among the overall 421 patients, 176 (42%) patients
showed abnormal karyotype with a median survival of 57
months. The most frequently observed isolate chromosome
alterations were trisomy 8 (22 cases), del(5q) (14 cases),
27/del(7q) (14 cases), del(20q) (13 cases) and loss of
chromosome Y (11 cases). A total of 118 (67%) patients
2
showed deletions or monosomies in their karyotypes and
104 (59%) cases involved, at least, one chromosome #5,
#7, #8, or #20 (Supporting Information Table 1s). Abnormal
karyotypes showed: one, two, three aberrations in 121
(69%), 26 (15%), and 29 (16%) cases, respectively.
In our series, it was observed that all chromosomes were
involved and different cytogenetic alterations were found.
From the overall 322 identified altered chromosomes: 109
(34%) showed deletions, 57 (18%) monosomies [total 1 partial losses 5 166 (52%)], 78 (24%) total or partial trisomies,
78 (24%) other structural alterations. The most frequently
involved chromosomes were #5 (41 cases), #7 (32), #8 (38),
#11 (14), #17 (13), #20 (26), and Y (14). The most common
cytogenetic aberrations were: del(5q) (29 cases, 17% of
patients with abnormal karyotype), 27/del(7q) (28, 16%), 18
(38, 22%), del(20q) (16, 9%), 121 (8, 5%), Y chromosome
loss (14, 8%) and other structural anomalies that involved
chromosomes #1 (7, 4%), #3 (7, 4%), and #11 (9, 5%) (Fig.
1; Supporting Information Table 2s) It is remarkable that
chromosome 8 was only implicated in total trisomies. Also,
marker chromosomes, ring chromosomes and doubles
minutes were observed in 16, 2, and 1 cases, respectively.
Analysis of prognostic factors and cytogenetic groups
of risk
Almost all analyzed variables, gender, number of cytopenias and percentage of BM blast, FAB and WHO classifications, IPSS and WPSS systems showed significant differences for predicting survival (Table I).
Cytogenetic findings had a clear impact on the outcome
of our patients (Table II, Fig. 2). Patients with an abnormal
karyotype showed a significant worse outcome than those
with a normal karyotype either including or excluding 11
patients with Y chromosome loss (P < 0.001). Among
patients with an abnormal karyotype (not including Y chromosome losses), those involving 3 altered chromosomes
[1], the presence of 2 aberrations [19] and cytogenetic
category of risk according to IPSS [2] (Fig. 2A) showed significant differences for predicting survival (Table II).
Seven patients showed an isolated autosomal monosomy, all of them were losses of chromosome 7 (Supporting
Information Table 2s), with a median survival of 15 months.
Monosomal karyotype, as was defined by Breems et al.
[15], was observed in other 23 patients, with median survival of 16 months. Due to the reduced number of cases
with an isolated monosomy 7 and the lack of differences
between them in terms of survival (P 5 0.890), they were
later analyzed as one group of monosomal karyotype
(MK1). Patients without monosomal karyotypes (MK2) and
non complex karyotypes (CK2) showed better outcome
(median survival: 32 months) than the rest of the patients
(P < 0.001). Patients with MK1 exhibited a similar behavior
than those with CK1 (P 5 0.866) (Fig. 2B). Also when
MK1 group (median survival: 16 months) was compared
against other poor findings according to the IPSS (median
survival: 17 months) no differences were observed in terms
of survival (P 5 0.626; Fig. 2C). A statistical comparison
(Fisher’s exact test) of the distribution of both groups
according to WHO (P 5 0.3451), FAB (P 5 0.5471), IPSS
(P 5 1.000), and WPSS (P 5 0.8026) was performed
showing similarities (Table I). Therefore, MK1 was grouped
together with other Poor prognostic findings.
In the Intermediate risk group, 30 patients presented
deletions in their karyotypes (median survival: 42 months)
and showed no difference in terms of survival when compared against other Intermediate findings according to the
IPSS (27 months, P 5 0.504). However, 19 patients who
presented isolated deletions exhibited a better outcome
American Journal of Hematology
research article
TABLE I. Demographic and Clinical Data of the Overall Population and its Distribution Among Cytogenetic Findings
Categories
Variables
Age (years)
Median
Mean
Range
>60
60
Sex
Female
Male
BM Blast (%)
<5
5–9
10–19
>19
N8 Cytopenias
0–1
2–3
FAB
RA
RARS
RAEB
RAEBt
CMML
WHOa
RA/RARS/5q2
RCMD/2RS
RAEB-I
RAEB-II
MDS-U
IPSS
Low
Intermediate-I
Intermediate-II
High
WPSS
Very low/Low
Intermediate
High
Very high
Survival
Normal 1 Y Lost
Good
Deletions, NC
Other
intermediate
Monosomal
karyotype
Poor
nonmonosomal
Total (%)
Events #
Median
(months)
71
67 ± 16
(17–93)
189 (74)
67 (26)
71
68 ± 13
(39–83)
22 (82)
5 (19)
62
60 ± 14
(21–80)
18 (60)
12 (40)
65
65 ± 12
(32–85)
35 (63)
21 (38)
65
61 ± 14
(29–81)
19 (63)
11 (37)
64
58 ± 19
(21–81)
13 (59)
9 (41)
69
65 ± 16
(17–93)
296 (70)
125 (30)
131
62
34
32
50.180
113 (44)
143 (56)
13 (48)
14 (52)
15 (50)
15 (50)
19 (36)
37 (66)
13 (43)
17 (57)
10 (46)
12 (55)
183 (44)
238 (56)
67
126
60
29
*<0.001
180 (70)
34 (13)
32 (13)
10 (4)
21 (78)
4 (15)
2 (7)
–
14 (47)
6 (20)
6 (20)
4 (13)
39 (70)
9 (16)
5 (9)
3 (5)
8 (27)
4 (13)
12 (40)
6 (20)
10 (46)
5 (23)
5 (23)
2 (9)
272 (65)
62 (15)
62 (25)
25 (6)
92
36
45
20
62
26
17
8
*<0.001
155 (61)
101 (40)
16 (59)
11 (41)
16 (53)
14 (47)
34 (61)
21 (38)
8 (27)
22 (73)
6 (27)
16 (73)
235 (56)
185 (44)
87
106
59
25
*<0.001
137 (54)
23 (9)
54 (21)
10 (4)
32 (12)
20 (74)
1 (4)
5 (19)
–
1 (4)
11 (37)
1 (3)
10 (33)
4 (13)
4 (13)
28 (50)
7 (13)
12 (21)
3 (5)
6 (11)
7 (23)
–
14 (47)
6 (20)
3 (10)
5 (23)
4 (18)
8 (36)
2 (9)
3 (14)
208 (49)
36 (9)
103 (25)
25 (6)
49 (12)
62
13
68
20
30
75
64
19
9
25
*<0.001
15 (7)
116 (57)
24 (12)
31 (15)
16 (8)
12 (48)
8 (36)
4 (16)
1 (8)
–
2
6
4
6
2
(10)
(30)
(20)
(30)
(10)
4 (11)
26 (59)
7 (16)
6 (14)
1 (2)
2 (11)
3 (16)
3 (16)
11 (6)
–
1 (6)
8 (50)
2 (13)
5 (31)
–
36 (11)
167 (51)
44 (13)
60 (18)
19 (6)
14
49
28
41
4
64
70
26
18
121
*<0.001
121 (49)
92 (36)
26 (10)
9 (4)
13 (50)
12 (46)
1 (4)
–
–
17 (57)
7 (23)
6 (20)
–
39 (72)
9 (16)
6 (11)
–
4 (13)
9 (30)
17 (57)
–
2 (10)
14 (67)
5 (24)
134 (33)
166 (41)
66 (16)
43 (11)
26
76
44
36
80
43
20
10
*<0.001
85 (48)
50 (28)
42 (24)
–
14 (64)
3 (14)
5 (23)
–
1 (6)
5 (28)
9 (50)
3 (17)
2 (5)
10 (26)
22 (58)
4 (11)
–
3 (16)
3 (16)
13 (68)
–
–
8 (57)
6 (33)
102 (35)
71 (25)
89 (31)
26 (9)
15
31
52
22
126
51
23
14
*<0.001
P value
NR: Not reached; NC: noncomplex; *: Log-Rank test (Mantel-Cox); RA: Refractory Anemia; RARS: RA with Ringed Sideroblasts; RAEB: RA with Excess of Blast;
RCMD: refractory cytopenia with multilinear dysplasia; RCMD-RS: RCMD with Ringed Sideroblasts; MDS-U: MDS unclassifiable.
a
Data on dysplasia was not available in 20 patients diagnosed as RA according to FAB.
Figure 1. Cytogenetic profile of all identified chromosome aberrations. Unbalanced translocations implies two alterations per chromosome: one translocation
and their corresponding partial gain or lost [i.e.: der(1;7) was described as derivative chromosome between chromosomes 1 and 7 that also involves partial trisomy
1q and 7q lost] [Color figure can be viewed in the online issue, which is available
at wileyonlinelibrary.com.].
with median survival of 49 months and no differences were
observed against normal karyotypes (56 months, P 5
0.654) or Good prognostic findings (43 months, P 5
0.371). The presence of a deletion plus other alteration
observed in 11 patients showed significant differences
against normal karyotypes (P 5 0.043) with a median survival of 31 months (Table II, Fig. 2C). Therefore isolated
American Journal of Hematology
deletions were placed together with Good prognostic findings while deletions plus other alteration remained into the
Intermediate ones.
This new categorization of karyotypes, where all isolated
deletions were placed into good prognostic findings and
monosomal karyotypes among the worse ones, allowed us
to better discriminate three groups of risk than the original
IPSS distributions (Tables II and III, Fig. 2D). Multivariate
analysis confirmed that the new characterization of cytogenetic findings was an independent predictor for survival
when tested versus % BM blast. Also, when analyzed versus the IPSS categorization it showed significant differences for the overall FAB classified population [*P 5 0.024,
exp(B) 1.452] and a borderline difference for the population
classified by WHO [P 5 0.063, exp(B) 0.1499] (Table III).
Discussion
Cytogenetic studies have been recognized as an independent prognostic factor in MDS since 1993 [1] and their
inclusion among different prognostic systems has contributed to the improvement in assessing prognosis.
In our population, the observed frequency of normal karyotypes was 58%, similar to other reports [2,10,12,20,21]. This
frequency varied in a wide range of 44–74% in different published MDS series and this may be related to difficulties in
assessing and discriminating between regional variations,
3
research article
TABLE II. Univariate Analysis of Cytogenetic Results for Survival
Survival
Cytogenetic findings
Karyotypes
Normal 1 Y losta
Abnormal
Abnormal karyotypesa
N8 Altered chromosomes (Lille, 1993)
1 1 2 chromosomes
3 chromosomes
N8 Aberrations (Lausanne-Bournemouth; 1995)
1 aberration
2 aberrations
IPSS (International Prognostic Scoring System, 1997)
Good risk findings
Intermediate risk findings
Poor risk findings
Monosomal karyotype (Breems et al., 2008)
MK2 CK2
MK2 CK1
MK1 CK2
MK1 CK1
Alterations
Good
Intermediate
Deletions (Isolate)
Deletions 1 Other alteration
Other intermediates
MK
Poor non MK
Re-categorization of cytogenetic findings
IPSS Good risk findings 1 isolate deletions
Other Intermediates risk findings
IPSS Poor risk findings 1 MK
Overall Population
Cytogenetic group of risk according to the IPSS
Good risk findings
Intermediate risk findings
Poor risk findings
Re-categorization of cytogenetic findings
IPSS Good risk 1 isolate deletions
Other Intermediates risk findings
IPSS Poor risk findings 1 MK
Patients (%)
Events
Median (months)
P value
256 (61)
165 (39)
N 5 165
102
91
56
26
*<0.001
127 (63)
38 (27)
74
28
28
19
*50.037
110 (67)
55 (33)
61
41
32
17
*50.002
27 (16)
90 (55)
48 (29)
12
53
37
43
31
16
*<0.001
123 (75)
12 (7)
13 (8)
17 (10)
68
10
11
13
32
18
15
16
*<0.001
27 (16)
12
43
50.141
19 (12)
11 (7)
56 (34)
30 (18)
22 (13)
8
7
34
24
17
49
31
27
16
17
46 (28)
67 (41)
52 (32)
N 5 421
20
41
41
50
27
16
*<0.001
283 (67)
90 (21)
48 (11)
103
53
37
56
31
16
*50.009
302 (72)
67 (16)
52 (12)
111
41
41
54
27
16
*<0.001
a
MK: Monosomal karyotype, CK: Complex karyotype.
a
11 patients with Y chromosome lost were considered together with 245 cytogenetically normal MDS patients.
differences in classification, and the inclusion/exclusion of
therapy-related MDS, AML, or of pediatric cases. Several differences have been reported between western and Asian
groups, but, little is known about the epidemiological patterns
of MDS in Latin American regions [8,12,21–23]. Most series
usually include patients classified according to FAB. The proportion of normal karyotypes in each FAB subgroup
decreased according to worsening prognosis FAB subgroup
from 64% in RA to 36% in RAEBt patients. However, the low
frequency of 6% of RAEBt patients in our series is remarkable, being less than half of the usually observed percentages in other reports. From the time the WHO classification
was published, Argentinean clinicians generally choose to
classify RAEBt patients as having AML. The prevalence of
RA subgroup (49%) was lower than in Asian and Brazilian series (>55%) but higher than in the European ones (<40%)
[2,3,8,11,12,23–25]. These epidemiological differences probably influence the percentage of normal karyotypes or other
cytogenetic findings.
It is widely accepted that partial or total chromosome
losses make up nearly half of chromosomal abnormalities,
followed by trisomies and, in less frequency, other structural
abnormalities [7]. Our data, in agreement with these observations, are clearly depicted in Fig. 1. This figure also
shows that chromosomes 5, 7, 11, 17, 20 and Y were the
most commonly affected, mainly by partial or total losses,
chromosomes 8 and 21 by trisomies, while other structural
abnormalities were also involved, predominantly, chromo-
4
somes 1, 3, and 11. The observed frequencies for the majority of chromosome alterations were similar to other
reports, though isolated del(5q) was at an intermediate
value from those reported in European or Asian series and
the presence of CK was lower [2,7,8,11,25].
The number of cytopenias, percentage of BM blast, gender, FAB and WHO classifications, IPSS and WPSS prognostic systems showed significant differences for predicting
outcome in our population (Table I). Also, the subdivision of
karyotypes into risk subgroups according to three systems
exhibited significant differences stratifying patients with
abnormal karyotypes into cytogenetic groups of risk with
different life expectancies (Table II) [1,2,19]. Lille system [1]
divided the presence CK versus other alterations while Lausanne-Bournemouth index [19] includes among bad prognostic karyotypes the presence of two aberrations. The
above mentioned studies did not explain the predictive significance of the types of cytogenetic abnormalities, considering that deletions and monosomies usually affect more
than 50% of abnormal karyotypes in MDS, as was
observed in our series. In 1997, the IPSS [2] recognized
that some deletions (5q-, 20q-, and 7q-) and monosomy 7
were associated with specific prognosis allowing us to differentiate three different cytogenetic categories of risk. This
modality of grouping karyotypes was adopted for the
WPSS in 2007 [10]. However, the Intermediate group
according to the IPSS is heterogeneous, including chromosome alterations not specified that are usually found in a
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research article
Figure 2. Cytogenetic Group of Risk of all abnormal Karyotypes not including Y chromosome losses (Survival plots, Kaplan–Meier curves Mantel Cox) [Color figure can
be viewed in the online issue, which is available at wileyonlinelibrary.com.].
TABLE III. Multivariate Analyses for Survival
Categories
FAB
WHO
Degree of freedom
P value
Exp (B)
New cytogenetic categories of risk
IPSS good risk findings 1 Isolate deletions
Other intermediate risk findings
IPSS poor risk findings 1 MK
BM blast (%)
<5
5–9
10–19
>19
2
1
1
*<0.001
*<0.001
*50.005
0.401
0.522
3
1
1
1
*<0.001
*<0.001
*<0.001
*50.014
0.119
0.293
0.503
New categories of risk
IPSS categories of risk
1
1
*50.024
50.958
1.452
0.991
New cytogenetic categories of risk
IPSS good risk findings 1 Isolate deletions
Other intermediate risk findings
IPSS poor risk findings 1 MK
BM blast (%)
<5
5–9
10–19
2
1
1
*<0.001
*<0.001
*50.027
0.353
0.546
2
1
1
*<0.001
*<0.001
*<0.042
0.227
0.598
New categories of risk
IPSS categories of risk
1
1
50.063
50.919
1.499
0.978
BM: Bone marrow; MK: Monosomal karyotype.
very low frequency while other authors tried to determine
the significance of some of these findings [3,7,11,13,14].
In our series, patients with deletions from the Intermediate group shared the same prognosis as the rest with Intermediate findings. However, when they were divided, isolated deletions showed a similar behavior than in patients
with normal karyotype and than those with del(5q) or
del(20). These findings are in agreement with recent
reports suggesting that del(12p), del(9q), del(11q) isolated
are associated with good prognosis [3,13,14]. Although
most of these deletions were found in a very low frequency
in our series, patients with del(12p) showed a good outcome (median survival of 60 months), similar to these other
American Journal of Hematology
reports [3,13,14]. Monosomal karyotypes have been proved
to be a better prognostic indicator of poor prognosis in a
series of 1975 AML patients [15]. When we tried to ascertain whether the presence of a monosomal karyotype had
a worse prognostic impact, the behavior of this group was
similar to the presence of a CK with or without monosomies, indicating a comparable prognostic impact.
Particular cytogenetic abnormalities, the most frequent
ones, have been considered as risk indicators. However,
there is a wide spectrum of low frequency aberrations that
stress the importance of large study groups where the
impact of such aberrations can be statistically evaluated. It
would be important to corroborate, in a largest group, our
5
research article
findings that all isolate deletions (excluding 7q-) are good
prognostic findings and that all monosomies (excluding Y
chromosome loss) are bad indicators. This new categorization of cytogenetic alterations, where three groups of risk
have been identified, showed an independent prognostic
assessment and a better discriminating power that the original IPSS categories of risk in our population classified
according to FAB or WHO.
It can be concluded that cytogenetic findings had a clear
impact on the clinical outcome and that the data analyzed
in the present series, the largest in Latin America, are coincident with recently published data suggesting that the intermediate cytogenetic group according to the IPSS should
be redefined.
Acknowledgments
The authors thank the investigators of the Argentinean
MDS’s Study Group organized by the Argentinean Society
of Hematology for the use of the Pilot Study for MDS
Registry database and Dr. Christine Dosne de Pasqualini,
PhD for revising the manuscript.
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