Skip to main content
Download PDF

Higher prevalence of poor prognostic markers at a younger age in adult patients with myelodysplastic syndrome – evaluation of a large cohort in India

Molecular Cytogenetics volume 17, Article number: 21 (2024) Cite this article

Abstract

Background

The karyotype is a major determinant of prognosis in myelodysplastic syndrome (MDS). Details of the cytogenetic profile of MDS in South Asia are limited because cytogenetic services are not widely available.

Methods

We performed a retrospective analysis of the cytogenetic and clinicopathologic profile of adult primary MDS seen consecutively at a tertiary-care centre in South India between 2003 and 2017. Patients were re-categorised according to the 2022 World Health Organisation (WHO) and the International Consensus classifications (ICC).

Results

There were 936 patients aged 18–86 years (median age 53, 65% males), with MDS with del 5q, low blasts and increased blasts in 7.5%, 58.4% and 34.1% respectively. Clonal abnormalities were seen in 55% of patients, with solitary abnormalities in 29.8% and complex karyotypes (CK, ≥ 3 abnormalities) in 15%. The most frequent abnormalities were monosomy 7/deletion 7q (16.1%), deletion 5q (14.5%), trisomy 8 (11.5%), and deletion 20q (5.1%). Cytogenetic prognosis groups were distributed as follows: very good, 2%; good, 55.6%; intermediate, 16.2%; poor, 15%; very poor, 11.2%. Clinical (IPSS-R) risk stratification (842 patients) showed: very low-risk, 3.9%; low-risk, 30.9%; intermediate-risk, 24.2%; high-risk, 21%; very high-risk, 20%. Age-adjustment (IPSS-RA) raised the very low-risk group to 12.4%; the other groups decreased by 1–3% each.

Conclusion

The most significant finding of this cytogenetic analysis of MDS in India is that abnormal karyotypes with poor prognosis markers including monosomy 7 and CK were more frequent than in most other reports, among patients who were overall younger. Trisomy 8, deletion 20q, the IPSS-R intermediate-risk and both high-risk groups were more common than in the West. Trisomy 8 was less common than in South-East Asia while CK and deletion 20q were comparable. Evaluation of such large cohorts highlights the unique features of MDS in different parts of the world. These findings suggest that there could be differences in predisposing factors, environmental or genetic, and emphasise the need for further exploration to better understand the varied nature of MDS.

Introduction

The myelodysplastic syndromes (MDS) are a group of bone marrow disorders characterised by at least one peripheral cytopenia and dysplasia of one or more haematopoietic lineages due to ineffective haemopoiesis associated with neoplastic transformation of haematopoietic stem cells [1]. These disorders show considerable variation with respect to the severity of cytopenia and dysplasia, clinical course, including risk of transformation to acute myeloid leukemia (AML), and response to therapy [1]. Cytogenetic abnormalities are seen in about 50% of MDS [2]. The presence of an abnormal karyotype provides evidence that a clonal proliferation underlies the refractory cytopenia being investigated [1, 2].

Earlier classifications of MDS have been revised by the World Health Organisation (WHO) since 2001 to include the subtype MDS with isolated del 5q (MDS-del 5q) which is based on the karyotype [3,4,5,6,7].

The most recent (2022) WHO classification and International Consensus classification (ICC) also describe two subtypes based on the presence of the SF3B1 mutation and biallelic TP53 inactivation [8, 9]. These subtypes are termed MDS with low blasts (LB) and SF3B1 mutation (MDS-SF3B1) and MDS with biallelic TP53 inactivation (MDS-biTP53) by the WHO [8]. The ICC refers to these two subtypes as MDS with mutated SF3B1 and MDS with mutated TP53. [9]. According to the 2022 WHO classification, the presence of ≥ 15% ring sideroblasts (RS) may substitute for the SF3B1 mutation and the subtype may also be termed MDS with low blasts and ring sideroblasts [8].

Cytogenetic findings have been used in prognostic scoring systems since 1997 because the chromosomal complement of the marrow is a major determinant of prognosis and response to therapy [1, 2, 10,11,12]. In the most frequently used Revised International Prognostic Scoring System (IPSS-R), the karyotype has the widest range of prognostic score values, emphasising its importance in determining the clinical risk score [12]. Although the risk-stratification of MDS is refined further by the use of the more recently described IPSS-Molecular (IPSS-M) which combines the mutational profile with haematological and cytogenetic parameters, it is likely that the IPSS-R will continue to be in use until advanced molecular testing is more widely available [13].

Analyses of cytogenetic findings in MDS from different parts of the world vary with respect to the classification systems used, modes of ascertainment of abnormalities and the numbers and subtypes of patients analysed [14,15,16,17,18,19,20,21,22,23,24,25,26,27,28]. Reports from India are relatively few, and except for two, describe small numbers of patients [29, 30]. We describe the karyotypes associated with primary MDS and their associated clinicopathological features in a large series of adult patients seen at a referral hospital in South India.

Patients and methods

Patient cohort

The study group consisted of all adults with primary MDS seen consecutively in the Department of Haematology, Christian Medical College (CMC), Vellore, India between 2003 and 2017, and who underwent conventional cytogenetic analysis (CCA). The diagnosis of MDS was based on a combination of clinical examination, blood and bone marrow findings and cytogenetic analysis as well as the absence of specific antecedent medical conditions.

Molecular genetic studies were not performed during the period of this study. Patients who had received chemotherapy and/or radiotherapy for an antecedent haematological or other neoplasm or had other causes of cytopenia including those associated with hypoplastic or cellular marrows with no dysplasia and normal cytogenetics were excluded from the analysis.

Haematological evaluation

All patients underwent complete blood count (CBC) analysis and morphological assessment of bone marrow aspirates and trephine biopsies at diagnosis using Romanowsky-stained slides, cytochemistry and reticulin staining as well as immunohistochemistry, as appropriate. The morphologic diagnosis was based on the WHO classification system in use at the time.

However, to provide contemporary relevance in this report, MDS subtypes were re-categorised according to the ICC and WHO 2022 classifications based on morphological and cytogenetic findings. MDS, unclassifiable (MDS-U) which comprised three sub-categories in the WHO 2016 classification and which has been removed from the WHO 2022 classification was re-categorised to the extent possible. Specifically, the sub-category of MDS-U, “MDS-U with single lineage dysplasia and pancytopenia” was categorised as “MDS with low blasts” while the sub-category “MDS-U with defining cytogenetic abnormality” was excluded from the cases in the WHO 2022 categories, but retained in the ICC 2022 which has termed this subtype “MDS, NOS without dysplasia”. We did not have any patients with the third sub-category, MDS-U with 1% blood blasts. MDS with low blasts was sub-categorised as proposed by the WHO 2022. Clinical risk scores (IPSS-R) were calculated as per available data, and adjusted for age (IPSS-RA) [12].

Cytogenetic analysis

Conventional cytogenetic analysis (CCA) was performed on all patients using standard protocols; FISH analysis using locus-specific probes for chromosomes 5, 7 and 20 was done for confirmation of suspected abnormalities [31, 32]. It is not our routine practice to use FISH panels for the work-up of patients with MDS. Karyotypes with < 15 metaphases were excluded unless a clonal abnormality was present. Karyotypes were categorised into prognostic groups according to the IPSS-R categories which are based on the comprehensive cytogenetic scoring system (CCSS) described by Schanz et al. [12, 15]. Complex karyotypes with 3 or > 3 abnormalities were classified separately based on their prognostic significance according to the IPSS-R.

Data collection and analysis

We performed a retrospective analysis of the cytogenetic and clinicopathologic profile of these patients. These data were extracted from the computerised hospital information system and laboratory databases that are carefully maintained for each patient as standard practice in our institution.

We also compared our findings with studies from the West (Europe, including Austria, Germany, Italy, Spain, Sweden and U.S.A), South-East (S.E) Asia (Japan, China, South Korea and Taiwan), South (S.) Asia (India and Pakistan) and Africa (Tunisia) which had at least 100 patients and did not include those with translocations which are now considered to be definitive for AML [14,15,16,17,18,19,20,21,22,23, 25, 28,29,30, 33,34,35]. Some of these studies used the French-American-British (FAB) classification and therefore included chronic myelomonocytic leukemia (CMML) and refractory anemia with excess blasts in transformation (RAEB-t) which were categorised as MDS at the time, as well as AML following MDS or myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and/or secondary MDS [14,15,16, 18]. Weighted averages were used to compare frequencies in each region (upto 13,428 patients from the West, 2713 from South-East Asia and 190–347 from S.Asia and Tunisia). The study was approved by the Institutional Review Board of CMC, Vellore.

Statistical analysis

Data were analysed using SPSS Statistics version 21.0 (IBM Corp) and SAS software, version 9.4 (SAS Institute). Descriptive measures such as median and range were presented for continuous variables. For categorical variables, counts and proportions were presented. Categorical variables were compared using the Chi-square test, unless the expected number of subjects in any one category was less than five, in which case Fisher’s exact test was used. The Mann Whitney-U test was used for comparing two independent groups, while the Kruskal-Wallis test was used for the comparisons involving more than two groups. All statistical tests were two-sided, and a p <0.05 level was considered as statistically significant.

Results

Patients

A total of 988 patients were diagnosed to have primary MDS during the period of this study. Adequate karyotypic data was available for 936 (94.7%) of them who were included for further analysis in this study.

The median age of the study cohort was 53 years (range 18–86). There were 607 (65%) males and 329 females (35%). Clonal cytogenetic abnormalities were seen in 515 (55%) patients, and normal karyotypes in 421 patients (45%) (Table 1).

Table 1 Clinical, haematological and cytogenetic features of adult primary myelodysplastic syndrome (MDS)
Full size table

Overview of age and sex distribution and cytogenetic subgroups. (Fig. 1; Table 2 & Additional File 1)

Fig. 1
figure 1

Age distribution of patients, normal and abnormal karyotypes and cytogenetic prognosis groups

Full size image
Table 2 Clinical and haematological features of cytogenetic subgroups and MDS subtypes
Full size table

The number of patients progressively increased from the second decade (4%) to the sixth decade (25%) and declined subsequently (60–69 years, 21% and ≥ 70 years, 12%) (Fig. 1A). A spike in the sixth decade (23–31%) was noted in all categories of abnormal karyotypes except those with independent non-complex clones (IncC, n = 25) which were most common (20% each) in the third and seventh decades (Fig. 1B, C).

Complex karyotypes (CK) with ≥ 3 abnormalities were seen in 15% of patients and abnormalities associated with a poor and very poor prognosis (unfavourable karyotypes) were seen in 26.2% of patients (27.4% and 47.6% of abnormal karyotypes, respectively). The clinical, haematological and cytogenetic features of these patients are shown in Tables 1 and 2 and Fig. 1, and details of the MDS subtypes as per the 2022 WHO and ICC classifications are shown in Additional File 1.

Frequently seen abnormalities and cytogenetic prognosis groups (Table 3, Figs. 2, 3, 4 and 5 & Additional File 2)

Table 3 Age & sex distribution of recurrent cytogenetic abnormalities in MDS
Full size table
Fig. 2
figure 2

Distribution of recurrent abnormalities in MDS

Full size image
Fig. 3
figure 3

Karyotypes of some common abnormalities A.47,XY,del(5)(q13q33),+21. B.46,XX,del(7)(q22q33). C.46,XY,del(20)(q12). D.45,XY,t(3;3)(q21;q26),-7

Full size image
Fig. 4
figure 4

Distribution of abnormalities in WHO subtypes

Full size image
Fig. 5
figure 5

Distribution of abnormalities in ICC subtypes

Full size image

Our most common abnormality was monosomy (minus) 7/ del 7q (7q-) in 151(16.1%) patients, and 159(17%), if der(1;7)(q10;p10) was included (29.3% and 30.9% of abnormal karyotypes respectively).

The del 5q (14.5%) and trisomy (plus) 8 (11.5%) were our next most common abnormalities (26.4% and 21% of abnormal karyotypes respectively). The del 5q was present in 79 non-complex karyotypes, 70 (88.6%) of which could be categorised as MDS-del 5q.

Apart from the del 20q (5.1%), the other MDS-related abnormalities accounted for ≤ 3.5% each. Monosomal karyotypes were seen in 113 (12.1%) patients, 98 of whom had CK while 15 had two abnormalities. Abnormalities usually seen as part of CKs included monosomies 5,17,18 and 20 (> 95%), trisomy 19, minus X (> 90%), monosomy 13 and marker chromosomes (> 80%). CKs were also seen in 35 of 38 (92%) karyotypes in which monosomy 7 (n = 25) /del 7q (n = 13) were associated with monosomy 5/del 5q.

There were 21 patients (2.2%) with “MDS-defining” translocations which comprised the t(3;3)(q21;q26.2) in 0.96% and the t(6;9)(p22;q34), t(1;3)(p36.3;q21.1), t(3;21)(q26.2;q22.1) and t(2;11)(p21;q23) in 0.2–0.4% each. Other recurrent translocations included the t(3;5)(q21;q31), t(4;12)(q12;p13), t(5;11)(q31;q23, t(11;19)(q23;p13.3) and t(20;21)(q13;q22) which were seen in 0.1–0.3% of patients (Additional File 2).

The inv(3)(q21q26.2), the t(11;16)(q23.3;p13.3), and the idic(X)(q13), also termed MDS-defining abnormalities were not seen in this cohort.

Clinical risk scores (Fig. 6)

Fig. 6
figure 6

Age distribution of IPSS-R and IPSS-RA subgroups

Full size image

Data for calculation of clinical risk scores as defined by the Revised International Prognostic Scoring System (IPSS-R) was available in 842 (90%) patients of whom 817 were ≥ 21 years and 630 were ≥ 40 years. The distribution of the IPSS-R intermediate-risk and both high-risk groups was similar (20–24%) compared to the low-risk (31%) and very low-risk groups (3.9%); however, when adjusted for age (IPSS-RA), the number of patients in the very low-risk group increased to 12.4% while the other groups decreased by 1–3% each.

Discussion

This first large series of adult patients with primary MDS from South India seen over a 15-year period documents in detail the clinico-pathologic and cytogenetic features and compares our major findings with the literature.

Age and sex distribution (Tables 4 and 5)

Table 4 Comparison of clinical features and cytogenetic abnormalities in primary MDS in the West, S.E. Asia & Tunisia
Full size table
Table 5 Comparison of clinical features and cytogenetic abnormalities in primary MDS in S.Asia
Full size table

The median age of 53 years in this cohort is one to two decades (13–22 years) lower than in reports from the West (66–75 years), as also in Japan (76 years) [12, 14,15,16,17,18, 36,37,38]. Previous reports from the rest of S.E Asia and Tunisia have recorded a similar age profile (45–57 years and 60 years respectively), two of which (from Tunisia and China) also included children [20,21,22,23,24,25, 33, 39,40,41]. The M: F ratio was also comparable to these reports (1.8 vs. 1.3-1.9 in the West and 1.1–2.1 in S.E. Asia and Tunisia [14,15,16,17,18,19,20,21,22,23,24,25, 28, 33,34,35,36,37, 39, 40]. The median age of our MDS-del 5q (57 years) was also lower than in Europe (65 years); it was more common in females (M: F ratio 0.6 vs. 0.49 and 1.0 in Europe) (Table 2 and Additional File 1) [42, 43].

Cytogenetic abnormalities (Tables 4 and 5, Additional Files 3 & 4)

The frequency of clonal abnormalities varied from 37 to 52% in large (968 to nearly 6000 patients) studies from the West and 35–68% in other studies from Europe, S.E Asia and Tunisia (224–665 patients) [14,15,16,17,18,19,20,21,22,23, 25, 33, 36, 37, 39, 40]. However, three of the large Western studies and those from Greece, Tunisia and China included patients with chronic myelomonocytic leukemia (CMML) and refractory anemia with excess blasts in transformation (RAEB-t) which were formerly classified as MDS, secondary MDS and myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) [14,15,16, 25, 36, 39]. Some also included secondary MDS and myelodysplastic syndrome/myeloproliferative neoplasm (MDS/MPN) [14, 18, 36, 37]. Clonal abnormalities were seen in 55% of our patients.

The del 5q, trisomy 8, monosomy 7/del 7q and del 20q are the most common abnormalities in MDS but their frequencies tend to vary in different parts of the world [1, 2, 19]. The deletion 5q was the most common abnormality in most Western studies followed by trisomy 8, monosomy 7/del 7q and del 20q [14,15,16,17,18,19, 44].

Trisomy 8 was the most common abnormality in S.E Asia followed by monosomy 20/del 20q, monosomy 7/del 7q and the del 5q. [19,20,21,22,23, 33]. However, the most common abnormalities in this cohort in decreasing order of frequency were monosomy 7/ del 7q, del 5q, trisomy 8, and del 20q.

Comparison of the cytogenetic profiles of our patients with weighted averages from each region showed differences and similarities. The frequencies of monosomy 7/del 7q, del 5q, trisomy 8 and del 20q were higher in our study than in the West. Monosomy 7/del 7q was almost four times as common (16.1% vs. 4.5%), and the del 5q, trisomy 8 and del 20q almost twice, or twice as common (14.5% vs. 8.3%, 11.5% vs. 5.7% and 5.1% vs. 2.5% respectively) as in the West (P < 0.001). Most of our other abnormalities, namely, del 11q (P = 0.001), isochromosome 17q (P = 0.017), der (1;7) (P = 0.004), abnormalities of chromosome 1, monosomy 13/del 13q, monosomy 17/del 17p, trisomy 19 and trisomy 21 were also more common than in the West (P < 0.001) but there were no significant differences in the frequencies of 3q abnormalities, del 12p, monosomy 18 / del 18q and minus Y (Additional File 3) [14,15,16,17,18,19].

Trisomy 8 was more common in S.E Asia than among our patients, its weighted average (14%, P = 0.05) trending towards significance although its frequency varied widely (4–20%) in individual studies. The isochromosome 17q was also more common (2.3%, P = 0.02) in S.E Asia, but we had higher frequencies of monosomy 17/del 17p (P = 0.014). We also had considerably higher (more than twice) frequencies of monosomy 7/ del 7q and del 5q than in S.E Asia (6.8% and 6% respectively P < 0.001). The frequencies of the del 20q and the other abnormalities were not significantly different from our study (Additional File 3) [19,20,21,22,23, 33].

Minus Y which occurs in MDS, but may also be seen in non-neoplastic marrows of older men, was the most common single abnormality (5%) reported by Berggren et al., with 90% occurring in men > 60 years of age [18]. We found minus Y in 2.6% with 79% seen in those ≥ 40 years, and 33% in those ≥ 60 years. This frequency was comparable to other reports from the West (1.8–3.4%) and Japan (1.1%) which also had older populations than ours, and S.E Asia (2.2–2.6%) [14,15,16,17, 19,20,21,22,23] (Table 4).

The frequency of our CKs (15%) was higher than in the West (12.1%, P = 0.011) although frequencies varied considerably (9-17.6%) in individual studies. There was no significant difference in the weighted average of CKs in S.E Asia (14.5%) although again, wide variations in frequency (8.5–22.4%) were noted in individual studies [14,15,16,17,18,19,20,21,22,23, 33]. Independent non-complex clones (IncCs) were seen in 2.7% of our patients compared to 0.9% in the report by Schanz et al. (Table 4 & Additional File 3) [15].

Salient differences between our findings and the report from Tunisia were a lower frequency of the del 12p (1.6% vs. 4%, P = 0.023) in our study and higher frequencies of monosomy 7/del 7q (P = 0.002), trisomy 8 (P < 0.001), trisomy 21 (P = 0.017), minus Y (P = 0.043) and CK (P = 0.006). There were no significant differences in the frequencies of del 5q and the other abnormalities (Table 4 & Additional File 3) [25].

Comparison with other reports from South Asia showed some differences [28, 34, 35]. We had higher frequencies of abnormal karyotypes (P = 0.001), del 5q (P < 0.001) and monosomy 7/del 7q (P < 0.001) and del 20q (P = 0.048) than in Pakistan while there were no significant differences between the frequencies of trisomy 8 and CK (Additional File 4) [28, 34, 35].

There are several studies from India but most are of small numbers (40–60) of patients and show wide variations in the frequencies of clonal abnormalities (35-64.5%) as well as monosomy 7/del 7q (8–16%), del 5q (3.5–27%) and trisomy 8 (1.2–12.5%); some mainly used FISH and/or included CMML and RAEB-t [29, 30, 45,46,47,48,49]. Comparison with the two largest reports from India (104–150 patients) showed that the frequencies of the del 5q (4.8%, P = 0.0003) and trisomy 8 (3.2%, P = 0.0005) were lower than in our study while there were no significant differences with respect to the other abnormalities (Additional File 4) [29, 30]. Being series of relatively small numbers of patients, referral bias could be the reason for these differences. It is also not clear whether consecutive patients were included in those series.

Cytogenetic prognosis groups (Table 6 & Additional File 5)

Table 6 Comparison of cytogenetic prognostic groups in MDS
Full size table

With 11.2% of very poor prognosis karyotypes in this series, this was higher than in the West, Japan and China (7%, P < 0.001; 6.3%, P = 0.004 and 7.8%, P = 0.007, respectively), while the poor prognosis group was considerably higher (two to three times) than in all three regions (15% vs. 4.3-7%, P < 0.001). These differences are explained by the higher frequencies of monosomy 7 and CK with > 3 abnormalities in our patients [12, 15, 18,19,20, 22].

The number of karyotypes in each of the other three prognostic groups was lower than in one or more of the other regions. We had almost half the number of karyotypes in the intermediate prognosis group as in China (16% vs. 30%, P < 0.001), fewer karyotypes in the good prognosis group than in the West and Japan (P < 0.001), and in the very good prognosis group than in the West (P = 0.005). These differences could be reflective of the frequency of trisomy 8 (intermediate prognosis) which was the most common abnormality in China, and the lower frequency of normal karyotypes (good prognosis) in our study compared to the West and Japan. The difference in the frequency of the very good prognosis group could possibly be due to the considerably higher frequency of minus Y in the study by Berggren et al. (Table 6 and Additional File 5) [12, 15, 18,19,20, 22].

Only two studies from South Asia (one each from India and Pakistan) described the cytogenetic prognosis groups [28, 30]. The study from Pakistan had more karyotypes in the very good (5.6%, P = 0.006) prognosis group and fewer karyotypes in the very poor prognosis group (P = 0.001). However, the frequencies of all five prognosis groups were comparable to the other study from India. (Tables 6 and Additional File 5).

Clinical risk groups (Figs. 6 and 7)

Fig. 7
figure 7

A. Distribution of IPSS-R and IPSS-RA risk groups. B. Comparison of IPSS-R risk groups with the West. C. Comparison of IPSS-R risk groups with Japan. D. Comparison of IPSS-R risk groups with China and Taiwan

Full size image

The distribution of clinical risk groups also varies in different parts of the world (Fig. 7.B, C, D). There were highly significant differences between Western studies (age ≥ 16 years, n = 17,228) and our study (n = 842) with respect to all five clinical risk groups ; we had fewer patients in both low-risk groups (34% vs. 66%) and more patients in the intermediate-risk (24% vs. 17%) and both high-risk (41% vs. 17%) groups (P = < 0.001) [12, 16, 18, 50,51,52].

Comparison with a study from Japan (age ≥ 40 years, n = 300 vs. n = 630 aged ≥ 40 years in our study) also showed that we had more patients in our high-risk (19% vs. 13%, P = 0.03) and very high-risk (21% vs. 13%, P = 0.004) groups and fewer patients in the very low-risk (4.4% vs. 10%, P < 0.001) and intermediate-risk (23% vs. 32%, P = 0.002) groups [19].

We had significantly more patients in the low-risk (31% vs. 25%, P = 0.006) group and fewer patients in the high-risk (21% vs. 25%, P = 0.03) group than in studies from China and Taiwan (age ≥ 16 years, n = 1170) [21, 53, 54].

This study has some limitations with respect to the lack of molecular studies and clinical follow-up. However, we believe that this report still brings out the lower age as well as the high frequency of complex karyotypes and poor prognosis markers in this population and will remain relevant with the updated WHO 2022 and ICC 2022 based classifications of entities included. Our data also provides a detailed description of the spectrum of cytogenetic abnormalities in MDS.

Conclusion

This large series of adult patients with MDS from India has several unique features. Apart from confirming the significantly lower age at presentation in India, it also documents the higher frequencies of monosomy 7, both poor prognosis groups and the IPSS-R high-risk groups among these younger patients than in the West. The reasons for these differences are unclear and could reflect differences in environmental exposures particularly to widely used pesticides and fertilisers, as well as possible genetic predispositions. Molecular analysis and detailed epidemiological studies would help in the identification of such predisposing factors, both inherited and environmental, and early recognition for more effective therapeutic interventions.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Abbreviations

abn:

abnormality/abnormalities

AML:

Acute myeloid leukemia

CK:

complex karyotype(s)

ANC:

absolute neutrophil count

CMML:

chronic myelomonocytic leukemia

CCSS:

comprehensive cytogenetic scoring system

CK:

complex karyotype

del:

deletion

der:

derivative

FISH:

fluorescence in situ hybridization

Hb:

haemoglobin

ICC:

International Consensus Classification of Acute Myeloid Leukemia

IncC:

independent non-complex clones

inv:

inversion

IPSS-R:

Revised International Prognostic Scoring System

IPSS-RA:

Age-adjusted Revised International Prognostic Scoring System

i:

isochromosome

Intrmdt:

intermediate

M:F ratio:

male:female ratio

mar:

marker chromosomes

MK:

monosomal karyotype(s)

MDS:

myelodysplastic syndrome

MDS-f:

MDS with fibrosis

MDS-h:

MDS, hypoplastic

MDSLB:

MDS with low blasts

MDS-LB-RS:

MDS with low blasts and ring sideroblasts

MDS-NOS-SLD:

MDS, not otherwise specified, with single lineage dysplasia

MDS-NOS-MLD:

MDS, not otherwise specified, with multilineage dysplasia

MDS wo dyspl:

MDS without dysplasia

MDS-EB:

MDS with excess blasts

MDS-IB:

MDS with increased blasts

Plt:

platelet count

RAEB-t:

refractory anaemia with excess blasts in transformation

S.Asia:

South Asia

S.E.Asia:

South-East Asia

t:

translocation

UK:

United Kingdom

USA:

United States of America

WHO:

World Health Organisation

References

  1. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, editors. WHO classification of Tumours of Haematopoietic and lymphoid tissues (revised 4th Fourth Edition). IARC: Lyon,; 2017.

  2. Heim S. In: Mitelman F, editor. Cancer cytogenetics: chromosomal and molecular genetic aberrations of Tumor cells. Fourth ed. Wiley Blackwell; 2015.

  3. Bennett JM, Catovsky D, Daniel MT, et al. Proposals for the classification of the Acute Leukaemias French-American-British (FAB) co-operative group. Br J Haematol. 1976;33(4):451–8. https://doi.org/10.1111/j.1365-2141.1976.tb03563.x.

    Article  CAS  PubMed  Google Scholar 

  4. Harris NL, Jaffe ES, Diebold J, et al. The World Health Organization classification of neoplasms of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting–Airlie House, Virginia, November, 1997. Hematol J. 2000;1(1):53–66. https://doi.org/10.1038/sj.thj.6200013.

    Article  CAS  PubMed  Google Scholar 

  5. Vardiman JW, Harris NL, Brunning RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood. 2002;100(7):2292–302. https://doi.org/10.1182/blood-2002-04-1199.

    Article  CAS  PubMed  Google Scholar 

  6. Vardiman JW, Thiele J, Arber DA, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937–51. https://doi.org/10.1182/blood-2009-03-209262.

    Article  CAS  PubMed  Google Scholar 

  7. Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405. https://doi.org/10.1182/blood-2016-03-643544.

    Article  CAS  PubMed  Google Scholar 

  8. Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: myeloid and Histiocytic/Dendritic neoplasms. Leukemia. 2022;36(7):1703–19. https://doi.org/10.1038/s41375-022-01613-1.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Arber DA, Orazi A, Hasserjian RP, et al. International Consensus classification of myeloid neoplasms and Acute Leukemias: integrating morphologic, clinical, and genomic data. Blood. 2022;140(11):1200–28. https://doi.org/10.1182/blood.2022015850.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Greenberg P, Cox C, LeBeau MM, et al. International Scoring System for evaluating prognosis in myelodysplastic syndromes. Blood. 1997;89(6):2079–88. https://doi.org/10.1182/blood.V89.6.2079.

    Article  CAS  PubMed  Google Scholar 

  11. Malcovati L, Germing U, Kuendgen A, et al. Time-dependent prognostic scoring system for predicting survival and leukemic evolution in myelodysplastic syndromes. J Clin Oncol. 2007;25(23):3503–10. https://doi.org/10.1200/JCO.2006.08.5696.

    Article  PubMed  Google Scholar 

  12. Greenberg PL, Tuechler H, Schanz J, et al. Revised International Prognostic Scoring System for Myelodysplastic syndromes. Blood. 2012;120(12):2454–65. https://doi.org/10.1182/blood-2012-03-420489.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Bernard E, Tuechler H, Greenberg PL, et al. Molecular International Prognostic Scoring System for Myelodysplastic syndromes. NEJM Evid. 2022;1(7):EVIDoa2200008. https://doi.org/10.1056/EVIDoa2200008.

    Article  PubMed  Google Scholar 

  14. Haase D, Germing U, Schanz J, et al. New insights into the prognostic impact of the karyotype in MDS and correlation with subtypes: evidence from a core dataset of 2124 patients. Blood. 2007;110(13):4385–95. https://doi.org/10.1182/blood-2007-03-082404.

    Article  CAS  PubMed  Google Scholar 

  15. Schanz J, Tüchler H, Solé F, et al. New comprehensive cytogenetic scoring system for primary myelodysplastic syndromes (MDS) and oligoblastic acute myeloid leukemia after MDS derived from an international database merge. J Clin Oncol. 2012;30(8):820–9. https://doi.org/10.1200/JCO.2011.35.6394.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Solé F, Luño E, Sanzo C, et al. Identification of novel cytogenetic markers with prognostic significance in a series of 968 patients with primary myelodysplastic syndromes. Haematologica. 2005;90(9):1168–78.

    PubMed  Google Scholar 

  17. Pozdnyakova O, Miron PM, Tang G, et al. Cytogenetic abnormalities in a series of 1,029 patients with primary myelodysplastic syndromes: a report from the US with a focus on some undefined single chromosomal abnormalities. Cancer. 2008;113(12):3331–40. https://doi.org/10.1002/cncr.23977.

    Article  PubMed  Google Scholar 

  18. Berggren DM, Folkvaljon Y, Engvall M, et al. Prognostic scoring systems for myelodysplastic syndromes (MDS) in a population-based setting: a report from the Swedish MDS register. Br J Haematol. 2018;181(5):614–27. https://doi.org/10.1111/bjh.15243.

    Article  Google Scholar 

  19. Miyazaki Y, Tuechler H, Sanz G, et al. Differing clinical features between Japanese and caucasian patients with myelodysplastic syndromes: analysis from the International Working Group for Prognosis of MDS. Leuk Res. 2018;73:51–7. https://doi.org/10.1016/j.leukres.2018.08.022.

    Article  PubMed  Google Scholar 

  20. Wang X, Liu W, Wang M, et al. Cytogenetic characteristics of 665 patients with myelodysplastic syndrome in China: a single-center report. Oncol Lett. 2021;21(2):126. https://doi.org/10.3892/ol.2020.12387.

    Article  PubMed  Google Scholar 

  21. Yan X, Wang L, Jiang L, et al. Clinical significance of cytogenetic and molecular genetic abnormalities in 634 Chinese patients with myelodysplastic syndromes. Cancer Med. 2021;10(5):1759–71. https://doi.org/10.1002/cam4.3786.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Qu S, Xu Z, Zhang Y, et al. Impacts of cytogenetic categories in the revised International Prognostic Scoring System on the prognosis of primary myelodysplastic syndromes: results of a single-center study. Leuk Lymphoma. 2012;53(5):940–6. https://doi.org/10.3109/10428194.2011.634049.

    Article  PubMed  Google Scholar 

  23. Jung SW, Lee SY, Jekarl DW, et al. Cytogenetic characteristics and prognosis analysis in 231 myelodysplastic syndrome patients from a single institution. Leuk Res. 2011;35(6):735–40. https://doi.org/10.1016/j.leukres.2010.11.009.

    Article  PubMed  Google Scholar 

  24. Phrommin S, Tantiworawit A, Rattanathammethee T, et al. Chromosomal abnormalities in Myelodysplastic Syndrome patients in Upper Northern Thailand. Asian Pac J Cancer Prev. 2020;21(3):639–45. https://doi.org/10.31557/APJCP.2020.21.3.639.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Gmidène A, Sennana H, Fenaux P, et al. Cytogenetic abnormalities in Tunisian de novo myelodysplastic syndrome: a comparison with other populations. Leuk Res. 2008;32(12):1824–9. https://doi.org/10.1016/j.leukres.2008.05.002.

    Article  PubMed  Google Scholar 

  26. Elnahass Y, Youssif L. Cytogenetic features in primary myelodysplastic syndrome Egyptian patients. J Adv Res. 2018;10:77–83. https://doi.org/10.1016/j.jare.2018.02.002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Paridar M, Zibara K, Ahmadi SE, et al. Clinico-Hematological and cytogenetic spectrum of adult myelodysplastic syndrome: the first retrospective cross-sectional study in Iranian patients. Mol Cytogenet. 2021;14(1):24. https://doi.org/10.1186/s13039-021-00548-z.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Mahmood R, Altaf C, Ahmed P, Khan SA, Malik HS. Myelodysplastic syndrome in Pakistan: clinicohematological characteristics, Cytogenetic Profile, and risk stratification. Turk J Haematol. 2018;35(2):109–15. https://doi.org/10.4274/tjh.2017.0130.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Vundinti BR, Kerketta L, Jijina F, Ghosh K. Cytogenetic study of myelodysplastic syndrome from India. Indian J Med Res. 2009;130(2):155–9.

    PubMed  Google Scholar 

  30. Gupta R, Rahman K, Singh MK, Kumari S, Yadav G, Nityanand S. Clinico-Pathological Spectrum and Novel Karyotypic findings in Myelodysplastic Syndrome: experience of Tertiary Care Center in India. Mediterr J Hematol Infect Dis. 2017;9(1):e2017048. https://doi.org/10.4084/MJHID.2017.048.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Dal Cin P. Metaphase harvest and cytogenetic analysis of malignant hematological specimens. Curr Protoc Hum Genet. 2003;Chap. 10:Unit 10.2. https://doi.org/10.1002/0471142905.hg1002s36.

  32. McGowan-Jordan J, Simons A, Schmid MISCN. 2016: An International System for Human Cytogenomic Nomenclature. Basel: S.Karger, 2016. In: 2016. https://doi.org/10.1159/ISBN.978-3-318-05979-3.

  33. Li L, Liu XP, Nie L, et al. Unique cytogenetic features of primary myelodysplastic syndromes in Chinese patients. Leuk Res. 2009;33(9):1194–8. https://doi.org/10.1016/j.leukres.2008.11.021.

    Article  PubMed  Google Scholar 

  34. Rashid A, Khurshid M, Shaikh U, Adil S. Chromosomal abnormalities in primary myelodysplastic syndrome. J Coll Physicians Surg Pak. 2014;24(9):632–5.

    PubMed  Google Scholar 

  35. Anwar N, Arshad A, Nadeem M, et al. Clinicohematological and cytogenetic profile of myelodysplastic syndromes in Pakistan-compare and contrast. Mol Cytogenet. 2017;10:17. https://doi.org/10.1186/s13039-017-0318-4.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Avgerinou C, Alamanos Y, Zikos P, et al. The incidence of myelodysplastic syndromes in Western Greece is increasing. Ann Hematol. 2013;92(7):877–87. https://doi.org/10.1007/s00277-013-1712-6.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Mądry K, Machowicz R, Waszczuk-Gajda A, et al. Demographic, hematologic, and clinical features of Myelodysplastic Syndrome patients: results from the First Polish Myelodysplastic Syndrome Registry. Acta Haematol. 2015;134(2):125–34. https://doi.org/10.1159/000375149.

    Article  PubMed  Google Scholar 

  38. Chihara D, Ito H, Katanoda K, Shibata A, Matsuda T, Sobue T, Matsuo K. Incidence of myelodysplastic syndrome in Japan. J Epidemiol. 2014;24(6):469 – 73 https://doi.org/10.2188/jea.je20140042 Epub 2014 Aug 2 PMID: 25088696; PMCID: PMC4213221.

  39. Chen B, Zhao WL, Jin J, et al. Clinical and cytogenetic features of 508 Chinese patients with myelodysplastic syndrome and comparison with those in western countries. Leukemia. 2005;19(5):767–75. https://doi.org/10.1038/sj.leu.2403688.

    Article  CAS  PubMed  Google Scholar 

  40. Lee JH, Lee JH, Shin YR, et al. Application of different prognostic scoring systems and comparison of the FAB and WHO classifications in Korean patients with myelodysplastic syndrome. Leukemia. 2003;17(2):305–13. https://doi.org/10.1038/sj.leu.2402798.

    Article  PubMed  Google Scholar 

  41. Jiang Y, Eveillard JR, Couturier MA, et al. Asian Population is more Prone to develop high-risk myelodysplastic syndrome, Concordantly with their propensity to exhibit high-risk cytogenetic aberrations. Cancers (Basel). 2021;13(3):481. https://doi.org/10.3390/cancers13030481.

    Article  CAS  PubMed  Google Scholar 

  42. Malcovati L, Porta MGD, Pascutto C, et al. Prognostic factors and life expectancy in myelodysplastic syndromes classified according to WHO criteria: a basis for clinical decision making. J Clin Oncol. 2005;23(30):7594–603. https://doi.org/10.1200/JCO.2005.01.7038.

    Article  PubMed  Google Scholar 

  43. Germing U, Strupp C, Kuendgen A, et al. Prospective validation of the WHO proposals for the classification of myelodysplastic syndromes. Haematologica. 2006;91(12):1596–604.

    PubMed  Google Scholar 

  44. Haase D. Cytogenetic features in myelodysplastic syndromes. Ann Hematol. 2008;87(7):515–26. https://doi.org/10.1007/s00277-008-0483-y.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Mansoor AM, Bharadwaj TP, Sethuraman S, et al. Analysis of karyotype, SCE, and point mutation of RAS oncogene in Indian MDS patients. Cancer Genet Cytogenet. 1993;65(1):12–20. https://doi.org/10.1016/0165-4608(93)90052-n.

    Article  CAS  PubMed  Google Scholar 

  46. Dakshinamurthy AG, Novitzky N, Bharadwaj R, Prakhya BM. Cytogenetic analysis of 52 Indian patients with de novo myelodysplastic syndromes-a comparative analysis of results with reports from Asia. Ann Hematol. 2005;84(5):298–303. https://doi.org/10.1007/s00277-004-0997-x.

    Article  PubMed  Google Scholar 

  47. Varma N, Varma S. Proliferative indices, cytogenetics, Immunophenotye and other Prognostic parameters in Myelodysplastic syndromes. Indian J Pathol Microbiol. 2008;51(1):97–101. https://doi.org/10.4103/0377-4929.40416.

    Article  PubMed  Google Scholar 

  48. Chaubey R, Sazawal S, Dada R, Mahapatra M, Saxena R. Cytogenetic profile of Indian patients with de novo myelodysplastic syndromes. Indian J Med Res. 2011;134:452–7.

    PubMed  PubMed Central  Google Scholar 

  49. Narayanan S. Clinical, hematological, and cytogenetic profile of adult myelodysplastic syndrome in a tertiary care center. J Blood Med. 2017;8:21–7. https://doi.org/10.2147/JBM.S129111.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Gangat N, Patnaik MM, Begna K, et al. Evaluation of revised IPSS cytogenetic risk stratification and prognostic impact of monosomal karyotype in 783 patients with primary myelodysplastic syndromes. Am J Hematol. 2013;88(8):690–3. https://doi.org/10.1002/ajh.23477.

    Article  PubMed  Google Scholar 

  51. Voso MT, Fenu S, Latagliata R, et al. Revised International Prognostic Scoring System (IPSS) predicts survival and leukemic evolution of myelodysplastic syndromes significantly better than IPSS and WHO Prognostic Scoring System: validation by the Gruppo Romano Mielodisplasie Italian Regional Database. J Clin Oncol. 2013;31(21):2671–7. https://doi.org/10.1200/JCO.2012.48.0764.

    Article  PubMed  Google Scholar 

  52. Della Porta MG, Tuechler H, Malcovati L, et al. Validation of WHO classification-based Prognostic Scoring System (WPSS) for myelodysplastic syndromes and comparison with the revised International Prognostic Scoring System (IPSS-R). A study of the International Working Group for Prognosis in Myelodysplasia (IWG-PM). Leukemia. 2015;29(7):1502–13. https://doi.org/10.1038/leu.2015.55.

    Article  CAS  PubMed  Google Scholar 

  53. Hou HA, Tsai CH, Lin CC, et al. Incorporation of mutations in five genes in the revised International Prognostic Scoring System can improve risk stratification in the patients with myelodysplastic syndrome. Blood Cancer J. 2018;8(4):39. https://doi.org/10.1038/s41408-018-0074-7.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Du MY, Xu M, Deng J, et al. Evaluation of different scoring systems and gene mutations for the prognosis of myelodysplastic syndrome (MDS) in Chinese population. J Cancer. 2020;11(2):508–19. https://doi.org/10.7150/jca.30363.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank Dr. Bijesh Yadav for his valuable suggestions regarding statistical analysis.

Funding

No funding was received for conducting this study.

Author information

Authors and Affiliations

  1. Department of Cytogenetics, Christian Medical College, Vellore, India

    Vivi M. Srivastava

  2. Department of Transfusion Medicine and Immunohaematology, Christian Medical College, Vellore, India

    Sukesh Chandran Nair

  3. Department of Biostatistics, Christian Medical College, Vellore, India

    Melvin Joy & L. Jeyaseelan

  4. Department of General Pathology, Christian Medical College, Vellore, India

    Marie-Therese Manipadam

  5. Department of Haematology, Christian Medical College, Vellore, India

    Uday P. Kulkarni, Anup J. Devasia, N.A Fouzia, Anu Korula, Kavitha M. Lakshmi, Aby Abraham & Alok Srivastava

  6. Leukaemia Research Cytogenetics Group, Centre for Cancer, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom

    Melvin Joy

  7. Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai Healthcare City, Dubai, UAE

    L. Jeyaseelan

Authors
  1. Vivi M. Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sukesh Chandran Nair
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melvin Joy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Marie-Therese Manipadam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Uday P. Kulkarni
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anup J. Devasia
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. N.A Fouzia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Anu Korula
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kavitha M. Lakshmi
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. L. Jeyaseelan
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Aby Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alok Srivastava
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

VMS: design, manuscript preparation, cytogenetic analysis, data analysis; SCN, MTM: Morphologic analysis, manuscript review; MJ, KML: Statistical analysis, data analysis; UPK, AK, AA: clinical data acquisition, manuscript review; AJD, FNA: clinical data acquisition, manuscript editing and review; LJ: Statistical analysis, manuscript review; AS: clinical data acquisition, literature search, manuscript editingand review. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Vivi M. Srivastava.

Ethics declarations

Ethics approval and consent to participate

This study was performed in accordance with the Declaration of Helsinki and was approved by the Institutional Review Board of the Christian Medical College, Vellore : IRB minute no. 13082 [Retro] June 2020.

Consent for publication

Approval for retrospective analysis granted by the Institutional Review Board of the Christian Medical College, Vellore as per institutional policy.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it.The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Srivastava, V.M., Nair, S.C., Joy, M. et al. Higher prevalence of poor prognostic markers at a younger age in adult patients with myelodysplastic syndrome – evaluation of a large cohort in India. Mol Cytogenet 17, 21 (2024). https://doi.org/10.1186/s13039-024-00687-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s13039-024-00687-z

Keywords

Molecular Cytogenetics

ISSN: 1755-8166