Sie sind auf Seite 1von 6

Hematology

ISSN: (Print) 1607-8454 (Online) Journal homepage: https://www.tandfonline.com/loi/yhem20

Myelodysplastic syndromes: classification and


prognostic scoring systems and their applicability
in Indian scenario-experience from a tertiary care
center

Rakhee Kar, Seema Rao & Renu Saxena

To cite this article: Rakhee Kar, Seema Rao & Renu Saxena (2009) Myelodysplastic syndromes:
classification and prognostic scoring systems and their applicability in Indian scenario-experience
from a tertiary care center, Hematology, 14:3, 145-149, DOI: 10.1179/102453309X402232

To link to this article: https://doi.org/10.1179/102453309X402232

Published online: 18 Jul 2013.

Submit your article to this journal

Article views: 55

View related articles

Citing articles: 6 View citing articles

Full Terms & Conditions of access and use can be found at


https://www.tandfonline.com/action/journalInformation?journalCode=yhem20
Myelodysplastic syndromes: classification
and prognostic scoring systems and their
applicability in Indian scenario-experience
from a tertiary care center
Rakhee Kar, Seema Rao and Renu Saxena
Department of Hematology, All India Institute of Medical Sciences, New Delhi, India

The myelodysplastic syndromes (MDS) are a group of clonal disorders characterized by


ineffective haematopoiesis, cytopenias, morphologic dysplasia and leukemic transformation.
Difficulties exist in classifying and prognosticating MDS. This study was done to evaluate FAB and
WHO classifications and the role of infection especially tuberculosis contributing to secondary
myelodysplasia. The clinico-hematological profile of all cases (n578) of MDS diagnosed over the
last one and a half years was analyzed. This included 73 cases of primary MDS and five cases of
infection associated myelodysplasia. There were 50 male and 28 female patients. Mean age at
presentation was 46.1 years (range: 9 to 82 years). Out of 73 cases, two progressed to AML
during the study period. Seventy cases could be classified based on FAB and 62 based on WHO
criteria. Five cases of FAB-RAEBt were AML by FAB. One case not classifiable as per FAB could
be categorized by WHO and four cases not classifiable as WHO could be categorized by FAB
classification. All fulfilled the minimal diagnostic criteria for MDS. The commonest subtype of MDS
was RA by FAB (55.7%) and RCMD (21%) and MDS-U (21%) by WHO. Four patients with
tuberculosis and one with HIV showed significant myelodysplasia along with reactive changes.
The consensus proposal of minimal diagnostic criteria for MDS was most helpful in cases difficult
to diagnose and classify. Coexisting infection especially tuberculosis causing secondary
myelodysplasia needs to be kept in mind especially in the Indian subcontinent.
Keywords: Myelodysplastic syndrome, classification, prognosis, tuberculosis

Introduction disease as patients present at a younger age with more


The myelodysplastic syndromes (MDS) are a hetero- severe disease and poorer response to treatment.1
geneous group of clonal disorders characterized by Another question which remains to be answered is
ineffective haematopoiesis, cytopenias, morphologic whether chronic infections such as tuberculosis which
dysplasia and a proclivity for transformation to acute are more common in a developing country like
leukemia. In general, myelodysplastic conditions are India alter the scenario? In addition, discrepancies
preleukemic disorders where the neoplastic clone is exist in classifying MDS as per different classification
established but not all cases of myelodysplasias systems.
terminate in acute leukemia. Indian MDS differs The first well defined classification system of MDS
from its western counterpart in terms of biology of which gained wide acceptance was the FAB classifi-
cation system2 which became a benchmark for
diagnosis and served as a rough predictor of
Correspondence to: Renu Saxena, MD, Professor and Head, Department prognosis. However, some pitfalls in the classification
of Haematology, IRCH Building, AIIMS, New Delhi 110029, India
E-mail: renusax@hotmail.com system came to light such as the terminology of
ß W. S. Maney & Son Ltd 2009
Received 2 June 2008; accepted 7 November 2008
DOI 10.1179/102453309X402232 Hematology 2009 VOL 14 NO 3 145
Kar et al. MDS: classification and prognostic scoring systems

refractory anemia,3 the arbitrary cut off of 30% blasts MDS/myelodysplasia diagnosed over the last one and
between MDS and AML4 and lack of allowance for a half years (Oct 2006–March 2008) at our institute.
unclassified patients.5 To address these and other The total number of cases clinically suspected to be
issues, the Society for Hematopathology and the MDS was 150 out of which 78 cases were analyzed
European Association of Hematopathologists jointly based on the of morphologic findings of significant
developed a classification of hematologic neoplasms dysplasia and no other marrow pathology. This
for the WHO6 which has gained wide acceptance as a included 73 cases of primary MDS and five cases of
classification system with prognostic value.5 In most infection associated myelodysplasia. The rest of the
cases, it is straightforward to diagnose MDS on the cases had absent/minimal myelodysplasia secondary
basis of WHO criteria. But in some cases it may still to other hematological disorder apparent on further
be difficult to arrive at a diagnosis of MDS and investigations which were excluded from further
categorize it further especially in patients with analysis. We also encountered two cases of persistent
cytopenias with minimal dysplasia or transfusion anemia refractory to treatment, with no other
dependent macrocytic anemia without karyotypic cytopenia, and negative for all tests and bone marrow
abnormalities and absent/minimal dysplasia which showing no dysplasia where clinical suspicion of
is negative for all further tests. Recently, a consensus MDS was strong. All cases were evaluated and
report from a working conference regarding minimal classified by two different observers based on the
diagnostic criteria for MDS has been proposed and morphologic findings of Jenner-Giemsa stained bone
for patients who do not fulfill these criteria the term marrow (BM) aspirate smears. Hematoxylin & eosin
idiopathic cytopenia of uncertain significance has and reticulin stained bone marrow biopsy smears
been suggested.7 were evaluated in cases if needed. There was a high
Staging or prognostic scoring strategies are helpful degree of interobserver concordance (96%). The few
in addressing a number of issues such as comparisons discrepant cases were resolved by joint conference
of results of different treatment approaches or in large and opinion from a third expert and consensus was
scale epidemiologic evaluations of changes in the reached.
incidence and disease outcome over time.8 During the
past quarter century, several staging systems in MDS Results
have been described that attempt to estimate the risk
There were 50 (64.1%) male and 28 (35.9%) female
of transformation to acute leukemia. One of these
patients with age ranging from 9 to 82 years. Mean
which gained wide acceptance was the Bournemouth
age at presentation was 46.1 years and median was
score of Mufti et al.9 based on hemoglobin, platelet
44.5 years. Six cases were pediatric patients with age
count, neutrophil count and per cent bone marrow
less than 17 years. Forty-three of our patients
blasts. In 1997, a group of investigators published the
required repeated blood transfusion (BT).
international prognostic scoring system10 based on
cytogenetic abnormalities, bone marrow blast percen- Classification of MDS cases (n571) as per FAB (n570) and
tage and the number of cytopenias. Recently Malcovati WHO (n562) criteria
et al.11 have developed WHO classification-based Out of 73 cases two cases progressed to AML during
prognostic scoring system (WPSS), which takes into the course of the study period and were excluded
account the WHO classification, transfusion require- from MDS classification and were included in the
ments, and the IPSS cytogenetic risk. category of secondary AML which was also meant
Keeping in view the difficulties in classifying and for accommodating cases of FAB-RAEBt diagnosed
prognosticating MDS and to ascertain if it makes any as AML in WHO (n55). Seventy cases could be
difference, our cases of MDS were classified as per classified based on FAB and 62 cases based on WHO
FAB and WHO criteria and Bournemouth prognos- criteria (Table 1). One case not classifiable as by FAB
tic scoring system was applied as cytogenetics was not could be categorized by WHO and four cases not
available in all cases. The role of infection especially classifiable by WHO could be categorized by FAB
tuberculosis contributing to significant myelodyspla- classification. The concordance and discordance in
sia was also evaluated. the two classification systems is presented in Table 2.
The six pediatric patients in our cohort were RA/RC/
Material and methods MDS-U (2 cases), RAEB/RAEB-2 (2 cases), RAEBt/
This was a retrospective study analyzing the AML (1 case), secondary AML (1 case) as per FAB/
clinico-hematological profile of all cases (n578) of WHO classification respectively. Transformation of

146 Hematology 2009 VOL 14 NO 3


Kar et al. MDS: classification and prognostic scoring systems

Table 1 MDS cases classified as per FAB and WHO Table 3 Transformation in MDS cases
criteria
Case FAB WHO
MDS cases as per FAB: (n570)
# RA-39 (RA-13, RA/RC-26) [55.7%] 1 RAEBRAML RAEB1RAML
# RARS-8 [11.4%] 2 RAEBtRAML RAEB2RAML
# RAEB-13 [18.6%] 3 RAEBRRAEBt RAEB2RAML
# RAEB t-8 [11.4%]
# CMML-2 [2.9%]
MDS cases as per WHO criteria: (n562) (granuloma, necrosis, AFB). All these cases were
# RA-6 [9.7%]
# RARS-6 [9.7%] advised close hematological follow-up for disappear-
# RCMD-13 [21%], RCMD-RS-2 [3.2%] ance of changes post-therapy. In seven cases of
# RAEB1-4 [6.5%] primary MDS/secondary AML, we had a past history
# RAEB 2-12 [19.4%]
# MDS-U-13 [21%] of tuberculosis with anti tuberculosis therapy. These
# 5q-syndrome-3 [4.8%] were RA/RC/MDS-U (1 case), RARS (1 case),
# MDS/MPD-3 [4.8%]
RAEB/RAEB-2 (2 cases), RAEBt/AML (2 cases),
secondary AML (1 case) as per FAB/WHO
MDS within our study period was seen in three cases respectively.
(Table 3).
Cases with unusual morphology
Cases not classifiable in one system reclassified in the There were two cases presenting with anemia and
other bone marrow showed erythroid hypoplasia (4 and
There was one case not classifiable by FAB. This 7%) with significant dyshematopoiesis. These were
patient presented with increasing weakness and categorized as MDS-RA by FAB and by WHO one
anemia requiring BT. Hemogram showed Hb case was categorized as 5q- and the other could not
6.8 g/dl, TLC-14 6103/ml with leukoerythroblastic be assigned any category. Two cases showed ery-
picture and platelet count of 5626103/ml. The throid hyperplasia (60 and 80%) with .5% blasts in
absolute monocyte count was 400/ml. Bone Marrow non-erythroid component. These were diagnosed as
was cellular, and showed significant dysmegakaryo- MDS-RAEB. One case showed 3% blasts with
poiesis and dysgraulopoiesis. This was classified as presence of Auer rods in occasional blast and was
MDS/MPD-U by WHO. There were four cases not diagnosed as RAEB t/ RAEB2 by FAB/WHO
classifiable by WHO. All cases presented with anemia respectively. One case showed cellularity ,20% with
requiring BT with significant bi/tri-lineage dysplasia significant dyshematopoiesis which was diagnosed as
in the bone marrow. All these were RA by FAB. All hypoplastic MDS.
these cases satisfied the minimal diagnostic criteria
Bournemouth scoring system
for MDS.7
Apart from the cases of 5q-, cytogenetics was
Myelodysplasia with associated infections available in five cases (three had normal cytogenetics,
Five patients with a known infection were evaluated one had complex cytogenetics and one case had
for associated cytopenias. Four patients had tuber- monosomy 7). Due to limited availability of cytoge-
culosis and one of them also had rheumatoid arthritis netics, IPSS scoring could not be applied universally.
and had received methotrexate earlier. One case was So Bournemouth scoring system was applied to all
HIV positive. In all these cases BM showed our cases classified as per FAB (Table 4) and WHO
significant dysplasia along with reactive changes (Table 5). As these cases were diagnosed in the
(monocytosis, plasmacytosis). However, there were previous one and half years, the follow-up was not
no changes attributable to infectious agent directly sufficiently long for survival statistics.
Table 2 FAB and WHO classification-concordance and discordance

FAB / WHO RA RARS RCMD RCMD-RS RAEB1 RAEB2 MDS-U 5q- MDS/MPD Sec AML Unclassified Total

RA 6 3 4 13
RA/RC 13 13 26
RARS 6 2 8
RAEB 4 9 13
RAEBt 3 5 8
CMML 2 2
Sec AML 2 2
Unclassified 1 1
Total 6 6 13 2 4 12 13 3 3 7 4

Hematology 2009 VOL 14 NO 3 147


Kar et al. MDS: classification and prognostic scoring systems

Discussion useful since we had one patient unclassified by FAB


Classification of diseases is a contentious process who could be assigned to this WHO category.
especially since many overlapping classification sys- One major problem faced in WHO was the
tems exist. Myelodysplastic syndrome is one such strictness of criteria for MDS-U. So in spite of
area where FAB classification existed long before having a category of MDS-U, four patients were still
WHO classification replaced it. In this study, the two not classifiable. These cases presented with only
classification systems were compared and relevant anemia with bi/tri-lineage dysplasia in the BM and
prognostic score was applied keeping in mind the could not fit into RA, RCMD and MDS-U as per the
limitation of lack of universally available cytogenetics criteria laid down.6 However, the consensus report by
facility There was a predominance of male patients Valent et al.7 helped in diagnosing these definitively
(64.1%) and the mean age (46.1 years) of presentation as MDS as they fulfilled the minimal diagnostic
was younger in conjunction with earlier reported criteria. We also encountered two cases of persistent
studies from our institute1,12 and from this region.13 anemia refractory to treatment, with no other
The present study enrolled 71 primary MDS patients cytopenia, negative for tests for PNH/ACD and bone
diagnosed over the last one and a half years. The marrow showing no dysplasia. These were fitting in
number of cases reported is significantly more the category of ICUS7 (Idiopathic cytopenia of
compared to other single institution data since this undetermined significance). Here a close hematologi-
is the largest tertiary care hospital where patients are cal follow-up was advised as suspicion of MDS was
referred from different regions of the country. strong.
The commonest subtype of MDS in this study was All cases of myelodysplasia are not MDS14 since it
RA by FAB (55.7%) where RA/RC comprised the could be secondary to some other etiology. In this
major portion. The split of the broad RA category of context infections play a major role and the common
FAB into simple RA and RA/RC (Table 2) is ones are leishmaniasis, HIV, tuberculosis and
deliberate as the latter group coincided with the malaria.14 Tuberculosis is much commoner in India
WHO RCMD and MDS-U categories similar to the than the west and in a previous case report MDS
study by Howe et al.5 where the major bulk of FAB associated with tuberculosis is reported which
RA was categorized as WHO RCMD. Consequently evolved into frank leukemia.15 In this study, there
the majority of our patients by WHO were either were five cases of diagnosed infection (4 tuberculosis,
RCMD (21%) characterized by cytopenias and bi/ 1 HIV) where bone marrow done for associated
multi-lineage dysplasia or MDS-U (21%) character- cytopenias showed significant myelodysplasia and
ized by cytopenias and unilineage dysplasia in reactive changes in the form of prominent monocytes
granulocytic or megakaryocytic series. When and lymphoplasmacytic cells. However, no pathology
Bournemouth scoring system was applied to our attributable to the infectious agent directly (granu-
cases as per FAB, the cases of RA/RC generally had loma, necrosis or AFB) was seen unlike leishmaniasis
score of 3 compared to RA with score of 1 and 2 where dyserythropoiesis along with the presence of
(Table 4). Similarly, when Bournemouth scoring LD bodies in the marrow is a known finding.16 In all
system was applied to our cases as per WHO, the these five cases close hematological follow-up was
cases of RCMD and MDS-U generally had score of 3 advised for the resolution of cytopenias and bone
compared to RA with score of 1 and 2 (Table 5) marrow dysplasia with therapy. Another interesting
thereby justifying the creation of a new category as it facet of this study was that seven cases diagnosed as
signifies higher risk. Again the split of RAEB into primary MDS had past history of intake of ATT.
RAEB 1 and 2 identifies patients with higher
prognostic score in RAEB 2 compared to RAEB1. Table 5 Bournemouth score applied to WHO
classification
The creation of the MDS/MPD category is also
WHO / Score 0 1 2 3 4
Table 4 Bournemouth score applied to FAB classification
RA 4 2
FAB / Score 0 1 2 3 4 RARS 1 5
RCMD 6 7
RA 9 4 RCMD-RS 1 1
RA/RC 3 7 16 RAEB1 1 2 1
RARS 2 6 RAEB2 1 5 6
RAEB 1 7 5 MDS-U 2 2 9
RAEBt 1 3 4 5q- 3
CMML 1 1 MDS/MPD 2 1

148 Hematology 2009 VOL 14 NO 3


Kar et al. MDS: classification and prognostic scoring systems

Although ATT especially isoniazid can cause limited availability of cytogenetics facility. So the old
acquired sideroblastic anemia14 which can be mis- Bournemouth score with the suggested modification
labeled as RARS, we encountered the entire spectrum of Bournemouth score along with BT Requirement
of MDS. In the Indian subcontinent TB/ATT may be and WHO subtype may be a good alternative to
an important contributor to secondary myelodyspla- WPSS in developing countries with limited resources.
sia even without direct evidence of TB in the marrow
thereby making it necessary to exclude the possibility References
of TB where clinically suspected before considering 1 Chatterjee T, Dixit A, Mohapatra M et al. Haematological and
histomorphological profile of adult myelodysplastic syndrome.
primary MDS. Study of 96 cases in a single institute. Eur J Haematol 2004; 73(2):
Myelodysplastic syndrome with red cell aplasia/ 93–97.
hypoplasia is an infrequently described entity and 2 Bennett JM, Catovsky D, Daniel MT et al. Proposals for the
classification of the myelodysplastic syndromes. Br J Hematol
may be mislabeled as PRCA. There were two cases 1982; 51: 189–199.
(2.8%) which fitted with the diagnosis, categorized as 3 Heaney ML, Golde DW. Myelodysplasia. N Eng J Med 1999; 340:
1649–1660.
FAB RA while by WHO one was 5q- and the other 4 Michaux JL, Martiat P. Chronic myelomonocytic leukemia
showing anemia with dysmegakarypoiesis and dys- (CMML)-a myelodysplastic or myeloproliferative syndrome?
granulopoiesis could not be categorized. A previous Leuk Lymphoma 1993; 9: 35–41.
5 Howe RB, Mac Donald AP, Wanat R, Tehranchi R, Hellstrom-
single institute study has reported 1.6% incidence.17 Lindberg E. The WHO classification does make a difference. Blood
Another study on pediatric MDS from North India 2004; 103: 3265–3270.
6 Harris NL, Jaffe ES, Diebold J et al. World Health Organization
reported three such cases among 13 patients diag- classification of neoplastic diseases of the hematopoietic and
nosed over 4 years.18 The exact mechanism of lymphoid tissues: report of the clinical advisory committee
meeting-Airlie House, Virginia, November 1997. J Clin Oncol
erythroid hypoplasia is unknown but presumably
1999; 17: 3835–3849.
has an autoimmune basis as a result of an intrinsic 7 Valent P, Horny H-P, Bennet JM et al: Definitions and standards
defect in the maturation and proliferation of ery- in the treatment of myelodysplastic syndromes: consensus state-
ments and report from a working conference. Leukemia Research
throid precursors as a part of the MDS.17 2007; 31: 727–736.
Prognostic scoring applied to FAB and WHO 8 Schiffer CA. World Health Organization and International
prognostic scoring system: the limitations of current classification
classifications showed higher scores with increasing systems in assessing prognosis and determining appropriate
order of MDS category, i.e. RAEB, RAEBt in FAB therapy in myelodysplastic syndromes. Semin Hematol 2008: 45:
and RAEB1 and 2 in WHO. However, this may 3–7.
9 Mufti GJ, Stevens JR, Oscier DG, Hamblin TJ, Machin D.
partly be due to the reason that the prognostic score Myelodysplastic syndromes: a scoring system with prognostic
itself takes into account some of the criteria taken to significance. Br J Haematol 1985; 59: 425–433.
10 Greenberg P, Cox C, LeBeau MM et al. International scoring
make the diagnostic categories. In other words, the system for evaluating prognosis in myelodysplastic syndromes.
diagnostic categories of MDS inherently have prog- Blood 1997; 89: 2079–2088. (Erratum in Blood 1998; 91: 1100)
nostic importance. A further refinement would be to 11 Malcovati L, Germing U, Kuendgen A et al. Time-dependent
prognostic scoring system for predicting survival and leukemic
include BT requirement to the prognostic score as evolution in myelodysplastic syndromes. J Clin Oncol 2007; 25:
done in the WPSS.11 This could also be applied to the 3503–3510.
12 Chatterjee T, Mahapatra M, Dixit A et al. Primary myelodysplas-
Bournemouth scoring system where cytogenetics is tic syndrome in children–clinical, hematological and histomorpho-
not available. In our series of 78 patients, 43 required logical profile from a tertiary care centre in India. Hematology
2005; 10(6): 495–499.
repeated blood transfusion. Since this is a recent 13 Dakshinamurthy AG, Novitzky N, Bharadwaj R, Prakhya BM.
study with limited follow up, survival data cannot be Cytogenetic analysis of 52 Indian patients with de novo
derived. Hence a longer duration study applying BT myelodysplastic syndromes-a comparative analysis of results with
reports from Asia. Ann Hematol 2005; 84(5): 298–303.
requirement to the prognostic score is warranted. 14 Mangles S, Bain BJ. When is myelodysplasia not a myelodysplastic
In conclusion, although WHO classification offers syndrome? In: Hematology Today 2008 by M. B. Agarwal, Pp-45–
51.
refinement over FAB, the consensus proposal of 15 Sen R, Yadav SS, Sen J, Singh S, Singh H. Myelodysplastic
minimal diagnostic criteria for MDS is most appro- syndrome and hypercoagulable state with Tuberculosis–a case
priate in difficult cases. Coexisting infection especially report. Ind J Tub 1991; 38: 29–32.
16 Kopterides P, Halikias S, Tsavaris N. Visceral leishmaniasis
tuberculosis causing secondary myelodysplasia needs masquerading as myelodysplasia. Am J Hematol 2003; 74: 198–199.
to be kept in mind especially in the Indian 17 Williamson PJ, Oscier DG, Bell AJ et al. Red cell aplasia in
myelodysplastic syndrome. J Clin Pathol 1991; 44: 431–432.
subcontinent. Regarding prognostic scoring, IPSS 18 Goyal R, Varma N, Marwaha RK. Myelodysplastic syndrome
and WPSS are difficult to apply universally due to with erythroid hypoplasia. J Clin Pathol 2005; 58: 320–321.

Hematology 2009 VOL 14 NO 3 149

Das könnte Ihnen auch gefallen