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Year : 2009  |  Volume : 52  |  Issue : 2  |  Page : 206-209
An analysis of 30 cases of myelodysplastic syndrome

1 Saumrut Laboratory, 402, Narayan complex, Near Navrangpura Bus Stand, Ahmedabad - 380 009, India
2 Conemaugh Memorial Medical center, 1086 Franklin street, johnstown PA 15905

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Myelodysplastic syndrome (MDS) is a clonal disorder of pluripotential stem cells of the bone marrow. The purpose of the study was to obtain epidemiological data of MDS. Thirty cases of MDS presented from April 1998 to May 2006 are included in this study. Complete blood counts were performed in an automated cell counter. Bone marrow aspiration, trephine biopsy and chromosomal study were carried out. The dry film was stained using a Romanwasky stain and Perl's stain. Fifteen cases were male and 15 cases were female. The mean age at presentation was 55 years (range 8-73 years). A majority of the patients presented with weakness (63.33%). Autoimmune manifestations in the form of joint pain were present in 13.33%. Patients were symptomatic for a prolonged period before diagnosis could be reached (average 358.8 days). A majority of the patients had MDS-refractory anemia (MDS-RA) or MDS-RA with excess blasts( MDS-RAEB-2) at presentation. Three patients had chromosomal abnormalities (27.27%). Eight patients (26.7%) were relatively young at presentation, less than 50 years of age. Three (10%) were children.
A majority of the patients opted for symptomatic treatment only.

Keywords: Myelodysplastic syndrome, thalidomide, cyclosporine, ciprofloxacin, autoimmune

How to cite this article:
Shah NM, Prajapati SG, Adesara RP, Patel AP. An analysis of 30 cases of myelodysplastic syndrome. Indian J Pathol Microbiol 2009;52:206-9

How to cite this URL:
Shah NM, Prajapati SG, Adesara RP, Patel AP. An analysis of 30 cases of myelodysplastic syndrome. Indian J Pathol Microbiol [serial online] 2009 [cited 2022 Jan 28];52:206-9. Available from: https://www.ijpmonline.org/text.asp?2009/52/2/206/48919

   Introduction Top

Myelodysplastic syndrome (MDS) is a clonal disorder of pluripotential stem cells of the bone marrow. A majority of the patients are affected in the middle age. The onset of the disease before 50 years is uncommon except in cases preceded by irradiation or chemotherapy. The patient can be asymptomatic or can have severe pallor, weakness, loss of sense of well being and exertional dyspnea, repeated infective episodes or bleeding. Some patients have features of autoimmune inflammation (like arthralgia) as the initial presentation. Hepatomegaly occurs in about 5-10% of the patients.

WHO classification [1] is now replacing FAB classification [2] [Table 1] The International Prognostic Scoring System (IPSS) is used to predict the median survival and chances of evolution in acute myeloid leukemia (AML) and hence it is useful in deciding the type of therapy. [3] The only curative treatment of MDS is bone marrow transplantation. Various other treatments are used for palliation: anabolic steroids, corticosteroids, amifostine, ciprofloxacin, pentoxifylline, cytosine arabinoside, thalidomide, erythropoietin, etc.

   Materials and Methods Top

Thirty patients seen from April 1998 to May 2006 at the hematology clinic are included in this study. Complete blood counts were performed on an automated cell counter. Bone marrow was performed in 23 cases. Iliac crest was the preferred site for bone marrow. Injection Glycopyrolate was given subcutaneously as a premedication to prevent vaso vagal shock. The procedure was performed as an outpatient procedure where local anesthesia was given. Short general anesthesia (Ketamine + midazolam) was used in uncooperative patients or children. Aspiration was performed followed by trephine from the same site but from different points. Bone marrow sample for cytogenetics study was also collected. Dry films were stained using a Romanwasky stain and Perl's stain.

Trephine biopsy specimens were decalcified and embedded in paraffin wax. Thin sections were cut and stained with hematoxylin and eosin.

Chromosomal study was performed in 12 cases. Bone marrow cells were collected in the collection medium and grown in RPMI 1640 (Himedia, Mumbai, India) supplemented with 20% fetal calf serum (Centron, Pune, India) for 24 h as per the standard protocol. The chromosome banding was performed using trypsin-giemsa staining. At least 20 well-spread metaphase plates were analyzed from each sample and three to four well-spread plates were photographed and karyotyped.

Response evaluation criteria [4]

The hematologic response was evaluated using the International Working Group criteria.

The erythroid response was classified as follows:

Major response:

  1. Increase in hemoglobin level > 2g/dL (pre-treatment level < 11gm%).
  2. Independence from red blood cell transfusions for transfusion-dependent patients.

Minor response:

  1. Increase in the hemoglobin level by 1-2 g/dL (pre-treatment level <11gm%).
  2. Decrease in the transfusion requirement by 50%.

The platelet response was identified as follows:

Major response:

  1. An absolute increase of 30,000/無 or more (pre-treatment platelet count <100,000/無).
  2. For the platelet transfusion-dependent patients, stabilization of the platelet counts and independence from transfusion.

Minor response:

  1. Increase in the platelet count by 50% or more with a net increase >10,000/無 but <30,000/無 (pre-treatment platelet count <100,000/無).

The neutrophil response was classified as follows:

Major response:

1. At least a 100% increase or an absolute increase of >500/無 (an absolute neutrophil count <1,500/無 before therapy).

Minor response:

2. An absolute neutrophil count increase of at least 100%, but an absolute increase <500/無 (an absolute neutrophil count <1,500/無 before therapy).

To be considered as a major or minor improvement, the hematologic improvements must have lasted for at least 2 months in the absence of therapy.

   Results Top

Thirty cases of MDS from April 1998 to May 2006 are included in this study. Fifteen were male and 15 were female, with a mean age of 55 years (range 8-73 years).

Pallor was present in 63.33% of the patients, 10% had bleeding from various sites, 6.66% had splenomegaly and 10% had hepatomegaly. Follow-up revealed weight loss in 30%, ashen grey skin in 3.33%, weakness in 16.66%, hepatomegaly in 3.33% and lymphadenopathy in 3.33%.

Patients were symptomatic for 358.8 days (range 1-7300 days) before diagnosis was made.

Pancytopenia was present in 37%, bicytopenia in 40.75%, anemia in 70%, leucopoenia in 46.66% and thrombocytopenia in 53.33%.

Cellularity of bone marrow was as follows: hypercellular 65.21%, cellular 8.66%, dry tap 21.79% and hypocellular 4.34%. Megakaryocytes were adequate in 34.78%, reduced in 30.43%, increased in 21.7% and absent in 13.03%. Myeloid dysplasia was present in 60.86%, which includes hypogranular cytoplasm, hypergranular cytoplasm, pelger-huet anomaly and large size of the cells. 4.34% had megakaryocytic dysplasia. Trephine biopsy measured 0.5-1.5 cm in length [Table 2].

A majority of the patients had myelodysplastic syndrome refractory anemia (MDS-RA) or myelodysplastic syndrome refractory anemia with excess blasts-2 (MDS-RAEB-2) at presentation [Table 3].

Chromosomal study was carried out in 12 cases. Three patients had complex chromosomal abnormalities (25%), eight had normal chromosomal study (66.66%) and in one case metaphases could not be obtained. The following abnormalities were seen in three patients:

Patient 1: 46, XY, -5, -7, -13, + marker I, II, III.

Patient 2: 46 XY, inv (3), (q 12, q 26).

Patient 3: 43-45, X, -5, -7, -22, + marker 1 and 2.

Of the 30 cases, according to the IPSS scoring, three cases were of low risk, 11 cases were of intermediate risk-I, eight cases were of intermediate risk-II and three cases were of high risk.

   Discussion Top

Weakness (46.66%) and breathlessness on exertion (16.66%) were the major complains on presentation. Bleeding (10%) and joint pain (3.33%) at presentation was uncommon. Ten percent of the patients developed joint pain on follow-up. Thus, 13.33% of the patients had autoimmune manifestations (AIMs) in the form of joint pain. This incidence is similar to the reported incidence of 18.7% by Giannouli et al. [5]

A majority of the patients were >50 years. However, three patients were children and five patients were less than 50 years of age. This finding is unlike the observation of the western literature. [6] A high incidence of MDS in relatively young patients is previously reported from India. [7]

Our series had more female patients (male:female ratio = 1:1), unlike the published literature. [6],[7]

A majority of the patients had a long history of symptoms (average 358.8 days) and 13 (43.3%) cases had a previous history of blood transfusions before the diagnosis. This is due to the lack of diagnostic facility or lack of awareness among the clinicians.

Of the 30 cases, seven patients were not classified into subgroups as bone marrow was performed elsewhere and slides/blocks were not available for review. A majority of the patients had MDS-RA, MDS-RAEB-1 and MDS-RAEB-2. The diagnosis of MDS was mainly based on morphology as cytogenetic study was performed in only 12 patients due to economical reasons. Only one patient had eosinophilia and none had basophilia. This is in contrast to the higher incidence (12.5% for eosinophilia and 11.8% for basophilia) reported by Takafumi et al. [8] One patient, a 53-year-old female, had severe erythroid hypoplasia (3% only) but she had thrombocytopenia (platelet count 30,000/cmm), 16% blasts and dysplasia and hence it was not confused with pure red cell aplasia. MDS with erythroid hypoplasia is uncommon and is reported in the literature also. [9]

Cytogenetic study could be performed in only 12 patients due to economical constraints. Two had poor cytogenetic abnormalities (Patient 1: 46, XY, -5, -7, -13, + marker I, II, III; Patient 2: 43-45, X, -5, -7, -22, + marker 1 and 2) while one had intermediate abnormality (46 XY, inv [3], [q 12, q 26]). Only 27.27% of the patients (three of the 11cases, one culture failed) had cytogenetic abnormalities. This is very low compared with the reported incidence of 53% by Takafumi et al. [8] but a similar low incidence of 33.82% is reported from India. [10]

According to the International Working Group criteria, two patients responded to the treatment. One patient had minor response in platelets with anabolic steroids (56 days) and prednisolone after 2 months of treatment. Another patient had major response in hemoglobin and minor response in platelet count after treatment of prednisolone (95 days), anabolic steroids-stenazolol (90 days) and ciprofloxacin (32 days).

Two patients had improvement in hemoglobin with hematinics as they had associated iron deficiency. One patient had a hemoglobin rise of 1gm% and in another it was 7gm%. None of the patients received any other treatment except hematinics. The patient with the hemoglobin rise of 7gm% was a 64-year-old male having MDS-RAEB-1. His marrow showed reduced iron stores. His hemoglobin became normal with iron therapy without any improvement in white cells or platelets with follow-up of 53 months. Maria Concetia Petti et al. reported a durable spontaneous improvement and there was improvement in all the three cell lines. [11] In our case, there was only improvement in hemoglobin. This could be because of the associated iron deficiency rather than spontaneous remission. Iron deficiency in our patient was nutritional and he had no evidence of hemolysis, blood loss or paroxysmal nocturnal hemoglobinuria clone.

One patient had improvement in hemoglobin of 2gm% after treatment with folic acid, vitamin B12 and prednisolone due to associated immune hemolytic anemia.

A 17-year-old female presented with fever, hepatosplenomegaly, pallor and knuckle pigmentation. Her hemoglobin was 6.2gm%, white blood cell was 0.67 10 9 /L (ANC-201) and platelet count was 14 10 9 /L. She received antibiotics + parentral B12 + folic acid. Her fever subsided and white cells improved to 2.73 10 9 /L (ANC-1283), but there was no improvement in hemoglobin or platelet count. Bone marrow at this stage confirmed the diagnosis of MDS-RAEB-2. Pancytopenia with marrow dysplasia is reported with infection and autoimmune disorders like ITP and systemic lupus erythematosis, but blast% is usually < 5%, whereas our patient had 12% blasts. [12] Her leucopenia and neutropenia at presentation were due to infection, which improved promptly with antibiotics.

Two patients did not respond to cyclosporin, anabolic steroids (stenazolol), ciprofloxacin, etoposide, erythropoietin, cyclophosphamide and thalidomide.

A majority of the patients opted for the palliative therapy, as evident from [Table 4]. The reason for opting for the palliation was economical in most of the cases while in old patients there was reluctance for hospital admission and intravenous chemotherapy.

Sixty percent of the patients were lost to follow-up and hence were not evaluable. Four (13.33%) patients expired due to septic shock, disseminated intravascular coagulation and intracranial bleeding.

The median follow-up was 128.9 days (0-970 days). The median survival was 119.2 days for RA (0-515 days), 302.7 days for RAEB-1 (0-970 days), 233.7 days for RAEB-2 (0-515 days) and 165 days for RA with multilineage dysplasia (0-330 days).

   Conclusions Top

MDS is not uncommon in the younger population (10% of the patients were < 18 years of age and 16.7% of the patients were < 50 years of age). Most of the patients were diagnosed late (average 358.8 days). AIMs are frequent in MDS (13.33%). All the patients opted for less-aggressive oral therapy for economical reasons.

   Acknowledgement Top

We are thankful to Dr. Freny Sheth, Genetic center, 20/1,Bimanagar, Ahmedabad - 380015 for doing chromosomal study, Mohak N.Patel for data compilation, analysis & manuscript preparation and all the patients whose data is included in this study.

   References Top

1.Vardiman JW, Harris NL, Brunnig RD. The World Health Organization (WHO) classification of the myeloid neoplasms. Blood 2002:100:2292-302.  Back to cited text no. 1    
2.Bennett JM, Catovsky D, Daniel MT, Flandrin G, Galton DA, Gralnick HR, et al . Proposals for the classification of the myelodysplastic syndromes. Br J Haematol 1982;51:189-99.  Back to cited text no. 2  [PUBMED]  
3.Greenberg P, Cox C, LeBeau MM, Fenaux P, Morel P, Sanz G, et al . International scoring system for evaluating prognosis in myelodysplastic syndromes. Blood 1997:89:2079-88.  Back to cited text no. 3    
4.Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, et al . World Health Organization (WHO) international working group: Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood 2000;96:3671-4.  Back to cited text no. 4  [PUBMED]  
5.Giannouli S, Voulgarelis M, Zintzaras E, Tzioufas AG, Moutsopoulos HM. Autoimmune phenomena in Myelodysplastic syndromes: A 4-year prospective study. Rheumatology (Oxford) 2004:43:626-32.  Back to cited text no. 5    
6.Lichtman MA, Brennan JK. Myelodysplastic disorders (Indolent clonal myeloid diseases and oligoblastic leukemia). In: Beutler E, Lichtman MA, Coller BS, editors. William′s hematology. 6 th ed. McGraw-Hill; 2001.p. 1029-46.  Back to cited text no. 6    
7.Das K, Das A, Samantray S, Satpathy S, Mohanty AK. An analysis of the Haematologic spectrum of Myelodysplastic syndrome-An institutional study. Indian J Haematol Blood Transf 2003;21:138-40  Back to cited text no. 7    
8.Matsushima T, Handa H, Yokohama A, Nagasaki J, Koiso H, Kin Y, et al . Prevalence and clinical characteristics of myelodysplastic syndrome with bone marrow eosinophilia or basophilia. Blood 2003;101:3386-90.  Back to cited text no. 8  [PUBMED]  
9.Goyal R, Varma N, Marwaha RK. Myelodysplastic syndrome with erythroid hypoplasia. J Clin Pathol 2005;58:320-1.  Back to cited text no. 9  [PUBMED]  [FULLTEXT]
10.Indian Council of Medical Research. Cytogenetic study of myelodysplastic syndrome. Available from: http://www.icmr.nic.in/annual/iih/2003-04/p4.pdf.  Back to cited text no. 10    
11.Petti MC, Latagliata R, Breccia M, Alimena G, Spadea A, D′Andrea M, et al . Spontaneous remission in adult patients with de novo myelodysplastic syndrome: A possible event. Haematologica 2001;86:1277-80.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Oka Y, Kameoka J, Hirabayashi Y, Takahashi R, Ishii T, Sasaki T, et al . Reversible bone marrow dysplasia in patients with systemic lupus erythematosus. Inter Med 2008;47:737-42.  Back to cited text no. 12    

Correspondence Address:
Ashwin P Patel
402, Narayan Complex, Near Navrangpura Bus Stand, Ahmedabad - 380 009
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.48919

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  [Table 1], [Table 2], [Table 3], [Table 4]

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