A Retrospective Study of the Clinical Profile and Outcome of Adult patients with Hypoplastic Myelodysplastic Syndrome (hMDS) in a Tertiary Centre in India.

Abstract

INTRODUCTION : Myelodysplastic syndromes (MDS) are a very heterogeneous group of clonal hematopoietic stem cell disorders that represents a spectrum of diseases characterized by; ineffective erythropoiesis and marrow failure limited by acute leukemias, chronic leukemias and myeloproliferative disorders at one end of the spectrum, in which hypercellular marrow is typical, to aplastic anemia at the other end. Hypoplastic Myelodysplastic syndromes (hMDS) refers to a morphological entity in which the bone marrow cellularity is low for the age (60 years). It represents approximately 10-15% of all MDS cases. Hypoplastic MDS however, does not represent a defined MDS category according to the WHO classification, but it rather denotes the morphologic status of other MDS categories. It is difficult to distinguish hMDS from acquired aplastic anemia (AA), because of considerable clinical, histologic, and cytologic similarities between the two disorders. Patients with hMDS tend to be younger, have more profound thrombocytopenia and neutropenia, lower percentage of blasts, lower probability to evolve to leukemia, and they are less likely to display abnormal karyotype, compared to patients with normocellular or hypercellular MDS. Compared to AA, hMDS have a poorer prognosis and have frequent karyotypic and FISH abnormalities and are prone to conversion to acute myeloid leukemia. The prognosis for hMDS falls between that of severe and very severe AA patients. The pathophysiology of hMDS is not very well known. Evidence suggests that immune mediated mechanisms may play a role. This subtype is most likely to respond to treatment with immunosuppressive agents. AIMS AND OBJECTIVES : 1. To analyze the clinical profile of adult patients with Hypoplastic Myelodysplastic syndrome (hMDS). 2. To assess the response to different drug therapies in patients with hMDS. 3. To identify the demographic, clinical, and laboratory parameters that can predict prognosis in hMDS. MATERIALS AND METHODS : This study protocol was approved by our Institutional Review Board (IRB). This is a retrospective analysis of patients diagnosed to have hMDS from January 1998 to June 2012. Diagnostic criteria: Hypoplastic MDS was diagnosed in patients presenting with cytopenia(s) (defined as per the recommendation in the IPSS for risk stratification in MDSs (i.e. Hemoglobin <10g%, Absolute neutrophil count <1800/mm3, and Platelets <100,000/mm3) associated with a hypoplastic bone marrow for the age, and with features of dysplasia in one or more cell lines, with or without increase in number of blasts/CD 34+ cells on bone marrow, or increase in reticulin content on bone marrow trephine, or abnormal karyotype showing malignant clonal cells (all favoring diagnosis of hMDS). Inclusion Criteria: 1. All adult patients (age≥18yrs) diagnosed to have hypoplastic myelodysplastic syndrome from January 1998 to June 2012. Exclusion Criteria: 1. Patients with other types of Myelodysplastic syndromes. 2. Patients with hMDS whose data are not retrievable. 3. Patients on drugs that can cause dysplasia (e.g. post renal transplant patients) 4. Patients with hypoplastic cytopenia(s) and positive test for PNH, or positive stress cytogenetic test (clastogenic stress-induced chromosomal breakage). RESULTS : Between January 1998 and June, 30, 2012, a total of 54413 out patients were seen in the Haematology department, of which 1225 (2.3%) were diagnosed to have primary MDS. Of this, 173 (14.1% of MDS; 0.32% of total patients) were diagnosed to have hypoplastic MDS. The year wise distribution of total MDS and hMDS is depicted in Figure:1. All patients (n=173) were included for the analysis of baseline characteristics. Out of the total 173 patients, only 111 (64.2%) who had a follow up of >8 weeks after initiation of treatment were considered ‘evaluable’ for assessment of response to treatment and for survival analysis. CONCLUSION : Hypoplastic MDS is a distinct subgroup of MDS of unknown etiology which needs to be distinguished from aplastic anemia. It is a disease associated with a relatively good prognosis, with significant response to immunosuppressive therapy and reasonable response to treatment with androgens, and a lower probability for leukemic transformation. Cytogenetic analysis at diagnosis is crucial in prognostic risk categorization of the patient. WHO classification based prognostic scoring system and revised IPSS appear to be better than IPSS in predicting survival