Myelodysplastic syndromes

Post by Subramani

Myelodysplastic syndrome (MDS) refers to a group of clonal stem cell disorders characterized by maturation defects resulting in ineffective hematopoiesis and an increased risk of transformation to AML. In patients with MDS, the bone marrow is partly or wholly replaced by the clonal progeny of a mutant multipotent stem cell that retains the capacity to differentiate into red cells, granulocytes, and platelets, but in a manner that is both ineffective and disordered. As a result, the bone marrow is typically hypercellular or normocellular, but the peripheral blood shows pancytopenia. MDS arises in two distinct settings:

Idiopathic or main MDS,occuring mainly in patients over age 50, frequently develops insidiously.

Therapy related MDS (t-MDS), a complication of previous myelosuppressive drug or radiation therapy, typically appears 2 to 8 years soon after exposure.

All forms of MDS can transform to AML, but transformation occurs most rapidly and with highest frequency in patients with t-MDS. Although characteristic morphologic adjustments are normally seen in the marrow and the peripheral changes are typically seen in the marrow and the peripheral blood, definitive diagnosis regularly demands correlation with other laboratory tests. Cytogenetic analysis is particularly helpful in confirming the diagnosis becauswe certain chromosomal aberrations are typically observed.

The pathogenesis of MDS is unknown. Although the marrow is typically hypercellular at diagnosis it could also be normocellular or, less commonly, hypocellular. Given this, the usual explanation for suppression of normal hematopoiesis (crowding out of regular elements) is challenging to apply, leading to the suggestion that MDS might arise out of a background of stem cell damage. Both main MDS and t-MDS occuring right after exposure to radiation or alkylating chemotherapeutic drugs are linked with comparable clonal chromosomal abnormalities, including monosomy 5 and monosomy 7 deletions of 5q and 7q trisomy 8 and deletions of 20q

Clinical Course

Primary MDS affects primarily individuals older than 60 years of age. As in acute leukemia patients with this disorder present with weakness, infections, and hemorrhages, all owing to pancytopenia. Approximately half of the patients are asymptomatic, and the disease is discovered following incidental blood tests.

On the basis of particular morphologic functions in the marrow and peripheral blood, primary MDS is divided into five categories, every with a somewhat diverse risk for transformation to overt AML. In general subtypes that are defined by having a higher proportion of blast cells in the marrow or peripheral blood are linked with a poorer prognosis. The presence of several clonal chromosomal abnormalities and the severity of peripheral blood cytopenias are independent risk aspects that also portend a worse outcome.

The median survival in primary MDS varies from 9 to 29 months, but some individuals in good prognostic groups could live for 5 years or more. Overall, progression to AML occurs in 10 to 40% of individuals and is usually accompanied by the appearance of extra clonal cytogenetic modifications. Other patients succumb to complications of thrombocytopenia (bleeding) and neutropenia (infection). The outlook is even far more grim in ptients with t-MDS, who have an overall median survival of only 4 to 8 months. Cytoopenias tend to be far more severe than in primary MDS, and many patients progress rapidly to AML.

Treatment choices in MDS are limited. In younger patients, allogeneic bone marrow transplantation provides some hope for reconstitution of typical hematopoiesis and long term survival. Older patients with MDS are treated supportively with antibiotics and blood product transfusions.

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