Myelodisplastic Syndrome: Is It Associated or Is It a Precursor of Myeloid Malignancies?.

Myelodisplastic syndrome (MDS) is a clonal haematopoietic stem cells disorder considered a pre-leukemic disease (about 30% of MDS turn into acute myeloid leukaemia (AML)) which is frequently associated with cytogenetic abnormalities and chromosomal instability: monosomy 7 or 7q - syndrome, 5q- syndrome, trisomy 8, inv(16), t (8;21), t (15;17), t (12;21), t (9;11), or sub microscopic DNA mutation of gene such as RAS, p53, FLT3, HSPA9, FMS and refractory cytopenias, with dysmyelopoiesis and increased apoptosis. We have identified 15 people aged between 54/67 years with MDS and we have examined their clinical presentation and their associated disorders.

• RA: refractory anaemia (7 patients)

• RARS: refractory anaemia with ringed sideroblasts (1 patient)

• 5q-syndrome (1 patient)

• RAEB refractory anaemia with excess blast: type 1 (5–10%) (3 patients); type 2 (11–20%) (1 patient) E) RAEB-T refractory anaemia in transformation (1 patient) F) CMML chronic myelomonocytic leukemia (1 patient)

The disease is characterized by chronic tiredness, headache, shortness of breath, increased susceptibility to infection especially in the lung with a prolonged fever, easy bruising, nosebleeds, pinpoint red spots, bleeding, splenomegaly, hepatomegaly, abdominal distress and pain are also common. VEGFR-1 and VEGFR-2 are strongly expressed in megakaryocytes, HLA-DR2 and HLA-DR15 are higher, immune dysfunction in MDS increases activated cytotoxic T-cells with higher percentage of CD8+CD28-, CD8+CD28- CD57+ with an increased level of CD4, and Fas ligand/Apo-1 (CD95). The RA, RARS, 5q-syndrome are more indolent disease with a lower rate of progression to AML and a prolonged clinical course; the RAEB, RAEB-T are slightly more advanced with a short course; in the CMML the progression is faster and it is frequently associated with the secondary chromosomal perturbation t(5;12), (q33;p13), or with the loss of specific portion 3p-, 7q- (7q22-7q33-). The goals of the therapy are to control symptoms and to decrease the progression to myelogenous leukaemia; our results show that a low intensity treatment in the low and intermediate groups with 5-azacitidine 75 mg/m2/day produces a high rate of response (72%, of which: complete remission: 18%, partial remission: 34%, improved: 20%), relapse 24%, disease-free survival at 3 years of 64%; with a low incidence of side effects (nausea 68%, vomiting 60%, chest pain 28%); on the other hand in the high risk group the 5-azacitidine with gentuzumab reverted to normal about 90% of the patients (complete remission: 6%, partial remission: 28%, improved: 56%), disease free survival at 3 years 52%, relapse 48%; however, the only curative treatment is stem cells transplantation from a tissue matching donor. Finally, it is very important to provide a supportive care with erythropoietin, G-CSF or GM-CSF, red cells transfusions, administration of broad-spectrum antibodies mostly for controlling symptoms, but also for preventing or treating complications.