This syndrome consists of a group of clonal haematopoietic disorders which represent steps in the progression to the development of leukaemia. Myelodysplastic syndrome (MDS)

It presents with consequences of bone marrow failure (anaemia, recurrent infections or bleeding), usually in older people (median age at diagnosis is 69 years). The overall incidence is 4/ in the population, rising to more than 30/ in the over-seventies

The blood film is characterised by 1- cytopenias 2-abnormal-looking (dysplastic) blood cells, including: macrocytic red cells and hypogranular neutrophils with nuclear hyper- or hyposegmentation. The bone marrow is hypercellular with dysplastic changes in all three cell lines. Blast cells may be increased but do not reach the 20% level which indicates acute leukaemia

1-MDS is associated with environmental exposures such as radiation and benzene; other risk factors have been reported inconsistently. Etiology

2-Secondary MDS occurs as a late toxicity of cancer treatment, usually with a combination of radiation and the radiomimetic alkylating agents such as busulfan, nitrosourea, or procarbazine (with a latent period of 5–7 years) or the DNA topoisomerase inhibitors (2 years).

3- Both acquired aplastic anemia following immunosuppressive treatment and Fanconi's anemia can evolve into MDS.

Anemia dominates the early course. Most symptomatic patients complain of the gradual onset of fatigue and weakness, dyspnea, and pallor, but at least one-half the patients are asymptomatic, and their MDS is discovered only incidentally on routine blood counts anemia or Fanconi's anemia. Clinical Features

. Previous chemotherapy or radiation exposure is an important historic fact. Fever and weight loss should point to a myeloproliferative rather than myelodysplastic process. Children with Down syndrome are susceptible to MDS, and a family history may indicate a hereditary form of sideroblastic anemia or Fanconi's anemia

The physical examination is remarkable for signs of anemia; approximately 20% of patients have splenomegaly. Some unusual skin lesions, including Sweet's syndrome (febrile neutrophilic dermatosis), occur with MDS. Autoimmune syndromes are not infrequent.

Skin lesions of Sweet syndrome may be few in number or numerous. They are characteristically tender and may be extremely painful. They persist for days to weeks. The limbs and neck are the most commonly affected sites, but other areas of skin and mucosa may be involved. In some patients, they arise only in sun-exposed areas. Sweet syndrome lesions may have a range of appearances.

Small papules (bumps) or vesicles (blisters) Larger thickened or swollen plaques (flat patches) or nodules (lumps) Pseudovesicular appearance (almost blistered) Annular (ring-shaped) lesions Erosions and ulcers resembling

Anemia is present in the majority of cases, either alone or as part of bi- or pancytopenia; isolated neutropenia or thrombocytopenia is more unusual. Macrocytosis is common, and the smear may be dimorphic with a distinctive population of large red blood cells. Platelets are also large and lack granules. In functional studies, they may show marked abnormalities, and patients may have bleeding symptoms despite seemingly adequate numbers Laboratory Studies Blood

. Neutrophils are hypogranulated; have hyposegmented, ringed, or abnormally segmented nuclei; contain Döhle bodies; and may be functionally deficient. Circulating myeloblasts usually correlate with marrow blast numbers, and their quantitation is important for classification and prognosis. The total white blood cell count (WBC) is usually normal or low, except in chronic myelomonocytic leukemia.

[MDS, REFRACTORY CYTOPENIA WITH MULTILINEAGE DYSPLASIA]. Refractory cytopenia with multilineage dysplasia (RCMD) is characterized by any combination of anemia, neutropenia, and thrombocytopenia and dysplasia in any two or all three marrow cell lines including erythroid, myeloid, and megakaryocytic lineages. Note dysplastic erythroid precursor with multi- nucleation and nuclear fragments (arrow) and dysplastic myeloid precursor with both eosinophilic and basophilic granulation (arrowhead).

The bone marrow is usually normal or hypercellular, but in 20% of cases it is sufficiently hypocellular to be confused with aplasia. No single characteristic feature of marrow morphology distinguishes MDS, but the following are commonly observed: dyserythropoietic changes (especially nuclear abnormalities) and ringed sideroblasts in the erythroid lineage; hypogranulation and hyposegmentation in granulocytic precursors, with an increase in myeloblasts; and megakaryocytes showing reduced numbers or disorganized nuclei. Megaloblastic nuclei associated with defective hemoglobinization in the erythroid lineage are common. Bone Marrow

Prognosis strongly correlates with the proportion of marrow blasts. Cytogenetic analysis and fluorescent in situ hybridization can identify chromosomal abnormalities.

Deficiencies of vitamin B12 or folate should be excluded by appropriate blood tests; vitamin B6 deficiency can be assessed by a therapeutic trial of pyridoxine if the bone marrow shows ringed sideroblasts. Marrow dysplasia can be observed in acute viral infections, drug reactions, or chemical toxicity but should be transient. More difficult are the distinctions between hypocellular MDS and aplasia or between refractory anemia with excess blasts and early acute leukemia. The WHO considers the presence of 20% blasts in the marrow as the criterion that separates acute myeloid leukemia (AML) from MDS. Differential Diagnosis

International Prognostic Scoring System (IPSS) for MDS Once a diagnosis of MDS is established, the doctor will calculate the IPSS score for each individual patient. The bone marrow blast percentage, chromosomal abnormalities and number of different blood types that are reduced determine the score. A score of 0 to 3.5 is assigned to each patient. Patients with lower score have a better prognosis and usually should not undertake treatment upon initial diagnosis. Patients with a higher score have more aggressive disease and should consider more aggressive treatment.

Prolymphocytic leukaemia This is a variant of CLL found mainly in males over the age of 60 years ;25% of the cases are of T –cell variety. There is a massive splenomegaly with little lymphadenopathy and a very high leucocyte count, often in excess of 400x 10 9, The characteristic cell is a large lymphocyte with prominent nucleolus.

This is a malignancy of medium-sized (about twice the size of a normal small lymphocyte), round lymphocytes with a prominent nucleolus and light blue cytoplasm on Wright's stain.

It dominantly affects the blood, bone marrow, and spleen and usually does not cause adenopathy. The median age of affected patients is 70 years and men are more often affected than women (male/female ratio is 1.6).

Clinical presentation is generally from symptoms of splenomegaly or incidental detection of an elevated WBC count. The clinical course can be rapid.

Nucleoside analogues like fludarabine and cladribine and combination chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisone, or CHOP) have produced responses. CHOP plus rituximab may be more effective than CHOP alone. Treatment :

but the disease is sufficiently rare that large series have not been reported. Splenectomy can produce palliation of symptoms but appears to have little or no impact on the course of the disease.

Treatment is generally unsuccessful and the prognosis very poor. Leukapharesis, splenectomy and chemotherapy May be tried

Hairy cell leukaemia This is a rare chronic lymphoprolifrative B-cell disorder. The male to female ratio is 6:1 and the median age at diagnosis is 50 years.

Some studies suggest that prior exposure to radiation and organic solvents is more frequent among HCL patients. Etiology Some investigators have speculated on an etiologic role for the Epstein-Barr virus in the development of HCL, but the proposal has been disputed.

Patients usually present with pancytopenia. Absolute neutropenia and Monocytopenia are nearly Constant features. The blood film and bone marrow biopsy contain hairy cell which are lymphocytes that have prominent cytoplasmic Projections and give the disease its name.

Clinical features: The diagnostic triad consist of pancytopenia, Splenomegaly and circulating hairy cells.

25%of patients present with fatigue and weakness. 25% present with easy bruising from thrombocytopenia or opportunistic infection from leucopenia, 25%present with early satiety or abdominal fullness from splenomegaly. 25%present with incidental finding of splenomegaly or abnormal blood count on routine examination for un unrelated condition.

Splenomegaly, which may be massive, is found in 90 percent of patients. Hepatomegaly can occur. Palpable superficial lymphadenopathy is uncommon and is usually localized when found. However, as a result of the routine use of computerized axial tomography scans in the evaluation of patients with lymphoproliferative disorders, significant deep adenopathy has been found to be present in up to one-third of patients with HCL.

In 3 % of patients, the disease manifests as a painful bony lesion (osteolytic) in the axial skeleton or long bones, most commonly involving the proximal femur.

Stages of Hairy Cell Leukemia Untreated hairy cell leukemia The hairy cell leukemia is newly diagnosed and has not been treated except to relieve signs or symptoms such as weight loss and infections. In untreated hairy cell leukemia, some or all of the following conditions occur: Hairy (leukemia) cells are found in the blood and bone marrow The number of red blood cells, white blood cells, or platelets may be lower than normal. The spleen may be larger than normal. Progressive hairy cell leukemia the leukemia has been treated with either chemotherapy or splenectomy and one or both of the following conditions occur: There is an increase in the number of hairy cells in the blood or bone marrow. The number of red blood cells, white blood cells, or platelets in the blood is lower than norm

Investigations: Sever neutropenia Monocytopenia The characteristic hairy cells in the blood film morphology and bone marrow. These cells usually type as B-lymphocytes And also characteristically express CD25 And CD103.

Laboratory Features Blood At the time of diagnosis, pancytopenia occurs in 50 percent of patients; the remaining half usually have bicytopenia.. Anemia is present in about three-quarters of patients and about one-third of patients have a hemoglobin of less than 9.0 g/dL.

treatment Over recent years a number of treatments Have been shown to produce long lasting Remissions. Cladribine and deoxycofromycin are Effective in producing long period of Disease control.

Treatment : 90% of patients require treatment at presentation or during the course of the disease. Indications : 1- anaemia when Hb% less than 8-10 g/dl. 2-thrombocytopenia when platelet countless than x10 /l. 3-Neutropenia with absolute neutrophil count less than x10/l, especially when associated with recurrent serious infection.