11 th lecture Chronic myeloid leukaemia By DR Fatehia Awny Faculty of Health Science Beirut Arab University

 CML is a clonal stem cell disorder characterised by increased proliferation of myeloid elements at all stages of differentiation.  Incidence increases with age, M > F. CHRONIC MYELOID LEUKEMIA

Chronic Myeloid Leukaemia C M L Is a rare form of leukaemia around 15% of leukaemia cases. C M L is characterised by an elevation in white cells consisting primarily of differentiated myeloid cells ( metamyelocytes,myelocytes, band,neutrophils & basophils ) In certain patients increase platelets & splenomegaly. 12/11/20173

CYTOGENETICS OF CML  Philadelphia (Ph) chromosome is an acquired cytogenetic abnormality in all leukaemia cells in CML  Reciprocal translocation of chromosomal material between chromosome 22 and chromosome 9. t(9;22)

Diagnosis of C M L Is very difficult and is assisted by the characterstic presence of pheladelphia chromosome ( ph ). This is result from translocation between chromosome No : 9 & chromosome No: 22. Part of chromosome 9 moved to chromosome 22 & on the other side part of ch 22 moved to ch 9 12/11/20175

The abnormal chromosome 22 is known as philadelphia chromosome. This is detected by fluorescent technique. 12/11/20178

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As the ph chromosome is an acquired abnormality of haemopoietic stem cells it is found in both myeloid, granulocytic, Erythroid, megakaryocytic,& lymphoid ( B & T cell lineage ). Clinical Picture :- Occurs in either sex. Male : Female /11/201710

Age :- 40 – 60 years. May occur in children, neonates & old. No predisposing factors but incidence increased in survivals of atomic bombs exposures in Japan. Symptoms :- 1- Weight loss, anorexia, night sweats. 2 – Splenomegaly. 12/11/201711

3- Features of anaemia,pallor, dyspnoea, tachycardia. 4- Bruising, epistaxis, haemorrhage ( low platelets count ). 5- Gout & renal impairment ( increase uric acid). 6- visual disturbances % of cases diagnosed during routine blood count. 12/11/201712

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Laboratory Findings :- 1- Leucocytosis > 50x 10 9 /L. Sometime up to 500x10 9 /L. Complete spectrum of myeloid cells is seen in peripheral blood level of neutrophils & myeloctes exceed those of blast cells & promyelocytes. 2-Increase circulating basophiles 3- Normocytic,normochromic anaemia. 12/11/201714

4- Platelets count may be increased,normal or decreased according to degree of BM infilteration. 5- Bone marrow is hyper cellular with granulocytic predominance. 6- ph chromosome in 98 % of cytogenic analysis. 7- Increase uric acid. Why ? Serum LDH elevated. 12/11/201715

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Transformation to an accelerate phase or acute leukaemia may occur Clinical out look & prognosis is now very good patient can expect long term control of disease.Chronic eosinophilic leukaemia is very rare. 12/11/201719

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1. LA P Score 2. Philadelphia Chromosome 3. Basophilia 4. Splenomegaly CML VS LEUKEMOID REACTION

CML & leukaemoid reaction CML WBC,s >50.000/cumm Myyeloid,neutrophils No toxic granulations. Basophils and neutrophils LAP score low. Bone marrow trilineage hyperplasia. Splenomegaly. Ph chromosome. Leukaemoid reaction <50.000/cumm. Band,neutrophils. Toxic granulations. No. LAP score high. Myeloid hyperplasia only. Normal.

LAP score or NAP score Leukocyte or neutrophil alkaline phosphatase. To differentiate between CML & leukaemoid reaction. It is a special granules found in the cytoplasm of neutrophils & bands. Variable intensity of blue staining. Can be seen in peripheral blood smear of patient with reactive leucocytosis.

Bone marrow or stem cells transplantation in leukemias Types of transplant 1.Autologous transplant 2.Allogeneic Transplant Purpose of transplant Autologous -To deliver a high dose of chemo to kill any residual cancer (lymphoma, multiple myeloma) Allogeneic -To eradicate residual leukemia cells -Graft vs leukemia effect

Bone marrow or PBSC transplantation in leukaemias Technique of transplantation  MHC + HLA matching(major histocompatibility complex, human leukocyte antigen ).  Chemotherapy  Total body irradiation  GVHD prophylaxis Complications of transplantation Prolonged BM suppression (graft failure) Serious infections Mucositis Graft versus host disease (GVHD)