Leukaemias
What are Leukemias
Neoplasm of white blood cell and its precursor
Clonal proliferations and accumulation of cells in marrow
Classify as
· Acute leukaemias
· Chronic leukaemias
Types of Leukaemia
Introduction- CML
· Clonal malignant myeloproliferative disorder characterized by increased proliferation of the granulocytic cell line without the loss of their capacity to differentiate
· Results in increases in myeloid cells, erythroid cells and platelets in peripheral blood and marked myeloid hyperplasia in the bone marrow
· Originate in a single abnormal haemopoietic stem cell
· Incidence :1 per 100,000 (UK)
· Accounts for 7-15% of all leukaemia in adults
· Median age : 53 years
· All age groups, including children, can be affected
Etiology
· Not clear
· Little evidence of genetic factors linked to the disease
· Increased incidence
o Survivors of the atomic disasters at Nagasaki & Hiroshima
o Post radiation therapy
Leukaemogenesis
· Philadelphia chromosome is an acquired cytogenetic anomaly that is characterizes in all leukaemic cells in CML
· 90-95% of CML pts have Ph chromosome
· Reciprocal translocation of chromosome 22 and chromosome 9
· BCR (breakpoint cluster region) gene on chromosome 22 fused to the ABL (Ableson leukemia virus) gene on chromosome 9
· Ph chromosome is found on myeloid, monocytic, erythroid, megakaryocytic, B-cells and sometimes T-cell proof that CML derived from pluripotent stem cell
· Molecular consequence of the t(9;22) is the fusion protein BCR–ABL, which has increased in tyrosine kinase activity
· BCR-ABL protein transform hematopoietic cells so that their growth and survival become independent of cytokines
· It protects hematopoietic cells from programmed cell death (apoptosis)
Clinical Features
o Disease is biphasic, sometimes triphasic
o 40% asymptomatic
o Chronic phase
o Splenomegaly often massive
o Symptoms related to hypermetabolism
o Weight loss
o Anorexia
o Lassitude
o Night sweats
o Features of anaemia
o Pallor, dyspnoea, tachycardia
o Abnormal platelet function
o Bruising, epistaxis, menorrhagia
o Hyperleukocytosis
o thrombosis
o Increased purine breakdown : gout
o Visual disturbances
o Priapism
o Lab features
o Peripheral blood film
o Anaemia
o Leukocytosis (usu >25 x 109/L, freq> 100 x 109/L
o WBC differential shows granulocytes in all stages of maturation
o Basophilia
o thrombocytosis
o Bone marrow
o Hypercellular (reduced fat spaces)
o Myeloid:erythroid ratio – 10:1 to 30:1 (N : 2:1)
o Myelocyte predominant cell, blasts less 10%
o Megakaryocytes increased & dysplastic
o Increase reticulin fibrosis in 30-40%
o Other lab features :
o NAP reduced
o Serum B12 and transcobalamin increased
o Serum uric acid increased
o Lactate dehydrogenase increased
o Cytogenetic : Philadelphia chromosome
Laboratory- summary
Lab investigation to confirm diagnosis
Full blood picture
Neutrophil alkaline phosphatase
Bone marrow cytogenetic
Phases
Accelerated phase
Median duration is 3.5 – 5 yrs before evolving to more aggressive phases
Clinical features
Increasing splenomegaly refractory to chemo
Increasing chemotherapy requirement
Lab features
Blasts>15% in blood
Blast & promyelocyte > 30% in blood
Basophil 20% in blood
Thrombocytopenia
Cytogenetic: clonal evolution
Phases
Blastic phase
Resembles acute leukaemia
Diagnosis requires > 30% blast in marrow
2/3 transform to myeloid blastic phase and 1/3 to lymphoid blastic phase
Survival : 9 mos vs 3 mos (lym vs myeloid)
General Management
o Discussion with family
o The disease & diagnosis
o Prognosis
o Choices of treatment
§ Cytotoxic drug vs bone marrow transplant
§ Side effect
o CML - principles of treatment
o Relieve symptoms of hyperleukocytosis, splenomegaly and thrombocytosis
o Hydration
o Chemotherapy (bulsuphan, Hydoxyurea)
o Control and prolong chronic phase (non-curative)
o alpha interferon+chemotherapy
o imatinib mesylate
o chemotherapy (hydroxyurea)
o CML - principles of treatment
o Treatment cont…
o Eradicate malignant clone (curative)
o allogeneic transplantation
o alpha interferon ?
o imatinib mesylate/STI 571 ?(Thyrosine kinase inhibitor)
o Chemotherapy
o Busulphan
o Alkylating agent
o Preferred in older pts (not candidate for transplant)
o Side effect :
§ prolonged myelosuppression
§ Pulmonary fibrosis
§ Skin pigmentation
§ infertility
o Chemotherapy
o Hydoxyures
o Fewer side effect
o Acts by inhibiting the enzyme ribonucleotide reductase
o Haematological remissions obtain in 80% for both drugs
o However disease progression not altered and persistence of Ph chromosome containing clone
o Chemotherapy
o Recombinant human α- Interferon
o Prolong chronic phase and increase survival
o Haematogical and cytogenetic remission
o Side effect
§ Flu like symptoms
§ Fever and chills
§ Anorexia
§ Depression
o CML - prognosis
o Median survival 3.5 yrs (range 2-8 yrs)
o Interferon + chemotherapy :6 years
o Transplant : 5+ years
o imatinib mesylate ?
Irrespective of receiving daily oral or future injectable depot therapies, these require health care visits for medication and monitoring of safety and response. If patients are treated early enough, before a lot of immune system damage has occurred, life expectancy is close to normal, as long as they remain on successful treatment. However, when patients stop therapy, virus rebounds to high levels in most patients, sometimes associated with severe illness because i have gone through this and even an increased risk of death. The aim of “cure”is ongoing but i still do believe my government made millions of ARV drugs instead of finding a cure. for ongoing therapy and monitoring. ARV alone cannot cure HIV as among the cells that are infected are very long-living CD4 memory cells and possibly other cells that act as long-term reservoirs. HIV can hide in these cells without being detected by the body’s immune system. Therefore even when ART completely blocks subsequent rounds of infection of cells, reservoirs that have been infected before therapy initiation persist and from these reservoirs HIV rebounds if therapy is stopped. “Cure” could either mean an eradication cure, which means to completely rid the body of reservoir virus or a functional HIV cure, where HIV may remain in reservoir cells but rebound to high levels is prevented after therapy interruption.Dr Itua Herbal Medicine makes me believes there is a hope for people suffering from,Parkinson's disease,Schizophrenia,Lung Cancer,Breast Cancer,Lupus,Lymne Disease,psoriasis,Colo-Rectal Cancer,Blood Cancer,Prostate Cancer,siva,Epilepsy Dupuytren's disease,Desmoplastic small-round-cell tumor Diabetes ,Coeliac disease,Brain Tumor,Fibromyalgia,Alzheimer's disease,Adrenocortical carcinoma Infectious mononucleosis. .Asthma,Allergic diseases.Hiv_ Aids,Herpe ,Copd,Glaucoma., Cataracts,Macular degeneration,Cardiovascular disease,Lung disease,Enlarged prostate,Osteoporosis,Dementia.(measles, tetanus, whooping cough, tuberculosis, polio and diphtheria),Chronic Diarrhea,Hpv,All Cancer Types,Diabetes,Hepatitis, I read about him online how he cure Tasha and Tara so i contacted him on drituaherbalcenter@gmail.com / . even talked on whatsapps +2348149277967 believe me it was easy i drank his herbal medicine for two weeks and i was cured just like that isn't Dr Itua a wonder man? Yes he is! I thank him so much so i will advise if you are suffering from one of those diseases Pls do contact him he's a nice man.
BalasHapus