Flashcards in Chapter 13: Chronic Myeloid Leukemias Deck (25):
What are chronic myeloid leukemias?
Leukemias characterized by a slower progression than acute leukemias. Chronic leukemias are also harder to cure
From what cell type does CML usually originate?
CML is a clonal disorder of pluripotent stem cells.
CML makes up what proportion of all leukemias?
What genetic abnormality is most commonly associated with CML?
Ph t(9; 22) philadelphia chromosome. This causes a fusion gene BCR-ABL which has excessive tyrosine kinase activity. (found in both myeloid and lymphoid cell lines)
What methods can be used to diagnose CML?
(1) microscopic karyotype analysis (in minority of patients.
What causes most of the clinical features associated with CML?
A substantial increase in total myeloid cell mass is responsible for the clinical features of CML.
What is the epidemiology of CML?
CML occurs in either sex, and is most prevalent between the ages of 40 and 60 years old. (can occur in all ages)
What are the signs and symptoms of CML?
(1) hypermetabolism (anorexia, weight loss)
(3) Anemia (pallor, dyspnea, tachycardia)
(4) Bruising, hemorrhage (abnormal platelet function)
(5) Gout (hyperuremia from purine breakdown)
(6) Visual disturbances and priapism (rare)
What are the laboratory findings of CML?
(1) WBC is high
(2) Basophils are high
(3) Normochromic, normocytic anemia
(4) Platelet count may be lower or higher (most common)
(5) Neutrophil ALP score is invariably low.
(6) Bone marrow is hypercellular with granulopoietic dominance.
(7) Philadelphia chromosome
(8) serum uric acid increased.
What is the first line treatment of chronic phase CML?
Imatinib is a tyrosine kinase inhibitor that is specific for BCR-ABL. It blocks the ATP binding site on BCR-ABL. Allopurinol may also be given to reduce hyperuricemia and gout.
What are some adverse effects of Imatinib?
(1) skin rash
(3) Muscle pains
G-CSF may be given to help manage the neutropenia.
How is a complete cytogenetic response to treatment defined?
The complete absence of Ph+ metaphases on cytogenetic analysis.
How is suboptimal response defined?
Failure to achieve significant or complete cytogeneticresponse after 6 months.
How are patients with sub-optimal treatment response managed?
(1) They are given alternative tyrosine kinase inhibitors (dasatinib, nilotinib)
(2) they may have their imatinib dose increased.
(3) Allogenic stem cell transplant.
What alternative second line chemotherapeutics may be used?
(1) hydroxyurea (can control WBC count) (needs to be given indefinitely)
(2) Busulfan (serious long term side effects)
(3) alpha-interferon (used after hydroxyurea to keep WBC low) (causes flu like symptoms)
What is the only established curative treatment for CML?
Stem cell transplant.
What is the age cutoff for stem cell transplant?
Only patients younger than 65 are good candidates for SCT.
What is the 5 year survival rate for SCT?
What is the most important prognostic indicator for CML?
Response to imatinib.
What is the common causes of death in CML?
Death usually occurs as a result of acute transformation, infection, or hemorrhage rather than from the chronic disease now that imatinib treatment is available.
What is blastic transformation or acceleration?
An acute increase in blast cells and or anemia/thrombocytopenia/granulocyte increase. It is often cause by additional mutations and may be treated as ALL or AML depending on the case. associated with a poor prognosis.
What is Ph negative CML?
Ph negative CML (less than 5%) lacks the BCR-ABL fusion protein. Prognosis is poor (imatinib will not work).
What is juvenile chronic myeloid leukemia?
A rare condition affecting younger children presents with
(1) skin rash
(4) recurrent infections
(5) high Hgb F
(7) normal ALP score
What are eosinophilic and chronic neutrophilic leukemia?
Rare conditions involving the pure proliferation of mature cells.