ACUTE LEUKEMIAS (Treatment * ( AML treatment: anthracycline, ara-c, 2-cda…
AML treatment: anthracycline, ara-c, 2-cda
ALL: pre-treatment with steroids(7 days), vincristin, epirubicin, PEG-asparaginase/ L-asparaginase, Ara-C+MTX+Dex
Goal: to achieve complete remission (CR)
Criteria for CR: PLT count of 100×109/L or higher, a ANC of 1×109/L or higher, and a bone marrow sample with 5% or less blasts
Bone marrow transplantation.
combination chemotherapy to obtain remission:
AML: difficult to treat and does not respond as well to chemotherapy. Bone marrow transplantation gives the best chance of remission or cure.
ALL: many patients achieve complete remission, relapses usually respond to treatment
Treatment of emergencies.
Antibiotics for infections.
Blood transfusion for anemia and platelet transfusion for bleeding
Acute myeloid leukemia (AML)
Acute promyelocytic leukaemia (APML)
variant of AML.
and often presents with pancytopenia.
treated with all-trans retinoic acid (ATRA) combined with chemotherapy anthracycline (Ida).
CR in at least 90%
very high D dimer
Other novel therapies that are being considered in AML include chemotherapy monoclonal antibodies (gemtuzumab ozogamicin) and hypomethylating agents (azacytidine).
Complete remission (CR) will be achieved in about 80% of patients under the age of 60. Failure is due to resistant leukaemia or death due to infection or bleeding.
stem cell transplant because they respond poorly to chemotherapy and have a high risk of relapse.
consolidation chemotherapy after an initial remis- sion has been achieved followed by allogeneic transplantation
treated with moderately intensive combination chemotherapy
anthracycline such as daunorubicin and cytosine arabinoside (cytarabine) with a minimum of four cycles of treatment given at 3–4-week intervals.
do not benefit from allogeneic stem cell transplantation during their first complete remission because the risks outweigh benefits.
mainly dependents on age and cytogenetics
Age >60, Male, Secondary disease, e.g. prior MDS or MPN, High WBC, MRD positivity, cytogenetics: -5, del(5q), -7
De novo, cytogenetics t(15;17) t(8; 21), CEBPA mutation, NPM1 mutation with FLT3 wild type
Neoplasm of myeloid progenitor cells
mostly in adults
Risk factors: radiation, myeloproliferative syndromes, Down syndrome, and chemotherapy (alkylating agents (e.g. melphalan) and topoisomerase II inhibitors (e.g. etoposide)).
DIC = Bleeding and bruising, Ecchymoses
Hyperuricaemia = Acute gout, Tumour lysis, Renal stones, Acute kidney failure
Gums = Gum hypertrophy
Skin = nodules
Marrow = Bone pain
Liver/spleen = Hepatosplenomegaly
Nodes = Lymphadenopathy
CNS = Headache, Cranial nerve palsies
Testes = Testicular enlargement
Mediastinum = Mediastinal mass, SVC obstruction
Symptoms: Dyspnea, Headache, Confusion, Visual problems
Signs: Hypoxia, pulmonary infiltrates, Retinal vein dilation, papilloedema, fundal haemorrhage
Symptoms: Bleeding and bruising
Signs: Petechiae, Gum bleeding, haemorrhage
Signs: Fever, Mouth ulcers
Symptoms: Dyspnea, Fatigue, Angina, Claudication.
Signs: Pallor, Cardiac flow murmur
Patients less than 15 most likely have All, while those greater than 65 typically have Cll. AMl and CMl both typically present from age 40 to 60.
neoplastic proliferation of abnormal WBCs, resulting in anemia and thrombocytopenia.
classified in two ways:
1) type of WBC affected:
granulocytes or monocytes = myeloid.
lymphocytes = lymphocytic
2) maturity of cells and the rapidity of progression.
rapid progression and immature cells = Acute
slowly progression and mature cells = Chronic
Radiation, Chemical and drugs, Genetic, Viruses (HTLV-1)
Acute lymphoid leukaemia (ALL)
Older age, >50×109/L for B-lineage >100×109/L for T-lineage, t(9;22) or t(4;11), Failure to achieve a CR within 3–4 weeks, MRD positive, CSF positive
Younger age, WBC <50×109/L for B-lineage <100×109/L for T-lineage, t(12;21), Minimal residual disease negative, CSF clear
neoplasm of early lymphocytic precursors.
most common malignancy in children under age 15
It is the leukemia most responsive to therapy
For planning therapy
Biochemistry, serum urate, renal and liver biochemistry.
Confirmation of diagnosis
Blood count. Hb low, WBC raised usually (sometimes low), platelets low.
Blood film. Blast cells
Bone marrow biopsy: Increased cellularity, >20% blasts, reduced erythropoiesis, reduced megakaryocytes.
cytologic, cytochemistry, immunophenotyping, cytogenetics
In ALL, you will see proliferation of lymphoblasts in the bone marrow (20% or greater)
In AML, you will see Auer rods, especially if it is the APL phenotype
Molecular tests (PCR)
Chest X-ray. Mediastinal widening often in T lymphoblastic leukaemia.
CSF examination: ALL (CNS involvement is high). less critical in AML.
Coagulation profile to exclude presence of DIC
COMPLETE REMISSION: 70-85%
DFS 5 YEARS: 10 – 15%
OS 5 YEARS AFTER BMT IN CR 45-60%
IN CR2 25-35%
Principles of leukemogenesis
a multistep process: leading to transformation of hematopoietic pleuripotent cell to neoplastic cell
dysregulation of cell cycle --> independent proliferation --> immature (blast) cells crossing the marrow-blood barrier