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ACUTE LEUKEMIAS (Treatment * (Treatment of emergencies. Antibiotics for…
ACUTE LEUKEMIAS
Treatment *
Treatment of emergencies.
Antibiotics for infections.
Blood transfusion for anemia and platelet transfusion for bleeding
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
Bone marrow transplantation.
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
AML treatment: anthracycline, ara-c, 2-cda
ALL: pre-treatment with steroids(7 days), vincristin, epirubicin, PEG-asparaginase/ L-asparaginase, Ara-C+MTX+Dex
Clinical features
Marrow failure
Anaemia
Symptoms: Dyspnea, Fatigue, Angina, Claudication.
Signs: Pallor, Cardiac flow murmur
Neutropenia
Symptoms: Infections
Signs: Fever, Mouth ulcers
Thrombocytopenia
Symptoms: Bleeding and bruising
Signs: Petechiae, Gum bleeding, haemorrhage
High WBC
Leucostasis
Symptoms: Dyspnea, Headache, Confusion, Visual problems
Signs: Hypoxia, pulmonary infiltrates, Retinal vein dilation, papilloedema, fundal haemorrhage
Tissue infiltration
Gums = Gum hypertrophy
AML
Skin = nodules
AML
Marrow = Bone pain
Liver/spleen = Hepatosplenomegaly
Nodes = Lymphadenopathy
CNS = Headache, Cranial nerve palsies
Testes = Testicular enlargement
ALL
Mediastinum = Mediastinal mass, SVC obstruction
ALL
Substance release
DIC = Bleeding and bruising, Ecchymoses
AML
Hyperuricaemia = Acute gout, Tumour lysis, Renal stones, Acute kidney failure
Acute myeloid leukemia (AML)
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)).
prognosis
Good risk
De novo, cytogenetics t(15;17) t(8; 21), CEBPA mutation, NPM1 mutation with FLT3 wild type
Poor risk
Age >60, Male, Secondary disease, e.g. prior MDS or MPN, High WBC, MRD positivity, cytogenetics: -5, del(5q), -7
mainly dependents on age and cytogenetics
Treatment
low risk
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.
intermediate risk
consolidation chemotherapy after an initial remis- sion has been achieved followed by allogeneic transplantation
high-risk
stem cell transplant because they respond poorly to chemotherapy and have a high risk of relapse.
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.
Other novel therapies that are being considered in AML include chemotherapy monoclonal antibodies (gemtuzumab ozogamicin) and hypomethylating agents (azacytidine).
Acute promyelocytic leukaemia (APML)
variant of AML.
characterized by
t(15;17)
and often presents with pancytopenia.
treated with all-trans retinoic acid (ATRA) combined with chemotherapy anthracycline (Ida).
arsenic trioxide
CR in at least 90%
very high D dimer
Leukemias
Aetiology
Radiation, Chemical and drugs, Genetic, Viruses (HTLV-1)
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
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.
Investigations
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
For planning therapy
Biochemistry, serum urate, renal and liver biochemistry.
Cardiac function
Acute lymphoid leukaemia (ALL)
neoplasm of early lymphocytic precursors.
most common malignancy in children under age 15
It is the leukemia most responsive to therapy
Prognostic factors
Good
Younger age, WBC <50×109/L for B-lineage <100×109/L for T-lineage, t(12;21), Minimal residual disease negative, CSF clear
Poor
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
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
Prognosis
COMPLETE REMISSION: 70-85%
DFS 5 YEARS: 10 – 15%
OS 5 YEARS AFTER BMT IN CR 45-60%
IN CR2 25-35%