ALL Flashcards
What is ALL and how does it arise?
o A clonal malignancy and proliferation of lymphoid precursors in the bone marrow.
o Can be due to the T- or B- cell lineage, although most are due to the B-cell lineage, and the stage of cancer is determined by the type of lymphocyte (e.g., mature B cell, pre-T cell) that is affected.
o Often caused by genetic lesions, causing chromosomal translocations. These account for 25% of all childhood ALL.
o E.g., t(12:21)(p12:q22) = TEL-AML1 fusion protein, which negatively impacts on the transcriptional control of haemopoiesis. This cause has a good prognosis.
o E.g., t(9:22)(q34:q11.2) = BCR-ABL1 fusion protein, AKA Philadelphia chromosome, which causes a constitutive tyrosine kinase for cell division. This is not the most common cause but has a poor prognosis.
What are the symptoms and their explanations?
o Lethargy, pallor, and fatigue/anaemia – this is due to the over-proliferation of lymphoid blasts inhibiting erythropoiesis. These blasts also release inhibitory cytokines for erythropoiesis.
o Fever, malaise and recurrent respiratory infections – this is due to the over-proliferation of immature lymphocytes, meaning there are not enough functioning lymphocytes to fight infections. These blasts also overcrowd the bone marrow meaning they negatively impact normal leucopoiesis, reducing numbers of other WBCs.
o Bruising on forearms – this is due to the over-proliferation of lymphoid blasts overcrowding the bone marrow and negatively impacting thrombopoiesis. This decreases the number of platelets, which means that blood doesn’t clot properly and minor injuries to capillaries do not clot properly so bruise easily instead.
o Hepatosplenomegaly – this is due to many immature lymphocytes being trapped in the reticuloendothelial system and removed in the spleen, causing the spleen and liver to become enlarged with the number of cells here.
o Bone pain or swollen lymph nodes – this is due to overcrowding of immature lymphoid cells in the bone marrow, causing swelling and pain in the long bones, and enlarged lymph nodes where these cells reside.
What are the laboratory findings?
o Normochromic, normocytic anaemia – low RBC count and Hb.
o Thrombocytopenia – low platelets.
o Hyperleukocytosis – increased number of WBCs.
o Neutropenia – decreased number of neutrophils, can also be normal.
o High number of immature lymphocytes.
o Blood film shows a large proportion of the WBCs as blasts >20% blasts, with these blasts having an enlarged nucleus (little cytoplasm), all varying in size, but smaller than those seen in AML. Agranular WBCs with condensed chromatin and poorly visible nucleoli.
What further tests can be done?
o Bone marrow aspirate – hypercellular with a high infiltration of blasts >20%.
o Sudan Black B stain and myeloperoxidase stain negative.
o Periodic Acid Schiff stain positive for B-ALL, and Acid Phosphatase stain positive for T-ALL.
o Bone marrow trephine – same tests as bone marrow aspirate. Allows architecture and structure of cells to be maintained. Not necessary.
o Immunophenotyping – looks for presence of certain markers like CD7 and CD10. Can then determine the subtype looking for markers like CD19 (B-ALL) and CD3 (T-ALL).
o Biochemistry tests – LFT, U&E, LDH, calcium.
o Coagulation tests – PT, APTT, TT, fibrinogen and D-dimer, Group and Save (in case of transfusion).
o Radiography – looks for mediastinal mass, caused by enlargement of the thymus oy lymph nodes, indicating a positive ALL diagnosis.
o Cytogenetics – karyotyping of chromosomes assessing genetic abnormalities. High hyper diploidy, where a child has between 51-67 chromosomes, accounts for 30% of B-ALL. This can be looked for in cytogenetics.
o Molecular studies – FISH and PCR to further analyse chromosomal rearrangements or abnormalities.
How is ALL treated?
o Chemotherapy using vincristine, dexamethasone and asparaginase. 4 stages: remission (4-6 weeks and aims for complete remission – less than 5% blasts), intensification (3 blocks of chemotherapy in different combinations, such as cytosine arabinoside and cyclophosphamide), CNS-directed therapy (ALL affects the CNS in 10-40% of adults) and maintenance (daily, 2 years for adults and girls, 3 years for boys, as the testicles act as a reservoir for the cancer).
o Packed red cells and platelet transplant – treats the anaemia and thrombocytopenia. Irradiated, CMV- blood must be used.
o Antibiotics/antifungals – used to treat the infection risk as a result of low lymphocyte numbers.
o Supportive therapy
o Radiation therapy
