Leukemia chpt 13 dsa Flashcards
Acute Leukemia- essentials of diagnosis
- short duration of sx’s, including fatigue, fever, bleeding
- cytopenias or pancytopenia
- > 20% blasts in bone marrow
- blasts in peripheral blood in 90% of pts
AML- favorable cytogenetics
- t(8;21))
- inv 16
AML- unfavorable cytogenetics
-monosomy 5 or 7
Acute promyelocytic leukemia (APL)- cytogenetics
- t(15;17)
- highly curable!- ATRA (all-trans-retinoic acid) and ATO (arsenic trioxide) in induction
Acute lymphoblastic leukemia (ALL)- better prognosis cytogenetics
- hyperdiploidy of 4, 10, 17
- t(12;21)
ALL- worse prognosis cytogenetics
- hypodiploidy
- t(9;22)
- t(4;11)
acute leukemia- sx and signs
- ill only for days-wks
- bleeding (thrombocytopenia)- skin and mucosal surfaces
- infection (neutropenia when < 500)
- gum hypertrophy
- bone pain
- hyperleukocytosis (elevated blast count)- causes impaired circulation- HA, confusion, dyspnea
- pale, purpura and petechiae
acute leukemia- lab findings
-pancytopenia with circulating blasts- hallmar!
DIC
- fibrinogen level reduced
- prothrombin time prolonged
- D-dimers elevated
Auer rod
- eosinophilic need-like inclusin in cytoplasm
- in AML!!!
AML- express what?
- CD 13, 33
- myeloperoxidase
- tdT
acute leukemia- differential diagnosis
- AML must be distinguished from other myeloproliferative disorders, CML, and myelodysplastic syndromes
- ALL
AML- treatment
-anthracycline plus cytarabine- remission in 90% of pts (
AML- post-remission therapy
- chemotherapy or allogeneic stem cell transplantation
- if favorable- chemotherapy alone or with autologous transplant
- if unfavorable- allogeneic stem cell transplantation
ALL- treatment
- chemotherapy including daunorubicin, vincristine, prednisone, and asparaginase
- if philadelphia chromosome positive- give a tyrosine kinase inhibitor (dasatinib)
ALL- remission induction therapy
less myelosuppressive than tx for AML
- CNS prophylaxis so that meningeal sequestration of leukemic cells dont develop
- either chemotherapy or chemotherapy and stem cell transplantation
- <39 yo- better outcomes with pediatric protocols`
AML- prognosis
- 80% of pts < 60 yo achieve complete remission
- 50% cured using risk-adapted post-remission therapy
- older pts- complete remission 50%
ALL- prognosis
-<29 yo- excellent outcomes after chemotherapy and risk-adated intestinfication and transplantation
AML- induction, consolidation, maintenance
- I- 3 + 7 (anthracycline and Ara-C)
- C-High dose Ara-C (HDAC)
- M- promyelocytic leukemia only (ATRA)
ALL- induction, consolidation, maintenance
- I- vincristine/prednisone plus others
- C- mult agents plus CNS prophylaxis (MTX or ARA-C)
- M- 6-MP and MTX
Chronic Myeloid Leukemia (CML)- essentials of diagnosis
- elevated white blood count
- left-shifted myeloid series but with a low percentage of promyelocytes and blasts
- BCR/ABL gene
CML- cytogenetics
-BCR/ABL gene (chrom 9 and 22)
CML- sx and signs
- 55 yo
- fatigue, night sweats, fevers
- splenomegaly (abd fullness)
- white blood count usually > 100,000
- progresses to accelerated and blast phases (>20% blasts in bone marrow)
CML- lab findings
- elevated white blood count
- peripheral blood- myeloid series is left shifted
- hallmark- PCR Test- BCR-ABL gene
CML- diff diagnosis
- differentiated from reactive leukocytosis (due to infection)- white blood count < 50,000, no splenomegaly, no BCR/ABL
- distinguish from other myeloproliferative diseases
CML- tx
- tyrosine kinase inhibitors (imatinib, nilotinib, dasatinib)- remission should occur within 3 months; major cytogenetic response within 3 months (<35% of metaphases contain philadelphia chrom)
- Imatinib mesylate- 98% control of chronic phase dz
- nilotinib and dasatinib-inc the rate of major molecular response
CML- tx- tyrosine kinase inhibitors should be monitored with?
- PCR assay
- if a consistent inc in BCR/ABL or those with a suboptimal molecular response- should be switched to a diff TK inhibitor and undergo ABL mutation testing
- T315I mutation in abl- resistant to imatinib, dasatinib, nilotinib, bosutinib- but sensitive to ponatinib (vascular thrombotic complications)
CML- advanced stage (accelerated phase or blast crisis)- tx
-tyrosine kinase inhibitor alone or with myelosuppressive chemotherapy
CML- prognosis
-pts with good molecular responses to TK inhibitor therapy- excellent prognosis 100% survival at 9 yrs
Chronic Lymphocytic Leukemia (CLL)- essentials of dx
- B cell lymphocytosis > 5000
- coexpression of CD19, CD5 on lymphocytes
CLL- signs and sx’s
- median age at 70 yo
- lymphadenopathy and spleen enlargement (50%)
- usually indolent
CLL- Rai classification, survival in months
- 0- lymphocytosis- 150 months
- 1- plus lymphadenopathy- 101
- 2- hepatosplenomegaly- 72
- 3- anemia- 22
- IV- thrombocytopenia- 11
- 0-1- low risk
- 2- intermediate risk
- 3-4- high risk
CLL- lab findings
- lymphocytosis
- CD19, 5, 23
- 17p- worst prognosis
- 11q- bad prognosis
- 13q- better prognosis
- hypogammaglobulinemia- in 50% of pts
CLL- complications
- Richter syndrome (transforms to diffuse large B-cell lymphoma)
- autoimmune hemolytic anemia
CLL- sx and complications that are an indication for tx
- fatigue, symptomatic lymphadenopathy, anemia, or thrombocytopenia
- autoimmune hemolytic anemia- rituximab, prednisone, or splenectomy
Hairy Cell Leukemia
- indolent B-cell leukemia
- BRAF V600E mutation
- CD 19, 20, 11c, 103
- TRAP positive
hairy cell leukemia- clinical manifestations
- pancytopenia and splenomegaly
- cytopenia due to bone marrow failure due to leukemic infiltration and hypersplenism
hairy cell leukemia- tx, prognosis
- cladribine- complete remission in 80% of pts
- Deoxycoformycin (adenosine deaminase inhibitor)- complete remission 80%, more SEs)
- 90% of treated pts live past 10 yrs
