PATHOPHYSIOLOGY DIAGNOSTIC APPROACH TREATMENT

Hematopoiesis Pathway Effects of ↑↑ Leukocytes (Chronic Phase) CBC w/ P.B.S. Tyrosine Kinase Inhibitors
80-85%
Agents: Imatinib
Chronic Phase
Splenomegaly CP-CML → normal
No symptoms
Hemocytoblast N/V M.S.C. (Accelerated Phase)AP/BP-CML → ↓↓RBC's

Anorexia CP-CML → ↑↑PLT's

Fullness ↑ No effect on RBS's
↑ AP/BP-CML → ↓↓PLT's
in this phase
M.S.C. L.S.C.
Thrombocytosis (increase number of PL ) C/P/AP ± BP-CML WBC↑↑
Deposition Leukocytosis↑↑
BCR-ABL
P.B.S. ↑neutrophils
TPO CSF EPO
Extramedullary Neutrophils↑↑ Pathophysiology
hematopoiesis CP-CML ↑eosinophils
Basophils↑↑ IL-1 ↓↓Blast cells (<10%) ↑basophils
Lymphoblasts increase produce bld cell Mature
Eosinophils INF-Alpha ↑↑Granulocytes AP/BP-CML Granulocutes
↑PLT’s Myeloblast RBC’s
Fevers + night sweats ↑↑Blast cells ↓↓Blast cells
↓↓Cell prolifiration ↑↑Apoptosis
B-cells T-cells
P.M.C.
Effects of ↑↑ Leukocytes (Accelerated Phase) Bone Marrow Biopsy
Bone Marrow Transplant
Splenomegaly Expand R.B.M. Bone Trigger Definitive Dx
Blast cells
Myelocyte pain 2/2 Failure of TKI’s
Splenic (9;22)t <10% → CP-CML
rupture 10-19% → AP-CML
↑ 2/2 BCR-ABL gene >20% → BP-CML
Metamyelocyte ↑ Cytoreduction
Deposition ↓Space ↑Cell prolif. ↓Apoptosis Granulocytes (↑↑Diff)
Hematopoiesis Refractory Thrombocytopenia Functional Symptomatic
(extra) Leukocytosis Bruising ↓Space Granulocytes↑↑ ↑↑WBC’s
↑↑Neutrophil ↑↑Eosinophil ↑↑Basophil Myelocytes CML >> AML
Basophils↑↑ Anemia Mut.
Bleeding Blast cells↑↑ Metamyelocytes ↑↑PLT’s
Pruritus Fatigue (10-19%)
bcz basophil produce a
Pallor Agent: Hydroxyurea
Causes of ↑↑ Leukocytes lot of histamin Space in
Dyspnea R.B.M. Genetic Studies
red bone marrow

1
Ionizing Radiation Effects of ↑↑ Leukocytes (Blast Phase) Cytogenetics PCR

Mutation ↑Mortality (+) Phil.

↑Cell prolif. chromosome
Oncogenes (9;22)t
M.S.C. (9;22)t
T. Suppressor ↓Apoptosis CML BCR-ABL (+)
genes Bone pain
AML TKI’s TKI’s
M.B.
2
Genetic Dx (9;22)t Additional Tests
↑Blast ↓Functional ↑↑Anemia
↑↑Replication P.M.C.
cells WBC's
Chromosomal Translocation
tyrosin kinase ↑↑Thrombocytopenia
↑↑Mutations 90% BCR-ABL T.K. CML VS Leukemoid Reaction
M.C.
gene Receptor ↑↑Infections ↑↑Cell prolif.
(9;22)t (9;22)t
↓↓Diff. M.S.C. ↓↓Apoptosis 2/2 (9;22)t 2/2 Infection
↓Apoptosis Time
M.M.C. Leukostasis ↑↑WBC (>50K) 2/2 Stress
CML ALL
Time ↑Cell prolifiration Mutations
(90%) (20%) T.L.S. LAP ↓↓LAP ↑↑WBC (<50%)
Tumor lysis syndrome ↓Diff. leukocyte alkaline phosphatase
↑↑LAP
↑↑ ↑↑ ↑↑ ↑↑Blast cells (>20%)
Splenic uls or CT abdomen

CHRONIC MYELOID LEUKEMIA