Leukemia
Chronic Myelogenous Leukemia
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Chronic Myelogenous Leukemia
, Chronic Myeloid Leukemia, CML
Epidemiology
Common in Atomic bomb survivors
Peak
Incidence
at ages 30 to 50 years old
Pathophysiology
Chronic phase (Mild, indolent course)
Excessive
Granulocyte
(
Neutrophil
s) proliferation
Blastic phase (Malignant, leukemic course)
Increased blasts and
Promyelocyte
s
Symptoms
Asymptomatic in 20% of patients
Weakness
Hypermetabolism
Weight loss
Fever
Arthralgia
s
Bone pain
Excessive bleeding (spontaneous or with surgery)
Signs
Splenomegaly
(90%)
Hepatomegaly
Lymphadenopathy
Labs
Philadelphia
Chromosome
(95%)
Reciprocal
Chromosome
translocation
Long arm of
Chromosome
22 (c-sis oncogene)
Long arm of
Chromosome
9 (c-abl oncogene)
Translocation of C-abl at bcr breakpoint
Forms bcr/abl
Complete Blood Count
Chronic Phase
White Blood Cell Count
> 200,000/uL
Granulocyte
s (especially
Neutrophil
s) predominate
Transitional Phase (50% of patients)
Leukocytosis
Thrombocytosis
or
Thrombocytopenia
Blast Phase
Increased
Leukocytosis
Thrombocytosis
Bone Marrow Biopsy
and
Peripheral Smear
Chronic Phase
Myeloblast
s represent <5% of cells
Blast Phase
Large proportion of immature cells
Images
Vitamin B12
markedly elevated
Leukocyte
Alkaline Phosphatase
reduced
Uric Acid
increased
Management
CML Treatment
Treatment for cure
Allogeneic
Stem Cell Transplant
(SCT)
Chronic Phase suppression
First Line
Tyrosine Kinase
inhibitor:
Imatinib
(Gleevac)
Gleevac is generic in U.S. as of February 2016
Interferon-alfa
with Cytarabine or
May be poorly tolerated
Studies to date show unclear efficacy
Baccarani (2002) Blood 99:1527 [PubMed]
Guilhot (1997) N Engl J Med 337:223 [PubMed]
Alternative (prior first line agents)
Hydroxyurea
(used to stabilize chronic phase)
Busulfan
Risk of myelosuppression
Hydroxyurea
is preferred
Other
Alkylating Agent
s (not in marrow transplant)
Cytarabine
Cyclophosphamide
Melphalan
Splenectomy rarely indicated
Hypersplenism
Repeated painful splenic infarctions
Consider
Bone Marrow Transplant
ation in first year
Results in 70% long-term disease free survival
Blast Crisis
Often refractory to treatment
Hydroxyurea
Try protocols for
Acute Lymphocytic Leukemia
Vincristine
Prednisone
Management
Surveillance of CML Survivors
Complete Blood Count
(CBC) every 3 months
Hematology
Consultation
for
Neutropenia
(ANC <1000/mm3) or
Thrombocytopenia
(
Platelet Count
<50k/mm3)
Symptom surveillance
Diarrhea
Fluid retention
Nausea
or
Vomiting
Headache
Myalgias
Rash
Patients treated with
Hematopoietic Stem Cell Transplant
ation
See
Hematopoietic Stem Cell Transplant
for protocol
Course
Initially indolent
Later progresses to leukemic phase (blast crisis)
Blast phase onset after 6-12 months post diagnosis
Annual progression to blast phase: 25% of patients
Prognosis
Five year survival
Age under 50 years old: 84% five year survival
Age over 50 years old: 48% five year survival
References
(2001) Med Lett Drugs Ther 43(1106):49-50
Druker in Abeloff (2004) Clinical Oncology p. 2899-915
Enright in Hoffman (2000) Hematology 40:1155-67
Davis (2014) Am Fam Physician 89(9): 731-8 [PubMed]
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