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Synonyms :
-chronic myelogenous leukemia;
-chronic myeloid leukemia;
-chronic myelocytic leukemia.
CGL-2
Etiology :
1. – Irradiation :
2. –Chemicals and drugs :
3. –Genetic background :
Epidemiology:
1. –incidence in the USA : 1,4/100,000 ;
2. –the higher incidence appears in the fourth and fifth decade ; the
CGL is uncommon in children and accounts for less than 5% of
all childhood leukemias ;
3. –a slightly higher incidence in men has been observed;
Pathogenesis:
CGL-3
B.-at cellular level :
1. -the transformed hematopoietic stem cell generates an increasingly
expanded pool of committed stem cells for granulocytic and, at
least initially, megakaryocytic and erythroid cell lines;
2. -the leukemic cells retain partially their maturation capacity: in
peripheral blood , a continuously increasing number of neutrophils
appears, as well as eosinophils and basophils; in earlier stages,
because megakaryocytes are increased in bone marrow, a great
number of platelets appears in peripheral blood;
3. -the leukemic cellular pool overwhelms the normal erythropoiesis and
extends to extramedullary sites;
C.-at clinical level :
1.-leukemic cells proliferate:
a.-in bone marrow :
• spontaneous pain of the sternum , accentuated by palpation;
• as the diseases progresses, pain appears in long bones,
especially of the lower extremities;
b.-in extramedullary sites :
• in spleen, they proliferate profusely, growing out from the red
pulp toward the white pulp, where progressively replace the
normal lymphoid population ;
• in liver, the leukemic cells proliferate within the sinusoids;
• as the disease progresses, the leukemic cells proliferate also
in lymph nodes and infiltrate diffusely or nodular other organs
and systems, including the central nervous system (CNS);
2.-as result :
a.-progressively involvement of the bone
marrow
• osseous pain associates with anemia, increased tendency to
infection, spontaneous bruising;
b.-involvement of extramedullary sites:
CGL-4
Clinical features:
A.-for a variable period, the patient is asymptomatic ;
• no splenic enlargement (or a small and painless splenic
enlargement only), neither liver or other organs or systems
involvement ; the diagnosis could be suggested by fortuitous
laboratory investigation and confirmed by specific tests (see
later);
B.- as the leukemic clone extends, appear :
• a “general malignant impregnation syndrome”: malaise,
decreased tolerance to exercise, loss of appetite, sweating, mild
fever;
• a progressive splenic enlargement, with discomfort, early
satiety and abdominal fullness ;
• a progressive liver enlargement, with local pain ;
C.- Some patients with chronic myelogenous leukemia (CML) progress
to a transitional or accelerated phase, which
may last for several months. The survival of patients diagnosed in this
phase is 1-1.5 years. This phase is characterized by poor control of the
blood counts with myelosuppressive medication and the appearance of
peripheral blast cells (>15%), promyelocytes (>30%), basophils (>20%),
and platelet counts less than 100,000 cells/μL unrelated to therapy.
CGL-5
Laboratory:
-Peripheral blood findings in patients with chronic myelogenous leukemia (CML) show a typical
Imaging investigation :
-hepatomegaly;
-splenic enlargement;
-in acute (blastic crisis) : sometimes, l;ymph nodes enlargement
CGL-6
TREATMENT:
-demonstrates the victory of the molecular therapy (“magic bullet”)
How ?
= to directly inhibit the molecular cause of the disease, that is, using a protein-tyrosine kinase inhibitor
that inhibits the bcr-abl tyrosine kinase, the constitutive abnormal tyrosine kinase created by the Ph
chromosome translocation abnormality:
DASATINIB;
TASIGNA
• Leukapheresis using a cell separator can lower WBC counts rapidly and
safely in patients with WBC counts greater than 300,000 cells/µL, and it can alleviate acute
symptoms of leukostasis, hyperviscosity, and tissue infiltration. Leukapheresis usually
reduces the WBC count only temporarily and is often combined with cytoreductive
chemotherapy for more lasting effects.
• Interferon alfa was the treatment of choice for most patients with chronic
myelogenous leukemia (CML) who are too old for bone marrow transplantation (BMT) or who
do not have a matched bone marrow donor. Interferon alfa is given at an average of 3-5
million IU/d subcutaneously after hematologic remission with hydroxyurea.
BMT should be considered early in young patients (<55 y) who have a matched sibling
donor.The mortality rate associated with BMT is 10-20% or less with a matched sibling and 30-40%
with an unrelated donor. The bone marrow registry approximates the cure rate for patients with chronic
myelogenous leukemia (CML) at 50%.
○ Transplantation is recommended within 1 year of diagnosis or after a 1-year trial of
interferon therapy without a complete or significant cytogenetic remission.
○ Most patients with MRD after transplantation require interferon maintenance therapy
anyway, or they may require a reinfusion of T cells collected from the donor.
• Transplantation has been relegated to patients who do not achieve molecular
remissions or show resistance to imatinib and failure to second-generation bcr-abl
kinase inhibitors such as dasatinib.
Surgical Care