leukemia Magdalena OlszewskaSzopa Definition Chronic lymphocytic leukemia CLL belongs to B cell lowgrade non Hodgkin lymphomas CLL is the most common form of leukemia in adults ID: 911037
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Slide1
Chronic lymphocytic leukemia
Magdalena Olszewska-Szopa
Slide2DefinitionChronic lymphocytic leukemia (CLL) belongs to B-cell low-grade non-Hodgkin lymphomas. CLL is the most common form of leukemia in adults.International Workshop on CLL (IWCLL) 2008 guidelines
Diagnostic
criteria
:
≥5 x 10
9
B
clonal
lymphocytes/L in the peripheral blood
for the duration of at least three months.
Slide3Epidemiology and risk factorsRisk factors:Advanced agePositive family history
Slide4Clinical presentationmany patients are asymptomatic at the moment of the diagnosis,fatigue, autoimmune hemolytic anemia (AIHA), infections, splenomegaly, hepatomegaly, lymphadenopathy (painless), extra-nodal infiltrates
–
rarely
.
B
symptoms
(
general
symptoms
)
Night
sweats
Weight
loss
Fever
Slide5Physical examinationLymphadenopathy present in 87%: cervical/axillary/inguinal/generalised.Splenomegaly present in 54%Hepatomegaly present in 15%
www.gp.online
Slide6Laboratory and imaging testsBlood smearImmunophenotyping – diagnosis confirmation and risk factors identification eg ZAP70 and CD38 statusInterphase fluorescence in situ hybridization (FISH) - indetifies genetic risk factors
eg
del17p
Serum marker beta-2
microglobulin
C
oncentration
of immunoglobulins in the blood
Ultrasound
of the abdomen and
chest
radiography
CT
scans
of the
chest
and abdomen (not mandatory) blood tests -
Slide7Laboratory and imaging tests Bone marrow tests usually are not needed.Lymph node biopsy usually is not needed.Biopsies are performed if the peripheral blood smear does not yield diagnostic clues, to confirm the diagnosis, or to differentiate CLL from other diseases (e.g., Hodgkin's disease).Histopathology or immunophenotyping of lymph
nodes
are
performed
in
case
of Richter syndrom
suspicion
.
Slide8Blood smear ASH Image Bank - American Society of HematologyGumprecht shadows – smudge cells - typical for CLL
CLL
cells
are
typically
small/medium
sized
normal
looking
lymphocytes
Slide9Immunophenotyping – flow cytometryThe test which is usually done from blood - determines whether the cells are clonal and recognizes
their
antigens
(
CD’s
).
Classical
findings
:
CD19+, CD20weak +, CD23+,
light
chain
restriction (kappa or lambda)
Adverse Flow-cytometry
factors:High proportion of CLL cells containing
ZAP-70 (20% or more) or CD38
(30% or more)
Slide10Rai staging and prognostic system:StageStage (revised)FindingsMedian survival0Low
risk
Isolated
lymphocytosis
> 150
months
I
Intermediate
risk
+
Lymphadenopathy
101
months
II
Intermediate
risk
+
Hepatomegaly
and/or
splenomegaly
71
months
III
High
risk
+ Anemia (
Hb
< 11 g/
dL
)
19
months
IV
High
risk+ Thrombocytopenia (< 100,000/μL)19 months
Leukemia and lymphoma society (2017)
Binet staging system:
StageFindingsAHb ≥10 g/dL and thrombocytes ≥100,000/uL and <3 involved nodal areasBHb ≥10 g/dL and thrombocytes ≥100,000/uL but ≥3 involved nodal areas CHb <10 g/dL or thrombocytes <1000,000/uL independently of numer of nodal areas involved
Adapted
from 2008 NCI
guidelines
Slide11Assesing patient fitnessEastern Cooperative Oncology Group (ECOG) Performance StatusCumulative Illness Rating Scale (CIRS)grade
ECOG
0
Fully active, able to carry on all
predisease
performance without restriction
1
Restricted in physically strenuous activity
but ambulatory and able
to carry out work of a light or sedentary nature, e.g., light house work, office work
2
Ambulatory and capable of all
selfcare
but unable to carry out any work
activities.
Up and about more than 50% of waking hours
3
Capable of only limited
selfcare
, confined
to bed or chair
more than 50% of waking hours
4
Completely disabled. Cannot carry on any
selfcare
. Totally confined to bed or
chair
Slide12Differential diagnosisSLL – small lymphocytic lymphoma. The same appearance of neoplastic cells. The tissue infiltration is situated in lymph nodes, spleen, or other organs but circulating B lymphocyte count <5 x 10 9/LNHL – other non hodgkin lymphomas. Histopathological tests
needed
.
Reactive
lymphocytosis
– the
cells
are
not
clonal
.
MBL
–
monoclonal B cel lymphocytosis. As many as 12% of healthy individuals >40 years of age may have low levels (<5 x 109/L) of circulating monoclonal B cells with no evidence of organ infiltration.
MBL progresses to CLL at a rate of 1%–2% of patients per yearOther
types of chronić leukemias,
eg: hairy cell
leukemia, prolymphocytic leukemia..
Slide13Prognostic factors Serum markers, such as beta2 –microglobulin Genetic markers, including immunoglobulin heavy chain variable region (IgHv), gene mutational status (se:
NOTCH1
gene
mutation
, tp53
mutation
)
Genetic
abnormalities
detected
by
fluorescence
in situ
hybridization (FISH) or metaphase cytogenetics
(se: del 17p
) Protein
markers, such as zeta-
chain-associated protein
kinase 70 ([ZAP]-70),
cluster
of
differentiation
CD38
,
or
CD49d
.
Lymphocyte
doubling
time
shorter than one yearIncreased fraction of prolymphocytes (an early form of the lymphocyte) in the blood Leukemia and Lymphoma society
Slide14Complications Immunosuppression with subsequent infections (most common cause of death) Autoimmune hemolytic anemia (AIHA) (of both the warm and cold agglutinin type)Immune Thrombocytopenic Purpura (ITP)Richter's transformation or Richter's syndrome: transformation into a high-grade NHL (approx. 5% of CLL cases)Secondary malignancies
Slide15TreatmentWatch and wait strategy - no benefits of early treatment for people with low-risk CLL have been shown. When to Begin Treatment (when at least one of the above is present): Enlarging lymph nodes noted over a series of clinical exams Enlarging liver and/or spleen noted over a series of clinical exams Decreased red blood cell counts (hemoglobin less than 11g/
dL
)
Decreased platelet counts (platelets less than 100,000/
uL
)
Autoimmune anemia and/or thrombocytopenia poorly responsive to standard therapy
Lymphocyte doubling time of less than 6 months (only in patients with lymphocytes greater than 30g/L)
Presence of
CLL
B -
symptom
s
Slide16TherapyThe therapy may consist of classical drugs and immunotherapy:Purine analogues and alkylating agentsAnti-CD20 antibodiesGlicocortycosteroids are part of the regimens
or
are
given
in
monotherapy
to
eliminate
autoimmunologic
cytopenias
.
Targeted
therapy is of increasing importance:
Bruton kinase
inhibitors, PI3K
inhibitors, Bcl-2
inhibitors
Slide17Therapy Autologous stem cel translantation (ASCT) – due to the lack of efficacy and relatively high risk of late complications ASCT is NOT a part of therapyAllogenic stem cel transplantation (Allo-SCT) – decreasing role in the era of new drugs
.
Still
an
option
for
young
high
risk
or
recurrent
patients
. Surgery or radiotherapy have no role in the therapy