Transcript Hairy cell leukemia is a chronic Lymphoprolifrative disorder. in 1952

Hairy cell leukemia is a chronic
Lymphoprolifrative disorder.
in 1952 was recognized.
Leukemic reticuloendotheliosis.
Lymphoid myelofibrosis.
Reticulum cell leukemia.
HCL
Neoblastic B Lymphocyte.
carry surface immunoglobulins of only one
light chain type Often isotype is of Gama class
or Multiple heavy chain.
H.cell express receptors for Fc portion of IgG. IgM
HCL reactivity with antibodies to CD19 .CD20,
CD22 , CD25 , CD103 and MLA-DR.
PCA-1 is detected in HC & Plasma cell.
( CD11c, CD25 and CD103 )
The hairy cells are 10 to 15 mm in
diameter with pale blue cytoplasm and a
nucleus with a loose chromatin structure
and one or two indistinct nucleoli.
Hairy Cell Leukemia
In PBS
Pancytopenia
Lymphocytosis
Hairy cell
Infection
Middle age
Male / female
Symptomatology:
Patients have fatigue due to anemia, fever,
weight loss, and/or abdominal discomfort.
Sometimes the disease is diagnosed when
patients have infection secondary to
granulocytopenia or monocytopenia.
The only consistent physical findings are
slight to marked splenomegaly (75 to 80%
of cases)
Bone marrow aspiration is usually
inadequate owing to increased reticulin,
collagen, and fibrin deposition; bone marrow
biopsy is usually necessary.
The biopsy demonstrates increased cellularity
with a diffuse or occasionally patchy infiltrate
with hairy cells.
The infiltrate is loose and spongy, with palestaining cytoplasm surrounding bland,
monotonous round or ovoid nuclei.
Etiology
No clear etiology
Benzene exposure
Radiation
The cytopenias are due to a combination of :
*Bone marrow production failure
caused by leukemic infiltration.
*Hypersplenism. (increased destruction)
Marrow failure may be due in part to
*inhibitory
factors (e.g., tumor necrosis
factor) produced by the leukemic infiltrate,
Laboratory abnormalities in HCL is as follows:
Anemia — 85%
Thrombocytopenia — 80%
Neutropenia — 80%
Monocytopenia — 80%
Azotemia — 30 %
Abnormal liver function tests — 20%
Hypergammaglobulinemia — 20%
Leukocytosis (WBC >10,000) 10 to 20%
The mucosal lymphocyte antigen, CD103:
is a sensitive marker for
HCL.
is a member of the integrin family The
presence of CD103 , when coexpressed,
is highly suggestive of HCL
In HCL:
Vasculitis.
Arthritis.
Polyarthritis nodosa.
Systemic Vasculitis.
Many patients complaint:
Arthitis or arthralgia.
Diagnosis:
Examination of the blood often suggests
the diagnosis of HCL.
In addition to the cytopenias the
peripheral blood film usually
demonstrates relative or absolute
lymphocytosis, composed of cells with
cytoplasmic projections, giving rise to
the name hairy cell leukemia
patients often experience
repeated infections and, more
rarely, a
systemic vasculitis
Resembling polyarteritis nodosa
TRAP test
Hairy cells exhibit a strong acid
phosphatase (isoenzyme 5).
Cytochemical reaction in more
95% of cases, a reaction that is
resistant to the inhibitory effect of
tartaric acid (TRAP).
Hairy cells express CD19, CD20, CD22
CD25 , CD11C , CD103 , FMC7,
but not CD21 or CD5.
Cell-surface immunoglobulins can be
immunoglobulin G (IgG) or
immunoglobulin A (IgA),
The cells demonstrate a κ or λ
light-chain phenotype
Clinical presentation
*Abdominal fullness or discomfort due to
*Splenomegaly, which may be massive.
*Systemic complaints (eg, fatigue,
weakness, and weight loss).
*Bruising and bleeding
*Recurrent infections, which may be lifethreatening, secondary to granulocytopenia
and monocytopenia.
*Splenomegaly or cytopenias
Annexin A1 : HCL has a gene
expression profile that is
distinct from that of other B
cell lymphomas, including
overexpression of the ANXA1
gene (annexin A1)
DIFFERENTIAL DIAGNOSIS
1-Small B cell lymphoproliferative disorders.
associated with splenomegaly .
2-Chronic lymphocytic leukemia (CLL),
3-Prolymphocytic leukemia .
The abnormal B cell in CLL usually stains positively
for CD5, B cell CLL is usually negative for CD103,
prolymphocytic leukemia present with splenomegaly,
marked elevation of the white blood cell count, and
the characteristic morphology of the prolymphocytes
Renal insufficiency in HCL due to:
Infiltration
Bleeding
Infections
Immune Complex
Protein excertion
Light chain deposition ( Nephrotic Syndrome)
Acquired Fanconi’s syndrome
( Proximal renal tubules)
A Microbicidal defect of the
neutrophils and
aggregation defect of platelets have
been reported in HCL
Patients with HCL have a predilection to
develop tuberculosis , atypical
mycobacterial infections, or fungal
infections,
perhaps related to the severe monocytopenia
that is characteristic of this disorder.
Pneumonia and
septicemia are common causes of
death in HCL.
(Treatment)
Splenoctomy
Interferon,
Cladribine
2-CDA,
pentostatin
Granulocyte colony-stimulating factor (G-CSF)
Rituximab
Anti-CD20 antibody)
Anti-CD22 antibody (BL22)
Anti-CD25 antibody (LMB-2)
Splenectomy, often used in the past
as the first treatment of most
patients with complications from
HCL, temporarily improves blood cell
counts in two thirds of patients,
usually within 1 to 4 weeks, but does
not decrease the infiltration of hairy
cells in the marrow or reduce the
incidence of infections.
A small proportion (<5%) of patients with
HCL do not require therapy.
Splenectomy, often used in the past as the
first treatment of most patients two thirds of
patients, usually within 1 to 4 weeks, but does
not decrease the infiltration of hairy cells in
the marrow or reduce the incidence of
infections.
Splenectomy is recommended mainly for
patients with splenic infarcts or massive
splenomegaly.
2-Chlorodeoxyadenosine (2-CDA), an
adenosine analogue deaminase ,
produces complete remissions in
more than 90% of HCL patients with
a single course of 0.1 mg/kg/day for 7
days by continuous intravenous
infusion.
Effect of 2-CDA
2- CDA 0.1 mg/kg body weight per day
by continuous intravenous infusion for
seven days
The complete and partial remission rates
were 91%. The overall survival was 96%
The relapse rates for patients achieving
CR ( after 10Y) were 16 % .
Cladribine (2-CdA)
Cladribine accumulates in lymphoid
cells presumably because they are
rich in deoxycytidine kinase. This
enzyme phosphorylates cladribine,
creating a deoxynucleotide that
cannot readily exit the cell. The net
effect is lymphotoxicity.
Cladribine and Pentostatin:
In one study of 219 patients followed for
a median period of 12.5 years, overall
response rates (100 versus 96 percent),
rates of complete remission
10-year survivals (100 versus 96 percent)
were similar for initial treatment with
either cladribine or pentostatin,
respectively.
Side effects:
Both Cladribine and Pentostatin
produce prolonged
immunosuppression
Opportunistic infections, Herpes zoster
Treatment Relapsed HCL
Retreatment with a second cycle of
Cladribine or Pentostatine leads to a
second complete remission in up to
70 percent of patients