92 Hairy Cell Leukemia Flashcards
The distinctive feature of Hairy Cell Leukemia
Cytoplasmic projections
Three separate malignancies were identified as being of particular concern in terms of increased overall risk in patients with hairy cell leukemia
Hodgkin lymphoma
Non-Hodgkin lymphoma
Thyroid cancer
HCL is a rare chronic B-cell lymphoid malignancy accounting for approximately ____ of adult leukemias
2%
There is an unexplained_________ predominance with this disease with a ratio of 4 to 1.
Male
- The mean age at diagnosis is 55 years
- There is also an unexplained racial difference with more than 90% of patients in the United States being of European origin.
TRUE OR FALSE
Younger patients respond better to therapy but may relapse and require retreatment to experience long-term survival benefits.
TRUE
Younger patients respond better to therapy but may relapse and require retreatment to experience long-term survival benefits.
TRUE OR FALSE
In patients who have mutated immunoglobulin genes, the disease appears to be more aggressive, as is the case in chronic lymphocytic leukemia.
FALSE
In patients who have unmutated immunoglobulin genes, the disease appears to be more aggressive, as is the case in chronic lymphocytic leukemia.
The neoplastic cells in classic HCL-c have hypermutated immunoglobulin genes in approximately 90% of the cases.
Prognosis: favorable or poor
Presence of VH4–34 gene
Poor
Prognosis: favorable or poor
p53
Poor
This mutation is detected in almost 100% of patients with HCL-c
BRAF V600E
Highly responsive form
Variant of HCL (HCL-v) express BRAF wild type
The most common presenting symptoms
Weakness and fatigue
The leading cause of death in patients with HCL
Infection
CBC features of HCL
Pancytopenia
Monocytopenia
Reflecting impaired hematopoiesis caused by marrow infiltration and splenic sequestration
Hairy cells are positive for this enzyme; In the past this was used as cytochemical staining for HCL
Tartrate-resistant acid phosphatase (TRAP)
Immunophenotype of HCL
Strongly positive for CD20 and are positive for CD11c+, CD25+, CD103+, and CD123+
Negative for CD5−, CD10−, CD27−, and CD43−
Hairy cells demonstrate moderate to high side scatter (SC) characteristics, resulting in their shift on flow plots into the region typically occupied by monocytes.
BMA finding in HCL
Marrow fibrosis is characteristic of this disease leading to a “dry” marrow aspirate
Severely hypocellular marrow
Mononuclear cells with non-overlapping cellular borders “fried egg–like” appearance
IHC stains used in BMA to diagnose HCL
- anti-CD20
- Annexin
- DBA.44
- BRAF V600E
TRUE OR FALSE
Before treatment, include an assessment of renal function as both of the commonly used purine nucleoside analogues are excreted by a renal route.
TRUE
Before treatment, include an assessment of renal function as both of the commonly used purine nucleoside analogues are excreted by a renal route.
Laboratory tests useful in patient monitoring
- Serial complete blood count
- Soluble interleukin-2 (IL-2) receptor
- Soluble CD22
Approximately 10% of HCL-c
Characterized by leukocytosis, lack of monocytopenia, and neoplastic B cells with nucleoli and convoluted nuclei.
HCL-v
Immunophnotype of HCL-v
CD25− and CD123− negative, annexin-1 negative, and negative for TRA
BRAF V600E mutation is not present
TRUE OR FALSE
HCL-v achieve durable responses with purine analogues as monotherapy.
FALSE
HCL-v do not achieve durable responses with purine analogues as monotherapy but may respond to combined therapies with a purine analogue and a monoclonal antibody.
The malignant cells in the blood are characterized by cytoplasmic villi or projections that are typically polar in distribution
Splenic marginal zone lymphoma/splenic marginal zone lymphoma with villous lymphocytes
Although the cells are positive for CD20, they are negative for CD25, annexin 1, and usually CD103
White pulp splenic involvement
An uncommon lymphoma that infiltrates the splenic red pulp in a diffuse pattern.
Splenic diffuse red pulp small B-cell lymphoma
The immunophenotypic profile shows strong expression of CD20 and negative staining for CD25, CD123, and annexin.
Criteria for initiation of treatment in HCL
Symptoms related to the disease or
Deterioration in blood counts
- Absolute neutrophil count <1000/μL
- Hemoglobin <11 g/dL
- Platelet count <100,000/μL
Approved for initial therapy of HCL
Cladribine
Approved for second-line therapy of HCL
Pentostatin
If it is not possible to control infection, initiating treatment with reduced-dose pentostatin should be considered to secure a durable response before using standard-dose purine analogs.
Dosing of Cladribine
- IV infusion 0.1 mg/kg/day for 7 days as a single course OR
- Daily IV infusion 0.14 mg/kg/day over 2 hours each day for 5 days.
Subcutaneous administration of cladribine has also been successful and may be more convenient.
When to perform a marrow biopsy after Cladribine therapy to determine the quality of the response
4–6 months after blood count recovery
- 3-5 months
Dosing of Pentostatin
4 mg/m2 IV every 2 weeks
Administered once every 2 weeks as a short IV injection followed by administration of approximately 1 L of fluid
When to perform a marrow biopsy after Pentostatin therapy to determine the quality of the response
When the blood counts and the spleen have returned to normal
At the time of best clinical response
If there are no visible areas of HCL by morphologic criteria, then two additional doses are usually administered as consolidation.
This drug is an inhibitor of BRAFV600E and has been shown to induce remission in relapsed or refractory HCL-c patients but is currently still “off-label”
Vemurafenib
Clinical approach for resistant hairy cell leukemia
- Combined chemoimmunotherapy (eg, purine analogue and rituximab)
- Immunotoxin conjugates (eg, moxetumomab pasudotox (HA22)
- BRAF V600E inhibitors (eg, vemurafenib)
The expression of which protein correlates with tumor burden and is a useful laboratory value in terms of disease monitoring?
Soluble interleukin 2 receptor
Soluble CD22 also can be followed in a similar manner as a correlate of leukemic cell burden. (but not yet indicated as important to monitor as response marker)
Defined as evidence of leukemic cells on the marrow biopsy that can be detected using IHC staining when there is no residual morphologic evidence of disease
MRD
TRUE OR FALSE
In general, if the patient achieved an initial response and subsequently relapses within 1–2 years, an alternate agent might be selected for retreatment.
TRUE
In general, if the patient achieved an initial response and subsequently relapses within 1–2 years, an alternate agent might be selected for retreatment.
In contrast, retreatment with the initial therapy can be considered if the first remission was durable.
An immunotoxin conjugate directed against CD22, has been approved by the FDA for the treatment of patients with HCL who have failed to respond to standard therapy
Moxetumomab pasudotox
