Case Study 1
55-year-old man is referred for mild lymphadenopathy and
lymphocytosis found during routine medical examination
• Findings:
– Patient has 2-3 cm bilateral
adenopathy in cervical and
axillary
chains
– Spleen and liver are not
palpable
– Patient is asymptomatic
except for occasional night
sweats
• Performance score is excellent
• CBC count:
– WBC count 36,000/µL (79%
mature lymphocytes, ANC
2,800 cells/mm3)
– Hgb 12.5 g/dL
– Platelets 167,000/µL
• Flow cytometry consistent
with CLL
CBC, complete blood cell; WBC, white blood cell; ANC, absolute neutrophil count; Hgb, hemoglobin.
Question 1
What treatment would you recommend for initial therapy?
1. Observation
2. Chlorambucil ± prednisone
3. Chlorambucil + obinutuzumab
4. Fludarabine + rituximab
5. Bendamustine + rituximab
6. Fludarabine, cyclophosphamide + rituximab
7. Pentostatin, cyclophosphamide + rituximab
Case Study 1 (cont.)
•
The patient is observed for the next 2 years then progressive
fatigue and dyspnea on exertion develop
•
CBC:
–
WBC 96,000/µL (87% mature lymphocytes, ANC 4,500
cells/mm3)
–
Hgb 9.5 g/dL
–
Platelets 87,000/µL
•
Evaluation for hemolysis and ITP is negative
•
No evidence of GI blood loss
•
Cytotoxic therapy is started
•
Patient is now 60 years old
CBC, complete blood cell; WBC, white blood cell; ANC, absolute neutrophil count; Hgb, hemoglobin; ITP, idiopathic thrombocytopenic purpura.
Question 2
Prior to starting therapy, which of the following
prognostic tests would be most important to perform?
1. None; the patient progressed quickly so we know his
prognosis is limited
2. β2-microglobulin
3. IgVH mutational status
4. ZAP-70 status
5. FISH analysis
6. CD38 expression
IgVH, immunoglobulin heavy chain variable; ZAP-70, zeta-chain–associated protein kinase 70;
FISH, fluorescence in situ hybridization.
Case Study 1 (cont.)
• FISH analysis is performed and shows del(11q) in 57% and
del(17p) in 6% of cells
FISH, fluorescence in situ hybridization.
Question 3
What treatment would you recommend at this time?
1. Observation
2. Chlorambucil ± prednisone
3. Chlorambucil + obinutuzumab
4. Alemtuzumab ± rituximab
5. Fludarabine + rituximab
6. Bendamustine + rituximab
7. Fludarabine, cyclophosphamide, + rituximab
8. Pentostatin, cyclophosphamide ,+ rituximab
Case Study 1 (cont.)
•
The patient is treated with FCR and achieves a partial
response
•
The patient does well for the next 18 months, but then
progresses and symptomatic anemia requiring therapy
develops again
•
The patient is now 62 years old
•
Prior to retreatment, FISH analysis was performed and shows
del(11q) in 27% and del(17p) in 86% of cells
FCR, fludarabine, cyclophosphamide, + rituximab; FISH, fluorescence in situ hybridization.
Question 4
What treatment would you recommend for second line?
1. Observation
2. Chlorambucil + obinutuzumab
3. Alemtuzumab ± rituximab
4. Fludarabine + rituximab
5. Bendamustine + rituximab
6. Fludarabine, cyclophosphamide, + rituximab
7. Pentostatin, cyclophosphamide ,+ rituximab
8. Ibrutinib
Case Study 2
76-year-old woman with diabetes and chronic stable angina
• Referred for mild
lymphadenopathy and
lymphocytosis found during
annual medical exam
• Findings:
– 2 cm adenopathy in the cervical,
axillary, and inguinal chains
– Spleen is palpable 4 cm below
left costal margin
– Completely asymptomatic
– Performance score is good
• CBC count
– WBC count 23,000/µL (81%
mature lymphocytes, ANC 3,500
cells/mm3)
– Hgb 13 g/dL
– Platelets 181,000/µL
• Flow cytometry is consistent with
CLL
• FISH analysis shows del 13q
in 52% of cells, unmutated
• β2-microglobulin of 3.4 µg/mL,
negative for ZAP-70
CBC, complete blood cell; WBC, white blood cell; ANC, absolute neutrophil count; Hgb, hemoglobin;
FISH, fluorescence in situ hybridization; ZAP-70, zeta-chain–associated protein kinase 70.
Question 1
What treatment would you recommend for initial therapy?
1. Observation
2. Chlorambucil ± prednisone
3. Chlorambucil + obinutuzumab
4. Fludarabine + rituximab
5. Bendamustine + rituximab
6. Fludarabine, cyclophosphamide, + rituximab
7. Pentostatin, cyclophosphamide, + rituximab
Case Study 2 (cont.)
•
•
•
•
•
•
•
Patient is observed for the next 6 years
Eventually progressive fatigue and dyspnea on exertion develops; she is now
82 years old
Patient had a mild stroke 2 years ago but has largely recovered
CBC count now shows:
– WBC count 126,000/µL (91% mature lymphocytes, ANC 6,300 cells/mm3)
– Hgb 8.9 g/dL
– Platelets 107,000/µL
– Evaluation for hemolysis is negative
There is no evidence of GI blood loss
FISH analysis repeated prior to starting therapy, showed del(13q) in 68% of
cells
Together with the patient, it has been decided it is time to start cytotoxic
therapy
CBC, complete blood cell; WBC, white blood cell; ANC, absolute neutrophil count; Hgb, hemoglobin;
FISH, fluorescence in situ hybridization.
Question 2
What treatment would you recommend at this time?
1. Observation
2. Chlorambucil ± prednisone
3. Chlorambucil + obinutuzumab
4. Fludarabine + rituximab
5. Bendamustine + rituximab
6. Fludarabine, cyclophosphamide, + rituximab
7. Pentostatin, cyclophosphamide,+ rituximab
Case Study 2 (cont.)
o Patient is treated with chlorambucil and obinutuzumab
and achieves a high-quality partial response
• She does well for the next 3 years but symptomatic
anemia that does not respond to treatment ultimately
develops
• Patient is now 84 years old with an ECOG PS of 2
ECOG = Eastern Cooperative Oncology Group.
Question 3
Prior to retreatment, which of the following prognostic
tests would be most important to perform?
1. None; at relapse in an older patient, these tests have little
practical utility
2. β2-microglobulin
3. IgVH mutational status
4. ZAP-70 status
5. FISH analysis
6. CD38 expression
IgVH, immunoglobulin heavy chain variable; ZAP-70, zeta-chain–associated protein kinase 70; FISH, fluorescence in situ hybridization.
Question 4
What treatment would you recommend for second line?
1. Observation
2. Chlorambucil + obinutuzumab
3. Alemtuzumab ± rituximab
4. Fludarabine + rituximab
5. Bendamustine + rituximab
6. Fludarabine, cyclophosphamide, + rituximab
7. Pentostatin, cyclophosphamide, + rituximab
8. Idelalisib + rituximab
9. Ibrutinib
Case Study 2 (cont.)
• The patient is treated with ibrutinib
• She shows improvement in anemia and lymphadenopathy,
and otherwise has stable disease