Hematology Oncology · Year 2 · from Hematology Oncology
Case 2: Chronic Lymphocytic Leukemia (CLL)
Patient Presentation
Demographics: 72-year-old female
Chief Complaint: Incidentally found lymphocytosis; now with progressive lymphadenopathy and fatigue
History of Present Illness: The patient was diagnosed with CLL 4 years ago when routine labs showed lymphocytosis. She was initially observed with "watch and wait" approach. Over the past 6 months, she has noticed enlarging lymph nodes in her neck and armpits, worsening fatigue, and unintentional 12-pound weight loss. She has had drenching night sweats for the past month. She has had 2 sinus infections in the past 4 months requiring antibiotics.
Physical Examination:
- Vital signs: BP 128/78, HR 82, RR 16, Temp 37.0C
- General: Fatigued-appearing elderly woman
- HEENT: Bilateral cervical lymphadenopathy (2-3 cm, non-tender)
- Axillae: Bilateral lymphadenopathy (3 cm)
- Cardiac: Regular rhythm
- Lungs: Clear
- Abdomen: Splenomegaly (6 cm below costal margin), no hepatomegaly
- Inguinal: Bilateral lymphadenopathy (2 cm)
Workup and Results
Complete Blood Count:
- WBC: 85,000/uL
- Absolute lymphocyte count: 78,000/uL
- Hemoglobin: 9.8 g/dL (baseline 4 years ago: 13.2)
- Platelets: 95,000/uL (baseline: 185,000)
Peripheral Blood Smear:
- Marked lymphocytosis with mature-appearing small lymphocytes
- Numerous smudge cells (basket cells)
- No blasts
Flow Cytometry:
- CD19+, CD5+, CD23+, CD20 (dim), FMC7 negative
- Light chain restriction: Kappa
Additional Workup:
- Beta-2-microglobulin: 5.8 mg/L (elevated)
- LDH: 320 U/L (elevated)
- Direct Coombs (DAT): Positive (IgG)
- Haptoglobin: 25 mg/dL (low)
- Reticulocyte count: 6% (elevated)
- FISH: del(13q14) only - favorable
- IGHV mutation status: Mutated - favorable
- TP53: Wild-type (no mutation or deletion)
CT Imaging:
- Diffuse lymphadenopathy above and below diaphragm
- Splenomegaly
Clinical Image
Peripheral blood smear in chronic lymphocytic leukemia demonstrating mature small lymphocytes and characteristic smudge cells (basket cells) from fragile CLL cells rupturing during smear preparation.
Diagnosis
Chronic Lymphocytic Leukemia - Rai Stage IV with Autoimmune Hemolytic Anemia
Staging and risk:
- Rai Stage IV (anemia + thrombocytopenia)
- IGHV mutated (favorable)
- del(13q) only (favorable)
- TP53 wild-type (favorable)
- B symptoms present
- Concurrent AIHA (DAT positive with hemolysis)
Treatment Plan
- Treatment indication (meets criteria):
- Progressive cytopenias (marrow failure)
- Constitutional symptoms (B symptoms)
- Progressive lymphadenopathy
- Bulky splenomegaly
- First-line therapy (without del(17p)/TP53 mutation):
- Venetoclax + obinutuzumab (time-limited therapy) OR
- BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib)
- Given IGHV mutated status, may also consider FCR if fit and young
- AIHA management:
- Prednisone 1 mg/kg for autoimmune hemolysis
- Will likely improve with CLL treatment
- Monitoring:
- CBC every 1-2 weeks initially
- Response assessment per iwCLL criteria
- Monitor for venetoclax tumor lysis (ramp-up dosing)
- Supportive care:
- IVIG if recurrent infections with hypogammaglobulinemia
- Vaccinations (pneumococcal, influenza)
- PJP prophylaxis with some regimens
Teaching Points
- CLL is the most common adult leukemia in Western countries
- The immunophenotype (CD5+, CD19+, CD23+, dim CD20) distinguishes CLL from mantle cell lymphoma
- Smudge cells result from fragile CLL lymphocytes rupturing during smear preparation
- IGHV mutation status and FISH cytogenetics are critical prognostic factors
- del(17p) or TP53 mutation predicts poor response to chemoimmunotherapy; BTK inhibitors preferred
- Autoimmune cytopenias (AIHA, ITP) are common complications of CLL
- Watch and wait is appropriate for early-stage asymptomatic disease
- Richter transformation to aggressive lymphoma occurs in ~5% of patients