Can Chronic Lymphocytic Leukemia (CLL) cause urinary symptoms like pressure urgency similar to a Urinary Tract Infection (UTI)?

Can CLL Cause UTI-Like Urinary Pressure and Urgency?

Yes, CLL can cause urinary pressure and urgency symptoms that mimic a UTI, though this occurs through two distinct mechanisms: direct bladder infiltration (extremely rare) or increased susceptibility to actual infections (common). 1, 2, 3

Direct CLL Bladder Involvement (Rare but Important)

Extramedullary CLL with bladder infiltration is exceedingly rare but can present with urinary symptoms including dysuria, frequency, urgency, and hematuria that clinically mimic UTI. 2, 3

Key Clinical Features:

• Patients present with recurrent urinary symptoms (dysuria, urgency, frequency) that persist despite negative urine cultures or fail to respond to antibiotics 2, 3
• Gross hematuria is the most common presenting symptom in bladder CLL 2, 3
• Sterile pyuria (white blood cells in urine without bacterial growth) with lymphocytes predominating on Wright stain is highly suggestive 4
• Symptoms may persist for months to years with multiple negative workups before diagnosis 2

Critical Diagnostic Pitfall:

Do not dismiss recurrent UTI-like symptoms in CLL patients as simple infections—if symptoms persist despite appropriate antibiotics or cultures remain negative, cystoscopy with biopsy is mandatory to exclude bladder infiltration. 2, 3

Increased Infection Risk (Common)

CLL patients have significantly increased susceptibility to actual bacterial UTIs due to immunosuppression, making true infections far more common than direct bladder involvement. 1, 5

Why CLL Patients Get More UTIs:

• Gram-negative Enterobacteriaceae cause most UTIs in CLL patients, similar to the general population 5
• Reinfections and superinfections occur frequently, particularly in acute lymphoblastic leukemia 5
• BTK and BCL-2 inhibitor therapies do not routinely require antibiotic prophylaxis, but recurrent infections warrant consideration per ESMO guidelines 1

Diagnostic Challenge in CLL:

CLL patients show decreased inflammatory responses to infection, making clinical symptoms unreliable and laboratory findings atypical. 5

• Non-stable clinical symptoms and multiple changes in urinalysis may be the only clues 5
• Urine culture is mandatory to confirm infection—do not treat empirically based on symptoms alone 1

Diagnostic Algorithm for CLL Patients with UTI-Like Symptoms

Step 1: Immediate Testing

• Urinalysis with microscopy and urine culture before any antibiotics 1
• Check for pyuria and perform Wright stain of urinary sediment—predominance of lymphocytes suggests CLL infiltration rather than infection 4
• Measure post-void residual (PVR) to exclude overflow incontinence from bladder dysfunction 6, 7

Step 2: Interpret Results

• If culture positive with typical bacteria: treat as true UTI 1, 5
• If sterile pyuria with lymphocyte predominance: suspect bladder CLL infiltration 4
• If symptoms persist despite negative cultures or appropriate antibiotic treatment: proceed to cystoscopy 2, 3

Step 3: When to Perform Cystoscopy

• Recurrent symptoms with negative cultures 2, 3
• Gross hematuria in any CLL patient 2, 3
• Sterile pyuria with lymphocyte predominance 4
• Failure to respond to appropriate antibiotics for documented infection 2

Treatment Implications

If bladder CLL is confirmed on cystoscopy with biopsy, systemic CLL-directed therapy (such as venetoclax) treats the bladder involvement and resolves urinary symptoms. 3

Surveillance Requirements:

• Bladder CLL requires close urologic follow-up with surveillance cystoscopy every 3-4 months, as progression to carcinoma in situ or other bladder malignancies can occur 2
• One reported case developed carcinoma in situ just 4 months after initial bladder CLL diagnosis 2

Common Pitfalls to Avoid

• Never assume all urinary symptoms in CLL are infections—sterile pyuria with lymphocytes demands cystoscopy 4
• Do not treat recurrent "UTIs" empirically without cultures in CLL patients—this delays diagnosis of bladder infiltration 2, 3
• Avoid dismissing persistent symptoms after negative workups—bladder CLL can evade diagnosis for years 2
• Remember that asymptomatic bacteriuria (10-50% prevalence in elderly) should not be treated, but symptomatic patients require culture confirmation 1, 8