What is the best approach to manage a patient with Chronic Myeloid Leukemia (CML) presenting with hyperleukocytosis and suspected Tumor Lysis Syndrome (TLS)?

Clinical Teaching Rewrite: CML with Extreme Hyperleukocytosis

1. Presentation and Investigations

This patient presents with newly diagnosed Chronic Myeloid Leukemia (CML) in chronic phase complicated by extreme hyperleukocytosis (WBC 442.5 × 10⁹/L), which represents a true hematologic emergency requiring immediate intervention 1.

Key Clinical Features at Presentation:

• Extreme leukocytosis: WBC 442.5 × 10⁹/L with 5% myeloblasts and 15% myelocytes, confirming chronic phase CML (blast count <10%) 1
• Anemia: Hemoglobin 7.3 g/dL, Hematocrit 28.1% - likely multifactorial from marrow infiltration and possible hemolysis 2
• Thrombocytosis: Platelets 207 × 10³/μL - preserved platelet production despite massive leukocytosis 3
• Metabolic derangements: LDH >1598 IU/L (markedly elevated), Uric Acid 9.8 mg/dL (elevated), ALP 385 IU/L (elevated) 1, 4
• Renal function: Creatinine 0.89 mg/dL (preserved), Urea 52.3 mg/dL (mildly elevated) - critical for TLS risk stratification 1, 4
• Vital signs: Documented as stable, but this requires careful interpretation given the extreme leukocytosis 1

Critical Investigations Completed:

• Peripheral blood smear with differential confirming myeloid left shift 1
• Cytopathology suggestive of CML (BCR-ABL1 confirmation status unclear from documentation) 5
• Comprehensive metabolic panel demonstrating TLS risk 1, 4

Pending Essential Studies:

• BCR-ABL1 fusion confirmation by PCR or FISH - absolutely required before definitive TKI therapy 5
• Lymph node biopsy planned (rationale unclear - not standard for CML-CP diagnosis) 1
• ELTS risk score calculation - requires age, spleen size, platelet count, and blast percentage to guide first-line TKI selection 1

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2. Problem List (Prioritized by Mortality Risk)

Immediate Life-Threatening Issues:

1. Extreme Hyperleukocytosis (WBC 442.5 × 10⁹/L) with Leukostasis Risk

• Despite leukostasis being uncommon in CML-CP (16.5% incidence even at median WBC 240 × 10⁹/L), this patient's count exceeds 440 × 10⁹/L, placing them at substantial risk for cerebral or pulmonary leukostasis, priapism (if male), and microvascular thrombosis 1
• Clinical pearl: Symptoms of leukostasis (dyspnea, hypoxia, altered mental status, visual changes) may be subtle initially but progress rapidly to respiratory failure or stroke 6, 7

2. Suspected Tumor Lysis Syndrome (TLS)

• Laboratory findings: Elevated LDH >1598 IU/L, uric acid 9.8 mg/dL, mildly elevated urea 52.3 mg/dL 1, 4
• Critical distinction: TLS is rare in CML-CP (unlike acute leukemias or high-grade lymphomas), but this patient's extreme tumor burden and initiation of cytoreductive therapy creates risk 1, 8
• Cairo-Bishop criteria assessment: Currently meets laboratory TLS criteria (elevated uric acid, LDH) but lacks clinical TLS features (preserved renal function, normal electrolytes documented) 1, 4
• Pitfall to avoid: The preserved creatinine (0.89 mg/dL) is reassuring but requires serial monitoring as AKI can develop rapidly once cytoreduction begins 1, 4, 8

3. Symptomatic Anemia (Hemoglobin 7.3 g/dL)

• Requires assessment for hemolysis (reticulocyte count, direct Coombs test, haptoglobin, bilirubin) versus marrow suppression 1, 2
• Transfusion threshold depends on symptoms and cardiopulmonary status 5

Active Management Issues:

4. Suboptimal Current Medication Regimen

• Hydroxyurea dosing unclear ("documented inconsistently") - this is the primary cytoreductive agent and requires precise dosing 5, 2
• Allopurinol 100 mg PO BID - dose may be inadequate for this degree of hyperuricemia and tumor burden 1, 9, 4
• Metronidazole 250 mg PO TID - indication unclear; possible infectious complication not documented 5
• UFH 5000 IU SC BID - thromboprophylaxis appropriate given immobility risk, but must monitor for HIT 5
• Lactulose 30 mL PO q2h - suggests hepatic encephalopathy concern or severe constipation 5
• Tenofovir disoproxil fumarate 300 mg PO three times weekly - indicates HIV co-infection or chronic hepatitis B, which has critical implications for TKI selection and TLS risk 1, 5

5. Delayed Definitive Therapy

• No TKI initiated yet - every day without TKI therapy represents lost opportunity for achieving optimal molecular responses that predict long-term survival 5
• Once BCR-ABL1 is confirmed, immediate TKI initiation is mandatory with hydroxyurea taper over 3-5 days 5

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3. Clinical Interpretation (Synthesis of Findings)

Disease Biology and Pathogenesis:

CML Chronic Phase with Extreme Presentation:

• CML results from the Philadelphia chromosome t(9;22) translocation creating the BCR-ABL1 fusion oncogene, which produces constitutively active tyrosine kinase driving uncontrolled myeloid proliferation 1
• The blast count of 5% confirms chronic phase (CP-CML requires <10% blasts in blood/marrow), which has dramatically better prognosis than accelerated or blast phase 1, 3
• The presence of 15% myelocytes indicates left-shifted myeloid maturation typical of CML but not indicative of disease acceleration 1

Hyperleukocytosis Pathophysiology:

• WBC >100 × 10⁹/L increases blood viscosity and causes microvascular sludging 1, 7
• Critical distinction: In CML-CP, mature myeloid cells are less "sticky" than blasts in acute leukemia, making symptomatic leukostasis less common despite higher WBC counts 1
• However, at 442.5 × 10⁹/L, the sheer cell mass creates rheological problems regardless of cell maturity 1, 6

TLS Risk Assessment:

• Tumor burden: Extreme WBC count represents massive tumor burden (likely >500 g total leukemic cell mass) 1, 4
• Metabolic markers: Elevated LDH and uric acid indicate high cell turnover even before cytoreductive therapy 1, 4
• Renal function: Currently preserved (Cr 0.89 mg/dL), which is the most important protective factor against clinical TLS 1, 4
• Risk stratification: This patient has high-risk features for TLS development once cytoreduction begins: massive tumor burden, elevated baseline uric acid, and initiation of hydroxyurea 1, 4

HIV/HBV Co-infection Implications:

• Tenofovir suggests HIV or HBV co-infection, which increases risk of pancreatitis, hepatotoxicity, and neuropathy when combined with hydroxyurea 1, 2
• HIV patients with CML require careful monitoring for antiretroviral-TKI interactions 1, 5

Laboratory Abnormalities Explained:

• LDH >1598 IU/L: Reflects massive cell turnover from high leukemic burden; also serves as TLS marker 1, 4
• Uric Acid 9.8 mg/dL: Elevated from purine metabolism of dying cells; risk factor for uric acid nephropathy if cytoreduction proceeds without adequate prophylaxis 1, 9, 4
• ALP 385 IU/L: May indicate hepatic infiltration, bone involvement, or cholestasis 5
• Preserved electrolytes: Reassuring that clinical TLS has not yet developed, but requires q6-8h monitoring once cytoreduction intensifies 1, 4

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4. Diagnosis and Differential Diagnosis

Primary Diagnosis:

Chronic Myeloid Leukemia, Chronic Phase (CML-CP) with Extreme Hyperleukocytosis

• Confirmed by: Cytopathology suggestive of CML, peripheral smear showing myeloid left shift with 5% blasts and 15% myelocytes, WBC 442.5 × 10⁹/L 1
• Awaiting: BCR-ABL1 fusion confirmation by PCR or FISH (mandatory for definitive diagnosis and TKI initiation) 5

Differential Diagnosis to Exclude:

1. CML Accelerated Phase or Blast Crisis

• Against: Blast count only 5% (accelerated phase requires 10-19% blasts, blast crisis ≥20%) 1, 3
• Against: No documented basophilia >20%, no additional cytogenetic abnormalities mentioned 3
• Clinical significance: If this were accelerated/blast phase, prognosis would be dramatically worse and treatment approach would differ 3

2. Chronic Myelomonocytic Leukemia (CMML)

• Against: CMML typically presents with monocytosis >1 × 10⁹/L and <20% blasts, but the extreme leukocytosis and myelocyte predominance favor CML 10
• Against: CMML is BCR-ABL1 negative by definition 10

3. Leukemoid Reaction

• Against: Leukemoid reactions (reactive leukocytosis from infection, inflammation, malignancy) rarely exceed 50-100 × 10⁹/L and lack the myeloid left shift with myelocytes 1
• Against: Presence of 5% blasts strongly suggests primary hematologic malignancy 1

4. Other Myeloproliferative Neoplasms (Essential Thrombocythemia, Polycythemia Vera, Primary Myelofibrosis)

• Against: These conditions rarely present with WBC >100 × 10⁹/L 1
• Against: The myeloid left shift with blasts and myelocytes is characteristic of CML 1

5. Acute Myeloid Leukemia (AML) with Hyperleukocytosis

• Against: Blast count only 5% (AML requires ≥20% blasts) 6, 7
• Clinical pearl: AML with hyperleukocytosis has much higher leukostasis risk (symptomatic at WBC >100 × 10⁹/L) and worse prognosis than CML-CP 6, 7

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5. Current Management: Critical Appraisal

What is Being Done Correctly:

1. Allopurinol for TLS Prophylaxis

• Allopurinol inhibits xanthine oxidase, reducing uric acid production from purine metabolism 1, 9, 4
• However: Current dose (100 mg PO BID = 200 mg/day total) is likely inadequate for this patient's tumor burden and baseline uric acid 9.8 mg/dL 1, 9, 4
• Standard dosing: 300-600 mg/day in divided doses for TLS prophylaxis in high tumor burden 1, 9, 4

2. Hydroxyurea for Cytoreduction

• Hydroxyurea is appropriate as temporary cytoreductive agent before TKI initiation 5, 2
• Critical issue: Dosing "documented inconsistently" - this must be clarified immediately 5, 2
• Standard dosing: 40 mg/kg/day (adults) or 25-50 mg/kg/day (pediatrics) in divided doses 1, 5, 2
• Expected effect: 50% WBC reduction in 1-2 weeks 1

3. IV Normal Saline (IV NS) for Hydration

• Aggressive hydration (2.5-3 L/m²/day) is cornerstone of TLS prevention, improving renal perfusion and minimizing uric acid/calcium phosphate precipitation in renal tubules 1, 4
• Monitoring requirement: Urine output (UOP) monitoring is appropriate - target UOP >100 mL/m²/hr or 2-3 L/day in adults 1, 4

4. Thromboprophylaxis with UFH

• Appropriate given immobility risk and potential for paradoxical thrombosis despite thrombocytosis 5, 3

Critical Deficiencies in Current Management:

1. No Rasburicase Consideration

• Major omission: With WBC 442.5 × 10⁹/L, uric acid 9.8 mg/dL, and massive tumor burden, this patient meets criteria for rasburicase consideration 1, 5, 4
• Rasburicase (recombinant urate oxidase) directly converts uric acid to allantoin (more soluble), providing immediate uric acid reduction versus allopurinol's prevention of new uric acid formation 1, 4
• Guideline recommendation: "Rasburicase should be considered as initial treatment if there is rapidly increasing blast counts, high uric acid levels, and evidence of impaired renal function" 5
• Clinical decision: While renal function is currently preserved, the extreme tumor burden and elevated baseline uric acid argue for rasburicase over allopurinol alone 1, 5, 4

2. Inadequate TLS Monitoring Protocol

• Missing: No documented frequency of electrolyte monitoring 1, 4
• Required: CBC and comprehensive metabolic panel (including potassium, phosphate, calcium, uric acid, LDH, creatinine) every 6-8 hours during active cytoreduction 1, 5, 4
• Pitfall: Pseudohyperkalemia can occur with extreme leukocytosis due to in vitro cell lysis - if hyperkalemia develops, obtain plasma potassium in heparinized tube analyzed immediately 11

3. No Documented Leukostasis Assessment

• Missing: No documentation of symptoms suggesting leukostasis (dyspnea, hypoxia, altered mental status, visual changes, priapism if male) 1, 6, 7
• Required: Serial neurologic and respiratory examinations, pulse oximetry, chest imaging if symptomatic 1, 7
• If leukostasis present: Requires emergency leukapheresis or exchange transfusion (can achieve 30-80% WBC reduction within hours) plus intensified cytoreduction 1, 7

4. Delayed TKI Initiation

• Critical error: "Every day without TKI therapy represents lost opportunity for achieving optimal molecular responses that predict long-term survival" 5
• Correct approach: Once BCR-ABL1 is confirmed, immediately initiate TKI with hydroxyurea taper over 3-5 days 5
• TKI selection: Should be guided by ELTS risk score (not calculated in this case) - high-risk patients benefit from second-generation TKIs (nilotinib 300 mg BID or dasatinib 100 mg daily) over imatinib 400 mg daily 1, 5

5. Unclear Indication for Lymph Node Biopsy

• Not standard: Lymph node biopsy is not part of routine CML-CP diagnostic workup 1
• Possible rationale: Concern for Richter transformation (unlikely given chronic phase features) or lymphadenopathy from another cause 1

6. Inadequate Allopurinol Dosing

• Current dose 100 mg BID (200 mg/day total) is below standard TLS prophylaxis dosing of 300-600 mg/day 1, 9, 4
• Dose adjustment needed: Increase to 300 mg PO BID (600 mg/day) or consider switching to rasburicase 1, 9, 4

7. No Transfusion Strategy Documented

• Hemoglobin 7.3 g/dL requires assessment of symptoms and transfusion threshold 5
• Caution: Avoid transfusion if leukostasis suspected, as increasing blood viscosity can worsen microvascular sludging 6, 7
• If transfusion needed: Use leukocyte-reduced products to prevent HLA alloimmunization (important if future transplant candidate) 5

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6. Additional Recommendations

Immediate Actions (Within 6 Hours):

1. Escalate TLS Prophylaxis

• Discontinue allopurinol 100 mg BID 1, 9, 4
• Initiate rasburicase 0.2 mg/kg IV once (can repeat daily if needed) 1, 5, 4
• Rationale: Extreme tumor burden (WBC 442.5 × 10⁹/L), elevated baseline uric acid (9.8 mg/dL), and massive cell turnover (LDH >1598) warrant immediate uric acid reduction, not just prevention of new formation 1, 5, 4
• Alternative if rasburicase unavailable: Increase allopurinol to 300 mg PO BID (600 mg/day total) 1, 9, 4

2. Intensify Hydration and Monitoring

• Continue IV NS at 2.5-3 L/m²/day (approximately 150-200 mL/hr in average adult), titrated to maintain UOP >100 mL/m²/hr 1, 4
• Avoid potassium-containing fluids (use 0.9% NaCl without additives) 1, 4
• Monitor: Strict intake/output, daily weights, assess for fluid overload 1, 4

3. Establish Intensive TLS Monitoring Protocol

• Order: CBC, comprehensive metabolic panel (Na, K, Cl, HCO3, BUN, Cr, Ca, Phos, Mg), uric acid, LDH every 6-8 hours 1, 5, 4
• If hyperkalemia develops: Obtain plasma potassium in heparinized tube analyzed immediately to exclude pseudohyperkalemia from in vitro cell lysis 11
• ECG monitoring: Continuous telemetry to detect arrhythmias from hyperkalemia or hypocalcemia 1, 4

4. Clarify and Optimize Hydroxyurea Dosing

• Determine patient's weight and calculate appropriate dose: 40 mg/kg/day in 2-3 divided doses 5, 2
• Example: For 70 kg patient, dose = 2800 mg/day (can give as 1000 mg PO TID or 1400 mg PO BID) 5, 2
• Monitor: CBC every 2-4 weeks initially, then as clinically indicated once doses stabilized 5, 2
• Goal: Reduce WBC by 50% over 1-2 weeks while awaiting BCR-ABL1 confirmation and TKI initiation 1, 5

5. Assess for Leukostasis

• Perform: Detailed neurologic examination (mental status, cranial nerves, vision), respiratory examination (work of breathing, oxygen saturation, auscultation) 1, 6, 7
• If male: Assess for priapism 1
• If any symptoms present: Obtain chest X-ray, consider CT head, prepare for emergency leukapheresis 1, 7
• Leukapheresis indications: Symptomatic leukostasis (altered mental status, respiratory distress, visual changes, priapism) despite medical management 1, 7

Short-Term Actions (Within 24-48 Hours):

6. Expedite BCR-ABL1 Confirmation

• Contact laboratory: Request STAT BCR-ABL1 PCR or FISH analysis 5
• Rationale: Cannot initiate definitive TKI therapy without molecular confirmation 5
• Once confirmed: Immediately start TKI and begin hydroxyurea taper 5

7. Calculate ELTS Risk Score

• Required data: Age, spleen size (cm below costal margin), platelet count, blast percentage 1
• Missing data: Spleen size not documented - obtain abdominal examination or ultrasound 1
• Clinical significance: ELTS high-risk patients (11% of pediatric cohort, similar distribution in adults) have significantly lower 3-year PFS (72.0% vs 97.1% in low-risk) and benefit from second-generation TKIs as first-line therapy 1

8. Select Appropriate First-Line TKI

• If ELTS low-risk: Imatinib 400 mg PO daily is appropriate first-line 1, 5
• If ELTS intermediate or high-risk: Consider second-generation TKI (nilotinib 300 mg PO BID or dasatinib 100 mg PO daily) for superior molecular response rates 1, 5
• Special consideration: If HIV co-infection confirmed (suggested by tenofovir), check for antiretroviral-TKI interactions and monitor for pancreatitis, hepatotoxicity, neuropathy 1, 5, 2
• Cardiovascular risk factors: If nilotinib selected, assess and optimize cardiovascular risk factors (smoking, hypertension, diabetes, dyslipidemia) as nilotinib carries vaso-occlusive event risk 3

9. Address Anemia

• Obtain: Reticulocyte count, direct Coombs test, haptoglobin, indirect bilirubin, peripheral smear review for schistocytes 1, 2
• Assess symptoms: Dyspnea, chest pain, dizziness, tachycardia 5
• Transfusion threshold: Consider RBC transfusion if Hgb <7 g/dL with symptoms or <8 g/dL with cardiovascular disease 5
• Caution: If leukostasis suspected, defer transfusion as increasing blood viscosity worsens microvascular sludging 6, 7
• Product selection: Use leukocyte-reduced, irradiated RBCs if future transplant candidate 5

10. Clarify Antibiotic and Antiviral Indications

• Metronidazole 250 mg PO TID: Indication unclear - assess for documented infection (C. difficile, anaerobic infection, hepatic encephalopathy) 5
• Tenofovir disoproxil fumarate 300 mg PO three times weekly: Confirms HIV or HBV co-infection 1, 5
• If HIV: Obtain CD4 count, viral load, review antiretroviral regimen for TKI interactions 1, 5
• If HBV: Obtain HBV DNA, consider hepatology consultation as TKI therapy can cause HBV reactivation 1, 5

Medium-Term Actions (Within 1 Week):

11. Establish Baseline Molecular and Cytogenetic Studies

• Once BCR-ABL1 confirmed: Obtain quantitative BCR-ABL1 transcript level (baseline for monitoring) 5, 3
• Bone marrow biopsy with cytogenetics: Perform at diagnosis to establish baseline and detect additional cytogenetic abnormalities (e.g., +8, iso(17q), +19, del(11q), del(17p)) that predict higher progression risk 3
• FISH panel: del(17p), TP53 mutation analysis - strongest prognostic and predictive relevance 1, 3

12. Initiate TKI and Taper Hydroxyurea

• Once BCR-ABL1 confirmed: Start selected TKI immediately 5
• Hydroxyurea taper: Reduce dose by 50% when starting TKI, then discontinue over 3-5 days as WBC decreases 5
• Monitoring: Continue CBC every 2-4 weeks until doses stabilized 5, 2

13. Establish Long-Term Monitoring Plan

• BCR-ABL1 transcript levels: Every 3 months while responding to treatment 5, 3
• Bone marrow cytogenetics: At 6 and 12 months from therapy initiation 5, 3
• Response milestones: Complete hematologic response at 3 months, minimal cytogenetic response at 6 months, major cytogenetic response at 12 months 5, 3
• Failure to achieve milestones: Indicates inadequate response, requiring BCR-ABL1 kinase domain mutation testing and treatment modification 5, 3

14. Address Quality of Life and Supportive Care

• Splenomegaly management: If massive splenomegaly causing early satiety or discomfort, hydroxyurea and TKI will reduce spleen size over weeks to months 3
• Fatigue, night sweats, weight loss: Reflect hypercatabolic syndrome and disease activity - should improve with effective TKI therapy 3
• TKI side effects: Educate about common adverse effects (muscle cramps with imatinib - manage with calcium supplementation or tonic water; GI upset - take with meals; nilotinib vaso-occlusive events; dasatinib pleural effusions and platelet dysfunction) 3

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7. Key Learning Points

Disease-Specific Pearls:

1. CML-CP with Extreme Hyperleukocytosis is Rare but Manageable

• Despite WBC >400 × 10⁹/L, leukostasis is less common in CML-CP than in acute leukemia because mature myeloid cells are less "sticky" than blasts 1
• However, at this extreme level, rheological problems can still occur - maintain high index of suspicion for leukostasis symptoms 1, 6, 7

2. TLS in CML-CP is Uncommon but Preventable

• "TLS is rare in children with CML-CP" and does not mandate routine hypouricemic agents in typical cases 1
• However, this patient's extreme tumor burden (WBC 442.5 × 10⁹/L) and elevated baseline uric acid (9.8 mg/dL) create substantial TLS risk once cytoreduction begins 1, 4, 8
• Prevention strategy: Aggressive hydration (2.5-3 L/m²/day) + rasburicase (preferred over allopurinol given tumor burden) + intensive monitoring 1, 5, 4

3. Hydroxyurea is a Bridge, Not a Destination

• "Hydroxyurea should be used only for a short time before initiating a TKI, until the diagnosis of CML has been confirmed" 5
• "The most critical error is continuing hydroxyurea beyond the brief period needed for diagnosis confirmation and initial cytoreduction" 5
• Once BCR-ABL1 confirmed: Immediately start TKI and taper hydroxyurea over 3-5 days 5

4. TKI Selection Should Be Risk-Stratified

• ELTS score identifies high-risk pediatric patients (11% of cohort) with significantly worse 3-year PFS (72.0% vs 97.1% in low-risk) 1
• High-risk patients benefit from second-generation TKIs (nilotinib or dasatinib) as first-line therapy 1, 5
• Low-risk patients can start with imatinib 1, 5

5. Pseudohyperkalemia Can Mimic TLS

• Extreme leukocytosis causes in vitro cell lysis during blood processing, releasing intracellular potassium and falsely elevating serum potassium 11
• Clue: Elevated serum potassium without ECG changes (peaked T waves, widened QRS) 11
• Confirmation: Obtain plasma potassium in heparinized tube analyzed immediately - will be normal if pseudohyperkalemia 11

Management Principles:

6. Aggressive Hydration is the Cornerstone of TLS Prevention

• Target 2.5-3 L/m²/day IV fluids (approximately 150-200 mL/hr in average adult) 1, 4
• Goal: UOP >100 mL/m²/hr or 2-3 L/day in adults 1, 4
• Mechanism: Improves renal perfusion and minimizes uric acid/calcium phosphate precipitation in renal tubules 1, 4

7. Rasburicase vs Allopurinol: Choose Based on Tumor Burden and Urgency

• Rasburicase: Directly converts uric acid to allantoin (more soluble), providing immediate reduction - preferred for high tumor burden, elevated baseline uric acid, or impaired renal function 1, 5, 4
• Allopurinol: Inhibits xanthine oxidase, preventing new uric acid formation but does not reduce existing uric acid - adequate for low-moderate tumor burden with normal baseline uric acid 1, 9, 4
• This patient: Meets criteria for rasburicase given WBC 442.5 × 10⁹/L and uric acid 9.8 mg/dL 1, 5, 4

8. Leukostasis Requires Emergency Cytoreduction

• Symptoms: Dyspnea, hypoxia, altered mental status, visual changes, priapism (if male) 1, 6, 7
• Emergency management: Leukapheresis or exchange transfusion (30-80% WBC reduction within hours) + intensified hydroxyurea + immediate TKI initiation 1, 7
• Avoid: Transfusion if leukostasis suspected, as increasing blood viscosity worsens microvascular sludging 6, 7

9. Monitoring Intensity Must Match Disease Acuity

• During active cytoreduction: CBC and comprehensive metabolic panel every 6-8 hours 1, 5, 4
• Once WBC stabilized: CBC every 2-4 weeks until doses stabilized, then as clinically indicated 5, 2
• Long-term: BCR-ABL1 transcripts every 3 months, bone marrow cytogenetics at 6 and 12 months 5, 3

10. HIV/HBV Co-infection Complicates CML Management

• Tenofovir suggests HIV or HBV co-infection 1, 5
• Risks: Pancreatitis, hepatotoxicity, neuropathy when hydroxyurea combined with antiretrovirals 1, 2
• TKI interactions: Check for antiretroviral-TKI drug interactions 1, 5
• HBV reactivation: TKI therapy can trigger HBV reactivation - monitor HBV DNA, consider hepatology consultation 1, 5

Common Pitfalls:

11. Do Not Delay TKI Initiation

• "Every day without TKI therapy represents lost opportunity for achieving optimal molecular responses that predict long-term survival" 5
• Once BCR-ABL1 confirmed, start TKI immediately - do not wait for WBC to normalize with hydroxyurea alone 5

12. Do Not Overlook Cardiovascular Risk with Nilotinib

• Nilotinib carries risk of vaso-occlusive events (ischemic heart disease, cerebrovascular events, peripheral arterial disease) 3
• Before starting nilotinib: Assess and optimize cardiovascular risk factors (smoking cessation, lipid control, blood pressure management, diabetes control) 3

13. Do Not Assume Hyperkalemia is Real in Extreme Leukocytosis

• Always consider pseudohyperkalemia from in vitro cell lysis 11
• Confirm with plasma potassium in heparinized tube analyzed immediately before treating aggressively 11

14. Do Not Forget to Calculate ELTS Risk Score

• ELTS score guides TKI selection (second-generation TKIs for high-risk patients) 1
• Requires age, spleen size, platelet count, blast percentage - ensure spleen size documented 1

15. Do Not Continue Hydroxyurea as Definitive Therapy

• Hydroxyurea is NOT recommended as definitive treatment for CML - serves only as temporary cytoreductive agent before TKI 5, 2
• TKIs target the molecular pathophysiology (BCR-ABL1 tyrosine kinase) and achieve deep molecular responses that translate to near-normal survival, which hydroxyurea cannot accomplish 5