What are the criteria for prophylaxis therapy in leukemia patients?

Prophylaxis Therapy Criteria Based on ANC for Leukemia Patients

Antifungal Prophylaxis

For acute myeloid leukemia (AML) patients undergoing intensive chemotherapy with prolonged neutropenia, antifungal prophylaxis with mold-active agents (posaconazole, itraconazole, or amphotericin) is recommended to reduce invasive fungal infections and mortality. 1

AML/MDS Patients on Intensive Chemotherapy

• Patients receiving cytotoxic chemotherapy for AML or myelodysplastic syndromes (MDS) should receive mold-active antifungal prophylaxis due to prolonged profound neutropenia 1, 2
• Posaconazole prophylaxis significantly reduced invasive fungal infections (2% vs 8%) and Aspergillus infections (1% vs 7%) compared to fluconazole/itraconazole in neutropenic AML/MDS patients 2
• Venetoclax-based regimens in AML result in prolonged neutropenia with invasive fungal infection rates of 6.6/100 cycles, predominantly Aspergillus, requiring mold-active prophylaxis rather than fluconazole 3

Chronic Lymphocytic Leukemia (CLL) Patients

• Universal antifungal prophylaxis is NOT recommended for CLL patients on BTK inhibitors (ibrutinib, acalbrutinib, zanubrutinib) or BCL-2 inhibitors (venetoclax) as monotherapy 1
• Consider prophylaxis only if additional risk factors present: prior fludarabine therapy, concurrent corticosteroids, or combination with anti-CD20 antibodies 1

Pneumocystis jirovecii Pneumonia (PJP) Prophylaxis

TMP-SMX prophylaxis should be administered to acute lymphoblastic leukemia (ALL) patients throughout antileukemic therapy and to allogeneic hematopoietic stem cell transplant (HSCT) recipients for at least 6 months post-transplant. 1

High-Risk Populations Requiring PJP Prophylaxis

• ALL patients: throughout entire treatment course 1
• Allogeneic HSCT recipients: minimum 6 months post-transplant and while receiving immunosuppressive therapy 1
• Patients receiving corticosteroids ≥20 mg prednisone daily (or equivalent) for ≥4 weeks 1
• Patients on alemtuzumab: for minimum 2 months after last dose and until CD4 count >200 cells/mcL 1
• Patients receiving temozolomide, copanlisib, idelalisib, or duvelisib + rituximab 1

CLL Patients - Limited Indications

• PJP prophylaxis is NOT routinely recommended for CLL patients on BTK or BCL-2 inhibitor monotherapy 1
• Consider prophylaxis only if: prior purine analogue therapy (fludarabine), prolonged high-dose corticosteroids, or concurrent alemtuzumab 1

Alternative Regimens for TMP-SMX Intolerance

• Dapsone 100 mg daily (check G6PD levels first) 1, 4
• Atovaquone 1500 mg daily 1, 4
• Aerosolized pentamidine 300 mg monthly via Respirgard II nebulizer 4

Antibacterial Prophylaxis

Fluoroquinolone prophylaxis (levofloxacin) should be considered for AML patients receiving intensive chemotherapy with expected prolonged profound neutropenia (ANC <100 cells/mcL for >7 days). 1, 5

Evidence for Fluoroquinolone Prophylaxis in AML

• Levofloxacin prophylaxis significantly reduced febrile neutropenia (OR 0.43), microbiologically documented infections (OR 0.45), and bacteremia (OR 0.45) in acute leukemia patients receiving intensive chemotherapy 5
• Antibiotic prophylaxis was independently associated with decreased infectious complications (p=0.030) during low-intensity therapeutic regimens for AML 6
• NCCN guidelines recommend considering fluoroquinolones for patients at high risk for opportunistic infections 1

CLL Patients - Not Recommended

• Antibiotic prophylaxis is NOT routinely recommended for CLL patients on targeted therapies (BTK or BCL-2 inhibitors) 1
• Consider only in cases of recurrent infections or when combined with other immunosuppressive agents 1

Important Caveats

• Drug-drug interactions: Ciprofloxacin (moderate CYP3A4 inhibitor) significantly increases ibrutinib and venetoclax plasma concentrations, requiring dose adjustments 1
• Risk of selecting resistant organisms including fluoroquinolone-resistant E. coli, viridans streptococci, and C. difficile 7
• Mortality benefit not demonstrated despite reduction in infectious complications 5

Hepatitis B Virus (HBV) Prophylaxis

All HBsAg-positive leukemia patients must receive antiviral prophylaxis with high-barrier agents (entecavir or tenofovir) starting at treatment initiation and continuing for at least 6-12 months after therapy completion. 1

HBsAg-Positive Patients

• Mandatory prophylaxis with entecavir or tenofovir 1
• Start at onset of treatment and continue ≥6-12 months post-therapy 1
• Monitor ALT and HBV-DNA during and for ≥12 months after discontinuation 1

HBsAg-Negative/HBcAb-Positive Patients

• If receiving BTK or BCL-2 inhibitor monotherapy: monitoring approach acceptable (ALT and HBsAg every 1-3 months) 1
• If receiving concurrent anti-CD20 therapy: prophylaxis strongly recommended, continue until ≥12 months after last anti-CD20 dose 1
• NCCN recommends prophylaxis for this population when receiving immunosuppressive therapy 1

Herpes Simplex Virus (HSV) Prophylaxis

HSV prophylaxis with acyclovir, valacyclovir, or famciclovir is recommended during periods of neutropenia and for at least 30 days post-HSCT. 1

Indications

• ALL patients during neutropenic periods 1
• HSCT recipients for minimum 30 days post-transplant 1
• Not routinely recommended for CLL patients on BTK or BCL-2 inhibitors unless additional risk factors present 1

Transfusion Support Thresholds

Prophylactic platelet transfusion threshold is 10 × 10⁹/L for stable patients without bleeding, fever, infection, or mucositis. 1

Platelet Transfusion Criteria

• Standard threshold: <10 × 10⁹/L 1
• Increase threshold to <20 × 10⁹/L if: mucosal bleeding, infection, severe mucositis, or fever present 1
• Use leukodepleted products to prevent alloimmunization 1