When can chemotherapy be restarted in a patient with lymphoma who has developed aspergillosis?

Restarting Chemotherapy in Lymphoma Patients with Aspergillosis

Chemotherapy for lymphoma can be safely restarted after a period of several weeks of antifungal treatment and clear evidence of response to therapy for aspergillosis, with continued antifungal therapy as secondary prophylaxis during subsequent chemotherapy. 1

Timing of Chemotherapy Resumption

• Invasive aspergillosis (IA) is not an absolute contraindication to additional chemotherapy or hematopoietic stem cell transplantation (HSCT) 1
• The ideal approach is to administer several weeks of antifungal therapy with clear evidence of response before restarting chemotherapy 1
• For patients with urgent need for chemotherapy (such as refractory or relapsed lymphoma), earlier resumption may be necessary with careful monitoring 1
• A key factor associated with successful chemotherapy resumption is <6 weeks from the start of antifungal therapy to subsequent treatment 1

Decision-Making Algorithm

1. Assess response to antifungal therapy:

   • Look for clinical improvement (fever resolution, reduced respiratory symptoms) 1
   • Radiological improvement on CT imaging 1
   • Declining serum galactomannan levels in appropriate patient populations 1

2. Consider lymphoma status:

   • Urgent need for chemotherapy (refractory disease) may necessitate earlier resumption 1, 2
   • For stable disease, allow longer antifungal treatment before resuming chemotherapy 1

3. Evaluate extent of aspergillosis:

   • Localized disease has better outcomes than disseminated infection 2, 3
   • Consider surgical resection of localized pulmonary lesions prior to intensive chemotherapy in selected cases 1, 2

4. Implement secondary prophylaxis:

   • Continue mold-active antifungal therapy during subsequent chemotherapy cycles 1, 4
   • Options include voriconazole, posaconazole, or liposomal amphotericin B 1

Risk Factors for Aspergillosis Recurrence

• Longer duration of neutropenia after chemotherapy 1
• Refractory lymphoma requiring more intensive chemotherapy 1, 3
• Less than 6 weeks from start of antifungal therapy to chemotherapy resumption 1
• Inadequate response to initial antifungal therapy 1, 2

Management Strategies

• Secondary antifungal prophylaxis: Essential during subsequent chemotherapy cycles to prevent recurrence or progression 1, 4
• Surgical consideration: For localized disease, surgical resection may be beneficial before resuming intensive chemotherapy, though antifungal therapy alone is often sufficient 1, 2
• Close monitoring: Regular CT imaging during chemotherapy to detect early signs of recurrence 1
• Collaborative approach: Decisions should involve both infectious disease specialists and hematologists/oncologists 1

Common Pitfalls and Caveats

• Resuming chemotherapy too early without adequate control of aspergillosis can lead to life-threatening progression 1, 2
• Failure to provide secondary antifungal prophylaxis during subsequent chemotherapy cycles significantly increases risk of recurrence 1
• Mistaking immune reconstitution inflammatory syndrome (IRIS) for treatment failure during neutrophil recovery 1
• Delaying chemotherapy unnecessarily when lymphoma is aggressive and requires urgent treatment 1, 3

Special Considerations

• For patients with refractory aspergillosis, consider changing antifungal class or using combination therapy before resuming chemotherapy 1
• Colony-stimulating factors may be considered to shorten duration of neutropenia during subsequent chemotherapy cycles 1
• Reducing doses of immunosuppressive agents when feasible can improve outcomes 1