In an adult with newly diagnosed non‑Hodgkin lymphoma who has completed a cycle of rituximab‑mini‑CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), has normal blood counts, and now presents with intermittent cough—after prior imaging showed a bulky right tonsillar mass, mediastinal lymphadenopathy, left upper‑lobe bronchial obstruction with collapse‑consolidation, eccentric tracheal wall thickening, and a partially occluding mass in the tracheoesophageal groove (TEG) and whose noisy breathing has resolved—what is the most appropriate next step in management?

Management of Post-Chemotherapy Cough in NHL Patient with Prior Airway Involvement

Obtain urgent repeat CT imaging of the chest to assess treatment response and evaluate for new pulmonary complications, given the patient's significant baseline airway involvement and new respiratory symptom. 1, 2

Immediate Diagnostic Evaluation

The intermittent cough in this clinical context requires prompt imaging reassessment because:

• Post-treatment imaging is essential to distinguish between treatment response (tumor shrinkage), residual disease, or new complications in patients with bulky mediastinal disease and airway involvement 1
• The resolution of noisy breathing suggests partial tumor response, but the new cough may represent:
  • Post-obstructive pneumonitis from the previously collapsed left upper lobe
  • Infection in the area of prior consolidation
  • Drug-induced pulmonary toxicity from rituximab or chemotherapy
  • Residual or progressive disease 3

Key Differential Considerations

Treatment-Related Pulmonary Toxicity

• Rituximab can cause hypersensitivity pneumonitis presenting as progressive dry cough, which has been documented as potentially fatal in NHL patients receiving R-CHOP 3
• This typically develops after rituximab initiation and may be associated with eosinophilia or elevated IgE 3

Infectious Complications

• PCP prophylaxis should be confirmed as trimethoprim-sulfamethoxazole or equivalent must be continued throughout treatment and for 6-12 months after completion 1
• Post-obstructive pneumonia in the previously collapsed left upper lobe remains a concern despite normal blood counts 1

Tumor Response Assessment

• PET-CT scanning post-treatment is essential for response assessment, particularly given the bulky mediastinal involvement and tracheal/TEG masses 1
• The timing after one cycle may be premature for formal restaging, but symptomatic changes warrant earlier imaging 1

Recommended Diagnostic Algorithm

1. Urgent chest CT with contrast to evaluate:

   • Status of the bulky right tonsillar mass
   • Mediastinal lymphadenopathy response
   • Left upper lobe re-expansion versus persistent collapse
   • Tracheal wall thickening and TEG mass
   • New infiltrates or ground-glass opacities suggesting drug toxicity 1, 2

2. Laboratory assessment:

   • Complete blood count with differential (to assess for eosinophilia) 1
   • Comprehensive metabolic panel 1
   • Consider serum IgE if drug hypersensitivity suspected 3

3. Clinical examination focusing on:

   • Oxygen saturation and respiratory rate
   • Auscultation for crackles, wheezing, or decreased breath sounds
   • Signs of superior vena cava syndrome resolution 4

Management Based on Imaging Findings

If Imaging Shows Treatment Response with Post-Obstructive Changes:

• Continue scheduled R-CHOP cycles as planned 1, 2
• Consider empiric antibiotics if infiltrate present
• Symptomatic cough management with antitussives

If Imaging Suggests Drug-Induced Pneumonitis:

• Corticosteroids are marginally efficacious but represent the primary treatment option 3
• Consider holding rituximab pending pulmonary consultation
• May require bronchoscopy with bronchoalveolar lavage for definitive diagnosis 3

If Residual Bulky Disease Persists:

• Continue chemotherapy as dose intensity must be maintained for curative intent 1, 2
• Plan for consolidative radiotherapy to sites of bulky disease after completing 6 cycles of R-CHOP 2, 5

Critical Pitfalls to Avoid

• Do not delay imaging assuming the cough is benign—the patient's baseline airway compromise makes any new respiratory symptom potentially serious 1
• Do not empirically treat as infection alone without imaging, as this could miss drug toxicity or progressive disease 3
• Do not reduce chemotherapy doses for subsequent cycles unless absolutely necessary; use G-CSF support instead to maintain dose intensity 1, 2
• Do not obtain PET-CT prematurely for routine restaging (typically done mid-treatment or post-treatment), but CT is appropriate for symptomatic evaluation 4, 1