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Late Effects



Chemotherapy Related Toxicity


Lung disease after chemotherapy may be obstructive, restrictiveinterstitial or mixed3.

Most long term toxicity to the lungs is the result of interstitial lung disease.

Chemotherapy induced lung fibrosis in children cancer survivors:

  • CCSS study indicated that the rate of first occurrence was highest during treatment36
  • may remain asymptomatic for many years or
  • can be symptomatic at any time

Chemotherapy agents associated with pulmonary toxicity include:

  • Bleomycin
  • Mitomycin-C
  • Alkylating agents:
    • BCNU
    • Busulfan (BU)
    • Cyclophosphamide (CY)
    • Melphalan
  • Antimetabolites:
    • 6-mercaptopurine
    • azathioprine
    • methotrexate
    • cytosine arabinoside
  • Procarbazine
  • VM-26

Generally pulmonary toxicity associated with chemotherapy is infrequent and sporadic

Table: Common used chemotherapy agents associated with pulmonary damage



Risk Factor


Interstitial Pneumonitis22


Pulmonary Fibrosis22


Acute respiratory distress syndrome22 (very rare)

Higher Cumulative dose22


Greatest risk Factors:

  • Dose ≥ 400 U/m2  
  • Younger age at treatment
  • Renal impairment3
  • Radiation therapy22
  • Fluid overload3
  • Combination chemotherapy with busulfan, carmustine and lomustine22

Alkylating agents (Busulfan, Carmustine, Lomustine)

Pulmonary Fibrosis22

The risk is highest with:
  • Higher cumulative doses22
  • Carmustine ≥ 600mg/m222
  • Busulfan ≥ 500mg- total dose (transplant doses)
  • Combination chemotherapy with bleomycin
  • Additional chest RT
  • Younger age at diagnosis
  • Atopic history
  • Smoking

Cytosine arabinoside

Non-cardiogenic pulmonary edema3

  • No clearly identified risk factors3


Interstitial pneumonitis


Non-cardiogenic pulmonary edema3


Pulmonary fibrosis3


  • No clearly identified risk factors3




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