Chlorambucil is an alkylating agent widely used in the treatment of lymphoproliferative diseases.
Clinical manifestations
General: fever, stomatitis, pharyngitis, conjunctivitis.
Cutaneous: toxic epidermal necrolysis, maculopapular erythema, urticaria.
Pulmonary: interstitial pneumonitis (14 cases up to 1994).
Hematological: immune hemolytic anemia (antibody able to bind complement to erythrocytes only in the presence of chlorambucil).
Diagnostic methods
Cutaneous testing.
Patch-tests: chlorambucil mixed in vaseline 5% and 10% positive in 2 cases of toxic epidermal necrolysis.
Cutaneous biopsy (toxic epidermal necrolysis).
Re-challenge test is often positive but harmful.
Unproven, but type III allergic reaction is likely (immune complex deposition).
Cross-reactivity between alkylating agents is exceptional.


  1. Aydogdu I, Ozcan C, Harputluoglu M, Karincaoglu Y, Turhan O, Ozcanu A, "Severe adverse skin reaction to chlorambucil in a patient with chronic lymphocytic leukemia", Anticancer. Drugs., 1997; 8 (5): 468-9
  2. Crestani B, Jaccard A, Israel-Biet D, Couderc L.J, Frija J, Clauvel J.P, "Chlorambucil - associated pneumonitis", Chest., 1994; 105 (2): 634-6
  3. Pietrantonio F, Moriconi L, Torino F, Romano A, Gargovich A, "Unusual reaction to chlorambucil: a case report", Cancer. Lett., 1990; 54 (3): 109-11
  4. Thompson-Moya L, Martin T, Heuft H.G, Neubauer A, Herrmann R, "Allergic reaction with immune hemolytic anemia resulting from chlorambucil", Am. J. Hematol., 1989; 32 (3): 230-1
  5. Hitchins R.N, Hocker G.A, Thomson D.B, "Chlorambucil allergy- a series of three cases", Aust. N.Z. J. Med., 1987; 17 (6): 600-2

As in all diagnostic testing, the diagnosis is made by the physican based on both test results and the patient history.