Correspondence

Secondary Acute Leukemia in Chronic Lymphocytic Leukemia

N Engl J Med 1998; 339:924September 24, 1998

Article

To the Editor:

Dighiero et al. (May 21 issue)1 conclude that the treatment of early-stage chronic lymphocytic leukemia (CLL) with alkylating agents not only is ineffective but also may adversely affect survival. This study confirms the long-held assumption that patients with early-stage disease should not be treated until there is evidence that the disease has progressed and that indiscriminate use of alkylating agents leads to an increased incidence of acute leukemia and epithelial cancers.

We were disappointed, though, by the statement in the discussion that secondary acute leukemia has not been reported in patients with CLL who are treated with chlorambucil. By 1977, 8 such cases had already been reported in the literature,2 and by 1996 the number of such reports had increased to 18.3 It is important to emphasize the risk of secondary leukemias, so that patients can be made aware of it before they enroll in trials. We assume that informed consent was obtained from each patient and that the study was approved by the institutional review boards, although neither assumption is directly addressed in the article by Dighiero et al.

Hans W. Grünwald, M.D.
Fred Rosner, M.D.
Mount Sinai Services at Queens Hospital Center, Jamaica, NY 11432

3 References

1. 1

   Dighiero G, Maloum K, Desablens B, et al. Chlorambucil in indolent chronic lymphocytic leukemia. N Engl J Med 1998;338:1506-1514
   Full Text | Web of Science | Medline

2. 2

   Zarrabi MH, Grunwald HW, Rosner F. Chronic lymphocytic leukemia terminating in acute leukemia. Arch Intern Med 1977;137:1059-1064
   CrossRef | Web of Science | Medline

3. 3

   Grünwald HW, Rosner F. Chemicals and leukemia. In: Henderson ES, Lister TA, Greaves MF, eds. Leukemia. 6th ed. Philadelphia: W.B. Saunders, 1996:179-94.
   

Author/Editor Response

The authors reply:

To the Editor: Unlike acute and chronic granulocytic leukemias, CLL has not been associated with previous irradiation.1 It has traditionally been assumed that secondary acute leukemia is a rare event in patients with CLL. This assumption contrasts with the increased incidence of acute leukemia reported in patients treated with chlorambucil when it is used as an immunosuppressive agent or for the management of polycythemia vera, multiple myeloma, Hodgkin's disease, breast cancer, or ovarian cancer.2

In our first trial, with a median follow-up period exceeding 11 years, the incidence of secondary leukemia in patients with CLL who received chlorambucil was low (1.4 percent). By comparison, in a study of patients receiving this treatment for polycythemia vera, secondary leukemia developed in 16 of 141 patients (11.3 percent) who received chlorambucil plus phlebotomy, as compared with 1 of 134 who underwent phlebotomy only.3

Our finding of six cases of acute leukemia among the 422 patients who received daily chlorambucil as initial or secondary treatment, as compared with no cases among the 145 who never received therapy, may be evidence that chlorambucil can increase the risk of secondary leukemia in patients with CLL.4 However, the small number of patients with secondary leukemia in our trial makes it impossible for any definitive conclusion to be drawn.

Our trials were approved by the ethics committee of the Groupe Hospitalier Pitié-Salpêtrière in Paris, but written informed consent was not required by French regulations in effect at the time.

Guillaume Dighiero, M.D., Ph.D.
Institut Pasteur, F-75724 Paris, France

Philippe Travade, M.D.
Hôtel-Dieu, F-63001 Clermont-Ferrand, France

Jacques-Louis Binet, M.D.
Groupe Hospitalier Pitié-Salpêtrière, F-75651 Paris, France

for the French Cooperative Group on Chronic Lymphocytic Leukemia

4 References

1. 1

   Dighiero G, Travade P, Chevret S, Fenaux P, Chastang C, Binet JL. B-cell chronic lymphocytic leukemia: present status and future directions. Blood 1991;78:1901-1914
   Web of Science | Medline

2. 2

   Grünwald HW, Rosner F. Chemicals and leukemia. In: Henderson ES, Lister TA, Greaves MF, eds. Leukemia. 6th ed. Philadelphia: W.B. Saunders, 1996:179-94.
   

3. 3

   Berk PD, Goldberg JD, Silverstein MN, et al. Increased incidence of acute leukemia in polycythemia vera associated with chlorambucil therapy. N Engl J Med 1981;304:441-447
   Full Text | Web of Science | Medline

4. 4

   Dighiero G, Maloum K, Desablens B, et al. Chlorambucil in indolent chronic lymphocytic leukemia. N Engl J Med 1998;338:1506-1514
   Full Text | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Jacques Gardais. (1999) Is there still a place for clinical staging in chronic lymphocytic leukaemia?. Leukemia Research 23:6, 589-592
   CrossRef