Correspondence

Chromosomal Abnormalities in Chronic Lymphocytic Leukemia

N Engl J Med 2001; 344:1254April 19, 2001

Article

To the Editor:

Döhner and colleagues (Dec. 28 issue)1 report that in a study of chromosomal abnormalities in patients with chronic lymphocytic leukemia, patients with 17p deletions had a poor prognosis, with a median survival time of 32 months. Of the 325 patients enrolled in the study, 77 (24 percent) had received prior chemotherapy. Although prior chemotherapy is not reported as a prognostic factor in this study, it is the standard of care for patients with advanced disease. Therefore, the high percentage of previously treated patients may have had a confounding effect on this important analysis. Can the authors state how many patients with 17p deletions had received prior treatment and perhaps repeat their analysis with the data for the previously treated patients censored?

Guillermo Garcia-Manero, M.D.
University of Texas M.D. Anderson Cancer Center, Houston, TX 77030

1 References

1
Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000;343:1910-1916
Full Text | Web of Science | Medline

Author/Editor Response

The authors reply:

To the Editor: Dr. Garcia-Manero raises the important point of the relation between prior chemotherapy and chromosomal aberrations in patients with chronic lymphocytic leukemia. When we analyzed the data for the 77 previously treated patients and the 248 previously untreated patients separately, we found the following differences in the proportions of patients with specific chromosomal aberrations: 13q deletion, 57 percent of previously untreated patients versus 48 percent of previously treated patients; 11q deletion, 14 percent versus 32 percent; 12q trisomy, 17 percent versus 14 percent; and 17p deletion, 5 percent versus 13 percent; 17 percent of the previously untreated patients had a normal karyotype, as compared with 21 percent of the previously treated patients. These results indicate that previously treated patients are more likely to have high-risk chromosomal aberrations (11q and 17p deletions) than are patients without previous treatment. These findings are in line with the more rapid progression of disease, reflected by a shorter time from diagnosis to initial treatment, in the groups with high-risk aberrations.1

The limitations of our study sample, particularly with respect to differences in the time at which treatment was initiated and variations in therapy, are obvious. However, the 325 consecutive patients at a single institution (University Hospital in Heidelberg, Germany) constituted a representative population of patients with chronic lymphocytic leukemia. We believe that a separate analysis of previously untreated patients would only introduce a bias toward the selection of patients with benign disease.

The incidence and prognostic importance of chromosomal aberrations in chronic lymphocytic leukemia are being studied prospectively by our group in connection with multicenter treatment trials. Preliminary results show that the rates of high-risk aberrations are similar among previously untreated patients. Even among patients at the earliest stage of chronic lymphocytic leukemia (Binet stage A) in the CLL1 trial of the German CLL Study Group, the incidences of 11q and 17p deletions were 8 percent and 6 percent, respectively.2 Moreover, the sequential analysis of chromosomal aberrations over time has shown that a clonal evolution in chronic lymphocytic leukemia occurs in 16 percent of patients, with 17p deletions being the most common additional aberration.3 The occurrence of additional aberrations can be observed in the absence of intercurrent treatment.

All the patients in our study were seen at University Hospital in Heidelberg, Germany. By the time we submitted the manuscript, our entire research group, including all the investigators involved in the study, had moved to University Hospital in Ulm, Germany.

Hartmut Döhner, M.D.
Stephan Stilgenbauer, M.D.
University of Ulm, 89081 Ulm, Germany

Peter Lichter, Ph.D.
Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany

3 References

1
Dohner H, Stilgenbauer S, Benner A, et al. Genomic aberrations and survival in chronic lymphocytic leukemia. N Engl J Med 2000;343:1910-1916
Full Text | Web of Science | Medline

2
Bullinger L, Krautle C, Krober A, et al. Genetic aberrations in ear-ly stage (Binet-A) B-CLL: correlation with clinical and biological risk factors in the CLL1 trial of the DCLLSG. Blood 2000;96:Part 2:1876-1876 abstract.

3
Leupolt E, Stilgenbauer S, Lichter P, Bentz M, Dohner H. Sequential FISH studies in B-CLL reveal clonal evolution with the acquisition of deletions involving 6q21, 11q22 and 17p13 (TP53 ). Blood 1999;94:Suppl 1:494-494 abstract.

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