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Blood, 15 July 2002, Vol. 100, No. 2, pp. 731-733
CORRESPONDENCE
To the editor:
New prognostic parameters for chronic myelomonocytic leukemia?
Onida et al recently reported on prognostic parameters in
chronic myelomonocytic leukemia (CMML) and proposed a new M. D. Anderson prognostic score (MDAPS).1 In a large
independent data- base, they essentially confirmed the clinical,
laboratory, cytogenetic, and prognostic findings that have been
described by other groups.2-8 What is new in their paper
is the finding that lymphocyte count was a variable independently
associated with survival in CMML. Lymphocyte count was therefore
included in the new scoring system. But the authors felt that their
finding warrants confirmation, and we think that we can provide some
evaluation. The large myelodysplastic syndrome (MDS) registry
in Düsseldorf, which allowed us to examine prognostic and
nosologic problems of CMML in the past,5,6,8 now includes
265 patients with CMML, among 2050 patients with MDS. The prognostic
parameters used in the MDAPS are completely available for 212 of our
CMML patients, who did not receive intensive chemotherapy or allogeneic stem cell transplantation. Onida et al studied 190 patients. We first performed univariate and multivariate analysis. Median
survival was 18 months. On univariate analysis, sex, splenomegaly, prior malignancy, hemoglobin level, platelet count, monocyte count, lactate dehydrogenase (LDH) level, medullary blast count,
proportion of medullary erythroblasts, and peripheral blood lymphocyte
count (Figure 1), as well as karyotype,
were identified as prognostic parameters. The presence of immature
myeloid precursors, identified as a prognostic marker by Onida et al,
had no impact on prognosis in our analysis. On multivariate analysis,
we identified as independent prognostic factors for survival: elevated
LDH level (not included in the MDAPS), medullary blast count above
10% (included), male gender (not included), hemoglobin level
below 12 g/dL (included), and lymphocyte count above 2500/µL
(included).
View larger version (13K):
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| Figure 1.
Kaplan-Meier survival curves of CMML patients
(n = 227) according to absolute lymphocyte count in peripheral blood.
Plots depict lymphocyte counts above 2500/µL and no more than
2500/µL.
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We then applied the MDAPS to our cohort of 212 CMML patients for whom
all MDAPS parameters were available (Figure
2). We confirmed that the MDAPS separates
4 risk groups. But there are disadvantages to the new score. First, the
low-risk group, which includes 39% of the patients, has a median
survival of only 36 months; it therefore does not really identify the
subgroup of CMML patients who have a very good prognosis. Second, there
is no significant difference in survival between the intermediate
groups I and II (16 versus 13 months, respectively). Third, only 6% of
the patients were classified as high risk.
View larger version (15K):
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| Figure 2.
Kaplan-Meier survival curves of CMML patients
(n = 212) according to the MDAPS.
Plots depict low-risk, intermediate-risk 1, intermediate-risk 2, and
high-risk groups.
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For comparison, we applied the Düsseldorf score, featuring 3 risk
groups (high, intermediate, low), to the same cohort of 212 CMML
patients (Figure 3). The low-risk group
was much more exclusive. Comprising 6% of patients, it showed a median
survival of 93 months. The high-risk group included 36% of patients
and showed a median survival of 11 months. Twenty percent of low-risk patients according to the MDAPS were (appropriately) classified as
high-risk patients by the Düsseldorf score. It appears that the
MDAPS does not represent a major improvement in predicting the survival
of CMML patients.
View larger version (13K):
[in this window]
[in a new window]
| Figure 3.
Kaplan-Meier survival curves of CMML patients
(n = 212) according to the Düsseldorf score.
Plots depict low-risk, intermediate-risk, and high-risk
groups.
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We further examined the prognostic value of lymphocyte counts in other
MDS patients. In the entire group of 1082 patients with MDS (excluding
CMML), the lymphocyte count could not be identified as an independent
prognostic marker. Therefore, it appears that the prognostic value of
lymphocyte counts is restricted to CMML patients.
Ulrich Germing, Corinna Strupp, Manuel Aivado, and Norbert Gattermann
Correspondence: Ulrich Germing, Department of Hematology,
Oncology and Clinical Immunology, Heinrich-Heine-University, Moorenstr
5, 40225 Düsseldorf, Germany; e-mail:
germing{at}med.uni-duesseldorf.de
References
1.
Onida F, Kantarjian HM, Smith TL, et al.
Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients.
Blood.
2002;99:840-849[Abstract/Free Full Text].
2.
Fenaux P, Beuscart R, Lai JL, Jouet JP, Bauters F.
Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases.
J Clin Oncol.
1988;6:1417-1424[Abstract/Free Full Text].
3.
Worsley A, Oscier DG, Stevens J, et al.
Prognostic features of chronic myelomonozytic leukaemia: a modified Bournemouth score gives the best prediction of survival.
Br J Haematol.
1988;68:17-21[Medline]
[Order article via Infotrieve].
4.
del Canizo MC, Sanz G, San Miguel JF, et al.
Chronic myelomonocytic leukemia- clinicobiological characteristics: a multivariate analysis in a series of 70 cases.
Eur J Haematol.
1989;42:466-473[Medline]
[Order article via Infotrieve].
5.
Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W.
Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system.
Leukemia.
1992;6:52-59[Medline]
[Order article via Infotrieve].
6.
Germing U, Gattermann N, Minning H, Heyll A, Aul C.
Problems in the classification of CMML: dysplastic vs proliferative type.
Leuk Res.
1998;22:871-878[CrossRef][Medline]
[Order article via Infotrieve].
7.
Morel P, Hebbar M, Lai JL, et al.
Cytogenetic analysis has a strong independent prognostic value in de novo myelodysplastic syndromes and can be incorporated in a new scoring system: a report on 408 cases.
Leukemia.
1993;7:1315-1323[Medline]
[Order article via Infotrieve].
8.
Germing U, Gattermann N, Strupp C, Aivado M, Haas R, Aul C.
Validation of the WHO proposals for the classification of myelodysplastic syndromes: a retrospective analysis of 1600 cases.
Leuk Res.
2000;24:983-992[CrossRef][Medline]
[Order article via Infotrieve].
Response:
Value of peripheral blood lymphocytes and MDAPS in CMML
The analysis performed by Dr Germing and colleagues in the
Düsseldorf population of patients with chronic myelomonocytic leukemia (CMML) is important and appreciated, since it is the first
evaluation of our findings1 in a population other than the
one from which we derived our scoring system (MDAPS). We are pleased
with the confirmation by Germing et al that survival time is
independently associated with 3 of the 4 factors identified by our
analysis and particularly that the absolute lymphocyte count in
peripheral blood a factor identified for the first time by our recent
reportindeed has prognostic value. Like Germing and colleagues, we
found no relationship between lymphocyte counts and survival time among
patients diagnosed with myelodysplastic syndromes (MDSs) other than
CMML. This suggests that lymphocytes may be specifically relevant to
the biology of CMML. It should be stressed that the populations of patients with CMML in the
Düsseldorf and M. D. Anderson Cancer Center cohorts differ
considerably. The median survival times were 18 months for patients in
the Düsseldorf cohort but only 12 months for patients at our
center, suggesting more advanced disease in our cohort. Furthermore,
prognostic systems may account for as little as 25% of variability in
patient outcome.2 Under these circumstances, discrepancies
between the 2 systems in stratifying patients according to prognosis
are not surprising. Lack of an association between the presence of circulating
immature myeloid cells (IMCs) and shorter survival times for the Düsseldorf cohort may reflect earlier stages of disease among this cohort than among the M. D. Anderson cohort; indeed,
increasing percentages of circulating IMCs (including blasts) are
commonly observed with disease progression. Inverse correlation between the presence of circulating IMCs and survival time was also reported by
Fenaux et al3 (107 patients) and by del Cañizo et
al4 (70 patients) in reports of the 2 other largest series
of patients with CMML published to date. In our study, elevated serum
LDH level was associated with shorter survival in univariate but not in
multivariate analysis. The Düsseldorf scoring system5 and the MDAPS were
both derived from analyses of still relatively limited cohorts of
patients, and both systems likely have advantages and disadvantages for risk stratification. However, among the current Düsseldorf cohort of 212 patients with CMML, only a small proportion (6%) was identified as low risk using the Düsseldorf scoring system, and the longer median survival time among these patients is a projection based on only
13 patients. Indeed, the survival curves provided by Germing et al show
that more than 45% of the patients in their low-risk category were
dead at 36 months. In contrast, the MDAPS identified 39% of the
patients in the Düsseldorf cohort as low risk, with a median
survival time of 36 months. Therefore, compared with the
Düsseldorf scoring system, the MDAPS appears to be able to identify a larger group of patients at low risk and hence not in urgent
need of experimental therapy. Using the MDAPS, the group of patients identified as high risk within
the Düsseldorf cohort (6%) is smaller than our high-risk group
of patients (currently 10% of 276 assessable patients). However, the
median survival time for the high-risk group is less than 6 months for
both cohorts, and we believe this finding may be clinically significant
for identification of patients who could benefit from new treatments
based on investigational drugs. The value of the MDAPS owes mainly to the fact that it was derived from
a population composed exclusively of patients with CMML. However,
considering the wide heterogeneity of the disease, both the MDAPS and
the Düsseldorf scoring systems are useful and may serve as a
basis for further improvements in the prognostic stratification of patients.
Francesco Onida, Elihu H. Estey, Gregory K. Ball, Hagop
M. Kantarjian, and Miloslav Beran
Correspondence: Francesco Onida, M. D. Anderson Cancer Center,
Leukemia Department, 1515 Holcombe Blvd, Houston, TX 77030
References
1.
Onida F, Kantarjian HM, Smith TL, et al.
Prognostic factors and scoring systems in chronic myelomonocytic leukemia: a retrospective analysis of 213 patients.
Blood.
2002;99:840-849[Abstract/Free Full Text].
2.
Simon R.
Importance of prognostic factors in cancer clinical trials.
Cancer Treat Rep.
1984;68:185-192[Medline]
[Order article via Infotrieve].
3.
Fenaux P, Beuscart R, Lai JL, Jouet JP, Bauters F.
Prognostic factors in adult chronic myelomonocytic leukemia: an analysis of 107 cases.
J Clin Oncol.
1988;6:1417-1424[Abstract/Free Full Text].
4.
del Cañizo MC, Sanz G, San Miguel JF, et al.
Chronic myelomonocytic leukemiaclinicobiological characteristics: a multivariate analysis in a series of 70 cases.
Eur J Haematol.
1989;42:466-473[Medline]
[Order article via Infotrieve].
5.
Aul C, Gattermann N, Heyll A, Germing U, Derigs G, Schneider W.
Primary myelodysplastic syndromes: analysis of prognostic factors in 235 patients and proposals for an improved scoring system.
Leukemia.
1992;6:52-59[Medline]
[Order article via Infotrieve].
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