Vol. 75 . No. 5
LETTERS TO THE EDITOR
765
FIG. 1 (upper). Irregular nuclear lobation and convolutions visible in several cells. Cell at lower left shows nuclear blebs. x3,600.
FIG. 2 (lower). Central cell shows large lysosomes, cell at left has extensive nuclear blebbing, and cell at right shows plasmacytic
differentiation. x4,600.
<
—
Significance of Leukocyte
Alkaline Phosphatase Index in
Hairy Cell Leukemia
To the Editor:—The paper by Aiba
and associates1 on the significance of
leukocyte alkaline phosphatase (LAP)
in hairy cell leukemia (HCL) prompted
us to review the data for our patients
having this disease. We included only
patients who were studied at the time of
diagnosis, i.e., before splenectomy,
and omitted all patients who were infected at the time of study and who may
have had increased LAP indices for that
reason. As shown in Table 1, for 21 patients with typical HCL, there was no
significant correlation between the absolute number of neutrophils and the
LAP index (r = -0.211, P > 0.05),
in contrast with thefindingsof Aiba and
associates, who reported a significant
correlation (r = -0.704, P < 0.001).
The differences between the results
of the two studies can be partly explained when two aspects are taken into
consideration. First, most of the patients of Aiba and associates (18 of 23)
were studied after splenectomy. Usually, the neutrophil count increases
significantly after splenectomy, and
counts as high as 5,000/mnr'1 are not
uncommon.4,5 On the other hand, severe
neutropenia is usually present before
splenectomy; in most studies, as in our
present series, more than 85% of the
patients had < 1,500/mm3 neutrophils
at the time of diagnosis.4,5 In the series
of Aiba and associates, however, 43%
of the patients (10 of 23) had > 1,500/
mm3 neutrophils. In fact, when only
patients with <2,000/mm'' neutrophils
are considered, there was no significant
correlation between the neutrophil
count and the LAP index in their series
(r = -0.210, P > 0.05).
Received October 30, 1980; accepted for
publication December 10, 1980.
Address reprint requests to Dr. Jansen:
Department of Hematology, Leiden University Medical Center, Leiden, The Netherlands.
Table I. Spleen Size, Neutrophil Count, and LAP Index* for 25 Patients
with Hairy Cell Leukemia
Typical hairy cell
leukemia
Patient 1
Patient 2
Patient 3
Patient 4
Patient 5
Patient 6
Patient 7
Patient 8
Patient 9
Patient 10
Patient 11
Patient 12
Patient 13
Patient 14
Patient 15
Patient 16
Patient 17
Patient 18
Patient 19
Patient 20
Patient 21
Slightly atypical
hairy cell leukemia
Patient 22
Patient 23
Patient 24
Patient 25
Age/Sex
Spleen Size
(cm Under
Costal Margin)
Neutrophil Count
(X109/1)
LAP Index
60/F
72/M
53/M
46/M
60/M
45/M
55/M
60/F
59/M
35/M
67/M
71/M
73/M
31/F
55/M
66/M
46/F
68/M
42/F
57/M
52/M
5
0
0
5
0
2
0
6
17
12
0
5
5
14
6
4
0
3
9
6
0
0.4
1.6
0.8
0.9
0.8
0.2
1.7
0.4
0.2
0.7
0.5
0.4
1.7
0.5
0.5
0.6
1.3
0.2
0.4
0.3
0.9
70
98
130
158
175
180
223
227
234
239
240
240
242
245
255
260
260
290
322
350
353
68/M
79/F
75/F
50/F
0
10
0
15
3.0
1.7
3.0
3.1
2
10
28
46
* Normal controls for leukocyte alkaline phosphatase (LAP): 15-100.
A second cause of difference may have
been the inclusion of slightly atypical
cases of HCL. Like other groups, Aiba
and associates reported that some of
their patients with low LAP indices had
slightly atypical features.2,1 These features may include cellular morphology,
cytochemistry, monocyte counts, and
others. As shown in Table 1, all of our
four patients with slightly atypical HCL
had normal LAP indices. When these
patients were included in the analysis,
the correlation between LAP index
and neutrophil count became highly
significant (r = -0.685, P < 0.01).
Although our data show that at the
time of diagnosis there is no close
correlation between neutrophil count
and LAP index, we agree with Aiba and
associates that the increased LAP index
probably reflects impaired bone-marrow
reserve. In the occasional patients
we followed-up longitudinally before
splenectomy, the LAP index increased
with the decrease of the neutrophil
count. In other patients, who obtained
long-lasting clinical remissions after
splenectomy, the LAP index decreased
to normal or near-normal values. We
also agree that the LAP index is a valuable parameter in the differential diagnosis of HCL, since greatly increased
LAP indices are uncommon in other
chronic lymphoproliferative disorders.
LETTERS TO THE EDITOR
766
Furthermore, in our experience, the
LAP index is of value for the distinction
of atypical cases of HCL, which may require a different therapeutic approach.2
JAN JANSEN,
M.D.
Department of Hematology
Leiden University Medical Center
Leiden, The Netherlands
A.J.C.P. • May 1981
References
1. Aiba M, Raffa PP, Katayama I:
Significance of leukocyte alkaline
phosphatase in hairy cell leukemia.
Am J Clin Pathol 74:297-300, 1980
2. Golomb HM, Vardiman J, Variakojis
D: Neutrophilic leukocyte alkaline
phosphatase scores in hairy cell leukemia (letter). Br J Haematol 43:
156-157, 1979
3. Hayhoe FGJ, Flemans RJ, Burns G, et
al: Leukocyte alkaline phosphatase
scores in hairy-cell leukaemia (letter).
Br J Haematol 37:158-159, 1977
4. Jansen J, Hermans J (for the collaborative study group): Splenectomy in
hairy-cell leukemia. A retrospective
multicenter analysis. Cancer (In press)
5. Sebahoun G, Bouffette P, Flandrin G:
Hairy cell leukemia. Leuk Res 2:
187-195, 1978
The Authors' Reply
To the Editor:—Earlier, by studying
23 patients in most of whom the effects
of hypersplenism had been excluded by
splenectomy, we suggested that high
leukocyte alkaline phosphatase (LAP)
scores characteristic of hairy cell leukemia (HCL) were secondary to decreased bone marrow granulocyte reserves.1 While agreeing with us on this
correlation between LAP scores and
marrow reserve of granulocytes, Dr.
Jansen saw no correlation between
peripheral blood neutrophil counts
(PNC) and LAP scores, as we did.
However, we are pleased to find his
data highly complementary to ours
when both series are combined for
analysis as below.
Figure 1 is a scatter diagram of PNCs
and LAP scores from both series. There
is an inverse linear correlation between
PNCs and LAP scores for the total of 48
patients (/-48 = -0.680, P < 0.001),
whereas no such correlation can be
made when 12 patients with normal LAP
values are excluded, as was the case in
Dr. Jansen's letter (rM = -0.167, P
>0.1). For further analysis, the 36
patients with elevated LAP values
are divided into 18 patients each at
PNC 788 and LAP score 225, producing groups I and II above PNC 788,
groups III and IV below PNC 788,
groups II and III below LAP 225, and
groups I and IV above LAP 225. Then it
becomes apparent that 53% of our patients belong to group II, characterized
by mild neutropenia and mild elevation
of LAP score, while 58% of Dr. Jansen's
Received and accepted for publication
December 10, 1980.
Address reprint requests to Dr. Aiba: Department of Pathology, Keio University
School of Medicine, Shinjuku, Tokyo 160,
Japan.
FIG. 1. Scatter diagram
of peripheral blood neutrophil counts and leukocyte
alkaline phosphatase scores
from our study and Jansen's
study. Open circles represent Jansen's 25 unsplenectomized patients. Closed
circles represent our 18
splenectomized patients,
and double circles represent our five unsplenectomized patients.
®
®
GROUP I
GROUP I
®
^8"JGROUPIII
100
^
200
° • GROUP IV
300
«00
LEUKOCYTE ALKALINE PHOSPHATASE SCORE
patients belong to group IV, characterized by severe neutropenia and
severe elevation of LAP. We may conclude that Dr. Jansen's patients had
both neutropenia and elevated LAP in a
more marked degree than our patients
(P < 0.02). This difference may derive
from different sets of clinical presentations of the two series. While our patients were all ambulatory outpatients
without signs or symptoms requiring
specific treatments, Dr. Jansen's patients were all studied at the time of
diagnosis in the presence of signs and
symptoms leading to such diagnostic
workup.
In conclusion, his data in combination
with ours suggest a splenic function
toward elevation of LAP scores in HCL.
Furthermore, both studies underscore
the value of LAP determination in the
differential diagnosis of HCL, particularly in the presplenectomy evaluation,
as pointed out by Dr. jansen.
MOTOHIKO AIBA, M. D.
Department of Pathology
Keio University School of Medicine
Tokyo, Japan
ISAO KATAYAMA, M. D.
Department of Pathology
Saitama Medical School
Saitama, Japan
Reference
1. Aiba M, Raffa PP, Katayama I: Significance of leukocyte alkaline phosphatase in hairy cell leukemia. Am J
Clin Pathol 74:297-300, 1980