Blood, Vol. 91 No. 8 (April 15), 1998:
pp. 3084-3085
CORRESPONDENCE
Might Essential Thrombocythemia Carry Ph Anomaly?
 |
LETTER |
To the Editor:
We read with interest the paper of Blickstein et al1
dealing with clinical presentation of 25 Ph
essential
thrombocythemia (ET) patients, 48% of which showed positivity for
BCR-ABL transcripts. On the basis of their findings, the investigators
suggest the possibility of a new variant of ET. We would like to make
some comments and report on our experience.
We investigated 20 patients (8 men and 12 women; median age, 54 years;
range, 24 to 86 years) diagnosed as ET following the criteria of the
Polycythemia Vera Study Group (PVSG)2; only
patients with a platelet count greater than 1,000,000/µL were
enrolled, considering a lower platelet count misleading for a correct
diagnosis of ET.2 In our group, the platelet count ranged
from 1,120,000 to 2,700,000/µL. The white blood cell count showed a
mean count of 8,900/µL, with less than 3% basophils and the absence
of immature cells in the peripheral blood. The leukocyte alkaline phosphatase (LAP) score was normal in 5 patients and increased
in 15. Splenomegaly (<3 cm palpable) was observed in 3 patients. For
6 newly diagnosed patients, the mean follow-up time was 7 months
(range, 6 to 8 months), whereas for the remaining 14 patients, the mean
follow-up time was 54.2 months (range, 13 to 144 months); 9 patients
were observed for 71 months (range, 32 to 144 months). All patients
were Ph at cytogenetic level at diagnosis. The study for
BCR-ABL transcripts by reverse transcriptase-polymerase chain reaction
(RT-PCR; sensitivity 1:105) showed the
chimeric product (b3a2 type) only in 1 patient (5%). The clinical and
hematologic features remained unchanged in all patients, with only 2 exceptions: 1 patient (BCR-ABL negative) showed a transformation to
idiopathic myelofibrosis (IM) 6 years after diagnosis; the other
patient (BCR-ABL positive) progressed to blastic crisis 12 years after
diagnosis, via IM detected 6 years after diagnosis. We already reported
on this patient,3 who was first considered to have
ET; the presence of BCR-ABL transcript was indeed detected on archival
specimens only recently.
Based on our data, we cannot confirm such a high percentage of
BCR-ABL-positive ET cases reported by Blickstein et al.1 It is unlikely that technical reasons may account for the discrepancy between the two studies, given the comparable sensitivity of the PCR
methods used. It should be taken in mind that Ph can be detected either
cytogenetically or by molecular analysis for the BCR
rearrangement.4 It is now well accepted that the presence
of BCR-ABL transcript is diagnostic of chronic myeloid leukemia (CML),
even in those cases that are Ph at cytogenetic level.
Thus, we suggest that the so-called BCR-ABL-positive ET should be
better considered clinical variants of CML, rather than of ET. On the
other hand, Ph+, BCR-ABL-positive CML of ET onset is a
well-recognized entity.5,6 Furthermore, we would like to
point out that the findings of Blickstein et al1 of similar
clinical and laboratory characteristics between their two groups of
patients (BCR-ABL negative and positive) and the absence of progression
of the disease in all cases is rather unexpected. The short follow-up
(20 and 22.5 months) and the inclusion in the study of patients with
less than 1,000,000/µL platelets are probably misleading. CML with ET
onset may develop the features of classical CML only several years
after diagnosis.7,8 We agree with the investigators that
the BCR-ABL status should be examined in all ET patients, but our
suggestion is that the CML variants, like the so-called
BCR-ABL-positive ET, need a longer follow-up period to allow a better
understanding of their clinical and biological
events.
Roberto Marasca
Mario Luppi
Patrizia Zucchini
Giuseppe Longo
Giuseppe Torelli
Giovanni Emilia
Department of Medical Sciences
Section of Internal
Medicine and Hematology
University of Modena
Modena, Italy
| |
REFERENCES |
1.
Blickstein D,
Aviram A,
Luboshitz J,
Prokocimer M,
Stark P,
Bairey O,
Sulkes J,
Shaklai M:
BCR-ABL transcripts in bone marrow aspirates of Philadelphia-negative essential thrombocythemia patients: Clinical presentation.
Blood
90:2768,
1997[Abstract/Free Full Text]
2.
Murphy S,
Iland H,
Rosenthal D,
Laszlo J:
Essential thrombocythemia: An interim report from the polycythemia vera study group.
Semin Hematol
23:177,
1986[Medline]
[Order article via Infotrieve]
3.
Emilia G,
Sacchi S,
Temperani P,
Longo R,
Vecchi A:
Progression of essential thrombocythemia to blastic crisis via idiopathic myelofibrosis.
Leuk Lymphoma
9:423,
1993[Medline]
[Order article via Infotrieve]
4.
Benn P,
Soper L,
Eisenberg A,
Silver RT,
Coleman M,
Cacciapaglia B,
Bennet L,
Baird M,
Silverstein M,
Berger C,
Bernhardt B:
Utility of molecular genetic analysis of bcr rearrangement in the diagnosis of chronic myeloid leukemia.
Cancer Genet Cytogenet
29:1,
1987[Medline]
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5.
Melo JV:
The diversity of BCR-ABL fusion proteins and their relationship to leukemia phenotype.
Blood
88:2375,
1996[Free Full Text]
6. (letter)
Emilia G,
Luppi M,
Marasca R,
Torelli G:
Relationship between BCR/ABL fusion protein and leukemia phenotype.
Blood
89:3889,
1997[Free Full Text]
7.
Cervantes F,
Colomer D,
Vives-Corrons JL,
Rozman C,
Montserrat E:
Chronic myeloid leukemia of thrombocythemic onset: A CML subtype with distinct hematological and molecular features?
Leukemia
10:1241,
1996[Medline]
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8.
Emilia G,
Luppi M,
Ferrari MG,
Temperani P,
Marasca R,
Giacobbi F,
Vaccari P,
Bandieri E,
Di Donato C,
Carapezzi C,
Torelli G:
Chronic myeloid leukemia with thrombocythemic onset may be associated with different BCR-ABL variant transcripts.
Cancer Genet Cytogenet
101:75,
1998[Medline]
[Order article via Infotrieve]
| |
RESPONSE |
We thank Marasca et al for their thoughtful comments. In their letter,
Marasca et al describe a retrospectively recruited cohort of 20 patients with platlet counts greater than 1,000 × 109/L. This cohort represents a selection bias in which
only part of ET patients were enrolled in the study, whereas the lower
limit of the PVSG criteria has been set at 600 × 109/L.1,2 It is not known how many ET patients
were excluded by this selection.
Although the maximal follow-up period reported by the Modena group was
144 months, 6 of their 20 patients were observed for 6 to 8 months
only. This period is admittedly too short to observe ET patients. By
contrast, our BCR-ABL-positive group has been observed for a minimum
of 17 months, including 7 patients for 17 to 24 months and 5 for as
long as 34 to 64 months. Thus, all of our patients were observed for a
longer period than one third of those of the Modena group.
The unreferenced statement of Marasca et al about the diagnostic value
of BCR-ABL transcript in Ph patients implies that all
our patients that lack any other clinical and laboratory evidence of
CML as well as the normal subjects of Birneaux et al3 were
in fact CML patients. Thus, one criterion of CML does not establish
the diagnosis. Furthermore, there is no evidence that BCR-ABL-positive
Ph ET patients will transform to CML. Otherwise, as the
statement of Marasca et al may imply, all of these subjects should
receive interferon therapy.
The fact that both groups of our study had similar clinical and
laboratory characteristics should not surprise the Modena group. Even
now, 18 months after the first stage of the study has been summarized
in our report, none of our patients transformed to acute leukemia or
CML. Moreover, all the patients reported in our study are still alive
(except for an 86-year-old patient who died of an intercurrent
infection).
Finally, Marasca et al cite Cervantes et al4 and their
unpublished material to support their concept. However, Cervantes et al
describe patients with chronic-phase Ph+ CML, whereas our
patients had neither Ph chromosome nor CML.
Taken together, our results strongly disagree with the suggestion of
Marasca et al that BCR-ABL-positive Ph ET patients are
CML variants. However, we concur with their opinion that a
longer follow-up period is needed to better understand the natural
history of this entity.
Dorit Blickstein
Adina Aviram
Jacob Luboshitz
Miron Prokocimer
Pinhas Stark
Osnat Bairey
Jaqueline Sulkes
Mati Shaklai
Division of Hematology
and Epidemiology Unit
Rabin Medical Center
Beilinson
Campus
Petah-Tikva, Israel
| |
REFERENCES |
1. Schafer AI: Essential (primary) thrombocythemia, in Beutler E,
Lichtman MA, Coller BS, Kipps TJ (eds): Williams Hematology (5th ed).
New York, NY McGraw-Hill, 1995, p 340
2. Hoffman R, Silverstein MN, Hromas R: Primary thrombocythemia, in
Hoffman R, Benz EJ Jr, Shattil SJ, Furie B, Cohen HJ, Silberstein LE
(eds): Hematology
Basic Principles and Practice (2nd ed). New York,
NY, Churchill Livingston, 1995, p 1174
3.
Biernaux C,
Leos M,
Sels A,
Huez G,
Stryckmans P:
Detection of major bcr-abl gene expression at a very low level in blood cells of some healthy individuals.
Blood
86:3118,
1995[Abstract/Free Full Text]
4.
Cervantes F,
Colomer D,
Vives-Corros JL,
Rozman C,
Montserrat E:
Chronic myeloid leukemia of thrombocythemic onset: A CML subtype with distinct hematological and molecular features?
Leukemia
10:1241,
1996
