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Blood, Vol. 91 No. 2 (January 15), 1998:
pp. 616-622
Acute Myeloid Leukemia and Myelodysplastic Syndromes Following
Essential Thrombocythemia Treated With Hydroxyurea: High Proportion
of Cases With 17p Deletion
By
Yvon Sterkers,
Claude Preudhomme,
Jean-Luc Laï,
Jean-Loup Demory,
Marie-Thérèse Caulier,
Eric Wattel,
Dominique Bordessoule,
Francis Bauters, and
Pierre Fenaux
From the Service des Maladies du Sang, Laboratoire
d'Hématologie, and Service de Cytogénétique, CHU
Lille; the Service d'Hématologie, Hôpital Saint Vincent,
Lille; and the Service d'Hématologie CHU Dupuytren, Limoges,
France.
 |
ABSTRACT |
Treatment with alkylating agents or radiophosphorous
(32P) has been shown to carry a certain leukemogenic risk
in myeloproliferative disorders (MPDs), including essential
thrombocytemia (ET). The leukemogenic risk associated to treatment with
hydroxyurea in ET, on the other hand, is generally considered to be
relatively low. Between 1970 and 1991, we diagnosed ET in 357 patients,
who were monitored until 1996. One or several therapeutic agents had been admistered to 326 patients, including hydroxyurea (HU) in 251 (as
only treatment in 201), pipobroman in 43, busulfan in 41, and
32P in 40. With a median follow-up duration of 98 months,
17 patients (4.5%) had progressed to acute myeloid leukemia (AML; six
cases) or myelodysplastic syndrome (MDS; 11 cases). Fourteen of these patients had received HU, as sole treatment in seven cases, and preceded or followed by other treatment in seven cases, mainly pipobroman (five cases). The remaining three leukemic progressions occurred in patients treated with 32P (two cases) and
busulfan (one case). The incidence of AML and MDS after treatment,
using 32P alone and 32P with other agents,
busulfan alone and with other agents, HU alone and with others agents,
and pipobroman alone and with other agents was 7% and 9%, 3% and
17%, 3.5% and 14%, and 0% and 16%, respectively. Thirteen of 17 patients who progressed to AML or MDS had successful cytogenetic
analysis. Seven of them had rearrangements of chromosome 17 (unbalanced
translocation, partial or complete deletion, isochromosome 17q) that
resulted in 17p deletion. They also had a typical form of
dysgranulopoiesis combining pseudo Pelger Hüet hypolobulation and
vacuoles in neutrophils, and p53 mutation, as previously described in
AML and MDS with 17p deletion. Those seven patients had all received
HU, as the only therapeutic agent in three, and followed by pipobroman
in three. The three patients who had received no HU and progressed to
AML or MDS had no 17p deletion. A review of the literature found
cytogenetic analysis in 35 cases of AML and MDS occurring after ET, 11 of whom had been treated with HU alone. Five of 35 patients had
rearrangements that resulted in 17p deletion. Four of them had been
treated with HU alone. These results show that treatment with HU alone
is associated with a leukemic risk of approximately 3.5%. A high
proportion of AML and MDS occurring in ET treated with HU (alone or
possibly followed by pipobroman) have morphologic, cytogenetic, and
molecular characteristics of the 17p syndrome. These
findings suggest that widespread and prolonged use of HU in ET may have
to be reconsidered in some situations, such as asymptomatic ET.
| |
INTRODUCTION |
ESSENTIAL THROMBOCYTHEMIA (ET) is a
clonal myeloproliferative disorder (MPD)1 characterized by
a persistent increase in platelet counts. Progression of ET to acute
myeloid leukemia (AML), preceded or not by myelodysplastic syndrome
(MDS), has been observed in 3% to 4% of cases, and, until recently,
mostly in patients who had received treatment with radiophophorous
(32P) or alkylating agents, especially
busulfan.2-15 Hydroxyurea (HU), which is considered to have
relatively low leukemogenic potential, has therefore been widely used
in ET in recent years. No characteristic morphologic or cytogenetic
features of AML and MDS occurring during the course of ET have been
described, by comparison to other therapy-related cases of AML or
MDS.2-15
Recently, we and others reported, in AML and MDS, a strong correlation
between 17p deletion, resulting from unbalanced translocations between
17p and another chromosome or less often from monosomy 17 or i(17q),
typical dysgranulopoiesis combining pseudo Pelger Hüet
hypolobulation and small vacuoles in neutrophils, and p53 mutation.16,17 This correlation suggested that a new
morphologic-cytogenetic-molecular entity or syndrome could be described
in MDS and AML. Approximately 30% of patients with these
characteristics had received chemotherapy for a prior
neoplasm.16
We reviewed cases of AML and MDS occurring in 357 ET patients diagnosed
from 1970 to 1991 in two hematologic centers and monitored until August
1996. Seventeen cases of AML and MDS were observed, generally in
patients treated exclusively or predominantly with HU. Seven of them
had 17p deletions and other characteristics of the 17p
syndrome.
| |
MATERIALS AND METHODS |
Patients.
Between 1970 and January 1991, the diagnosis of ET was made at two
institutions (Centre Hospitalier Universitaire [CHU], Lille, and
Hopital St Philibert, Lomme, France) in 357 patients, according to the
following criteria: (1) platelet count greater than 700 × 109/L on two different counts separated by a 1-month
interval; (2) no known cause for reactive thrombocytosis, ie, no iron
deficiency based on normal serum iron level and transferrin-binding
capacity, presence of stainable iron in marrow, and, in recent
patients, normal serum ferritin; absence of inflammatory disease based
on normal values of erythrocyte sedimentation rate, protein
electrophoresis, and serum fibrinogen level; absence of splenectomy or
of an underlying neoplasm; and (3) exclusion of thrombocytosis of other
myeloproliferative disorders, ie, normal total erythrocyte volume
considered when, in the absence of iron deficiency, the hematocrit was
greater than 47% in women and 50% in men; absence of myelofibrosis
when a leukoerythroblastic reaction or morphologic abnormalities of erythrocytes was present; absence of Philadelphia chromosome when hematologic data were compatible with chronic myelogenous leukemia (CMI) with thrombocythemic onset; and absence of MDS, such as acquired
idiopathic sideroblastic anemia or the 5q-syndrome, both of which can
be associated with thrombocytosis.
The Lille center started to diagnose ET patients in 1970, and the Lomme
center in 1982. Characteristics of the 147 patients diagnosed in Lille
before July 1987, and their follow-up data to July 1988, have been
previously reported.5 Follow-up data of patients from the
two centers were analyzed on the reference date of August 31, 1996.
Treatment.
Cytoreductive therapy was generally started when patients met one of
the following criteria: platelet count greater than 1 × 1012/L; age older than 65 years; symptomatic disease; and
presence of another major risk factor for vascular disease (diabetes
mellitus, severe hypertension, hypercholesterolemia, or heavy smoking), or of previous symptomatic artery disease (involving the coronary, cerebral or legs arteries).
Until 1980, first-line therapy generally consisted of busulfan (6 mg/d)
or 32P (0.1 mCi/kg). After 1980, first-line therapy was
generally with HU (at the starting dose of 1.5 g/d), except in some
elderly patients who still received 32P. In patients in
whom HU did not allow permanent control of platelet counts at less than
0.5 × 109/L, HU was generally replaced by pipobroman
(Vercyte; Abbott, Rungis, France) at the starting dose of
1 mg/kg/day. Indeed, after several of our ET patients had experienced
thrombotic episodes at platelet counts of 0.5 to 0.6 × 109/L, we had aimed, in patients in whom treatment
indicated, to maintain platelet counts at less than 0.5 × 109/L.5
Overall, 326 of 357 patients had received at least one cytoreductive
agent, including 32P in 40 patients, busulfan in 41, HU in
251, pipobroman in 43, and other drugs in five.
Methods.
Cytogenetic analysis was performed with conventional banding
techniques, and abnormalities were classified according to the International system for cytogenetic nomenclature.18
MDS and AML were classified according to French-American-British (FAB)
criteria.19 Bone marrow smears obtained at diagnosis of MDS
and AML were reviewed, with particular emphasis on analysis of
myelodysplastic features.
Analysis of p53 mutations was made by single-strand conformation
polymorphism (SSCP) analysis of exons 4 to 10 of the p53 gene
and/or by immunocytochemical analysis of p53 protein using monoclonal antibodies, as previously described.20
Statistical analysis were performed with the chi-square test or
Fisher's exact test.
| |
RESULTS |
Clinical and hematologic features of cases of AML and MDS occurring
after ET.
With a median follow-up duration of 98 months (range, 22 to 265), 17 (4.5%) patients had progressed to AML (six cases) or MDS (11 cases).
Fourteen cases were diagnosed among 334 patients monitored in Lille,
and three among 23 patients monitored in Lomme. The characteristics and
outcome of those patients are listed in Table
1. Fourteen patients had received HU,
during a median period of 53 months (range, 3 to 96); seven of them had
received HU alone, and seven had also received other treatments,
including pipobroman in five (during a median period of 48 months;
range, 4 to 76), 32P in one, melphalan in one, and busulfan
in one (one patient had received three successive treatment regimens).
The remaining three patients had received no HU, but had received
32P alone in two cases and busulfan alone in one case.
The median age of the 17 patients at diagnosis of ET was 62 years
(range, 30 to 75), and there were 11 men and six women. The median
interval between diagnosis of ET and diagnosis of AML or MDS was 84 months (range, 55 to 147). Six patients had AML not preceded by a phase
of MDS, including five with M2 and one with M4 AML. Eleven patients had
MDS, including refractory anemia (RA) in two cases, refractory anemia
with excess of blasts (RAEB) in one, RAEB in transformation (RAEB-T) in
six, and chronic myelomonocytic leukemia (CMML) in two. After the
diagnosis of AML or MDS was made, two patients received intensive
chemotherapy and one received low-dose cytarabine, with no response.
Two patients were allografted as first-line therapy: one relapsed after
3 months and died, and one remained in complete remission after 72 months. The remaining patients were treated symptomatically. All
patients except the allografted patient who was still in complete
remission had died 1 to 36 months (median, 6) after the diagnosis of
MDS or AML.
Cytogenetic and molecular features of AML and MDS occurring after ET.
Thirteen of 17 patients had successful cytogenetic analysis at the time
of progression to AML or MDS. Seven of them (41% of the 17 patients,
and 54% of the karyotyped cases) had 17p deletions, resulting from
unbalanced translocation between 17p and another chromosome in three
cases (chromosome 5 in two and undetermined chromosome in one), del 17p
in one, i(17q) in one, and monosomy 17 in the two remaining patients.
Six of seven patients with a 17p deletion had additional cytogenetic
abnormalities, involving in particular chromosome 5 and/or 7 (Table 1). Typical dysgranulopoiesis, including pseudo Pelger
Hüet hypolobulation and small vacuoles in greater than 5%
neutrophils, as previously described,16,17 was seen in all
of them. p53 mutation by SSCP analysis and/or p53
overexpression by immunocytochemistry (which in our experience in MDS
and AML is always associated with the presence of a p53 missense
mutation)20 was demonstrated in the six assessable cases.
The remaining patients had normal cytogenetics (two cases), complex
cytogenetic findings without 17p involvement, where chromosome 5 but
not 7 was involved (three cases), isolated acquired trisomy 21 (one
case), or were not karyotyped (four cases). None of the 10 patients
without 17p deletion had dysgranulopoïesis typical of 17p
deletion cases and, among them, none of the four who were tested had a
p53 mutation and/or overexpression.
Nine of 17 patients who progressed to AML or MDS had been karyotyped at
diagnosis of ET, and cytogenetic findings were normal in all nine. They
included five patients who had 17p deletions at the time of
progression.
Incidence and features of AML and MDS according to cytoreductive
treatment.
The incidence of progression to AML and MDS according to cytoreductive
treatment is shown in Table 2. It was 7.5%
after 32P (7% after 32P alone), 5% after
busulfan (3% after busulfan alone), 5.5% after HU (3.5% after HU
alone), and 12% after pipobroman (zero of 12 patients treated with
pipobroman alone). Differences were not significant among the four
agents when used alone. However, progression was significantly more
frequent after HU combined with other agents (seven of 50) than after
HU alone (seven of 201, P = .01) and after one of the three
other agents used alone (three of 76, P = .04)
The seven patients who progressed to AML and MDS with a 17p deletion
had all received HU, as the sole cytoreductive agent in three of them,
preceded or followed by pipobroman in three, and by busulfan and
32P in one case each. The median duration of treatment with
HU in those seven patients had been 57 months. The three cases of AML or MDS that occurred in patients who had not received HU showed no 17p
rearrangement. Thus, four cases of AML and MDS with 17p deletion
occurred among 50 patients treated with HU and other drugs, as compared
with three cases among 201 patients treated with HU alone
(P = .03) and none among 106 patients who received no HU
(P = .02).
| |
DISCUSSION |
The incidence of AML and MDS during the course of ET observed in this
study where prolonged follow-up data were available in most patients
(4.5%), was similar to that previously reported in other series of ET.
Indeed, by combining the 14 published series (to our knowledge) of ET
that included more than 30 patients,2-15 an incidence of
progression to MDS or AML of 3.5% was found.
Most of the patients who developed MDS or AML in our study had received
HU, generally for prolonged periods, and HU was the only cytoreductive
agent used in seven of them. The incidence of MDS and AML in patients
who had received HU alone was not significantly different than that of
patients who had received busulfan alone or 32P alone, two
treatments that are known to be leukemogenic. Most of our ET patients
diagnosed before 1980 had received busulfan or 32P. After
1980, to avoid the leukemogenic effects of busulfan and 32P, patients were generally treated with HU. However, in
Lille, we observed only one progression to AML among the first 147 patients monitored until 1988,5 whereas 13 new cases were
diagnosed between 1988 and 1996.
These findings confirm that HU has some leukemogenic potential in ET.
HU is a nonalkylating myelosuppressive agent that inhibits DNA
synthesis by inhibition of ribonucleoside diphosphate reductase, but
also inhibits DNA repair.21 The leukemogenic potential of HU has been mainly studied in polycythemia vera (PV). In PV treated with HU alone, the incidence of progression to AML had initially been
reported to be only 1% to 3% in two cohorts of approximately 100 cases followed over a median of 5 years.22,23 This was less
than the 6% to 10% and 12% to 13% reported after 32P
and chlorambucil, respectively, by the PV Study Group (PVSG) and other
groups.24,25 On the other hand, the incidence of progression to AML in PV treated with HU alone was 8% at 12 years and
5.9% at 8.5 years in two recently published large series with prolonged follow-up evaluation26,27 as compared with 1.5%
after phlebotomy alone.27 To our knowledge, after excluding
cases with Philadelphia chromosome at diagnosis, 103 cases of acute leukemia and MDS occurring during the course of ET have been
reported.2-15,30-60 Seven of them were acute lymphocytic
leukemia and the remaining cases were AML or MDS. At least 34 of them
had been treated with HU, and 19 with HU alone (Table
3). By combining published series of ET in
which treatment and evolution were available,2-15 we found
that 10 of 293 patients (3.4%) treated with HU alone had progressed to
acute leukemia, a figure similar to our results.
In PV, long-term results of a large study that randomized patients to
receive, after a first course of 32P, maintenance with HU
versus no maintenance (and additional 32P if required)
showed a significantly higher incidence of AML in the group maintained
with HU, although the other group had received higher cumulative doses
of 32P.28 In another study, leukemias in ET
treated with HU occurred mainly in patients who, because of incomplete
response to this drug, were switched to alkylating
agents.29 Thus, HU also appears to increase the leukemic
risk of other cytoreductive treatments administered in PV and ET. Our
findings of a significantly higher incidence of evolution to AML and
MDS in patients treated with HU and other agents as compared with HU
alone or with other agents alone are in agreement with those reports.
Five of 17 patients reported here had, in addition to HU, received
pipobroman, a bromide derivative of piperazine, which, although its
formula is close to that of the alkylating agents, mainly appears to
act as a metabolic competitor of pyrimidine bases.61
Pipobroman, in our experience and that of some other groups, often
allows better control of platelet counts than HU.5,62 Three
of the five MDS and AML cases occurring in patients who had received
pipobroman had 17p deletions. The incidence of AML and MDS in patients
who had received pipobroman was relatively high (12%), but AML and MDS
occurred in patients who had also received other drugs, and none of the
12 patients treated with pipobroman alone had leukemic evolution. This
suggests that the leukemic risk of pipobroman is found mainly in
patients who also received other drugs, principally HU in our
experience. Pipobroman has not been widely used in ET, and the risk of
leukemia with this drug has not been previously well defined. In two
series of 21 and 24 ET patients treated with pipobroman, no progression to AML had occurred, but the follow-up duration was relatively short.63,64 In PV, the risk of leukemia after pipobroman
was considered to be 6% and 9% after 5 and 7 years of treatment,
respectively, in one series,65 and 4.5% in
another.66 Recently, in a randomized prospective study, it
was evaluated at 8% after 12 years, similar to that observed with
HU.26
Our study also found that approximately 40% of the AML and MDS cases
occurring in ET treated predominantly with HU had 17p deletions and
other characteristics of what we and others described as the
17p syndrome, ie, typical dysgranulopoiesis and p53
mutation.16,17 The seven ET patients who progressed to AML
or MDS with a 17p deletion presented here had all received HU, which,
in three of them, was the only antineoplastic agent used, whereas three
other cases had also received pipobroman. Of the 103 cases of
transformed ET reported until now, to our knowledge, 35 had cytogenetic
analysis, and 17p deletion was found in five
patients.4,13,42,51 Three of these five patients had
monosomy 17 and additional complex cytogenetic findings, one had i(17q)
(Table 4), and the last patient had deletion of chromosome
17.51 Four of these five patients had received HU as the
sole antineoplastic agent, during 17, 24, 64, and 92 months,
respectively (Table 4), and the last patient51 had received
busulfan and low-dose cytarabine. At transformation, they were
classified as M2 AML, acute undifferentiated leukemia, Mo AML, and
RAEB-T, respectively, in four cases (Table 4), and not classified in
the last case.51 No mention of dysgranulopoiesis was made
in the five case reports. Patients with 17p deletions after treatment
with HU alone constituted four of the 11 reported cases of ET that
progressed to MDS or AML after HU alone and where karyotype was
available (Table 3).
Morphologic, cytogenetic, and molecular features of the
17p syndrome have not only been reported in AML and MDS,
but also in CML in blast crisis. Indeed, in blast crisis CML, Sessarego et al67 found a strong correlation between pseudo Pelger
Hüet hypolobulation and 17p deletion, often resulting from
i(17q). Furthermore, in blast crisis CML, a correlation between p53
mutation and 17p deletion has been reported.68 Because
blast crisis is the "natural" evolution of CML, one could suggest
that blast crisis of other myeloproliferative disorders with features
of the 17p syndrome could also result from their natural
evolution. However, in untreated ET, leukemic evolution appears to be
rare: only two of 46 evolutions of ET to acute leukemia recorded in
large series of patients (Table 3) occurred in untreated patients.
The relatively high incidence of chromosome 17 involvement in MDS and
AML following ET treated by HU in the literature and our findings
suggests that prolonged use of HU in ET may lead to or at least
increase the risk of MDS and AML with loss of 17p chromosomal material
and p53 mutation. The incidence was particularly high (four of 50 cases) in patients treated with HU and other drugs. In particular,
three cases occurred in patients who had received HU and pipobroman.
Thus, a role for pipobroman in the pathogenesis of MDS and AML with 17p
deletion, which could be additive to that of HU, is also possible in
ET. Recently, Gaidano et al69 also found p53 mutations in
four of 10 cases of AML following ET, in a study so far published only
in abstract form. No data on treatment received by those patients was
available, but they came from centers in which HU is generally used as
first-line therapy in ET. Data on dysgranulopoiesis and karyotype at
the time of progression to AML were not available. However, because of
the high correlation between 17p deletion and p53 mutations observed in
myeloid malignancies,15,16,67,70 it is probable that
several of those patients had 17p deletions.
Overall, our findings in a large series of patients, with prolonged
follow-up evaluation, confirm a certain leukemogenic potential for HU
in ET. The use of HU probably also increases the leukemic risk of other
cytoreductive treatments given in ET. We also found that MDS and AML
occurring after treatment with HU (and possibly pipobroman) often had a
17p deletion, confirming a few previously published case reports.
However, our findings need to be confirmed. We therefore encourage the
publication of all cases of AML and MDS occurring during the course of
ET treated with HU, with special emphasis on their morphologic and
cytogenetic characteristics. Description of larger numbers of MDS and
AML with 17p deletions after HU could lead to reconsideration of the
widespread use of this drug and to more limited use, for instance, in
asymptomatic ET. It would also possibly encourage larger use of drugs
that are probably nonleukemogenic, such as interferon and
anagrelide,62 when treatment is required in ET. From a more
fundamental viewpoint, description of other cases of MDS and AML with
17p deletion after HU would also point to a possible relationship
between HU and genes located in chromosome 17 (including the p53 gene),
whose disruption could participate in the leukemogenic process.
| |
FOOTNOTES |
Submitted May 12, 1997;
accepted September 9, 1997.
Address reprint requests to Pierre Fenaux, MD, Service des
Maladies du Sang, CHU, 1 place de Verdun, 59037 Lille, France.
The publication costs of this article were defrayed in part by page
charge payment. This article must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. section 1734 solely
to indicate this fact.
| |
REFERENCES |
1.
Fialkow PJ,
Faguet GR,
Jacobson RJ,
Vaidya K,
Murphy S:
Evidence that essential thrombocythemia is a clonal disorder within a multipotent stem cell.
Blood
58:916,
1981[Abstract/Free Full Text]
2.
Cervantes F,
Tassies D,
Salgado C,
Rovira M,
Pereira A,
Rozman C:
Acute transformation in nonleukemic chronic myeloproliferative disorders: Actuarial probability and main characteristics in a series of 218 patients.
Acta Haematol
85:124,
1991[Medline]
[Order article via Infotrieve]
3.
Chistolini A,
Mazzucconi MG,
Ferrari A,
La Verde G,
Ferrazza G,
Dragoni F,
Vitale A,
Arcieri R,
Mandelli F:
Essential thrombocythemia: A retrospective study on the clinical course of 100 patients.
Haematologica
75:537,
1990[Medline]
[Order article via Infotrieve]
4.
Löfvenberg E,
Nordenson I,
Wahlin A:
Cytogenetic abnormalities and leukemic transformation in hydroxyurea treated patients with Philadelphia chromosome negative chronic myeloproliferative disease.
Cancer Genet Cytogenet
49:57,
1990[Medline]
[Order article via Infotrieve]
5.
Fenaux P,
Simon M,
Caulier MT,
Laï JL,
Goudemand J,
Bauters F:
Clinical course of essential thrombocythemia in 147 cases.
Cancer
66:549,
1990[Medline]
[Order article via Infotrieve]
6.
Kwong YL,
Liang RHS,
Chui EKW,
Lie AKW,
Chan LC,
Todd D,
Chan TK:
Essential thrombocythemia: A retrospective analysis of 39 cases.
Am J Hematol
49:39,
1995[Medline]
[Order article via Infotrieve]
7.
Bellucci S,
Janvier M,
Tobelem G,
Flandrin G,
Charpak Y,
Berger R,
Boiron M:
Essential thrombocythemias: Clinical evolutionary and biological data.
Cancer
58:2440,
1986[Medline]
[Order article via Infotrieve]
8.
Hehlmann R,
Jahn M,
Baumann B,
Köpcke W:
Essential thrombocythemia: Clinical characteristics and course of 61 cases.
Cancer
61:2487,
1988[Medline]
[Order article via Infotrieve]
9.
Sessarego M,
Defferrari R,
Dejana AM,
Rebuttato AM,
Fugazza G,
Salvidio E,
Ajmar F:
Cytogenetic analysis in essential thrombocythemia at diagnosis and at transformation. A 12 years study.
Cancer Genet Cytogenet
43:57,
1989[Medline]
[Order article via Infotrieve]
10.
Cortelazzo S,
Finazzi G,
Ruggeri M,
Vestri O,
Galli M,
Rodeghiero F,
Barbui T:
Hydroxyurea for patients with essential thrombocythemia and high risk of thrombosis.
N Engl J Med
332:1132,
1995[Abstract/Free Full Text]
11.
Hattori A,
Nagayama R,
Kishi K,
Fuse I,
Hanano M,
Takizawa SI,
Takeshiga T,
Shibata A:
Primary thrombocythemia in Japan: A survey of 225 patients.
Leuk Lymphoma
4:177,
1991
12. (suppl 1, abstr)
Turlure P,
Le Prise PY,
Letortorec S,
Linassier C,
Ifrah N,
Desablens B,
Tourani JM,
Lejeune F,
Sensebe L,
Briere JB:
Essential thrombocythemia. Clinical course and results of a multicenter prospective study.
Blood
82:197a,
1993
13.
Colombi M,
Radaelli F,
Zocchi L,
Maiolo AT:
Thrombotic and hemorragic complications in essential thrombocythemia. A retrospective study of 103 patients.
Cancer
67:2926,
1991[Medline]
[Order article via Infotrieve]
14.
Liozon E,
Brigaudeau C,
Trimoreau F,
Desangles F,
Fermeaux V,
Praloran V,
Bordessoule D:
Is treatment with hydroxyurea leukemogenic in patients with essential thrombocythemia? An analysis of three new cases of leukaemic transformation and review of the literature.
Hematol Cell Ther
39:11,
1997 [Medline]
[Order article via Infotrieve]
15. Peterson P, Murphy S, Iland HJ, Geller SA, Ellis JT: Occurrence
of acute leukemia in treated essential thrombocythemia. Lab Invest
70:118-A, 1994
16.
Lai JL,
Preudhomme M,
Zandecki M,
Flactif M,
Vanrumbeke M,
Wattel E,
Fenaux P:
Myelodysplastic syndromes and acute myeloid leukemia with 17p deletion. An entity characterized by specific dysgranulopoiesis and a high incidence of p53 mutations.
Leukemia
8:1342,
1995
17.
Jary L,
Mossafa H,
Fourcade C,
Genet P,
Pulik M,
Flandrin G:
The 17p-syndrome: A distinct myelodysplastic syndrome entity?
Leuk Lymphoma
25:163,
1997[Medline]
[Order article via Infotrieve]
18. International System for Cytogenetic Nomenclature: Guidelines
for cancer cytogenetics. Supplement to Mitelman T (ed): An
International System for Human Cytogenetic Nomenclature. Basel, Switzerland, Karger, 1991
19.
Bennett JM,
Catovsky D,
Daniel MT,
Flandrin G,
Galton D,
Gralnick H,
Sultan C:
Proposals for the classification of the myelodysplastic syndromes.
Br J Haematol
51:189,
1982[Medline]
[Order article via Infotrieve]
20.
Lepelley P,
Preudhomme C,
Vanrumbeke M,
Quesnel B,
Cosson A,
Fenaux P:
Detection of p53 mutations in hematological malignancies: Comparison between immunocytochemistry and DNA analysis.
Leukemia
8:1342,
1994[Medline]
[Order article via Infotrieve]
21. (suppl 9)
Yarbro JW:
Mechanism of action of hydroxyurea.
Semin Oncol
19:1,
1992[Medline]
[Order article via Infotrieve]
22.
Donovan PB,
Kaplan ME,
Golberg JD:
Treatment of polycythemia vera with hydroxyurea.
Am J Hematol
17:329,
1984[Medline]
[Order article via Infotrieve]
23.
West WO:
Hydroxyurea in the treatment of polycythemia vera: A prospective study of 100 patients over a 20 year period.
South Med J
80:323,
1987[Medline]
[Order article via Infotrieve]
24.
Landaw SA:
Acute leukemia in polycythemia vera.
Semin Hematol
23:156,
1986[Medline]
[Order article via Infotrieve]
25.
Najean Y,
Deschamps A,
Dresch C,
Faille C,
Rain JD:
Acute leukemia and myelodysplasia in polycythemia vera. A clinical study with long-term follow-up.
Cancer
61:89,
1988[Medline]
[Order article via Infotrieve]
26.
Najean Y,
Rain JD:
Treatment of polycythemia vera: The use of hydroxyurea and pipobroman in 242 patients under the age of 65 years.
Blood
90:3370,
1997[Abstract/Free Full Text]
27. Berk PD, Wasserman LR, Fruchtman SM, Golberg JD: Treatment of
Polycythemia Vera. A Summary of Clinical Trials Conducted by the PVSG.
Philadelphia, PA, Saunders, 1995, p 166
28.
Najean Y,
Rain JD:
Treatment of polycythemia vera. Use of 32P alone or in combination with maintenance therapy using hydroxyurea in 434 patients over the age of 65 years.
Blood
89:2319,
1997[Abstract/Free Full Text]
29. (abstr)
Murphy S,
Peterson P,
Iland HJ,
Fruchtman S:
Hydroxyurea and other myelosuppressive agents in the treatment of essential thrombocytemia: Analysis of leukemogenic potential.
Thromb Haemost
69:564a,
1993
30.
Furgerson JL,
Vukelja SJ,
Baker WJ,
O'Rourke TJ:
Acute myeloid leukemia evolving from essential thrombocythemia in two patients treated with hydroxyurea.
Am J Hematol
51:137,
1996[Medline]
[Order article via Infotrieve]
31.
Van Den Anker-Lugtenburg PJ,
Sizoo W:
Myelodysplastic syndrome and secondary acute leukemia after treatment of essential thrombocythemia with hydroxyurea.
Am J Hematol
33:152,
1990[Medline]
[Order article via Infotrieve]
32.
Murphy PT,
Sivakumaran M,
Van Rhee F,
Watmoret AE,
Mitchell VE:
Acute lymphoblastic transformation of essential thrombocythaemia.
Br J Haematol
89:921,
1995[Medline]
[Order article via Infotrieve]
33.
Ferrari D,
Ticozzelli G,
De Vizzi M,
Corigliano P,
De Vizzi G:
Essential thrombocythemia and acute leukemia.
Haematologica
78:401,
1993[Medline]
[Order article via Infotrieve]
34.
Weinfeld A,
Swolin B,
Westin J:
Acute leukaemia after hydroxyurea therapy in polycythaemia vera and allied disorders: Prospective study of efficacy and leukaemogenicity with therapeutic implications.
Eur J Haematol
52:134,
1994[Medline]
[Order article via Infotrieve]
35.
Higuchi T,
Okada S,
Mori H,
Niikura H,
Omine M,
Terada H:
Leukemic transformation of polycythemia vera and essential thrombocythemia possibly associated with an alkylating agent.
Cancer
75:471,
1995[Medline]
[Order article via Infotrieve]
36.
Shibata K,
Shimamoto Y,
Suga K,
Sano M,
Matsuzaki M,
Yamaguchi M:
Essential thrombocythemia terminating in acute leukemia with minimal myeloid differentiation A brief review of recent literature.
Acta Haematol
91:84,
1994[Medline]
[Order article via Infotrieve]
37.
Sedlacek SM,
Curtis JL,
Weintraub J,
Levin J:
Essential thrombocythemia and leukemic transformation.
Medicine
65:353,
1986 [Medline]
[Order article via Infotrieve]
38. (suppl 3)
Lopes E,
Ribeiro MM,
Silva MJ,
Gandra M,
Principe F,
Granato C:
Essential thrombocythemia. Clinical features, therapy and follow-up of 12 cases.
Leukemia
6:138s,
1992
39.
Boros L,
Markhan RE,
Brernan JK:
Primary thrombocythemia and acute leukemia.
JAMA
253:1721,
1985
40.
O'Hea AM,
Erber W,
O'Connor NTJ,
Bunch C:
Acute transformation of essential thrombocythaemia: Report of two cases.
J Clin Pathol
39:1296,
1986[Abstract/Free Full Text]
41.
Kimura A,
Fujimoto T,
Inada T,
Imamura N,
Oguma N,
Kajihara H,
Mbasiwa DN,
Kahoh O,
Fujimura K,
Kuramoto A:
Blastic transformation in essential thrombocythemia In vitro differentiation of blast cells into granulocytic, erythroid, and megakaryocytic lineages.
Cancer
65:1538,
1990[Medline]
[Order article via Infotrieve]
42. Groupe Français de Cytogénétique
Hématologique: Cytogenetic of acutely transformed chronic
myeloproliferative syndromes without a philadelphia chromosome: A
multicenter study of 55 patients. Cancer Genet Cytogenet 32:157, 1998 (abstr)
43.
Higuchi T,
Okada S,
Mori H,
Niikura H,
Omine M,
Terada H:
Leukemic transformation of polycythemia vera and essential thrombocythemia possibly associated with an alkylating agent.
Cancer
75:471,
1995
44.
Okuda M,
Shishido T,
Sato A,
Najai T,
Sujaware T,
Kameoba J,
Karreda K,
Mejuro K,
Fujuhera O,
Sukurai T:
Essential thrombocythemia transformed to acute myeloid leukemia.
Jpn J Clin Hematol
31:1689,
1990
45.
Honna K:
Blastic transformation of essential thrombocythemia. A case report.
Acta Pathol Jpn
39:670,
1989[Medline]
[Order article via Infotrieve]
46.
Woronzoff-Dashoff K,
Litz GE:
Acute lymphoblastic leukemia in a case of essential thrombocythemia.
Am J Clin Pathol
106:206,
1996[Medline]
[Order article via Infotrieve]
47.
Patino-Sarcinelli F,
Knecht H,
Pechet L,
Pihan G,
Savas L,
Snyder M:
Leukemia with megakaryocytic differentiation following essential thrombocythemia and myelofibrosis.
Acta Hematol
95:122,
1996
48.
Rios R,
Soli F,
Pérez M,
Gascon F,
Garcia F,
Gonzalez PM:
t(2;3) in a case of blastic transformation of essential thrombocythemia.
Br J Haematol
92:769,
1996[Medline]
[Order article via Infotrieve]
49.
Chen YH,
Mishoulam H,
Mir JA,
Choiy S,
Schadi ST:
Blastic transformation in a case of essential thrombocythemia.
South Med J
80:1040,
1987[Medline]
[Order article via Infotrieve]
50.
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]
51.
Frei-Lahr D,
Barton JC,
Hoffman R,
Burkett LL,
Prchal JT:
Blastic transformation of essential thrombocythemia. Dual expression of myelomonoblastic/megakaryoblastic phenotypes.
Blood
63:866,
1984[Abstract/Free Full Text]
52. (suppl 1, abstr)
Nand S,
Stock W,
Godwin J,
Fisher S:
Leukemogenic risk of hydroxyurea therapy in polycythemia vera, essential thrombocythemia and myeloid metaplasia with myelofibrosis.
Blood
86:798a,
1995
53.
Geller SA,
Shapiro E:
Acute leukemia as a natural sequel to primary thrombocythemia.
Am J Clin Pathol
77:353,
1982[Medline]
[Order article via Infotrieve]
54.
Gris JC,
Schved JF,
Arnaud A,
Chawet C:
Myelodysplastic syndrome and secondary acute leukemia after treatment of essential thrombocythemia with melphalan.
Am J Hematol
30:47,
1989[Medline]
[Order article via Infotrieve]
55.
Raman SBK,
Mahmood A,
Van Slyck EJ:
Essential thrombocythemia with transition into acute leukemia.
Ann NY Acad Sci
370:145,
1981[Medline]
[Order article via Infotrieve]
56.
Vinti H,
Taillan B,
Pesce A,
Dujandin P:
Megakaryoblastic transformation of essential thrombocythemia, hypercalcemia and lytic bone lesions.
Acta Haematol
83:53,
1990[Medline]
[Order article via Infotrieve]
57.
Yonekura S,
Nagao T,
Arimori S:
Essential thrombocythemia developing into refractory anemia and complicated by acute leukemia.
Intern Med
31:1224,
1992[Medline]
[Order article via Infotrieve]
58.
Asano Y,
Naritomi Y,
Kimura H,
Maeda Y,
Kusata T,
Yoshizawa S,
Shiraishi G:
Low dose aclarubicin in blastic transformation of essential thrombocythemia.
Ann Hematol
62:194,
1991[Medline]
[Order article via Infotrieve]
59.
Toh BT,
Gregory SA,
Knospe WH:
Acute leukemia following treatment of polycythemia vera and essential thrombocythemia with uracil mustard.
Am J Hematol
28:58,
1988[Medline]
[Order article via Infotrieve]
60.
Berkhan LC,
Nelson J,
Ockelford PA,
Browett PJ:
Transformation of essential thrombocythaemia to acute lymphoblastic leukaemia.
Leuk Lymphoma
20:347,
1996[Medline]
[Order article via Infotrieve]
61.
Boivin P:
Indications, procedure and results for the treatment of polycythaemia vera by bleeding, pipobroman and hydroxyurea.
Nouv Rev Fr Hematol
35:491,
1993
62. (suppl)
Barbui T,
Finazzi G,
Dupuy E,
Kiladjian JJ,
Brière J:
Treatment strategies in essential thrombocythemia. A critical appraisal of various experiences in different centers.
Leuk Lymphoma
22:149,
1996
63.
Mazzucconi MG,
Francesconi M,
Chistolini A,
Falcione E,
Ferrari A,
Tirindelli MC,
Mandelli F:
Pipobroman therapy of essential thrombocythemia.
Scand J Haematol
37:306,
1986[Medline]
[Order article via Infotrieve]
64.
Brusamolino E,
Canevari A,
Salvaneschi L,
Merante S,
Bernasconi C:
Efficacy trial of pipobroman in essential thrombocythemia. A study of 24 patients.
Cancer Treat Rep
68:1339,
1984[Medline]
[Order article via Infotrieve]
65.
Brusamolino E,
Salvaneschi L,
Canevari A,
Bernasconi C:
Efficacy trial of pipobroman in polycythemia vera and incidence of acute leukemia.
J Clin Oncol
2:558,
1984[Abstract]
66.
Najman A,
Stachowiak J,
Parlier Y,
Gorin NC,
Duhamel G:
Pipobroman therapy of polycythemia vera.
Blood
59:890,
1982[Abstract/Free Full Text]
67.
Sessarego M,
Ajmar F:
Correlation between acquired pseudo-Pelger-Huët anomaly and involvement of chromosome 17 in chronic myeloid leukemia.
Cancer Genet Cytogenet
25:265,
1987[Medline]
[Order article via Infotrieve]
68.
Ahuja H,
Bar Eli E,
Arlin Z:
The spectrum of molecular alterations in the evolution of chronic myeloid leukemia.
J Clin Invest
87:2042,
1991
69. (suppl 1, abstr)
Gaidano G,
Pastore C,
Santini A,
Gamberi B,
Resegotti L,
Mazza U,
Rossi Ferrini P,
Lo Coco F,
Saglio G:
Blastic transformation of polycythemia vera and essential thrombocythemia frequently associates with mutations of p53.
Blood
88:98a,
1996
70.
Fenaux P,
Jonveaux P,
Quiquandon I,
Lai JL,
Pignon JM,
Loucheux-Lefebvre MH,
Bauters F,
Berger R,
Kerckaert JP:
P53 gene mutations in acute myeloid leukemia with 17p monosomy.
Blood
78:1652,
1991[Abstract/Free Full Text]
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|
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|
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|
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|
|
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|
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2000(1):
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|
|
|
|
|
|
|
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November 1, 1999;
81(5):
437 - 439.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Clinical and Applied Thrombosis/Hemostasis,
October 1, 1999;
5(4):
247 - 251.
[Abstract]
[PDF]
|
|
|
|
|
|
|
S. D. Nimer
Essential Thrombocythemia: Another "Heterogeneous Disease" Better Understood?
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93(2):
415 - 416.
[Full Text]
[PDF]
|
|
|
|
|
|
|
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A Large Proportion of Patients With a Diagnosis of Essential Thrombocythemia Do Not Have a Clonal Disorder and May Be at Lower Risk of Thrombotic Complications
Blood,
January 15, 1999;
93(2):
417 - 424.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Tefferi;, P. Fenaux, C. Preudhomme, J.-L. Lai, and Y. Sterkers
Is Hydroxyurea Leukemogenic in Essential Thrombocythemia?
Blood,
August 15, 1998;
92(4):
1459 - 1461.
[Full Text]
[PDF]
|
|
|
|
|
|
|
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Multiple Factors in the Transformation of Essential Thrombocythemia to Acute Leukemia or Myelodysplastic Syndrome
Blood,
August 15, 1998;
92(4):
1465 - 1466.
[Full Text]
[PDF]
|
|
|
|
|
Abstract
Introduction
Abstract