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Blood, 1 December 2000, Vol. 96, No. 12, pp. 4007-4007
CORRESPONDENCE
To the editor:
Serious myeloproliferative reactions associated with the use of
thalidomide in myelofibrosis with myeloid metaplasia
Current treatment in myelofibrosis with myeloid metaplasia (MMM)
is inadequate: only a small proportion of patients derive benefit from
bone marrow transplantation, splenectomy, or drug therapy.1 We have recently demonstrated a prognostically
detrimental increase in bone marrow microvessel density in the majority
of patients with MMM.2 Because thalidomide may inhibit
angiogenesis,3 its therapeutic activity in MMM is worth investigating. Before initiating a currently ongoing phase II treatment trial with
thalidomide in MMM, we had piloted the drug in 6 patients (age range,
41-71 years; 3 males, 3 females) with symptomatic disease under a
compassionate-use protocol approved by the institutional review board.
Treatment in all patients was initiated at a daily oral dose of 200 mg,
and further dose increments were not tolerated. The duration of
treatment ranged from 9 days to 9 months. Of the 6 patients, 3 had
concomitant treatment with a cytoreductive agent and were therefore not
eligible for accurate assessment of the thalidomide effect on blood
counts or spleen size. The remaining 3 patients were treated with
thalidomide alone a minimum of 2 months after discontinuing previous
specific therapy. The effect of treatment in these 3 patients is as follows. One patient experienced severe upper left quadrant pain and fever
that suggested a splenic infarct after only 9 days of treatment with
thalidomide, without associated changes in blood count or spleen size.
The second patient had a marked increase in both his previously stable
peripheral platelet count (277-1082 × 109/L) and his
leukocyte count (7.2-23.6 × 109/L) after only 20 days of
treatment with thalidomide (200 mg/day) and required short-term therapy
with hydroxyurea. The platelet count increased
(152-440 × 109/L) also in the third patient during
treatment with thalidomide and returned to baseline after cessation of
therapy (9 months at 50 mg per day). The last-mentioned patient also
had a durable increase in hemoglobin level (10.9-13.3 g/dL). The preliminary observations from our current phase II study
confirm probable drug-related steep increases in platelet and leukocyte
counts in some patients. These changes occurred in the initial 4 to 8 weeks of treatment with thalidomide and were often associated with
marked basophilia. We have documented the development of pericardial
effusion secondary to extramedullary hematopoiesis in one patient. The
mechanism of action and net effect of this biologic activity remain to
be determined. But the potential for precipitation of serious
disease-related complications exists, and the use of this drug outside
a protocol setting is discouraged.
Ayalew Tefferi and Michelle A. Elliott
Division of Hematology and Internal Medicine Mayo Clinic and
Mayo Foundation Rochester, MN
References
1.
Tefferi A.
Myelofibrosis with myeloid metaplasia.
N Engl J Med.
2000;342:1255-1265[Free Full Text].
2.
Mesa RA, Hanson CA, Rajkumar SV, Schroeder S, Tefferi A.
Evaluation and clinical correlations of bone marrow angiogenesis in myelofibrosis with myeloid metaplasia.
Blood.
2000;96:3374-3380[Abstract/Free Full Text].
3.
D'Amato RJ, Loughnan MS, Flynn E, Folkman J.
Thalidomide is an inhibitor of angiogenesis.
Proc Natl Acad Sci U S A.
1994;91:4082-4085[Abstract/Free Full Text].
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