Haematologica 2003 - Supplements

362
EOSINOPHILIA IS A VERY COMMON FINDING IN
MYELOMA PATIENTS TREATED WITH THALIDOMIDE
AND CYCLOPHOSPHAMIDE
F. Di Raimondo, A. Pennisi, D. Buglio, P. Fiumara, GA
Palumbo.
Dept. of Medical Sciences – Section of Hematology – University of
Catania, Italy
Although thalidomide represents one of the major improvements
in the treatment of multiple myeloma its mechanism of action
remains to be fully elucidated. Moreover, thalidomide side effects
are quite variable among different series and their incidence and
severity appears to be different if this drug is used alone or in
combination. Among modifications of hematological parameters,
increase in eosinophil count has been reported in conjunction to
other side effects induced by thalidomide. However, by treating
patient with thalidomide, we observed an high frequency of
eosinophilia. On these basis we retrospectively examined medical
records of 39 patients affected by resistant or refractory multiple
myeloma treated with a combination of thalidomide 200 mg,
cyclophosphamide 100 mg, both daily, and dexamethasone 40 mg
for 4 days every month. Before starting therapy, median
eosinophilic count of the whole group was 0.52 x10e9/l and it
increased to 0.85 x10e9/l after the first month (p 0.08), 1.30
x10e9/l after the second month (p 0.01), and 1.12 x10e9/l after
the third month (p 0.001). Mean determination of eosinophil
count recorded during entire duration of treatment was higher
than pretreatment count in 31 out of 39 patients. Three patients
only did not respond to this combination therapy and their median
eosinophil count during treatment was 0.26 x10e9/l vs 1.12
x10e9/l of responding patients. However, no difference in the
eosinophil count or in the magnitude of increase was observed
among the groups of patients with different degree of response
(minimal or complete response). In addition, no correlation was
found between percentage of plasma cell bone marrow infiltration
and the eosinophil count or the entity of its increase. None of the
common thalidomide side effects were correlated to the
eosinophilia.
In conclusion, we found that in myeloma patients treated with a
combination of thalidomide, cyclophosphamide and
desamethasone, increase of eosinophil count was a very common
event. This finding cannot be ascribed to desamethasone because
actually it may induce eosinopenia. On the contrary, the
combination of thalidomide and cyclophosphamide may be
responsible for eosinophilia and the increase of eosinophil count
could be related to thalidomide mechanism of action. In fact, in
non responding patients eosinophil count was lower than in
responsive ones but the number of the former is too small to be
significant.
363
EVALUATION OF THROMBOPHYLIC STATES IN
MYELOMA PATIENTS RECEIVING THALIDOMIDE
AB Santos,P Llamas,A Román,E Prieto,R de Oña,J
Fernández de Velasco,D Subirá, C Soto,E Vizcarra,JL
López,I Marco*, JF Tomás
Fundación Jiménez Díaz. Hematology Department.UAM *Grant
from Fundación Conchita Rábago
Introduction: An increased incidence of deep venous thrombosis
(DVT) has been described in multiple myeloma (MM). Its
pathogenesis is multifactorial but the presence of other states of
inherited or acquired thrombophilia can increase this
hypercoagulability. Thalidomide has been used in refractory MM.
An increased risk of thrombosis has been reported in combination
with other chemotherapeutic agents. We present a patient with
MM, homozygous carrier of the C677T mutation of the MTHFR
gene who developed DVT and pulmonary embolism (PE) during
thalidomide treatment.
Case Report: A 60-year-old male with stage IIIA Bences Jones
(BJ) MM was treated at diagnosis with conventional
chemotherapy and he obtained a complete response. During the
treatment, the patient suffered DVT in the right subclavian vein
with a central venous catheter. After relapse, thalidomide was
initiated with a 200mg/day dose with 15-day cycles of
dexamethasone. The thalidomide was increased 200mg/day every
two weeks as tolerated. With the 400mg/day dose, he presented
constipation and drowsiness. Upon reaching 800mg/day, he had a
slight polyneuropathy which ceded with 600mg/day. In the 7th
month of treatment, the patient presented progressive dyspnea
without other symptoms. Patient was obese, eupnoeic at rest and
had normal cardiopulmonary examination. He presented slight
malleolar oedema without signs of DVT. Laboratory studies:
haemoglobin 10.7g/dl, normal leukocyte, platelet count, PT,
TTPA and biochemical; fibrinogen 488mg/dl; proteinuria
700mg/24 hours without evidence of BJ. D-Dimer (ELISA):
2428µg/l (68-494µg/l). Chest X-ray normal. Pulmonary perfusion
scintigraphy and helical CT were suggestive of PE. An echodoppler
of the lower limbs detected thrombosis of the right
popliteal vein. With the diagnosis of PE and DVT, anticoagulant
treatment was initiated. Thrombophilia study detected he was
homozygous for the C677T mutation of the MTHFR. High serum
levels of homocysteine, 26 IU/ml (normal