12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
to patients with isolated palpebral infiltration. Ophtalmological examination
revealed grade 3 palpebral infiltration without abnormal ocular
motility in all cases. Other ocular signs were noted such as clinical exophtalmia
and upper lid retraction both suggesting Basedow’s disease features.
These signs were confirmed with MRI showing a grade 1-2 exophtalmia
with adipous hypertrophy, a normal aspect of the muscles but an
evident palpebral modification with oedema and adipous hypertrophy
both with WT1 hyper signal and hyper WT2 signal. Endocrinological
investigations including TSH dosage, T3, T4 and auto antibodies against
thyroglobulin were performed and ruled out the hypothesis of
endocrinopathy. Discussions and Conclusions. We point out this particular
complication of imatinib that mimics endocrinological features. Diuretics
were efficient in reducing generalized oedema in the 2 patients concerned,but
did not improve the palpebral infiltration in any patient. The
dose of imatinib was reduced in 3 pts. We then observed a significant
decrease of palpebral infiltration in those patients. Our observations
strongly suggest that imatinib is able to induce muscular infiltrations and
adipous hypertrophy noted in MRI imaging. Our hypothesis that imatinib
could interfere with lipogenesis warrant further studies.
1344
IGHV3-21-EXPRESSED CLL CASES IN UKRAINE
N. Bilous1 , I. Abramenko2 , I. Kryachok2 , A. Chumak2 1 Research Center for Radiation Medicine, KIYV, Ukraine; 2 Research Centre for
Radiation Medicine, KIYV, Ukraine
Neoplastic B-lymphocytes in patients with chronic lymphocytic
leukemia (CLL) expressed restricted set of immunoglobulin variable
heavy chain (IGHV) genes which may determine the clinical course of
disease. First of all, an overexpression of IGHV3-21 gene was found in
Scandinavian CLL patients with progressive clinical course and poor
survival. The aim of our work was to check these data in Slavianian
population (Ukraine). IGHV genes were studied in 168 CLL patients
with from Ukraine using polymerase chain rection and direct sequence
analysis. In a total, 165 in-frame rearrangements were amplified. The
most frequent IGHV gene was IGHV1-69, which was identified in 36
cases (21.8%); followed by IGHV4-34 (11 cases; 6.7%), and IGHV3-21
(9 cases; 5.4%). Using the 98% cut off for homology to germ line, 47
(28.5%) of all in-frame cases were classified as mutated, and 118 cases
were identified as unmutated (71.5%). IGHV3-21 was the 4th among the
unmutated cases (5 cases; 4.3%) and the 3rd among the mutated cases
(4 cases; 8.5%). Only 2 IGHV3-21-expressed CLL cases belonged to
common-HCDR3 subset (mutated, IGHV3-21/IGHD-/IGHJ6, DANG-
MDV and DMNAMDV HCDR3 sequences, IGLV3-21*02/IGLJ3*01,
QVWDSSSDHPWV LVDR3 sequence in both cases). Others 7 IGHV3-
21-expressed cases belonged to nonhomogeneous-HCDR3 subset. By
the frequency of IGHV3-21 expression and the ratio of common/nonhomogeneous
cases our cohort was closer to Mediterranean cohort
described by Ghia, 2005 (2.9% IGHV3-21-positive cases, range 0.86-
4.12%; 7/9 common/nonhomogeneous cases) than Scandinavian cohort
described by Tobin, 2003 (11.7% IGHV3-21-posivite cases, 21/10 common/nonhomogeneous
cases). In addition, two our cases had homology
with CLL cases from Mediterranean cohort: case F9 (HCDR3
DSDYDFWSGSWGYYGMDV) displayed homology with CLL case
DQ987781 (HCDR3 DGDYDFWSGQWGYYGMDV), and case E89
(HCDR3 NRYTEYCSSTSCHPSYYYYYGMDV) displayed homology
with Greece CLL case Gre6 (HCDR3 DRLLGYCSSTSCWDSYYYYYG-
MDV). Median overall survival in the whole CLL group was 104 months
(among unmutated cases it was not reached and was equal to 90 months
in mutated subgroup). Median overall survival for IGHV3-21-expressed
cases was not reached, 3 dead IGHV3-21-expressed patients had unmutated
gene with nonhomogeneous HCDR3 (overall survival 8, 43, and
73 months). Both IGHV3-21-expressed cases with common HCDR3 are
alive (272 and 123 months) and had quite long progression-free period
(183 and 96 months) during which they did not need treatment. Such
data are differing from described earlier aggressive clinical course of
common HCDR3 IGHV3-21-espressed CLL cases. It could be assumed,
that possible potential antigenic stimulation via common HCDR3 may
be under influence of environmental factors in different geographic
regions.
484 | haematologica/the hematology journal | 2007; 92(s1)
1345
ZOSTER-RELATED PAIN IN HAEMATOLOGICAL MALIGNANCIES: DURABLE
PAIN RELIEF BY OXYCODONE
P. Niscola, 1 C. Cartoni, 2 G Del Poeta, 1 D. Piccioni, 1 M. Palombi, 1
L. Scaramucci, 1 L. Cupelli, 1 A. Tendas, 1 C. Romani, 3 G.A. Brunetti, 2
G.M. DElia, 2 L. Maurillo, 1 M. Giovannini, 1 A.P. Perrotti, 1 P. De Fabritiis1 1 Tor Vergata University, S.Eugenio Hosp., ROME, Italy; 2 „La Sapienza„ University,
ROME, Italy; 3 Armando Businco Cancer Center, CAGLIARI, Italy
Background. Herpes Zoster Virus (HZV) outbreak is a significant cause
of morbidity in the setting of blood-related malignancies, occurring mostly
among patients affected by lymphoproliferative disorders (LPD) and
in those submitted to haematopoietic stem cell transplantation (HSCT),
among which HZV reactivation is reported between 15-45% in the autologous
setting; one-third of these HZV patients developed post herpetic
neuralgia (PHN). Moreover, in patients submitted to allogeneic HSCT,
HZV reactivation is reported ranging from 41 to 59%. Early treatment of
acute zoster pain (AZP) can reduce the incidence of post herpetic neuralgia
(PHN). We treated with oxycodone 9 consecutive HZV-pain patients
unresponsive to several agents, including anticonvulsants and analgesics.
Case series. First PHN patient was a woman with a PHN diagnosed 30
months before. About three years later she has suffered from painful
shingles in a thoracic dermatomal early treated with acyclovir and
gabapentin. Given the persistence of neuropathic complaints, after three
months gabapentin was replaced by high doses of pregabalin that the
patient received for six months without any benefit. Given the lack of
response to pregabalin alone, this agent was reintroduced by us at standard
dose (150 mg/day) in addition to tramadol (200 mg twice daily).
Only transiently pain relief was achieved for which tramadol was
replaced with oxycodone that was titrated until 10 mg thrice daily, allowing
a stable control of pain. The second PHN patient was a man affected
by acute lymphoblastic leukaemia who received oxycodone because
of a severe PHN lasting from 4 months, achieving a rapid and a stably
maintained pain relief. Patients 3 was affected by acute myeloblastic
leukaemia and presented PHN afflicting the trigeminal region and unresponsive
to pregabalin and tramadol, that was replaced by oxycodone in
escalating dose until an acceptable pain relief. Patients 4 to 9 were affected
by LPD, for which they have received several cytotoxic regimens,
including long term steroids. They presented similar herpetic clinical features,
receiving antivirals associated with non-opioid analgesics and with
gabapentin or amitriptyline without significant benefits. We successfully
treated them with combination of gabapentin-oxycodone without any
side effect and, remarkably, none of them developed PHN after a median
follow-up of 7 (1-18) months. Conclusions. Opioids suppress the central
and the primary afferent nociceptors response; thus they should be
most useful when PHN pain is maintained by input from dysfunctional
afferents. Moreover, convincing evidences of their provided benefits in
this setting have been reported by controlled studies and metanalysis. In
particular, oxycodone and tramadol were reported as effective to relieve
neuropatic pain. Although the short follow-up, the presented experience
suggests that: 1) an opioid should be taken into account in patients with
painful HZ outbreak or PHN even when tramadol failed in relieving pain;
2) a prompt intervention is highly recommendable in the aim to prevent
PHN and, in this view, oxycodone, an opioid provided of beneficial effect
in relieving neuropathic pain, can represent a suitable option.
1346
A RAPID ASSAY OF CYTOSINE ARABINOSIDE UPTAKE AND METABOLISM BY ACUTE
MYELOBLASTIC LEUKAEMIC CELLS USING A BIOLUMINESCENT BACTERIAL BIOSENSOR
J.G. Smith, 1 H. Alloush, 2 J. Angell, 2 P. Hill, 3 M. Smith, 4 V. Salisbury2 1 Frimley Park Hospital, CAMBERLEY; 2 University of the West of England, BRIS-
TOL; 3 Nottingham University, NOTTINGHAM; 4 Royal Marsden Hospital,
SUTTON, United Kingdom
Acute myeloblastic leukaemia (AML) is a heterogeneous group of
haematological disorders resulting from the malignant transformation of
myeloid precursor cells. This leads to the proliferation of immature and
undifferentiated cells in the blood and bone marrow. Effective treatment
of AML is still challenging and the clinical outcome is disappointing
and unpredictable.Only 70% of newly diagnosed patients receiving
standard regimens with Cytosine Arabinoside (Ara-C) respond to treatment.
Furthermore,a large proportion of these patients fail to achieve
long-term remission and develop resistance to subsequent therapy. The
nucleoside analogue Ara-C is one of the most active anti-cancer agents
and has been the mainstay element of treatment used in AML for over