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

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Hodgkin’s disease is well known, but association with o<strong>the</strong>r lymphoproliferative<br />

disorders is rare. To our knowledge, this is <strong>the</strong> second case <strong>of</strong> follicular lymphoma<br />

associated with LCH. In <strong>the</strong> first case, LCH was diagnosed simultaneously<br />

with <strong>the</strong> lymphoma. By contrast, in our case, LCH was diagnosed 3 years<br />

after <strong>the</strong> lymphoproliferative disease, when <strong>the</strong>re were no evidence <strong>of</strong> follicular<br />

lymphoma progression. The origin <strong>of</strong> LCH is not clear, and <strong>the</strong>re is controversy<br />

as to whe<strong>the</strong>r it represents a true independent clonal neoplasm or a reactive<br />

and/or <strong>the</strong>rapy-related phenomenon. Reviewing <strong>the</strong> literature, FDG-PET study<br />

appears to have higher sensitivity than bone scintigraphy, radiography and MR<br />

imaging for <strong>the</strong> identification <strong>of</strong> active osseous lesions in LCH. However, it also<br />

has a limited spatial resolution and requires complementary CT or MR imaging<br />

to define <strong>the</strong> area <strong>of</strong> increased glucose metabolism. In summary, FDG-PET atypical<br />

uptakes appearing in a patient with lymphoproliferative disease in complete<br />

remission should not be considered as lymphoma progression without confirmation<br />

by histologic examination.<br />

1511<br />

FLUDARABINE PLUS CYCLOPHOSPHAMIDE (FC) IN PATIENTS WITH PREVIOUSLY<br />

UNTREATED LOW-GRADE LYMPHOMA<br />

M. Dell’Olio, C. Bodenizza, A.M. Carella, A. Falcone, M.M. Greco,<br />

A. La Sala, S. Mantuano, L. Melillo, E. Merla, M. Nobile, G. Sanpaolo,<br />

P. Scalzulli, N. Cascavilla<br />

Casa Sollievo della S<strong>of</strong>ferenza Hosp., SAN GIOVANNI ROTONDO, Italy<br />

Background. In <strong>the</strong> last years, fludarabine alone or in combination with<br />

o<strong>the</strong>r drugs has been reported to be effective in <strong>the</strong> treatment <strong>of</strong> previously<br />

treated low-grade non-Hodgkin’s lymphomas (LG-NHL). The aim<br />

<strong>of</strong> this study was to define <strong>the</strong> <strong>the</strong>rapeutic efficacy and toxicity <strong>of</strong> a<br />

combination <strong>of</strong> fludarabine and cyclophosphamide (FC regimen) in<br />

untreated LG-NHL. Patients and Methods. Between January 2002 and June<br />

2006, forty-five previously untreated patients with LG-NHL, were<br />

enrolled in <strong>the</strong> study. All patients (M/F: 28/17, median age 62 years) vere<br />

treated with three-day courses <strong>of</strong> fludarabine 25 mg/m2 /day, cyclophosphamide<br />

300 mg/m2/day, every four weeks for a maximum <strong>of</strong> six courses.<br />

Granulocyte colony-stimulating factor and Pneumocystis Carinii prophylaxis<br />

was given. Among 45 patients, 21 (46%) were diagnosed with<br />

small lymphocytic, 9 (20%) with malt gastric, 8 (18%) follicular grade I,<br />

and 7 (16%) with immunocytoma subtypes. Results. Of <strong>the</strong> 45 patients,<br />

43 (94%) achieved complete response (CR), 1 (3%) partial response,<br />

while <strong>the</strong> remaining 1 (3%) showed no benefit from <strong>the</strong> treatment.<br />

Regarding histology, in <strong>the</strong> follicular and malt gastric subtype we<br />

observed an overall response (OR) rate and CR rate <strong>of</strong> 100%. Median<br />

duration <strong>of</strong> follow-up was more than 27 months. Overall survival and<br />

disease-free survival rates were 93% and 88%. Hematologic grade 3-4<br />

toxicity was seen in only five (11%) patients; no opportunistic infections<br />

or deaths were associated with <strong>the</strong> administration <strong>of</strong> <strong>the</strong> FC regimen<br />

Conclusion. These preliminary data show that <strong>the</strong> FC regimen is a<br />

high level <strong>of</strong> activity, with prolonged CR, well-tolerated combination<br />

chemo<strong>the</strong>rapy for untreated patients with LG-NHL.<br />

1512<br />

MANAGEMENT OF SEVERE MUSCULOSKELETAL PAIN CAUSED BY IMATINIBE MESYLATE<br />

WITH DULOXETINE HYDROCHLORIDE IN A PATIENT WITH CHRONIC MYELOID LEUKEMIA<br />

(CML). A CASE REPORT<br />

S. Vakalopoulou, E. Pagourelias, Z. Katsarou, V. Perifanis,<br />

S. Theodoridou, V. Garipidou<br />

Ippokration General Hosital,Thessaloniki, THESSALONIKI, Greece<br />

Imatinibe mesylate is an orally administered inhibitor <strong>of</strong> <strong>the</strong> breakpoint<br />

cluster region-Abl tyrosine kinase, which is capable <strong>of</strong> blocking<br />

proliferation and inducing apoptosis in chronic myeloid leukemia cell<br />

lines. Its introduction in everyday clinical practice led to an advantageous<br />

hematological and cytogenetic response in patients suffering from<br />

CML, even though mild or more severe adverse effects <strong>of</strong> <strong>the</strong> drug may<br />

present, affecting patients’ compliance or even calling for treatment withdrawal.<br />

We present <strong>the</strong> case <strong>of</strong> a 23 year old patient with chronic<br />

myeloid leukemia under imatinibe mesylate (Gleevec 400 mg once daily)<br />

who developed severe musculoskeletal pain located at <strong>the</strong> lower<br />

extremities (due to <strong>the</strong> above treatment) and its management with<br />

Duloxetine Hydrochloride. After <strong>the</strong> patient was diagnosed to suffer<br />

from CML (G-banding karyotype showed 46,XX,t(9;22)(q34;q11) and a<br />

BCR-ABL transcript was demonstrated by reverse transcription-polymerase<br />

chain reaction (RT-PCR) on bone marrow), a treatment with<br />

Gleevec begun. After two weeks <strong>of</strong> treatment (400 mg once daily) <strong>the</strong><br />

patient complained for acute dysaes<strong>the</strong>sias and paraes<strong>the</strong>sias <strong>of</strong> <strong>the</strong> legs<br />

as long as for severe pain on <strong>the</strong> same area. The above symptoms had<br />

12 th <strong>Congress</strong> <strong>of</strong> <strong>the</strong> <strong>European</strong> <strong>Hematology</strong> Association<br />

<strong>the</strong> typical distribution <strong>of</strong> an acute polyneuropathy. Despite that and<br />

<strong>the</strong> findings <strong>of</strong> <strong>the</strong> clinical examination a full laboratory investigation<br />

(including X Rays <strong>of</strong> <strong>the</strong> area, biochemical analysis and an electromyogramm)<br />

didn’t prove <strong>the</strong> existence <strong>of</strong> polyneuropathy. Because <strong>of</strong> <strong>the</strong><br />

severity <strong>of</strong> pain <strong>the</strong> patient received large doses <strong>of</strong> paracetamol plus<br />

codeine or even dextropropoxyphene hydrochloride without satisfactory<br />

analgetic results. subsequently, duloxetine hydrochloride (Xeristar)<br />

was administered initially at doses <strong>of</strong> 30 mg once daily for <strong>the</strong> first four<br />

days and continuing with 60 mg once daily. The patient responded to<br />

<strong>the</strong> treatment. One week later she needed no more opiates while after<br />

two weeks <strong>the</strong> symptoms were fully relieved. Duloxetine Hydrochloride<br />

is a new SSRI approved by FDA both for <strong>the</strong> treatment <strong>of</strong> depression as<br />

along as for <strong>the</strong> management <strong>of</strong> diabetic polyneuropathy. As far as we<br />

know it is <strong>the</strong> first time for this drug to be used successfully in <strong>the</strong> management<br />

<strong>of</strong> acute musculoskeletal pains due to imatinibe mesylate. It is<br />

certain that prospective studies are needed to evaluate <strong>the</strong> efficacy and<br />

safety <strong>of</strong> <strong>the</strong> drug under conditions similar to <strong>the</strong> above. However, duloxetine<br />

hydrochloride <strong>of</strong>fers a new alternative choise for pain alleviation<br />

in patients receiving Gleevec which seems to be much more attractive<br />

than treatment withdrawal.<br />

1513<br />

GRAFT VERSUS HOST DISEASE AFTER ALLOGENEIC STEM CELL TRANSPLANTATION AND<br />

ITS PREDICTION BY PROTEOMIC APPROACHES<br />

A.K. Kaplanova<br />

Department <strong>of</strong> Hematooncology, BRNO, Czech Republic<br />

Background. Acute graft-versus-host disease (GvHD) is a frequent complication<br />

<strong>of</strong> allogeneic stem cells transplantation (allo-SCT). The rapid<br />

diagnosis <strong>of</strong> acute GvHD following allo-SCT is important for optimizing<br />

<strong>the</strong> management <strong>of</strong> this life-threatening complication. Differentially<br />

expressed or excreted polypeptides and proteins have potential for early<br />

and accurate diagnosis <strong>of</strong> GvHD and o<strong>the</strong>r complications <strong>of</strong> allo-SCT.<br />

Aims. Search for blood plasma proteins useful as potential biomarkers for<br />

early detection <strong>of</strong> GvHD. Methods. 2-dimensional gel electrophoresis (2-<br />

DE) was used for separation <strong>of</strong> blood plasma proteins. Proteins considered<br />

as potential biomarkers for early prediction <strong>of</strong> GvHD were selected<br />

by image analysis. Protein spots with different expression levels were<br />

characterized by matrix-assisted laser desorption/ionization - time <strong>of</strong><br />

flight mass spectrometry (MALDI-TOF-MS) using peptide mass fingerprinting.<br />

Samples <strong>of</strong> blood plasma, urine and lymphocytes, collected<br />

from <strong>the</strong> same patient before and after allo-SCT were analyzed.<br />

Analysed samples were collected at three time points: (1) approx. 10<br />

days before GvHD manifestation, (2) approx. 2 days before GvDH manifestation<br />

and (3) during GvHD manifestation. Results. Proteomic analysis<br />

revealed several proteins differentially expressed during GvHD development.<br />

These potential biomarkers included serum natural proteinases<br />

(macroglobulin α2 and α1 anti-trypsin), components <strong>of</strong> complement<br />

(complement 4 binding protein and complement factor I), proteins <strong>of</strong><br />

acute phase (haptoglobin, C-reactive protein and amyloid related serum<br />

protein (SAA)) and o<strong>the</strong>r proteins such as fibrin, fibrinogen, inter-α (globulin)<br />

inhibitor H4 and hemopexin precursor. Concentration <strong>of</strong> serum<br />

natural proteinases, haptoglobin, inter-α (globulin) inhibitor H4 and<br />

hemopexin precursor in blood plasma were significantly decreased in<br />

both samples collected prior to GvHD manifestation. In <strong>the</strong>se samples<br />

was detected also slightly decreased expression <strong>of</strong> analyzed components<br />

<strong>of</strong> complement in comparison to samples collected during GvHD manifestation.<br />

On <strong>the</strong> o<strong>the</strong>r hand, expression <strong>of</strong> C-reactive protein and SAA<br />

was detected only 14 days before GvHD manifestation and <strong>the</strong>se proteins<br />

completely disappeared 1 day before onset <strong>of</strong> disease and during<br />

its manifestation. Summary/Conclusions. These potential biomarkers could<br />

improve early prediction and treatment <strong>of</strong> GvHD and <strong>the</strong>reby reduce<br />

GvHD incidence and complications.<br />

This study was supported by several grant projects: IGA MZ CR NR8448-<br />

3/205 and NR9293-3/2007, and grant projects <strong>of</strong> Ministry <strong>of</strong> Education, Youth<br />

and Sports: MSM0021622430, MSM0021624215 and LC 06034.<br />

1514<br />

HER-2/NEU MRNA IN PERIPHERAL BLOOD & BONE MARROW IN FEMALE BREAST<br />

CANCER PATIENTS<br />

A. Abd El Hamid, 1 M. Elkamash, 1 G. Eskander, 1 A. Hassan, 1 F. Abdel<br />

aziz, 1 F. Attia, 1 S. Hassan, 2 M. Hassan2 1 Suez Canal Univers, Faculty <strong>of</strong> Medicine, ISMAILIA,EGYPT, Egypt; 2 Karolinska<br />

University Hospital, STOCKHOLM, Sweden<br />

Background. The prognostic significance <strong>of</strong> <strong>the</strong> bone marrow<br />

haematologica/<strong>the</strong> hematology journal | 2007; 92(s1) | 537

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