- Email: [email protected]
P109 Systemic mastocytosis with partial response to cladribine
Posters, ISH EAD 2007, Budapest, Hungary, 29 August (6/155), high white cell number (13/155) (red cell unit) or low thrombocyte number (14/125) (thrombocyte unit). Summary: Donors with low hemoglobin levels have to be excluded from the blood donation service for 3 months. So, in theory haemoglobin concentration of all total blood units is suitable for preparation the good quality basic units. If we systematically check the quality of the basic units, we can avoid or repair the technical faults of production.
CMPD, Friday 31 August 2007 P107 Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase S. Jootar *. Ramathibodi Hospital, Rama 6 Road, Bangkok 10400, Thailand Introduction: Cases of chromosomal abnormalities in Philadelphia chromosome (Ph)-negative metaphases have been reported in patients with CML in chronic phase during treatment with interferon and, more recently, with imatinib. This phenomenon is different from true clonal evolution in that the additional cytogenetic abnormality occurs in Ph-negative cells. The incidence of this phenomenon varied from 1% to 15%. Most publications are case reports or small studies. There were only seven series with more than 100 cases and the incidence was between 1.5 to 3.8%. We report here a series of 100 patients with 15% incidence. Methods: One hundred cases of CML in chronic phase treated with imatinib mesylate were analyzed for the frequency and the significance of chromosomal abnormalities in Philadelphia chromosome negative metaphases. Results: After a median follow up of 32 months (range, 18 75 months), 15 patients (15%) developed chromosomal abnormalities in Ph-negative cells. The median time from the treatment with imatinib to the appearance of the abnormalities was 12 months (range, 9 57 months) The most common cytogenetic abnormality was trisomy 8 (53%). Twelve of 15 patients achieved complete (Ph 0%) cytogenetic response (80%), one patient had partial cytogenetic response (Ph chromosome less than 35%) and two patients had minor cytogenetic response (Ph chromosome 35 95%). After a median follow up of 32 months (range, 18 75 months) fourteen patients were alive, one patient died in blastic crisis. Twelve of them were in chronic phase and in complete hematological response. One patient had minor cytogenetic response and remained in chronic phase. One patient lost his partial cytogenetic response and progressed to accelerated phase. None of the patients showed features of myelodysplasia. Conclusion: Cytogenetic abnormalities occur in Ph-negative cells in a fraction of patients with CML in chronic phase treated with imatinib. With a short follow up, no clear clinical consequences can be identified. P108 Central nervous system blastic phase in chronic myeloid leukaemia during imatinib treatment A. Kiss1 *, A. Ujfalusy2 , T. Csepany3 , Gy. Remenyi1 , P. Batar1 , E. Balogh2 , M. Udvardy1 . 1 2nd Department of Medicine, 2 Pediatry, 3 Neurology Clinic, University Debrecen, Hungary Introduction: Since the Hungarian introduction (2002) of Glivec (imatinib mesylate), the fundamental life-expectancy of Ph1 CML-patients has changed in Hungary. As Glivec is a new drug, it might have adverse side-effects and may be responsible for the development of a so called “haematological crisis condition”. Materials and Methods: The currently 63-year-old female patient was diagnosed with the disease in July 2003.
2 September 2007
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Her laboratory data showed an extreme leukocyte number (400×109 /L). After fast therapy changes (hydroxyurea and interferone) she was in complete haematological, and partial cytogenetical remission within six months due to the influence of Glivec. In the 31st month of her disease (02. 2006), she developed a stiffness of the limbs and of the right side of the face, temporary aphasia, dizziness and nausea. Results: Her blood picture was characteristic of a quiet phase. Molecular-biological examinations verified a sufficient partial remission in this phase of complete remission (the pcr value of bcr/abl was 0.39). During a characteristic seizure-like attack of the symptoms of the disease the findings of a liquor test verified that the central nervous system was in a myeloid CML blastic phase. Glivec dosage was increased via intrathecale combined chemotherapy (methotrexate, cytosine arabinoside, dexamethasone) and cranial irradiation. The patient’s condition stabilised, and her life-quality was adequate in the past eleven months. Conclusion: A complication of the central nervous system is very rare during Glivec therapy, however, some cases are mentioned in the literature. Some of the reasons for the complication can be a high tumor mass at the onset of the disease and the inadequate liquor-blood penetrability for Glivec. Similar complications may be expected to occur in other haematological centres in the future. P109 Systemic mastocytosis with partial response to cladribine ˇ oloviˇ N. C c *, M. Sretenoviˇ c, T. Terziˇ c, M. Colovic, V. Juriˇsiˇ c. Institute of Hematology, Clinical Center of Serbia, Koste Todoroviˇca 2, Belgrade, Serbia Introduction: Systemic mastocytosis is a heterogeneous group of hematological disorders characterized by accumulation of mast cells in different organs. Therapy for aggressive forms of systemic mastocytosis consisted of cytoreductive agents and interferon-alpha. We here present a rare case of systemic mastocytosis treated with cladribine. Material and Method: A 41 year-old caucasian woman presented with 2 year history of fatigue, occasional diarrhea, mild fever and rash. Clinical inspection revealed pale skin with disseminated itching rash, splenomegaly 4 cm below left costal margin. Laboratory data showed severe anemia with hemoglobin59 g/l, thrombocytopenia 18×109 /l, white cell blood count 5.l×109 /l (differential leukocyte formula: myelocytes 1%, bands 3%, segmented 29%, eosinophils 3%, lymphocytes 51%, monocytes 13%, erythroblasts 21/100). Level of serum histamine and lactate dehydrogenase (786 U/l) was significantly increased. Cytologic and histologic investigation of bone marrow revealed a marked increase of mast cells. Immunohistochemistry of these cells showed CD117+, CD68+, CD34 , MPO , CD15 . Cytogenetic analysis revealed normal female karyotype 46,XX. Cultures of hematopoietic progenitor cells showed increased number of CFU-GM colonies, spontaneous growth of BFUE and increased number of eritropoetin stimulated BFU-E, comparing to control and absence of CFU-MK. Serum ferritin was 743.0 mg/l (normal range 5.00 170.00). As reported in the literature, this patient presents with a classical picture of systemic mast cell disease*. The systemic mast cell disorders are clinically defined by some or all of the following: anemia, thrombocytopenia, monocytosis, leukocytosis with increased neutrophils, qualitative peripheral smear changes, increased serum alkaline phosphatase, LDH, and histamine, and the physical findings of hepatosplenomegaly and lymphadenopathy. The bone marrow findings are consistent with systemic mast cell disease type 2, also known as malignant mastocytosis*. The patient was treated with cladribine 0.15 mg/kg body weight from day 1 to day 5, 6 cycles. She achieved a good partial response with normalization of spleen size and CBC. Response lasted 10 months when she relapsed with splenomegaly and
S122
Posters, ISH EAD 2007, Budapest, Hungary, 29 August
bicytopenia (anemia and thrombocytopenia). She is again transfusion dependent and on H1 and H2 blockers. Conclusion: Cladribine therapy is efficient in patient with systemic mastocytosis but response is transient so there is need for new therapy options in this rare hematologic disease. P110 Defect of JAK2/STAT5 signalling pathway in essential thrombocythemia and myelofibrosis. (Hypothesis: Malignant Stem Cell transformation) as1 , A. K´ arp´ ati1 , K. Krist´ o1 , A. Matolcsy2 , E. Gulya1 *, P. Gomb´ Z. M´ atrai3 , K. Pecze4 . 1 Central Hospital of MI, Oncology, 2 Sememelweis Univ., Dept. of Pathology and Experimental Cancer Research, 3 National medical Center, Dept. of Hematol. ´ rp´ ad K´ orh´ az Budapest, and Stem Cell Transplantation, 4 A Hungary Introduction: Essential thrombocythemia (ET) and myelofibrosis with myeloid metaplasia (MMM) are clonal myeloproliferative disorders of the multipotent hemopoietic stem cell (Fialkow PJ, et al. 1981, Jakobson RJ. et al. 1978, Reeder TL, et al. 2003. These stem cell diseases are characterized by the JAK2V617F tyrosine kinase mutation (Tefferi A., 2005, 2006) and belong to the BCR/ABL negative myeloproliferative disorders Tefferi A, Gilliland DG (in press). Materials and Methods: ET of 75 year old man was discovered in 1992 and treated with low dose dibromomannitol (Mitobronitol, Kelemen E., Gulya E., 1975) for 5 years. In 2002 MMM of patient identified by bone marrow biopsy. Therapy for MMM consisted of thalidomide (50 mg/day), prednisone (16 mg/day) and irradiation of spleen (24 Gray/3 years), because of splenomegaly. 73 year old female with ET was received low dose dibromomannitol (1500 mg/3 days) 3 4 monthly for 4 years. In 1996 the ET of patient transformed to megakaryocytic leukemia (M7). She was treated with CytosarNovantron (5+1) chemotherapy/ 4 cycles). Results: The thalidomide treatment prolonged the survival of patient with MM, who died in 2006. Patient with leukemia died 11 months later, after the chemotherapy and partial remission because of sepsis. Conclusions: In both cases the ET and dibromomannitol treatment formed the starting points. The JAK2V617F tyrosine kinase mutation are associated with the defect of JAK2/STAT5 signalling pathway (Tefferi A., Gilliland DG, 2005), that causes initial genetic changes in the stem cell niche and the final step may be malignant stem cell transformation (M7), Masters JR et al, 2003, Gulya et al, 2004, 2006. P111 Glivec treatment in the 2nd Department of Medicine, University of Debrecen, Hungary (2000 2007) o1 , G. Rem´ enyi1 , P. Bat´ ar1 , A. Kiss1 *, B. Telek1 , L. Rejt˝ as Antal3 , V. J´ ozsa1 , E. Balogh2 , A. Ujfalusy2 , P. Szalm´ M. Udvardy1 . 1 2nd Department of Medicine, 2 Pediatry, 3 Central Laboratory, University of Debrecen, Hungary Introduction: Since the Hungarian introduction (2002) of Glivec (imatinib mesylate), the fundamental life-expectancy of Ph1 CML-patients has changed. In the last seven years, the authors’ patients have been receiving, at first sporadic, and since 2003, regular Glivec therapy. Materials and Methods: 58 patients were treated: 26 men and 32 women. Their average age was 55.9±14.9 years (extreme values: 25 80 years). The length of the average Glivec therapy was 27.5±20.6 months. We developed essentially two types of therapy: (1) Secondary: earlier hydroxyurea-, interferon-, oral citosin arabinozid-treatment of insufficient result followed by Glivec-therapy (26 patients) and, (2) Primary: Glivec-treatment; generally after short-term hydroxiurea cellreduction (32 patients). Results: So far 10 patients reached complete (17.2%), and seven patients partial molecular remission (12%). The remaining
2 September 2007
32 patients are in a partial cytogenetic remission (to be noted: 17 patients received Glivec treatment in 2006). All patients reached a complete haematological remission in two months’s time. The question of Glivec resistance arose in the case of three patients (5.1%). Five patients died (8.6%). Four of them belonged to the first group. The reason for these deaths was blastic phase. One patient died of a generalised prostate cancer. We were unable to follow up four patients (6.8%). One patient was successfully treated of a central nervous system blastic phase, a complaint that developed during Glivec therapy (she is currently in partial molecular remission). Conclusion: A growing number of experiences and observations are being amassed in connection with Glivec treatment in the Eastern regions of Hungary. For accurate follow-up cytogenetics, FISH, and bcr/abl quantitative and qualitative techniques are indispensable requirements. P112 Defects in platelet surface antigens in chronic myeloproliferative syndrome identified by flow cytometry analysis H. Bumbea1 *, A.-M. Vladareanu1 , S. Radesi1 , V. Vasilache1 , C. Ciufu1 , A. Petre1 , D. Cisleanu1 , M. Begu1 , I. Voican1 , C. Marinescu1 , V. Popov2 , M. Onisai1 , M. Dervesteanu1 . 1 Emergency Universitary Hospital, Department of Hematology, Bucharest, Romania , 2 County Hospital, Pitesti, Romania Background: Hemorrhagia, thrombotic events and platelet defects compose the clinical picture of all myeloproliferative diseases. The complications associated with them unfortunately have a huge impact over global morbidity. Therefore a more specific characterization of platelet behavior appears to be necessary. Aim: The aim of our study is to examine the flow cytometry markers of platelet activation (CD 63, CD 62p) adhesion (CD 42a, CD 42b) and aggregation (CD 41, CD61) in the clinical context of the patients with myeloproliferative disorders. Methods: Whole blood flow cytometry analysis for platelets surface proteins (Glycoprotein [GP] Ib-IX [CD42b, CD42a], Glycoprotein IIb-IIIa [CD41, CD61], P-selectin [CD62P], granulophysin [CD63]) was fulfilled in patients with chronic myeloproliferative syndrome in different stages of diagnosis and therapy (n = 16) in comparison with healthy human controls (n = 10). The group of patients with chronic myeloproliferative disorders (MPD) included chronic myelogenous leukemia (CML) 4 patients, unclassified myeloproliferative disease 2 patients, chronic idiopathic myelofibrosis (IMF) 3 patients, policythemia vera 4 patients and essential trombocythemia 3 patients. A retrospective analysis of our patients’ history, clinical evolution and treatment was initiated. For each patient the following parameters were collected: presentation at diagnosis, a complete blood count in dynamic, presence of hemorrhage or thromboses and treatment. Results: Graphically obvious, our results show a decrease (Figure 1) in CD42b the von Willebrand receptor (p < 0.01)) expression in patients (median: 14.57%) versus controls (median: 96.26%).unaccompanied by a similar difference in the CD42a value range (p = 0.448). The CD61/CD41 expression (GP IIb-IIIa) presents also lower values in patients (median: CD61 = 87.14%; CD 41 = 74.56%) versus controls (median: CD61 = 98.98%; CD 41 = 91.27%), but only CD61 behaviour is statistic significant (P = 0.05 versus 0.064 for CD41). Discussion: A larger number of patients is necessary to confirm the occurrence of type 2 acquired von Willebrand disease. We also intend to examine the expression of von Willebrand receptor in relation with the number of platelets, with common coagulation tests and clinically and laboratory assessed haemorrhage and thrombosis. As previously reported in literature The GP Ib decrease is associated with an aIIb b3 reduction in expression and possible in intracellular signalling mechanism. We intend to evaluate the correlation between
CMPD, Friday 31 August 2007 P107 Chromosomal abnormalities in Philadelphia chromosome-negative metaphases appearing during imatinib mesylate therapy in patients with Philadelphia chromosome positive chronic myeloid leukemia in chronic phase S. Jootar *. Ramathibodi Hospital, Rama 6 Road, Bangkok 10400, Thailand Introduction: Cases of chromosomal abnormalities in Philadelphia chromosome (Ph)-negative metaphases have been reported in patients with CML in chronic phase during treatment with interferon and, more recently, with imatinib. This phenomenon is different from true clonal evolution in that the additional cytogenetic abnormality occurs in Ph-negative cells. The incidence of this phenomenon varied from 1% to 15%. Most publications are case reports or small studies. There were only seven series with more than 100 cases and the incidence was between 1.5 to 3.8%. We report here a series of 100 patients with 15% incidence. Methods: One hundred cases of CML in chronic phase treated with imatinib mesylate were analyzed for the frequency and the significance of chromosomal abnormalities in Philadelphia chromosome negative metaphases. Results: After a median follow up of 32 months (range, 18 75 months), 15 patients (15%) developed chromosomal abnormalities in Ph-negative cells. The median time from the treatment with imatinib to the appearance of the abnormalities was 12 months (range, 9 57 months) The most common cytogenetic abnormality was trisomy 8 (53%). Twelve of 15 patients achieved complete (Ph 0%) cytogenetic response (80%), one patient had partial cytogenetic response (Ph chromosome less than 35%) and two patients had minor cytogenetic response (Ph chromosome 35 95%). After a median follow up of 32 months (range, 18 75 months) fourteen patients were alive, one patient died in blastic crisis. Twelve of them were in chronic phase and in complete hematological response. One patient had minor cytogenetic response and remained in chronic phase. One patient lost his partial cytogenetic response and progressed to accelerated phase. None of the patients showed features of myelodysplasia. Conclusion: Cytogenetic abnormalities occur in Ph-negative cells in a fraction of patients with CML in chronic phase treated with imatinib. With a short follow up, no clear clinical consequences can be identified. P108 Central nervous system blastic phase in chronic myeloid leukaemia during imatinib treatment A. Kiss1 *, A. Ujfalusy2 , T. Csepany3 , Gy. Remenyi1 , P. Batar1 , E. Balogh2 , M. Udvardy1 . 1 2nd Department of Medicine, 2 Pediatry, 3 Neurology Clinic, University Debrecen, Hungary Introduction: Since the Hungarian introduction (2002) of Glivec (imatinib mesylate), the fundamental life-expectancy of Ph1 CML-patients has changed in Hungary. As Glivec is a new drug, it might have adverse side-effects and may be responsible for the development of a so called “haematological crisis condition”. Materials and Methods: The currently 63-year-old female patient was diagnosed with the disease in July 2003.
2 September 2007
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Her laboratory data showed an extreme leukocyte number (400×109 /L). After fast therapy changes (hydroxyurea and interferone) she was in complete haematological, and partial cytogenetical remission within six months due to the influence of Glivec. In the 31st month of her disease (02. 2006), she developed a stiffness of the limbs and of the right side of the face, temporary aphasia, dizziness and nausea. Results: Her blood picture was characteristic of a quiet phase. Molecular-biological examinations verified a sufficient partial remission in this phase of complete remission (the pcr value of bcr/abl was 0.39). During a characteristic seizure-like attack of the symptoms of the disease the findings of a liquor test verified that the central nervous system was in a myeloid CML blastic phase. Glivec dosage was increased via intrathecale combined chemotherapy (methotrexate, cytosine arabinoside, dexamethasone) and cranial irradiation. The patient’s condition stabilised, and her life-quality was adequate in the past eleven months. Conclusion: A complication of the central nervous system is very rare during Glivec therapy, however, some cases are mentioned in the literature. Some of the reasons for the complication can be a high tumor mass at the onset of the disease and the inadequate liquor-blood penetrability for Glivec. Similar complications may be expected to occur in other haematological centres in the future. P109 Systemic mastocytosis with partial response to cladribine ˇ oloviˇ N. C c *, M. Sretenoviˇ c, T. Terziˇ c, M. Colovic, V. Juriˇsiˇ c. Institute of Hematology, Clinical Center of Serbia, Koste Todoroviˇca 2, Belgrade, Serbia Introduction: Systemic mastocytosis is a heterogeneous group of hematological disorders characterized by accumulation of mast cells in different organs. Therapy for aggressive forms of systemic mastocytosis consisted of cytoreductive agents and interferon-alpha. We here present a rare case of systemic mastocytosis treated with cladribine. Material and Method: A 41 year-old caucasian woman presented with 2 year history of fatigue, occasional diarrhea, mild fever and rash. Clinical inspection revealed pale skin with disseminated itching rash, splenomegaly 4 cm below left costal margin. Laboratory data showed severe anemia with hemoglobin59 g/l, thrombocytopenia 18×109 /l, white cell blood count 5.l×109 /l (differential leukocyte formula: myelocytes 1%, bands 3%, segmented 29%, eosinophils 3%, lymphocytes 51%, monocytes 13%, erythroblasts 21/100). Level of serum histamine and lactate dehydrogenase (786 U/l) was significantly increased. Cytologic and histologic investigation of bone marrow revealed a marked increase of mast cells. Immunohistochemistry of these cells showed CD117+, CD68+, CD34 , MPO , CD15 . Cytogenetic analysis revealed normal female karyotype 46,XX. Cultures of hematopoietic progenitor cells showed increased number of CFU-GM colonies, spontaneous growth of BFUE and increased number of eritropoetin stimulated BFU-E, comparing to control and absence of CFU-MK. Serum ferritin was 743.0 mg/l (normal range 5.00 170.00). As reported in the literature, this patient presents with a classical picture of systemic mast cell disease*. The systemic mast cell disorders are clinically defined by some or all of the following: anemia, thrombocytopenia, monocytosis, leukocytosis with increased neutrophils, qualitative peripheral smear changes, increased serum alkaline phosphatase, LDH, and histamine, and the physical findings of hepatosplenomegaly and lymphadenopathy. The bone marrow findings are consistent with systemic mast cell disease type 2, also known as malignant mastocytosis*. The patient was treated with cladribine 0.15 mg/kg body weight from day 1 to day 5, 6 cycles. She achieved a good partial response with normalization of spleen size and CBC. Response lasted 10 months when she relapsed with splenomegaly and
S122
Posters, ISH EAD 2007, Budapest, Hungary, 29 August
bicytopenia (anemia and thrombocytopenia). She is again transfusion dependent and on H1 and H2 blockers. Conclusion: Cladribine therapy is efficient in patient with systemic mastocytosis but response is transient so there is need for new therapy options in this rare hematologic disease. P110 Defect of JAK2/STAT5 signalling pathway in essential thrombocythemia and myelofibrosis. (Hypothesis: Malignant Stem Cell transformation) as1 , A. K´ arp´ ati1 , K. Krist´ o1 , A. Matolcsy2 , E. Gulya1 *, P. Gomb´ Z. M´ atrai3 , K. Pecze4 . 1 Central Hospital of MI, Oncology, 2 Sememelweis Univ., Dept. of Pathology and Experimental Cancer Research, 3 National medical Center, Dept. of Hematol. ´ rp´ ad K´ orh´ az Budapest, and Stem Cell Transplantation, 4 A Hungary Introduction: Essential thrombocythemia (ET) and myelofibrosis with myeloid metaplasia (MMM) are clonal myeloproliferative disorders of the multipotent hemopoietic stem cell (Fialkow PJ, et al. 1981, Jakobson RJ. et al. 1978, Reeder TL, et al. 2003. These stem cell diseases are characterized by the JAK2V617F tyrosine kinase mutation (Tefferi A., 2005, 2006) and belong to the BCR/ABL negative myeloproliferative disorders Tefferi A, Gilliland DG (in press). Materials and Methods: ET of 75 year old man was discovered in 1992 and treated with low dose dibromomannitol (Mitobronitol, Kelemen E., Gulya E., 1975) for 5 years. In 2002 MMM of patient identified by bone marrow biopsy. Therapy for MMM consisted of thalidomide (50 mg/day), prednisone (16 mg/day) and irradiation of spleen (24 Gray/3 years), because of splenomegaly. 73 year old female with ET was received low dose dibromomannitol (1500 mg/3 days) 3 4 monthly for 4 years. In 1996 the ET of patient transformed to megakaryocytic leukemia (M7). She was treated with CytosarNovantron (5+1) chemotherapy/ 4 cycles). Results: The thalidomide treatment prolonged the survival of patient with MM, who died in 2006. Patient with leukemia died 11 months later, after the chemotherapy and partial remission because of sepsis. Conclusions: In both cases the ET and dibromomannitol treatment formed the starting points. The JAK2V617F tyrosine kinase mutation are associated with the defect of JAK2/STAT5 signalling pathway (Tefferi A., Gilliland DG, 2005), that causes initial genetic changes in the stem cell niche and the final step may be malignant stem cell transformation (M7), Masters JR et al, 2003, Gulya et al, 2004, 2006. P111 Glivec treatment in the 2nd Department of Medicine, University of Debrecen, Hungary (2000 2007) o1 , G. Rem´ enyi1 , P. Bat´ ar1 , A. Kiss1 *, B. Telek1 , L. Rejt˝ as Antal3 , V. J´ ozsa1 , E. Balogh2 , A. Ujfalusy2 , P. Szalm´ M. Udvardy1 . 1 2nd Department of Medicine, 2 Pediatry, 3 Central Laboratory, University of Debrecen, Hungary Introduction: Since the Hungarian introduction (2002) of Glivec (imatinib mesylate), the fundamental life-expectancy of Ph1 CML-patients has changed. In the last seven years, the authors’ patients have been receiving, at first sporadic, and since 2003, regular Glivec therapy. Materials and Methods: 58 patients were treated: 26 men and 32 women. Their average age was 55.9±14.9 years (extreme values: 25 80 years). The length of the average Glivec therapy was 27.5±20.6 months. We developed essentially two types of therapy: (1) Secondary: earlier hydroxyurea-, interferon-, oral citosin arabinozid-treatment of insufficient result followed by Glivec-therapy (26 patients) and, (2) Primary: Glivec-treatment; generally after short-term hydroxiurea cellreduction (32 patients). Results: So far 10 patients reached complete (17.2%), and seven patients partial molecular remission (12%). The remaining
2 September 2007
32 patients are in a partial cytogenetic remission (to be noted: 17 patients received Glivec treatment in 2006). All patients reached a complete haematological remission in two months’s time. The question of Glivec resistance arose in the case of three patients (5.1%). Five patients died (8.6%). Four of them belonged to the first group. The reason for these deaths was blastic phase. One patient died of a generalised prostate cancer. We were unable to follow up four patients (6.8%). One patient was successfully treated of a central nervous system blastic phase, a complaint that developed during Glivec therapy (she is currently in partial molecular remission). Conclusion: A growing number of experiences and observations are being amassed in connection with Glivec treatment in the Eastern regions of Hungary. For accurate follow-up cytogenetics, FISH, and bcr/abl quantitative and qualitative techniques are indispensable requirements. P112 Defects in platelet surface antigens in chronic myeloproliferative syndrome identified by flow cytometry analysis H. Bumbea1 *, A.-M. Vladareanu1 , S. Radesi1 , V. Vasilache1 , C. Ciufu1 , A. Petre1 , D. Cisleanu1 , M. Begu1 , I. Voican1 , C. Marinescu1 , V. Popov2 , M. Onisai1 , M. Dervesteanu1 . 1 Emergency Universitary Hospital, Department of Hematology, Bucharest, Romania , 2 County Hospital, Pitesti, Romania Background: Hemorrhagia, thrombotic events and platelet defects compose the clinical picture of all myeloproliferative diseases. The complications associated with them unfortunately have a huge impact over global morbidity. Therefore a more specific characterization of platelet behavior appears to be necessary. Aim: The aim of our study is to examine the flow cytometry markers of platelet activation (CD 63, CD 62p) adhesion (CD 42a, CD 42b) and aggregation (CD 41, CD61) in the clinical context of the patients with myeloproliferative disorders. Methods: Whole blood flow cytometry analysis for platelets surface proteins (Glycoprotein [GP] Ib-IX [CD42b, CD42a], Glycoprotein IIb-IIIa [CD41, CD61], P-selectin [CD62P], granulophysin [CD63]) was fulfilled in patients with chronic myeloproliferative syndrome in different stages of diagnosis and therapy (n = 16) in comparison with healthy human controls (n = 10). The group of patients with chronic myeloproliferative disorders (MPD) included chronic myelogenous leukemia (CML) 4 patients, unclassified myeloproliferative disease 2 patients, chronic idiopathic myelofibrosis (IMF) 3 patients, policythemia vera 4 patients and essential trombocythemia 3 patients. A retrospective analysis of our patients’ history, clinical evolution and treatment was initiated. For each patient the following parameters were collected: presentation at diagnosis, a complete blood count in dynamic, presence of hemorrhage or thromboses and treatment. Results: Graphically obvious, our results show a decrease (Figure 1) in CD42b the von Willebrand receptor (p < 0.01)) expression in patients (median: 14.57%) versus controls (median: 96.26%).unaccompanied by a similar difference in the CD42a value range (p = 0.448). The CD61/CD41 expression (GP IIb-IIIa) presents also lower values in patients (median: CD61 = 87.14%; CD 41 = 74.56%) versus controls (median: CD61 = 98.98%; CD 41 = 91.27%), but only CD61 behaviour is statistic significant (P = 0.05 versus 0.064 for CD41). Discussion: A larger number of patients is necessary to confirm the occurrence of type 2 acquired von Willebrand disease. We also intend to examine the expression of von Willebrand receptor in relation with the number of platelets, with common coagulation tests and clinically and laboratory assessed haemorrhage and thrombosis. As previously reported in literature The GP Ib decrease is associated with an aIIb b3 reduction in expression and possible in intracellular signalling mechanism. We intend to evaluate the correlation between