- Email: [email protected]
P008 Characterization of umbilical cord blood hematopoietic stem, progenitor cell subsets and mesenchymal stem cell lines: a Hungarian cord blood bank report
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Posters, ISH EAD 2007, Budapest, Hungary, 29 August
(26.1%) patients after PR, in 9 (39.1%) after HCT and in 7 (30.4%) at the time of BM recovery. GPBB became elevated in 5 (21.7%) patients after PR, in 5 (21.7%) after HCT and remained elevated in 2 (8.7%) at the time BM recovery. CK-MB mass, cTnT, cTnI, FABP remained negative after PR and HCT in all patients. Conclusion: Our results suggest that administration of PR and HCT is in most acute leukemia patients associated with acute neurohumoral activation (significant rise in NT-proBNP). In our study, NT-proBNP remained markedly elevated in 7 (30.4%) patients at the time of BM recovery. These persistent NTproBNP elevations indicate subclinical cardiotoxicity (risk for development of heart failure) and require further follow-up. From markers of myocardial ischemia and necrosis, only GPBB became elevated after PR and HCT. These changes could be considered a sign of subclinical cardiotoxicity. CK-MB mass, cTnT, cTnI, FABP does not seem to be of value in detection of cardiotoxicity in peritransplant period. These findings need to be confirmed in larger studies with longer follow-up. Supported by Research Project MO 0FVZ 0000503.
P006 Infusion of hematopoietic cell graft and its impact on blood pressure and heart rate J.M. Horacek1,2 *, L. Jebavy1,2 , M. Jakl1 , L. Slovacek1,2 , P. Zak2 , M. Brndiar1 , L. Kacerovky1 . 1 Faculty of Military Health Sciences, Department of Internal Medicine, Hradec Kralove, Czech Republic, 2 Charles University Hospital, Department of Medicine II, Clinical Hematology, Hradec Kralove, Czech Republic Introduction: Dimethylsulfoxide (DMSO) is the most commonly used substance for cryopreservation of hematopoietic cell (HC) graft. The maximum recommended daily dose of DMSO is 1 g/kg of the recipient body weight. DMSO may lead to changes in blood pressure (BP) and heart rate (HR). In most studies, increase in BP and HR was reported. However, the results are inconsistent. The aim of the study was monitoring of BP and HR during HC graft infusion and assessment of impact of DMSO cryopreservation. Materials and Methods: 153 HC graft infusions in 153 consecutive hematological patients were evaluated. The group of patients consisted of 80 males and 73 females with a mean age of 49.1±12.6 years. 42 patients were treated for arterial hypertension and were well compensated before HC transplantation. Cryopreservation with DMSO was used in 133 grafts (DMSO group), 20 grafts were infused directly without cryopreservation (control group). 115 grafts were autologous and 38 allogeneic. Systolic BP (SBP), diastolic BP (DBP) and HR were measured immediately before and after HC graft infusion. Results: SBP and DBP significantly increased after graft infusion SBP from 122.3±17.9 mmHg to cryopreserved with DMSO 127.7±18.1 mmHg (p < 0.0001), DBP from 70.9±12.3 mmHg to 74.1±12.6 mmHg (p < 0.01). Changes in HR were not significant in DMSO group. Increase in BP and HR correlated with increasing DMSO dose (as from DMSO dose 0.8 g/kg of the recipient body weight). In the control group, changes in SBP, DBP and HR were not significant. Changes in BP and HR were not significantly different in patients treated for arterial hypertension and other patients. Conclusion: Our results show that HC graft infusion cryopreserved with DMSO caused statistically significant increase in SBP and DBP. Increase more than 10 mmHg was seen in 31.6%, respectively 23.3% patients. Changes in HR were not statistically significant. These changes were mostly transient and asymptomatic and did not require therapeutic intervention. However, they may cause complications, especially in patients with preexisting cardiovascular disease. These patients should be observed closely during HC transplantation. Supported by Research Project MO 0FVZ 0000503.
2 September 2007
P007 Galectin-1 inhibits hematopoietic stem and progenitor cell mobilization J. Kiss1 *, A. Kunst´ ar1 , R. Fajka-Boja2 , V. Dudics1,3 , J. T´ ov´ ari4 , ˙. Monostori2 , F. Uher1 . 1 Stem Cell Biology, ´ . L´ A egr´ adi2 , E NMC, Budapest, Hungary, 2 Lymphocyte Signal Transduction Laboratory, BRC, Szeged, Hungary, 3 Polyclinic of Hospitaller Brothers of St. John of God, Budapest, Hungary, 4 Dep. of Tumor Progression, NIO, Budapest, Hungary Introduction: The anti-inflammatory activity of galectin-1 (Gal-1) has been well established in experimental in vivo animal models and in vitro studies. Since the proliferation and migration of leukocytes represent a necessary and important step in response to the inflammatory insult, we have investigated whether Gal-1 affects the mobilization of hematopoietic stem and progenitor cells (HSPC). Materials and Methods: Bone marrow HSPCs were mobilized with CY/G-CSF or CY/G-CSF plus Gal-1 in BDF1 mice. Bone marrow (BM) and blood cells were taken at different time points and analyzed for their in vivo repopulating ability in lethally irradiated syngeneic animals. The number of myeloid progenitor cells in BM and blood samples was determined by colony-forming cell assay. Expression of surface markers on nucleated marrow cells was measured by flow cytometry. The lymphocytes, granulocytes and monocytes in blood samples were counted after Giemsa-staining. Results: Gal-1 dramatically inhibited CY/G-CSF-induced HSPC migration to the periphery as well as decreased peripheral neutrophilia and monocytosis in a dose- and time-dependent manner. In contrast, Gal-1 itself, stimulated HSPC expansion and accumulation within the BM. The presence of the lectin for inhibition of HSPC mobilization was essential during the second half of the treatment. Moreover, Gal-1 inhbited transendothelial migration of BM-derived HPCs in response to SDF-1 in vitro. Conclusion: Gal-1 blocked HSPC migration induced by CY/GCSF-treatment, indicating a novel anti-inflammatory function of the lectin. P008 Characterization of umbilical cord blood hematopoietic stem, progenitor cell subsets and mesenchymal stem cell lines: a Hungarian cord blood bank report V. Vas1 *, K. Vrauk´ o1 , N. Reg´ eczy2 , R. Schw´ ab3 , B. Sarkadi2 . Medical Center, Stem Cell Biology, Hungary, 2 NMC, Institute of Hematology and Immunology, Membrane Research Group, Hungary, 3 NMC, Human Biotech KKK, Hungary 1 National
Introduction: The Hungarian Private Cord Blood Bank program was initiated in 2005. The study goals were to develop a protocol for cord blood banking and to set up the standard values of the stem and progenitors of the banked cord blood units. In addition to the umbilical cord blood (UCB) hematopoesis repopulating progenitor cells newly discovered regenerative cells are identified from this source referred as mesenchymal stem cells (MSC). Human MSC are pluripotent, have the capabilities for self renewal, and being the precursors of marrow stroma, bone, cartilage, muscle and connective tissue. In this study we examined the ability of UCB harvests to generate in culture cells with characteristic of MSC. Materials and Methods: The hematopoietic progenitor cell subsets and stem cell content of approximately 600 banked CB units were characterized and these results were correlated with donor birth weight, gestational age, sex and type of delivery. For research purpose UCB was collected on delivery with informed consent (n = 10). After mononuclear cell separation we seeded the cells in expansion medium and than adherently growing cells were replated after reached confluence. For cell surfaces marker analysis we performed FACS methods and for the differentiation assays toward fat and bone we used osteogenic and adipogenic medium for two weeks.
Posters, ISH EAD 2007, Budapest, Hungary, 29 August Results: The results provide a standard and a range for uniformly processed HSC, and the present work could be of relevance for our region since up to the present time there are no similar records. The mesenchymal culture experiments showed that we could generate three out of 10 cord blood sample in vitro well expanding MSC lines. This rare populations grows adherently shows fibroblast-like morphology and can be expanded to 10(8) cell without loosing MSC characteristics. The immunophenotype of these clonally expanded cells (also after 10 passages) is consistent with that reported for bone marrow (BM) MSC: the FACS analysis showed the cord blood MSC were positive for CD90, CD105, CD72 and negative for CD45, CD34, CD133. Under appropriate induction conditions these cells could differentiate into bone and fat and demonstrated a multilineage capacity. Because MSC can be isolated from full-term UCB donations, we also regard UCB as an additional stem cell source for experimental and potential clinical purposes. Conclusion: Because BM-derived cells, witch are the main sources of MSC, are not always acceptable due to a significant drop in their cell number and proliferative/differentiation capacity with age, human UCB are good substitutes for BM cells due to the immature of newborn cells. P009 “High-risk” patients with aggressive non-Hodgkin lymphoma should benefit from autologous stem cell transplantation in first remission (single-centre experience) S. Genadieva Stavrik *, L. Cevreska, Z. Stojanoski, A. Pivkova, A. Stojanovik, S. Krstevska Balkanov, O. Karanfilski, B. Georgievski. University Clinical Center, Department of Hematology Skopje, Macedonia Autologous stem cell transplantation used as first-line therapy can improve overall survival in selected group of patients with aggressive Non-Hodgkin lymphoma. To make the right and optimal therapeutic approach we need to stratify those patients in subgroups of patients with “high” and “low” risk, which was achieved with this study. This study comprises 211 patients with histopathology diagnosis of aggressive non-Hodgkin’s lymphoma (by the REAL classification in Diffuse large B cell, Peripheral T cell, Anaplastic large cell, Angioimunoblastic, Lymphoblastic) treated at the Department of Hematology in the period 1989 2002, which gave us the observation period of 48 to 204 months. There were 131 male patients, median age 53 years and 80 female, median age 52 years. The patients were treated with antracicilin included regiments, most of them being CHOP regiment. After initial chemotherapy complete remission was achieved in 60%, partial response in 4% and there was no response in 32% with early deaths in 4%. According to the univariante analysis the following parameters significantly influenced the overall survival in the patients with aggressive non-Hodgkin’s lymphoma: initial anemia, initial LDH, the stage of the disease, ECOG score, bone marrow infiltration, number of sites of extranodal infiltration, lymphoma subgroup according to various classification systems, morphology of the lymphoma cell, imunophenotype profile, percent of Ki-67 positively, bcl-2 positively, time to complete remission. The multiply progression analysis produce mathematical model through which we can anticipate the expected survival in each patients individually based on the statistically most influential prognostic markers, those achieving stratification of the patients in risk groups. In our study 32% of the patients with “high” risk are alive and "low risk patients have 70% 5-years overall survival. This prognostic model for aggressive non-Hodgkin’s lymphoma enables the clinical hematologist to create the optimal individual therapeutic approach for each patient with aggressive Non-Hodgkin’s lymphoma. The patients with “high” risk are group of patients where beside the standard chemotherapy,
2 September 2007
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use of aggressive chemotherapy and haematopoietic stem cell transplantation would improve therapeutic results and overall survival. P010 Zevalin-beam conditioning therapy by autologous peripheral stem cell transplantation in follicular non-Hodgkin lymphoma patients ar1 , R. Sz´ asz1 , G. Radv´ anyi2 , Gy. Rem´ enyi1 *, A. Kiss1 , P. Bat´ 1 1 M. Udvardy . University of Debrecen, Debrecen, Hungary, 2 Internal Medicine of Semmelweis Hosp., Miskolc, Hungary Introduction: The yttrium-90 (90Y)-labelled ibritumomab tiuxetan (Zevalin, IDEC-Biogen, San Diego CA) is an accepted therapy for relapsed or therapy refracter B-cell non-Hodgkin lymphomas. The results of the therapy of the “therapy refracter” follicular lymphoma patients are not reassuring. The first reports about the inclusion of Zevalin in the conditioning regimen given prior to auto SCT were published recently. These researchers concluded that Zevalin-BEAM was associated with a lower treatment-related mortality, than a standard TBI, Vepesid, Cytoxan regimen in patients with poor risk NHL [1]. Results: This study included 6 pts, mean of age 42±8.6 (SEM) years (range 35 65), an average mean of months [43.7±13.1 (SEM)] from diagnosis. Histology were follicular lymphomas, grade 3 by 3 pts, grade 2, by 2 pts and grade 1 by 1 patient. Four of the all 6 pts engrafted in a mean 10.75±0.5 days after the auto-SCT. There were no early infusion reactions associated with Zevalin. The transplantation and the Zevalin-BEAM conditioning therapy of two patients follow in the following two months. The four transplanted pts are in a complet remission 9±2.2 months after the transplantation (range 7 12 months). One patient participates at present in a maintenance Mabthera therapy. Conclusion: Inclusion of Zevalin in the conditioning therapy prior to auto-SCT is after the data of the authors this study, safe and improves the outcome in pts with refractory follicular non-Hodgkin lymphoma. Reference(s) [1] Krishnan, A.Y. et al., 2006, Blood. 108, 865a.
P011 Myeloablative stem cell transplantation for imatinib resistant advanced phase CML: chronic GVHD indicates better disease control A. B´ atai *, P. Rem´ enyi, B. Kap´ as, A. Sipos, Z. Csukly, S. Lueff, M. R´ eti, V. Goda, T. Masszi. National Medical Centre, BMT Unit, Budapest, Hungary The importance of allogeneic stem cell transplantation (HSCT) for CML in the imatinib era significantly decreased in the past few years based on the results of IRIS study. For the imatinib resistant patients HSCT still remains a therapeutic option. In the last two years in our department 6/219 patients (median age 27.2 y; female:male 3/3) received allogeneic HSCT after 12 Gy total body irradiation and 120 mg/bwkg cyclophosphamide conditioning regimen for imatinib resistant CML. 3 patients were treated with salvage tyrosin kinase inhibitor and 2 patients received AML induction chemotherapy before transplant. At transplant 2 patients achieved major cytogenetic response after salvage therapy, 3 patients were in second chronic phase and 1 in accelerated phase. 4/6 patients HLA identical sibling 2/6 unrelated donor. Patients with sibling donor received peripheral stem cell graft, while 105 /bwkg CD3 positive unrelated cells were transplanted. Graft v. host prevention was tacrolimus/sirolimus combination in all patients. Grade I-II acute GVHD developed in 3/6 patients, without grade III-IV one. All patients were alive after 3 months. Hematologic relapse developed in 2/6 patients; both received donor lymphocyte infusion (1×105 /kg and 4 times 1×108 /kg respectively) and imatinib for relapse; one of them developed limited chronic GVHD and complete cytogenetic response after finishing imatinib therapy, the other patient died of
Posters, ISH EAD 2007, Budapest, Hungary, 29 August
(26.1%) patients after PR, in 9 (39.1%) after HCT and in 7 (30.4%) at the time of BM recovery. GPBB became elevated in 5 (21.7%) patients after PR, in 5 (21.7%) after HCT and remained elevated in 2 (8.7%) at the time BM recovery. CK-MB mass, cTnT, cTnI, FABP remained negative after PR and HCT in all patients. Conclusion: Our results suggest that administration of PR and HCT is in most acute leukemia patients associated with acute neurohumoral activation (significant rise in NT-proBNP). In our study, NT-proBNP remained markedly elevated in 7 (30.4%) patients at the time of BM recovery. These persistent NTproBNP elevations indicate subclinical cardiotoxicity (risk for development of heart failure) and require further follow-up. From markers of myocardial ischemia and necrosis, only GPBB became elevated after PR and HCT. These changes could be considered a sign of subclinical cardiotoxicity. CK-MB mass, cTnT, cTnI, FABP does not seem to be of value in detection of cardiotoxicity in peritransplant period. These findings need to be confirmed in larger studies with longer follow-up. Supported by Research Project MO 0FVZ 0000503.
P006 Infusion of hematopoietic cell graft and its impact on blood pressure and heart rate J.M. Horacek1,2 *, L. Jebavy1,2 , M. Jakl1 , L. Slovacek1,2 , P. Zak2 , M. Brndiar1 , L. Kacerovky1 . 1 Faculty of Military Health Sciences, Department of Internal Medicine, Hradec Kralove, Czech Republic, 2 Charles University Hospital, Department of Medicine II, Clinical Hematology, Hradec Kralove, Czech Republic Introduction: Dimethylsulfoxide (DMSO) is the most commonly used substance for cryopreservation of hematopoietic cell (HC) graft. The maximum recommended daily dose of DMSO is 1 g/kg of the recipient body weight. DMSO may lead to changes in blood pressure (BP) and heart rate (HR). In most studies, increase in BP and HR was reported. However, the results are inconsistent. The aim of the study was monitoring of BP and HR during HC graft infusion and assessment of impact of DMSO cryopreservation. Materials and Methods: 153 HC graft infusions in 153 consecutive hematological patients were evaluated. The group of patients consisted of 80 males and 73 females with a mean age of 49.1±12.6 years. 42 patients were treated for arterial hypertension and were well compensated before HC transplantation. Cryopreservation with DMSO was used in 133 grafts (DMSO group), 20 grafts were infused directly without cryopreservation (control group). 115 grafts were autologous and 38 allogeneic. Systolic BP (SBP), diastolic BP (DBP) and HR were measured immediately before and after HC graft infusion. Results: SBP and DBP significantly increased after graft infusion SBP from 122.3±17.9 mmHg to cryopreserved with DMSO 127.7±18.1 mmHg (p < 0.0001), DBP from 70.9±12.3 mmHg to 74.1±12.6 mmHg (p < 0.01). Changes in HR were not significant in DMSO group. Increase in BP and HR correlated with increasing DMSO dose (as from DMSO dose 0.8 g/kg of the recipient body weight). In the control group, changes in SBP, DBP and HR were not significant. Changes in BP and HR were not significantly different in patients treated for arterial hypertension and other patients. Conclusion: Our results show that HC graft infusion cryopreserved with DMSO caused statistically significant increase in SBP and DBP. Increase more than 10 mmHg was seen in 31.6%, respectively 23.3% patients. Changes in HR were not statistically significant. These changes were mostly transient and asymptomatic and did not require therapeutic intervention. However, they may cause complications, especially in patients with preexisting cardiovascular disease. These patients should be observed closely during HC transplantation. Supported by Research Project MO 0FVZ 0000503.
2 September 2007
P007 Galectin-1 inhibits hematopoietic stem and progenitor cell mobilization J. Kiss1 *, A. Kunst´ ar1 , R. Fajka-Boja2 , V. Dudics1,3 , J. T´ ov´ ari4 , ˙. Monostori2 , F. Uher1 . 1 Stem Cell Biology, ´ . L´ A egr´ adi2 , E NMC, Budapest, Hungary, 2 Lymphocyte Signal Transduction Laboratory, BRC, Szeged, Hungary, 3 Polyclinic of Hospitaller Brothers of St. John of God, Budapest, Hungary, 4 Dep. of Tumor Progression, NIO, Budapest, Hungary Introduction: The anti-inflammatory activity of galectin-1 (Gal-1) has been well established in experimental in vivo animal models and in vitro studies. Since the proliferation and migration of leukocytes represent a necessary and important step in response to the inflammatory insult, we have investigated whether Gal-1 affects the mobilization of hematopoietic stem and progenitor cells (HSPC). Materials and Methods: Bone marrow HSPCs were mobilized with CY/G-CSF or CY/G-CSF plus Gal-1 in BDF1 mice. Bone marrow (BM) and blood cells were taken at different time points and analyzed for their in vivo repopulating ability in lethally irradiated syngeneic animals. The number of myeloid progenitor cells in BM and blood samples was determined by colony-forming cell assay. Expression of surface markers on nucleated marrow cells was measured by flow cytometry. The lymphocytes, granulocytes and monocytes in blood samples were counted after Giemsa-staining. Results: Gal-1 dramatically inhibited CY/G-CSF-induced HSPC migration to the periphery as well as decreased peripheral neutrophilia and monocytosis in a dose- and time-dependent manner. In contrast, Gal-1 itself, stimulated HSPC expansion and accumulation within the BM. The presence of the lectin for inhibition of HSPC mobilization was essential during the second half of the treatment. Moreover, Gal-1 inhbited transendothelial migration of BM-derived HPCs in response to SDF-1 in vitro. Conclusion: Gal-1 blocked HSPC migration induced by CY/GCSF-treatment, indicating a novel anti-inflammatory function of the lectin. P008 Characterization of umbilical cord blood hematopoietic stem, progenitor cell subsets and mesenchymal stem cell lines: a Hungarian cord blood bank report V. Vas1 *, K. Vrauk´ o1 , N. Reg´ eczy2 , R. Schw´ ab3 , B. Sarkadi2 . Medical Center, Stem Cell Biology, Hungary, 2 NMC, Institute of Hematology and Immunology, Membrane Research Group, Hungary, 3 NMC, Human Biotech KKK, Hungary 1 National
Introduction: The Hungarian Private Cord Blood Bank program was initiated in 2005. The study goals were to develop a protocol for cord blood banking and to set up the standard values of the stem and progenitors of the banked cord blood units. In addition to the umbilical cord blood (UCB) hematopoesis repopulating progenitor cells newly discovered regenerative cells are identified from this source referred as mesenchymal stem cells (MSC). Human MSC are pluripotent, have the capabilities for self renewal, and being the precursors of marrow stroma, bone, cartilage, muscle and connective tissue. In this study we examined the ability of UCB harvests to generate in culture cells with characteristic of MSC. Materials and Methods: The hematopoietic progenitor cell subsets and stem cell content of approximately 600 banked CB units were characterized and these results were correlated with donor birth weight, gestational age, sex and type of delivery. For research purpose UCB was collected on delivery with informed consent (n = 10). After mononuclear cell separation we seeded the cells in expansion medium and than adherently growing cells were replated after reached confluence. For cell surfaces marker analysis we performed FACS methods and for the differentiation assays toward fat and bone we used osteogenic and adipogenic medium for two weeks.
Posters, ISH EAD 2007, Budapest, Hungary, 29 August Results: The results provide a standard and a range for uniformly processed HSC, and the present work could be of relevance for our region since up to the present time there are no similar records. The mesenchymal culture experiments showed that we could generate three out of 10 cord blood sample in vitro well expanding MSC lines. This rare populations grows adherently shows fibroblast-like morphology and can be expanded to 10(8) cell without loosing MSC characteristics. The immunophenotype of these clonally expanded cells (also after 10 passages) is consistent with that reported for bone marrow (BM) MSC: the FACS analysis showed the cord blood MSC were positive for CD90, CD105, CD72 and negative for CD45, CD34, CD133. Under appropriate induction conditions these cells could differentiate into bone and fat and demonstrated a multilineage capacity. Because MSC can be isolated from full-term UCB donations, we also regard UCB as an additional stem cell source for experimental and potential clinical purposes. Conclusion: Because BM-derived cells, witch are the main sources of MSC, are not always acceptable due to a significant drop in their cell number and proliferative/differentiation capacity with age, human UCB are good substitutes for BM cells due to the immature of newborn cells. P009 “High-risk” patients with aggressive non-Hodgkin lymphoma should benefit from autologous stem cell transplantation in first remission (single-centre experience) S. Genadieva Stavrik *, L. Cevreska, Z. Stojanoski, A. Pivkova, A. Stojanovik, S. Krstevska Balkanov, O. Karanfilski, B. Georgievski. University Clinical Center, Department of Hematology Skopje, Macedonia Autologous stem cell transplantation used as first-line therapy can improve overall survival in selected group of patients with aggressive Non-Hodgkin lymphoma. To make the right and optimal therapeutic approach we need to stratify those patients in subgroups of patients with “high” and “low” risk, which was achieved with this study. This study comprises 211 patients with histopathology diagnosis of aggressive non-Hodgkin’s lymphoma (by the REAL classification in Diffuse large B cell, Peripheral T cell, Anaplastic large cell, Angioimunoblastic, Lymphoblastic) treated at the Department of Hematology in the period 1989 2002, which gave us the observation period of 48 to 204 months. There were 131 male patients, median age 53 years and 80 female, median age 52 years. The patients were treated with antracicilin included regiments, most of them being CHOP regiment. After initial chemotherapy complete remission was achieved in 60%, partial response in 4% and there was no response in 32% with early deaths in 4%. According to the univariante analysis the following parameters significantly influenced the overall survival in the patients with aggressive non-Hodgkin’s lymphoma: initial anemia, initial LDH, the stage of the disease, ECOG score, bone marrow infiltration, number of sites of extranodal infiltration, lymphoma subgroup according to various classification systems, morphology of the lymphoma cell, imunophenotype profile, percent of Ki-67 positively, bcl-2 positively, time to complete remission. The multiply progression analysis produce mathematical model through which we can anticipate the expected survival in each patients individually based on the statistically most influential prognostic markers, those achieving stratification of the patients in risk groups. In our study 32% of the patients with “high” risk are alive and "low risk patients have 70% 5-years overall survival. This prognostic model for aggressive non-Hodgkin’s lymphoma enables the clinical hematologist to create the optimal individual therapeutic approach for each patient with aggressive Non-Hodgkin’s lymphoma. The patients with “high” risk are group of patients where beside the standard chemotherapy,
2 September 2007
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use of aggressive chemotherapy and haematopoietic stem cell transplantation would improve therapeutic results and overall survival. P010 Zevalin-beam conditioning therapy by autologous peripheral stem cell transplantation in follicular non-Hodgkin lymphoma patients ar1 , R. Sz´ asz1 , G. Radv´ anyi2 , Gy. Rem´ enyi1 *, A. Kiss1 , P. Bat´ 1 1 M. Udvardy . University of Debrecen, Debrecen, Hungary, 2 Internal Medicine of Semmelweis Hosp., Miskolc, Hungary Introduction: The yttrium-90 (90Y)-labelled ibritumomab tiuxetan (Zevalin, IDEC-Biogen, San Diego CA) is an accepted therapy for relapsed or therapy refracter B-cell non-Hodgkin lymphomas. The results of the therapy of the “therapy refracter” follicular lymphoma patients are not reassuring. The first reports about the inclusion of Zevalin in the conditioning regimen given prior to auto SCT were published recently. These researchers concluded that Zevalin-BEAM was associated with a lower treatment-related mortality, than a standard TBI, Vepesid, Cytoxan regimen in patients with poor risk NHL [1]. Results: This study included 6 pts, mean of age 42±8.6 (SEM) years (range 35 65), an average mean of months [43.7±13.1 (SEM)] from diagnosis. Histology were follicular lymphomas, grade 3 by 3 pts, grade 2, by 2 pts and grade 1 by 1 patient. Four of the all 6 pts engrafted in a mean 10.75±0.5 days after the auto-SCT. There were no early infusion reactions associated with Zevalin. The transplantation and the Zevalin-BEAM conditioning therapy of two patients follow in the following two months. The four transplanted pts are in a complet remission 9±2.2 months after the transplantation (range 7 12 months). One patient participates at present in a maintenance Mabthera therapy. Conclusion: Inclusion of Zevalin in the conditioning therapy prior to auto-SCT is after the data of the authors this study, safe and improves the outcome in pts with refractory follicular non-Hodgkin lymphoma. Reference(s) [1] Krishnan, A.Y. et al., 2006, Blood. 108, 865a.
P011 Myeloablative stem cell transplantation for imatinib resistant advanced phase CML: chronic GVHD indicates better disease control A. B´ atai *, P. Rem´ enyi, B. Kap´ as, A. Sipos, Z. Csukly, S. Lueff, M. R´ eti, V. Goda, T. Masszi. National Medical Centre, BMT Unit, Budapest, Hungary The importance of allogeneic stem cell transplantation (HSCT) for CML in the imatinib era significantly decreased in the past few years based on the results of IRIS study. For the imatinib resistant patients HSCT still remains a therapeutic option. In the last two years in our department 6/219 patients (median age 27.2 y; female:male 3/3) received allogeneic HSCT after 12 Gy total body irradiation and 120 mg/bwkg cyclophosphamide conditioning regimen for imatinib resistant CML. 3 patients were treated with salvage tyrosin kinase inhibitor and 2 patients received AML induction chemotherapy before transplant. At transplant 2 patients achieved major cytogenetic response after salvage therapy, 3 patients were in second chronic phase and 1 in accelerated phase. 4/6 patients HLA identical sibling 2/6 unrelated donor. Patients with sibling donor received peripheral stem cell graft, while 105 /bwkg CD3 positive unrelated cells were transplanted. Graft v. host prevention was tacrolimus/sirolimus combination in all patients. Grade I-II acute GVHD developed in 3/6 patients, without grade III-IV one. All patients were alive after 3 months. Hematologic relapse developed in 2/6 patients; both received donor lymphocyte infusion (1×105 /kg and 4 times 1×108 /kg respectively) and imatinib for relapse; one of them developed limited chronic GVHD and complete cytogenetic response after finishing imatinib therapy, the other patient died of