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193 Clinical observation of HA-G regimen chemotherapy in remission induction for elderly patients with acute leukemia and myelodysplastic syndrome
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Posters / Leukemia Research 35 (2011) S27–S142
CR) with a median duration of response of 3 months (range [2–6+]). 14pts remained stable and 10 progressed during treatment. With a median follow up of 9 months, the median overall survival was 7.3 months. Conclusions: The phase I results presented here show that 400 mg/day vorinostat can be combined to LDAC and given for 10 days (arm A) to 14 days (armB) with acceptable side effects.
193 Clinical observation of HA-G regimen chemotherapy in remission induction for elderly patients with acute leukemia and myelodysplastic syndrome
192 Response to 5-azacytidine in therapy-related malignant neoplasms (t-MN)
Aims: To evaluate the clinical effect of G-CSF priming combined with low-dose chemotherapy (HA-G regimen) in remission induction for elderly patients (aged ≥60 years) with acute myeloid leukemia (AML) and myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB). Methods: The clinical features of 21 cases with AML and 11 cases with MDS-RAEB treated by HA-G regimen in remission induction were retrospectively analyzed, including the complete remission (CR) rate, overall response rate as well as their toxicities. 13 of the AML patients were refractory or relapsed cases. The HA-G regimen consisted of cytarabine 10 mg/12 hr by subcutaneous injection, days 1–14, homoharringtonine 1 mg/day by intravenous continuous infusion, days 1–14, and granulocyte colony-stimulating factor (GCSF) 200 mg/m2 /day by subcutaneous injection, days 0–14. Results: Ten of the 21 (47.6%) elderly patients with AML achieved complete remission and 4/21 achieved partial remission (PR) treated by HA-G regimen, the overall response rate was 66.7% (14/21). In 11 elderly patients with MDS-RAEB, including 3 cases of RAEB-1 and 8 cases of RAEB-2, the total CR rate was 54.5% (6/11). There were no statistical differences between AML and MDS-RAEB patients. The main toxicities of HA-G regimen were infections and bleeding secondary to hematopoiesis suppression after chemotherapy. But all of patients were well tolerated to HA-G regimen. Conclusions: The HA-G regimen is much effective in remission induction for elderly patients with AML and MDS-RAEB.
M.T. Voso1 , L. Fianchi2 , M. Criscuolo2 , A. Levis3 , C. Finelli4 , P. Musto5 , L. Maurillo2 , E.N. Oliva6 , M. Greco2 , L. Pagano2 , G. Leone2 . 1 Hematology, 2 Universita’ Cattolica Sacro Cuore, Roma, 3 Ospedale di Alessandria, Alessandria, 4 Universita’ di Bologna, Bologna, 5 Centro di riferimento Oncologico Basilicata, Rionero in Vulture, 6 Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy Introduction: Therapy-related malignant neoplasms, including acute myeloid leukemia (AML) and mielodysplastic syndromes (MDS) are characterized by poor outcome, due to previous chemotherapy and/or radiotherapy used to treat the primary tumor, patients’ performance status and biology of t-MN, characterized by high rates of chromosomal aberrations, with frequent chromosome 7 involvement. The hypomethylating drug 5-Azacitidine (5-AZA, CelgeneTM ) has shown efficacy in higher-risk MDS, in particular in the presence of chromosome 7 deletions. Purpose: We aimed at evaluating the efficacy of 5-AZA in the treatment of t-MN. Patients and Methods. In this multicenter study, we evaluated the clinical records of 25 patients (12 males, 13 females; median age: 65 yrs, range 50–84 yrs), diagnosed with t-MN and treated with 5-AZA at 8 Italian Hematology Centers. All patients had previously received chemotherapy (18 patients), radiotherapy (3) or a combination of both (4) for their primary malignancy (4 multiple myeloma, 9 lymphoproliferative diseases, 2 AML, 2 myeloproliferative diseases, 5 solid tumors, 4 unknown). According to morphology there were 6 AML and 19 MDS (8 RCMD, 4 RAEB-1 and 7 RAEB-2). In MDS, the WPSS was low in 2, high in 12 and very-high in 5 patients. Karyotype was unfavourable in 12 patients, intermediate and favourable in 5 and 4 patients, respectively. Twelve patients had received a previous treatment for their t-MN (4 with chemotherapy, 7 with erythropoietin and 1 with G-CSF). Azacitidine was administered at a median dose of 75 mg/sqm/day (range 50–75 mg/sqm) for 7 days, every 4 weeks for a median of 4 cycles (range 1–15). Response was assessed according to the modified International Working Group (IWG-2006) criteria. Results: Treatment response was evaluated in 23 patients (19 MDS and 4 AML) after a median of 4 cycles (range 1–8). 5-Azacytidine was generally well tolerated. In MDS, the overall response rate was 26% (5 of 19), with 2 complete remissions, 1 partial remission, 2 hematologic improvements, 7 stable diseases and 7 disease progressions. None of the 4 AML patients responded to treatment. At a median follow-up of 8.7 months (range 1–28), seven patients died, 6 due to AML transformation. Median overall survival was 18 months. Conclusions: Our data show that in therapy-related MN, although inducing few responses, 5-AZA is associated to improved overall survival, when taking into account the unfavourable profile of this patient-group. Larger studies including higher patient numbers and prolonged follow-up are needed to confirm this finding.
J. Wang1 , W. Zhang2 , A. He2 , Y. Yang2 , L. Gu2 . 1 Department of Hematology, 2 2nd Hospital Affiliated to Xian Jiaotong University Medical College, Xian, China
194 Phenotypical and functional characterization of mesenchymal stem cells derived from patients affected by Shwachman–Diamond syndrome V. Andre´ 1 , D. Longoni2 , M. Cipolli3 , A. Biondi1,2 , G. D’Amico1 . 1 M. Tettamanti Research Center, 2 Pediatric Clinics, San Gerardo Hospital, Monza, 3 Cystic Fibrosis Center, Ospedale Civile Maggiore, Verona, Italy Shwachman–Diamond Syndrome (SDS) is an inherited marrow failure disorder characterized by varying cytopenias, pancreatic dysfunction, and metaphyseal dysostosis. Neutropenia plays a crucial role in the occurrence of recurrent and severe infectious complications representing one of the major causes of death in SDS patients. The aim of our study is to better comprehend the marrow dysfunction occurring in SDS patients, by analyzing the functional properties of bone marrow (BM)-derived mesenchymal stem cells (MSCs). After informed consent, BM cells obtained from 20 SDS patients were plated in sterile tissue culture flasks. At the third passage of the culture, cells were tested for the expression of specific surface markers, their ability to differentiate into mesengenic lineages, their capability to abrogate T cell proliferation and their capacity to prevent neutrophil apoptosis. MSCs derived from SDS patients (SDS-MSCs) displayed typical fibroblastoid morphology; they were consistently devoid of contaminating hematopoietic cells, being negative for CD34, CD45, HLA-DR, CD11b, CD19, and CD14, but expressed common MSC markers including CD90, CD73, CD105 and HLA-ABC. Similarly to MSCs obtained from healthy donors (HD-MSCs), these cells were able to differentiate into adipocytes and osteoblasts. In addition, SDS-MSCs drastically decreased the mitogen-induced lymphocyte proliferation, in a dose dependent manner. We also cultured neutrophils obtained from HD in presence or absence of MSCs at different time points. We demonstrated that SDS-MSCs were comparable to HD-MSCs in supporting the viability of neutrophils. Importantly, SDS-MSC were able to produce high amount of IL-6 (mean = 2658 pg/ml, range = 2086–3229 pg/ml),
Posters / Leukemia Research 35 (2011) S27–S142
CR) with a median duration of response of 3 months (range [2–6+]). 14pts remained stable and 10 progressed during treatment. With a median follow up of 9 months, the median overall survival was 7.3 months. Conclusions: The phase I results presented here show that 400 mg/day vorinostat can be combined to LDAC and given for 10 days (arm A) to 14 days (armB) with acceptable side effects.
193 Clinical observation of HA-G regimen chemotherapy in remission induction for elderly patients with acute leukemia and myelodysplastic syndrome
192 Response to 5-azacytidine in therapy-related malignant neoplasms (t-MN)
Aims: To evaluate the clinical effect of G-CSF priming combined with low-dose chemotherapy (HA-G regimen) in remission induction for elderly patients (aged ≥60 years) with acute myeloid leukemia (AML) and myelodysplastic syndrome-refractory anemia with excess blasts (MDS-RAEB). Methods: The clinical features of 21 cases with AML and 11 cases with MDS-RAEB treated by HA-G regimen in remission induction were retrospectively analyzed, including the complete remission (CR) rate, overall response rate as well as their toxicities. 13 of the AML patients were refractory or relapsed cases. The HA-G regimen consisted of cytarabine 10 mg/12 hr by subcutaneous injection, days 1–14, homoharringtonine 1 mg/day by intravenous continuous infusion, days 1–14, and granulocyte colony-stimulating factor (GCSF) 200 mg/m2 /day by subcutaneous injection, days 0–14. Results: Ten of the 21 (47.6%) elderly patients with AML achieved complete remission and 4/21 achieved partial remission (PR) treated by HA-G regimen, the overall response rate was 66.7% (14/21). In 11 elderly patients with MDS-RAEB, including 3 cases of RAEB-1 and 8 cases of RAEB-2, the total CR rate was 54.5% (6/11). There were no statistical differences between AML and MDS-RAEB patients. The main toxicities of HA-G regimen were infections and bleeding secondary to hematopoiesis suppression after chemotherapy. But all of patients were well tolerated to HA-G regimen. Conclusions: The HA-G regimen is much effective in remission induction for elderly patients with AML and MDS-RAEB.
M.T. Voso1 , L. Fianchi2 , M. Criscuolo2 , A. Levis3 , C. Finelli4 , P. Musto5 , L. Maurillo2 , E.N. Oliva6 , M. Greco2 , L. Pagano2 , G. Leone2 . 1 Hematology, 2 Universita’ Cattolica Sacro Cuore, Roma, 3 Ospedale di Alessandria, Alessandria, 4 Universita’ di Bologna, Bologna, 5 Centro di riferimento Oncologico Basilicata, Rionero in Vulture, 6 Azienda Ospedaliera Bianchi-Melacrino-Morelli, Reggio Calabria, Italy Introduction: Therapy-related malignant neoplasms, including acute myeloid leukemia (AML) and mielodysplastic syndromes (MDS) are characterized by poor outcome, due to previous chemotherapy and/or radiotherapy used to treat the primary tumor, patients’ performance status and biology of t-MN, characterized by high rates of chromosomal aberrations, with frequent chromosome 7 involvement. The hypomethylating drug 5-Azacitidine (5-AZA, CelgeneTM ) has shown efficacy in higher-risk MDS, in particular in the presence of chromosome 7 deletions. Purpose: We aimed at evaluating the efficacy of 5-AZA in the treatment of t-MN. Patients and Methods. In this multicenter study, we evaluated the clinical records of 25 patients (12 males, 13 females; median age: 65 yrs, range 50–84 yrs), diagnosed with t-MN and treated with 5-AZA at 8 Italian Hematology Centers. All patients had previously received chemotherapy (18 patients), radiotherapy (3) or a combination of both (4) for their primary malignancy (4 multiple myeloma, 9 lymphoproliferative diseases, 2 AML, 2 myeloproliferative diseases, 5 solid tumors, 4 unknown). According to morphology there were 6 AML and 19 MDS (8 RCMD, 4 RAEB-1 and 7 RAEB-2). In MDS, the WPSS was low in 2, high in 12 and very-high in 5 patients. Karyotype was unfavourable in 12 patients, intermediate and favourable in 5 and 4 patients, respectively. Twelve patients had received a previous treatment for their t-MN (4 with chemotherapy, 7 with erythropoietin and 1 with G-CSF). Azacitidine was administered at a median dose of 75 mg/sqm/day (range 50–75 mg/sqm) for 7 days, every 4 weeks for a median of 4 cycles (range 1–15). Response was assessed according to the modified International Working Group (IWG-2006) criteria. Results: Treatment response was evaluated in 23 patients (19 MDS and 4 AML) after a median of 4 cycles (range 1–8). 5-Azacytidine was generally well tolerated. In MDS, the overall response rate was 26% (5 of 19), with 2 complete remissions, 1 partial remission, 2 hematologic improvements, 7 stable diseases and 7 disease progressions. None of the 4 AML patients responded to treatment. At a median follow-up of 8.7 months (range 1–28), seven patients died, 6 due to AML transformation. Median overall survival was 18 months. Conclusions: Our data show that in therapy-related MN, although inducing few responses, 5-AZA is associated to improved overall survival, when taking into account the unfavourable profile of this patient-group. Larger studies including higher patient numbers and prolonged follow-up are needed to confirm this finding.
J. Wang1 , W. Zhang2 , A. He2 , Y. Yang2 , L. Gu2 . 1 Department of Hematology, 2 2nd Hospital Affiliated to Xian Jiaotong University Medical College, Xian, China
194 Phenotypical and functional characterization of mesenchymal stem cells derived from patients affected by Shwachman–Diamond syndrome V. Andre´ 1 , D. Longoni2 , M. Cipolli3 , A. Biondi1,2 , G. D’Amico1 . 1 M. Tettamanti Research Center, 2 Pediatric Clinics, San Gerardo Hospital, Monza, 3 Cystic Fibrosis Center, Ospedale Civile Maggiore, Verona, Italy Shwachman–Diamond Syndrome (SDS) is an inherited marrow failure disorder characterized by varying cytopenias, pancreatic dysfunction, and metaphyseal dysostosis. Neutropenia plays a crucial role in the occurrence of recurrent and severe infectious complications representing one of the major causes of death in SDS patients. The aim of our study is to better comprehend the marrow dysfunction occurring in SDS patients, by analyzing the functional properties of bone marrow (BM)-derived mesenchymal stem cells (MSCs). After informed consent, BM cells obtained from 20 SDS patients were plated in sterile tissue culture flasks. At the third passage of the culture, cells were tested for the expression of specific surface markers, their ability to differentiate into mesengenic lineages, their capability to abrogate T cell proliferation and their capacity to prevent neutrophil apoptosis. MSCs derived from SDS patients (SDS-MSCs) displayed typical fibroblastoid morphology; they were consistently devoid of contaminating hematopoietic cells, being negative for CD34, CD45, HLA-DR, CD11b, CD19, and CD14, but expressed common MSC markers including CD90, CD73, CD105 and HLA-ABC. Similarly to MSCs obtained from healthy donors (HD-MSCs), these cells were able to differentiate into adipocytes and osteoblasts. In addition, SDS-MSCs drastically decreased the mitogen-induced lymphocyte proliferation, in a dose dependent manner. We also cultured neutrophils obtained from HD in presence or absence of MSCs at different time points. We demonstrated that SDS-MSCs were comparable to HD-MSCs in supporting the viability of neutrophils. Importantly, SDS-MSC were able to produce high amount of IL-6 (mean = 2658 pg/ml, range = 2086–3229 pg/ml),