- Email: [email protected]
PO020 Primary MDS: analysis of survival and risk of leukemia transformation according to FAB, WHO, IPSS and WPSS classifications
S138
Publication Only
PRO information specialist. Only the most relevant diseasespecific questionnaires (n = 22) were selected for analysis. These included 6 questionnaires for thrombocytopenia, 2 for MDS, 8 for hemophilia, and 6 for other bleeding disorders. None of the non-thrombocytopenia questionnaires identified captured the effects of thrombocytopenia in MDS and were eliminated from further review. Specific PRO questionnaires related to thrombocytopenia included the European Organisation for Research and Treatment of Cancer (EORTC) QOL Questionnaire-Myeloma Module, Functional Assessment of Cancer Therapy-Thrombocytopenia (FACT-Th), FACT Anemia (FACT-An) Idiopathic Thrombocytopenia Purpura (ITP)-QOL disorders, ITP-Child QOL and ITP-Parental Burden QOL. Common issue areas covered within these questionnaires included fatigue, bleeding, treatment-related problems, activities, social impact, and emotional impact. These questionnaires need further validation in order to be used for measuring the HRQoL impact of thrombocytopenia in MDS patients. Discussion: Although several existing questionnaires have been used to measure quality of life impact of thrombocytopenia in patients with cancer and/or bleeding disorders, none have been specifically used in MDS patients with thrombocytopenia. Common themes identified across these questionnaires should be considered in adapting existing questionnaires to insure that they capture the HRQoL impact of thrombocytopenia in MDS patients.
RAEB-t, respectively. 2 patients with RAEB who attained remission relapsed after 8.6 and 6.2 months and died. 8 patients with RAEB-t received stem cell transplantation (SCT) and have been followed-up in remission for a median of 13.5 months. Median time to neutrophil recovery over 100/mL and over 500/mL were 21 and 24 days, respectively. Among these, 1 patient died of sepsis. 4 patients relapsed after a median of 5.4 months and died, and 2 patients just completed cytoreductive chemotherapy in preparation for DLI. Discussion: Patients with RAEB and RAEB-t had a high rate of composite karyotype. AML Rx in patients with RAEB and RAEB-t who tend to have poor prognosis may benefit from AML Rx but long-term remission is rare. Considering long-term survivors in the SCT recipients, SCT should be considered for patients with an appropriate donor.
PO019 Acute myelogenous leukemia (AML) type induction chemotherapy for the patients with myelodysplastic syndrome (MDS)
Introduction: The study intended to evaluate global survival time and the risk to transform into leukemia according to FAB, WHO, IPSS and WPSS classifications of 235 MDS patients diagnosed from Mar, 1988 till Jan, 2007, at two university hospitals in S. Paulo, Brazil. Methods: From the 235 patients classified by FAB and WHO, 154 had risk defined by IPSS, 145 by WPSS, and 159 had their cytogenetic groups defined by IPSS. For statistical analysis, patients that were submitted to allogeneic stem cell transplantation or to chemotherapy were censored at the time of therapeutic intervention. The actuarial probabilities of overall survival (OS) and leukemia-free survival (LFS) were estimated using Kaplan-Meier product limit method. Results: Median age was 68 years (15−99) and 56.2% were male. According to WHO, patients were classified as: RA: 14%; RARS: 12.3%; RCMD: 24.7%; RCMD-RS: 6.4%; RAEB-1: 16.6%; RAEB-2: 20.9%; MDS-U: 3.8%; and 5q−: 1.3%. According to FAB, patients were classified as: RA: 43.4%; RARS: 19.1%; RAEB: 31.1%; and RAEB-t: 6.4%. According to IPSS, patients were classified as: Low Risk: 37.7%; Int-1: 43.5%; Int-2: 11%; and High: 7.8%. According to WPSS, patients were classified as: Very Low: 9%; Low: 32.4%; Int: 21.4%; High: 27.6%; and Very high: 9.7%. According to karyotype, patients were classified as: Good: 78%; Int: 12.6% and Poor: 9.4%. Median follow up was 43 mo, global survival was 33 mo and the risk to transform into leukemia at 48 mo was 29%.
D.-Y. Kim ° , J.-S. Kim, B.-S. Kim, S.-M. Bang, I. Kim, S.-S. Yoon, S. Park, B.K. Kim. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea *E-mail: [email protected] Introduction: Patients with refractory anemia with excess blasts in transformation (RAEB-t) and RAEB receive AML type chemotherapy (AML Rx) less often than do patients with AML. This study evaluated remission rate and remission duration of AML Rx in patients with RAEB and RAEB-t. Methods: From April 1997 to July 2005, we treated 5 patients with RAEB and 29 with RAEB-t. Patients received myelosuppressive combination chemotherapy; Ara-C with daunorubicin (AD) or idarubicin (Aid). Results: The male to female ratio was 1.2:1 (19:16) and median age was 48.0 years old (range 21−73). Among 32 patients whose karyotypes were available, 16 patients (50.0%) had composite cytogenetics. 4 patients received AD and 30 patients received Aid. 31 patients were assessable for the response. AML Rx produced a complete remission rate of 51.6%; 50% (2/4) for RAEB and 51.9% (14/27) for
PO020 Primary MDS: analysis of survival and risk of leukemia transformation according to FAB, WHO, IPSS and WPSS classifications E.R.P. Velloso1 , L.F. Pracchia1 , B. Beitler1 , R.F. Pinheiro2 , M.L.L.F. Chauffaille2 ° . 1 Hematology Service of Hospital das Clinicas S˜ao Paulo Medical School, 2 Hematology Department, Federal University of S. Paulo, UNIFESP, Brazil *E-mail: [email protected]
Publication Only WHO Overall survival RA + RARS+5q−: 88 mo RCMD +RCMD-RS: 25 mo RAEB-1: 20 mo RAEB-2: 8.7 mo p < 0.000 Rate of leukemia at 48 mo RA+ RARS+5q−: 2% RCMD +RCMD-RS: 33% RAEB-1: 43% RAEB-2: 80% p < 0.000
FAB
IPSS
WPSS
Cytogenetics
RA: 66.1 mo RARS: 55 mo RAEB: 14.8 mo RAEBt: 9.2 mo p < 0.000
Low: 88 mo Int-1: 36 mo Int-2: 11 mo High: 9.2 mo p < 0.000
Very low + low: 66 mo Int: 102 mo High: 17 mo Very high: 11 mo p < 0.000
Good: 51.8 mo Int: 38.1 mo Poor: 16 mo
RA: 15% RARS: 17% RAEB: 53% RAEBt: 100% p < 0.000
Low: 7% Int-1: 23% Int-2: 63% High: 100% p < 0.000
Very low + low: 12% Int: 33% High: 43% Very high: 63% p < 0.000
p < 0.000 Good: 25% Int: 57% Poor: 48% p = 0.27
Conclusion: All variables studied were useful to define global survival and the risk to leukemia (except for karyotype for leukemia risk).
PO021 Characteristics and survival of 115 Irish patients with myelodysplastic syndrome: pilot study for establishment of a national database
S139
were identified, likely representing approximately 60% of all newly-diagnosed patients in Ireland. Discussion: This study documents the clinical characteristics and survival in a large cohort of Irish patients with MDS, which will serve as a historical control for the proposed National Database. Significant problems were encountered with establishment of the database primarily related to lack of a formal infrastructure for research of this kind. It is possible, however, to collect comprehensive information regarding individual MDS patients nationwide. Successful establishment of a National Database will allow regional and international comparison, and facilitate planning of services and clinical trial participation for patients with MDS.
PO022 Autoimmune phenomena, myelodysplastic syndromes, cytogenetics: a case report
H. Enright ° , J. Quinn, R. Morell. Department of Haematology, Adelaide and Meath Hospital, Dublin, Ireland *E-mail: [email protected]
B. Crescenzi1 , L. Berchicci1 , F. Aversa1 , S. Ballanti1 , R. La Starza1 , G. Lupattelli2 , M.F. Martelli1 , C. Matteucci1 , C. Mecucci1 ° . 1 Hematology, IBiT Foundation, 2 Unit of Internal Medicine, Angiology and Arteriosclerosis, University of Perugia, Italy *E-mail: [email protected]
Introduction: Myelodysplastic syndromes (MDS) are clonal, often pre-leukaemic haematopoietic stem cell disorders with an incidence internationally of 4/100,000/year. The incidence and epidemiological patterns of MDS in the Irish population are unknown. Our aims were to examine the clincal and epidemiological features of MDS in Ireland and the feasibility of establishing a national MDS database. Methods: We retrospectively identified patients with MDS presenting to a single institution from 1999–2007. As part of a pilot study for the establishment of a national database, we collected comprehensive diagnostic and treatment information regarding all newly diagnosed MDS patients. Results: We initially identified 115 patients with MDS presenting to our institution from 1999–2007. Median age at presentation was 71 years (15−88 years). Six patients had a family history of MDS or AML. Sixty-three patients had RA or RCMD (55%), 27 had RAEB (23%), 12 had RARS or RCMD-RS (10%), and 8 had CMML. Cytogenetic analysis was available in 78 patients and was normal in 41 (52%). Fifty-five percent of patients were red blood cell and/or platelet-transfusion dependent. 29 patients (25%) transformed to AML. At follow-up, 57 patients remain alive and 51 have died. The cause of death was related to MDS or AML in 34 patients. Most patients were conservatively managed. Nine patients received AML induction-type therapy. Three patients received allogeneic transplants, one of whom remains alive 4 years later. Three patients received 5-azacytidine, one of whom (with monosomy 7) had a major cytogenetic response. Only 6 patients with RAEB survived >24 months. The National Registry pilot study examined data for 1 year. During that time 105 new patents
A 56 year-old woman affected since 1992 by idiopathic thrombocytopenia not responding to corticosteroid therapy and splenectomy, was referred to our Institute in 2003 because of moderate anemia (10.5 g/dl), slight fever and serologically negative arthritis. MDS was not diagnosed on bone marrow morphology but cytogenetics revealed a 47,XX,del(20)(q11q13),+del(20)(q11q13) karyotype. In 2004 the patient presented worsening thrombocytopenia and polyarthritis resistant to methotrexate and prednison. In 2005, Refractory Anemia with Excess of Blasts (RAEB) was diagnosed on bone marrow aspirate (10% of blasts) with stable cytogenetics. An anti-TNFa antibody was administered from September 2005 till July 2006. Clinical, hematological conditions and cytogenetics remained stable until October 2006 when anemia worsened (6 g/dl). In January 2007 bone marrow aspirate and biopsy findings indicated a progressive MDS with reduced normal haematopoietic progenitors, marked dysplasia, and 20% blast cells. Cytogenetics revealed additional numerical chromosome anomalies: 47,XX,del(20)(q11q13),+del(20)(q11q13)/ 48,idem,+10/50,idem,+8,+18, confirming clonal evolution. FISH confirmed these changes appeared at time of evolution. One month later acute myeloid leukaemia was diagnosed. Comments: As far as we know this is the first case of seconday leukaemia in a patient with MDS and autoimmune phenomena, including polyarthritis, treated with an antiTNFa antibody. In this patient with cytopenia and arthritis in the absence of MDS a del(20q) emerged in a double copy at first cytogenetic analysis, ten years after the first autoimmune phenomena, and one year before overt MDS.
Publication Only
PRO information specialist. Only the most relevant diseasespecific questionnaires (n = 22) were selected for analysis. These included 6 questionnaires for thrombocytopenia, 2 for MDS, 8 for hemophilia, and 6 for other bleeding disorders. None of the non-thrombocytopenia questionnaires identified captured the effects of thrombocytopenia in MDS and were eliminated from further review. Specific PRO questionnaires related to thrombocytopenia included the European Organisation for Research and Treatment of Cancer (EORTC) QOL Questionnaire-Myeloma Module, Functional Assessment of Cancer Therapy-Thrombocytopenia (FACT-Th), FACT Anemia (FACT-An) Idiopathic Thrombocytopenia Purpura (ITP)-QOL disorders, ITP-Child QOL and ITP-Parental Burden QOL. Common issue areas covered within these questionnaires included fatigue, bleeding, treatment-related problems, activities, social impact, and emotional impact. These questionnaires need further validation in order to be used for measuring the HRQoL impact of thrombocytopenia in MDS patients. Discussion: Although several existing questionnaires have been used to measure quality of life impact of thrombocytopenia in patients with cancer and/or bleeding disorders, none have been specifically used in MDS patients with thrombocytopenia. Common themes identified across these questionnaires should be considered in adapting existing questionnaires to insure that they capture the HRQoL impact of thrombocytopenia in MDS patients.
RAEB-t, respectively. 2 patients with RAEB who attained remission relapsed after 8.6 and 6.2 months and died. 8 patients with RAEB-t received stem cell transplantation (SCT) and have been followed-up in remission for a median of 13.5 months. Median time to neutrophil recovery over 100/mL and over 500/mL were 21 and 24 days, respectively. Among these, 1 patient died of sepsis. 4 patients relapsed after a median of 5.4 months and died, and 2 patients just completed cytoreductive chemotherapy in preparation for DLI. Discussion: Patients with RAEB and RAEB-t had a high rate of composite karyotype. AML Rx in patients with RAEB and RAEB-t who tend to have poor prognosis may benefit from AML Rx but long-term remission is rare. Considering long-term survivors in the SCT recipients, SCT should be considered for patients with an appropriate donor.
PO019 Acute myelogenous leukemia (AML) type induction chemotherapy for the patients with myelodysplastic syndrome (MDS)
Introduction: The study intended to evaluate global survival time and the risk to transform into leukemia according to FAB, WHO, IPSS and WPSS classifications of 235 MDS patients diagnosed from Mar, 1988 till Jan, 2007, at two university hospitals in S. Paulo, Brazil. Methods: From the 235 patients classified by FAB and WHO, 154 had risk defined by IPSS, 145 by WPSS, and 159 had their cytogenetic groups defined by IPSS. For statistical analysis, patients that were submitted to allogeneic stem cell transplantation or to chemotherapy were censored at the time of therapeutic intervention. The actuarial probabilities of overall survival (OS) and leukemia-free survival (LFS) were estimated using Kaplan-Meier product limit method. Results: Median age was 68 years (15−99) and 56.2% were male. According to WHO, patients were classified as: RA: 14%; RARS: 12.3%; RCMD: 24.7%; RCMD-RS: 6.4%; RAEB-1: 16.6%; RAEB-2: 20.9%; MDS-U: 3.8%; and 5q−: 1.3%. According to FAB, patients were classified as: RA: 43.4%; RARS: 19.1%; RAEB: 31.1%; and RAEB-t: 6.4%. According to IPSS, patients were classified as: Low Risk: 37.7%; Int-1: 43.5%; Int-2: 11%; and High: 7.8%. According to WPSS, patients were classified as: Very Low: 9%; Low: 32.4%; Int: 21.4%; High: 27.6%; and Very high: 9.7%. According to karyotype, patients were classified as: Good: 78%; Int: 12.6% and Poor: 9.4%. Median follow up was 43 mo, global survival was 33 mo and the risk to transform into leukemia at 48 mo was 29%.
D.-Y. Kim ° , J.-S. Kim, B.-S. Kim, S.-M. Bang, I. Kim, S.-S. Yoon, S. Park, B.K. Kim. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, South Korea *E-mail: [email protected] Introduction: Patients with refractory anemia with excess blasts in transformation (RAEB-t) and RAEB receive AML type chemotherapy (AML Rx) less often than do patients with AML. This study evaluated remission rate and remission duration of AML Rx in patients with RAEB and RAEB-t. Methods: From April 1997 to July 2005, we treated 5 patients with RAEB and 29 with RAEB-t. Patients received myelosuppressive combination chemotherapy; Ara-C with daunorubicin (AD) or idarubicin (Aid). Results: The male to female ratio was 1.2:1 (19:16) and median age was 48.0 years old (range 21−73). Among 32 patients whose karyotypes were available, 16 patients (50.0%) had composite cytogenetics. 4 patients received AD and 30 patients received Aid. 31 patients were assessable for the response. AML Rx produced a complete remission rate of 51.6%; 50% (2/4) for RAEB and 51.9% (14/27) for
PO020 Primary MDS: analysis of survival and risk of leukemia transformation according to FAB, WHO, IPSS and WPSS classifications E.R.P. Velloso1 , L.F. Pracchia1 , B. Beitler1 , R.F. Pinheiro2 , M.L.L.F. Chauffaille2 ° . 1 Hematology Service of Hospital das Clinicas S˜ao Paulo Medical School, 2 Hematology Department, Federal University of S. Paulo, UNIFESP, Brazil *E-mail: [email protected]
Publication Only WHO Overall survival RA + RARS+5q−: 88 mo RCMD +RCMD-RS: 25 mo RAEB-1: 20 mo RAEB-2: 8.7 mo p < 0.000 Rate of leukemia at 48 mo RA+ RARS+5q−: 2% RCMD +RCMD-RS: 33% RAEB-1: 43% RAEB-2: 80% p < 0.000
FAB
IPSS
WPSS
Cytogenetics
RA: 66.1 mo RARS: 55 mo RAEB: 14.8 mo RAEBt: 9.2 mo p < 0.000
Low: 88 mo Int-1: 36 mo Int-2: 11 mo High: 9.2 mo p < 0.000
Very low + low: 66 mo Int: 102 mo High: 17 mo Very high: 11 mo p < 0.000
Good: 51.8 mo Int: 38.1 mo Poor: 16 mo
RA: 15% RARS: 17% RAEB: 53% RAEBt: 100% p < 0.000
Low: 7% Int-1: 23% Int-2: 63% High: 100% p < 0.000
Very low + low: 12% Int: 33% High: 43% Very high: 63% p < 0.000
p < 0.000 Good: 25% Int: 57% Poor: 48% p = 0.27
Conclusion: All variables studied were useful to define global survival and the risk to leukemia (except for karyotype for leukemia risk).
PO021 Characteristics and survival of 115 Irish patients with myelodysplastic syndrome: pilot study for establishment of a national database
S139
were identified, likely representing approximately 60% of all newly-diagnosed patients in Ireland. Discussion: This study documents the clinical characteristics and survival in a large cohort of Irish patients with MDS, which will serve as a historical control for the proposed National Database. Significant problems were encountered with establishment of the database primarily related to lack of a formal infrastructure for research of this kind. It is possible, however, to collect comprehensive information regarding individual MDS patients nationwide. Successful establishment of a National Database will allow regional and international comparison, and facilitate planning of services and clinical trial participation for patients with MDS.
PO022 Autoimmune phenomena, myelodysplastic syndromes, cytogenetics: a case report
H. Enright ° , J. Quinn, R. Morell. Department of Haematology, Adelaide and Meath Hospital, Dublin, Ireland *E-mail: [email protected]
B. Crescenzi1 , L. Berchicci1 , F. Aversa1 , S. Ballanti1 , R. La Starza1 , G. Lupattelli2 , M.F. Martelli1 , C. Matteucci1 , C. Mecucci1 ° . 1 Hematology, IBiT Foundation, 2 Unit of Internal Medicine, Angiology and Arteriosclerosis, University of Perugia, Italy *E-mail: [email protected]
Introduction: Myelodysplastic syndromes (MDS) are clonal, often pre-leukaemic haematopoietic stem cell disorders with an incidence internationally of 4/100,000/year. The incidence and epidemiological patterns of MDS in the Irish population are unknown. Our aims were to examine the clincal and epidemiological features of MDS in Ireland and the feasibility of establishing a national MDS database. Methods: We retrospectively identified patients with MDS presenting to a single institution from 1999–2007. As part of a pilot study for the establishment of a national database, we collected comprehensive diagnostic and treatment information regarding all newly diagnosed MDS patients. Results: We initially identified 115 patients with MDS presenting to our institution from 1999–2007. Median age at presentation was 71 years (15−88 years). Six patients had a family history of MDS or AML. Sixty-three patients had RA or RCMD (55%), 27 had RAEB (23%), 12 had RARS or RCMD-RS (10%), and 8 had CMML. Cytogenetic analysis was available in 78 patients and was normal in 41 (52%). Fifty-five percent of patients were red blood cell and/or platelet-transfusion dependent. 29 patients (25%) transformed to AML. At follow-up, 57 patients remain alive and 51 have died. The cause of death was related to MDS or AML in 34 patients. Most patients were conservatively managed. Nine patients received AML induction-type therapy. Three patients received allogeneic transplants, one of whom remains alive 4 years later. Three patients received 5-azacytidine, one of whom (with monosomy 7) had a major cytogenetic response. Only 6 patients with RAEB survived >24 months. The National Registry pilot study examined data for 1 year. During that time 105 new patents
A 56 year-old woman affected since 1992 by idiopathic thrombocytopenia not responding to corticosteroid therapy and splenectomy, was referred to our Institute in 2003 because of moderate anemia (10.5 g/dl), slight fever and serologically negative arthritis. MDS was not diagnosed on bone marrow morphology but cytogenetics revealed a 47,XX,del(20)(q11q13),+del(20)(q11q13) karyotype. In 2004 the patient presented worsening thrombocytopenia and polyarthritis resistant to methotrexate and prednison. In 2005, Refractory Anemia with Excess of Blasts (RAEB) was diagnosed on bone marrow aspirate (10% of blasts) with stable cytogenetics. An anti-TNFa antibody was administered from September 2005 till July 2006. Clinical, hematological conditions and cytogenetics remained stable until October 2006 when anemia worsened (6 g/dl). In January 2007 bone marrow aspirate and biopsy findings indicated a progressive MDS with reduced normal haematopoietic progenitors, marked dysplasia, and 20% blast cells. Cytogenetics revealed additional numerical chromosome anomalies: 47,XX,del(20)(q11q13),+del(20)(q11q13)/ 48,idem,+10/50,idem,+8,+18, confirming clonal evolution. FISH confirmed these changes appeared at time of evolution. One month later acute myeloid leukaemia was diagnosed. Comments: As far as we know this is the first case of seconday leukaemia in a patient with MDS and autoimmune phenomena, including polyarthritis, treated with an antiTNFa antibody. In this patient with cytopenia and arthritis in the absence of MDS a del(20q) emerged in a double copy at first cytogenetic analysis, ten years after the first autoimmune phenomena, and one year before overt MDS.