- Email: [email protected]
P116 Comparison of MDS patients with long survival to short survival patients. Analysis of cases with discrepancy between low IPSS and survival
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Posters
whereas in the S group early death (n = 4) or engraftment failure (n = 3) was seen in 22%. With the limited follow-up, F-RIC also compared favorably to standard conditioning for aGvHD (44% vs. 53%) and severity of aGvHD grade III-IV (7% vs. 53%). Discussion: F-RIC for allogeneic SCT is effective with acceptable toxicity for high risk pts. with MDS and sAML. Longer follow-up and prospective trials are required to define its therapeutic benefit and the optimal timing for MDS and sAML subgroups.
P115 Prognostic factors in chronic myelomonocytic leukaemia: a retrospective analysis of 113 patients A. Stamatoullas1 ° , A. Waultier1 , M.P. Callat2 , D. Penther3 , H. Tilly1 , C. Bastard3 . 1: D´epartement d’H´ematologie, Centre Henri Becquerel; 2 Laboratoire d’H´ematologie, CHU; 3 D´epartement de biologie mol´eculaire Oncologique, Centre Henri Becquerel, Rouen, France *E-mail: [email protected] Chronic myelomonocytic leukaemia (CMML), initially recognized by the FAB classification as a myelodysplastic syndrome (MDS), is currently included in the new category of myelodysplastic/myeloproliferative disorders according to the WHO classification. CMML is characterized by an increased number of monocytes in peripheral blood and in bone marrow, associated with various dysplasia. Clinically, 50% of patients present with an organ involvement. CMML is a heterogeneous disease with no cytogenetic signature in which the most common chromosomal defects are monosomy 7 and trisomy 8. The prognosis can be evaluated using the International prognostic scoring system (IPSS) but other prognostic factors have been reported by F Onida et al in 2002. In order to apply these prognostic factors to our series of patients (pts), we retrospectively analysed 113 CMML pts recruited between October 1991 and July 2005. Median age was 73 years (46−94), gender ratio was 44F/69M. 15 pts presented with hepatomegaly, and 23 pts with splenomegaly. 23 pts progressed to AML. The median overall survival was 19 months. LDH level was available for 39 pts and 27 were abnormal. Karyotypes were performed in 72 pts and 29 were abnormal, with trisomy 8 in 7 pts, −7/7q in 5 pts, 11q23 rearrangements in 5 pts, complex karyotypes in 3 pts, −X in 3 pts, −Y in 3 pts, −5/5q in 2 pts, 17p defects in 2 pts and trisomy 14 in 1 pt. IPSS could be evaluated in 71 pts (25 low risk, 28 intermediate1, 10 intermediate 2, 8 high risk), even for those with proliferative CMML. Univariate analysis showed that high intermediate2/high risk IPSS, hemoglobin level <10 g/dl, marrow blasts >10%, peripheral blasts >5%, monocytosis >4×109 /L and presence of circulating immature myeloid cells were poor prognostic
factors but not abnormal LDH level, white blood cell count >10×109 /L, platelets level <100×109 /L. In conclusion, the characteristics of our patients were similar to those published previously. The prognosis was strongly linked to IPSS. The other factors not involved in IPSS which could easily be used in routine practice are the percentage of peripheral blasts, monocytosis and the proportion of immature myeloid cells.
P116 Comparison of MDS patients with long survival to short survival patients. Analysis of cases with discrepancy between low IPSS and survival R. Neuwirtova1 ° , H. Krejcova, A. Smolikova, E. Polonyova, P. Kessler, A. Jonasova. Czech Cooperative MDS group. 1 1st Med. Dept., Charles University Hospital, Prague, Czech Republic *E-mail: [email protected] Introduction: Prognosis of majority MDS patients (pts) is determined by IPSS and some other parameters. Nevertheless there are cases where the course of disease is unexpected. We have analyzed pts with exceptionally long and short survival and have found some positive and negative prognostic markers. Material: We have collected data from 164 MDS pts. Seventy six lived >5 years including 21 pts living more then 10 years (group A), 68 pts died within 1 year (group B1) and 20 within 2 years (B2). We compare all groups by age, gender, MDS type, primary or secondary MDS, hematologic data, cytogenetics, IPSS and a course of disease. Results: Females predominated in the group A. Median age was 67 for group A, 74 for group B1 and 72 for group B2. In terms of diagnosis there were 75% RA and RARS, 3% RAEB, 6% CMML and 15% pts with thrombocytosis including 5q− pts in group A. In B1 group there were 46% RA and RARS and 42% high risk MDS. In B2 there were 40% low risk and 30% high risk pts. CMML was diagnosed in 10% in both groups. Thrombocytosis was found only in 4 pts in both B groups (all <500×109 /L). AML transformation was 7% in A, 37% in B1 and 30% in B2 group. The highest IPSS was 1.5 in A group, B groups had all range of IPSS. Cytogenetic analysis showed poor karyotype in 4% in A and 30% in both B groups. Secondary MDS was diagnosed in 4% A pts and 15% B pts. Among positive prognostic markers in A group belong good karyotype in all secondary MDS pts in contrast to poor karyotype in B sec. MDS pts. Only 4 A pts had thrombocytopenia <50×109 /L and 23 A pts had ANC <1.5×109 /L. But no one of these pts had thrombocytopenia together with low ANC. Further favorable markers for long survival were gender, low risk diagnosis RA, RARS and 5q− syndrome, younger age without polymorbidity and high platelet count.
6. Diagnostic and prognostic tools II – Prognostic factors and scoring systems In B group with low IPSS and good karyotype we found combination of thrombocytopenia with absolute neutropenia as negative prognostic marker for AML transformation. Frequent cause of short survival in this group was also infection complication for pts with low ANC, and non hematologic cause of short survival. Conclusion: Combination of thrombocytopenia and low ANC, polymorbidity, and higher age are the important negative prognostic markers for short living MDS pts with favorable IPSS. On the contrary good karyotype, absence of combination of thrombocytopenia and low ANC, thrombocytosis and the age below 70 are positive markers for long survival.
P117 Prevalence of cardiac disease among a US medicare population with myelodysplastic syndromes S.L. Goldberg1 , N. Mody-Patel2 , N. Warnock3 ° . 1 Cancer Center, Hackensack University Medical Center, 2 Novartis Pharmaceuticals, Florham Park, NJ, 3 Quorum Consulting, San Francisco, CA, USA *E-mail: [email protected] Background: The myelodysplastic syndromes (MDS) are a heterogeneous group of marrow failure syndromes frequently resulting in chronic anemia requiring red blood cell transfusions. It is known that iron overload resulting from chronic transfusion dependence contributes to cardiac diseases and other conditions. In a retrospective review, Malcovati (JCO 2005;23:7594) noted cardiac failure as the most common cause of non-leukemic death in MDS occurring in 51% of cases, and being more frequent among transfusion dependent patients. The aim of this analysis is to describe the prevalence of cardiac conditions in newly diagnosed MDS patients (pts) followed over a three year period compared to those without MDS in the Medicare population. Methods: The Medicare Standard Analytic File 5% (SAF5%) claims database was used to identify pts with a new primary MDS diagnosis code from Jan-Mar 2003 and followed till Dec 2005 or death to identify cardiac events including, congestive heart failure (CHF), myocardial infarctions (MI), arrhythmias, and other (other acute forms of ischemic heart disease, angina pectoris, conductions disorders, and cardiomyopathy). Pts with myeloid leukemia or anemias of known causes in the previous year were excluded. Results: Of the 1,713,502 pts in SAF5%, 705 (40 per 100,000) developed MDS from Jan-Mar 2003, including 159 with a previous history of unexplained anemia (23%), 43 chemotherapy or radiotherapy exposure (6%), and 503 de novo (71%). Mean age was 76 (range 29−98); 49% male, 90% Caucasian. During the 3-year study, 522 of the 705 MDS pts (74%) suffered a cardiac related event,
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including 142 MIs (20%), 344 CHF (48%), 374 arrhythmias (53%) and 415 other cardiac related events (58%). 46% of pts that developed MDS received blood transfusions and 6% received iron chelation therapy over the 3 years of follow up. 256 (79%) pts receiving transfusions were diagnosed with a cardiac event as compared with 175 (54%) that did not receive transfusions (p = 0.0001). Of interest, 383/705 MDS patients (54%) had no prior history of cardiac disease in 2002, and among this cohort 228 (60%) developed cardiac disease. For comparison, of the approximately 1.7 million individuals in this Medicare database, 726,936 (42.7%) were coded as having cardiac disease during the 3-year study, which was significantly less than the MDS cohort (74%; p = 0.002). Conclusions: Cardiac disease is a major co-morbid condition among elderly patients with MDS. Since chronic anemia causes myocardial ischemia and transfusional iron overload is also known to contribute to cardiac dysfunction, strategies to improve anemia and maintain adequate iron balance through the administration of iron chelation therapy are critical in MDS pts receiving blood transfusions.
P118 Detection of cardiac iron by T2* MRI in transfusion dependent patients with acquired anemias S. Deplano, A. Di Tucci, M. Pettinau, E. Usala, E. Angelucci ° . U.O. Ematologia e CTMO, Ospedale A. Businco, Cagliari, Italy *E-mail: [email protected] We measured cardiac MRI T2* in 21 consecutive transfusion dependent unchelated patients (14 males, 7 females) affected by myelodysplastic syndromes (13), myelofibrosis (6) and pure red cell aplasia (2), aged 46−82 years, (median age 68). They had received a median number of 61 (range16–225) packed red blood cell units equivalent to 3.2−45 (median12) grams of iron. Serum ferritin levels ranged from 1300 to 6241 mg/L (median value 2095). None of the patients presented signs or symptoms of cardiac failure at the time of the study. Cardiac MRI T2* values obtained ranged from 5.6 to 58.7 (median value 42.5) milliseconds. Pathologic cardiac T2* value (<20 ms) was detected in 3 patients (5.6, 12.4 and 8.5 ms, respectively). They had received 48, 101 and 225 units of red blood cell transfusion, corresponding to 9.6, 20 and 45 grams of iron, respectively. Genetic analysis was performed on the patient who had received 48 packed red blood cells transfusions and a condition of heterozygosis for the H63D mutation and homozygosis for V221 ferroportin gene mutation was found. This last mutation has been reported to be associated with clinical significant iron overload. All of the patients with a pathologic T2* value died within few months after the end of the study and in one case
Posters
whereas in the S group early death (n = 4) or engraftment failure (n = 3) was seen in 22%. With the limited follow-up, F-RIC also compared favorably to standard conditioning for aGvHD (44% vs. 53%) and severity of aGvHD grade III-IV (7% vs. 53%). Discussion: F-RIC for allogeneic SCT is effective with acceptable toxicity for high risk pts. with MDS and sAML. Longer follow-up and prospective trials are required to define its therapeutic benefit and the optimal timing for MDS and sAML subgroups.
P115 Prognostic factors in chronic myelomonocytic leukaemia: a retrospective analysis of 113 patients A. Stamatoullas1 ° , A. Waultier1 , M.P. Callat2 , D. Penther3 , H. Tilly1 , C. Bastard3 . 1: D´epartement d’H´ematologie, Centre Henri Becquerel; 2 Laboratoire d’H´ematologie, CHU; 3 D´epartement de biologie mol´eculaire Oncologique, Centre Henri Becquerel, Rouen, France *E-mail: [email protected] Chronic myelomonocytic leukaemia (CMML), initially recognized by the FAB classification as a myelodysplastic syndrome (MDS), is currently included in the new category of myelodysplastic/myeloproliferative disorders according to the WHO classification. CMML is characterized by an increased number of monocytes in peripheral blood and in bone marrow, associated with various dysplasia. Clinically, 50% of patients present with an organ involvement. CMML is a heterogeneous disease with no cytogenetic signature in which the most common chromosomal defects are monosomy 7 and trisomy 8. The prognosis can be evaluated using the International prognostic scoring system (IPSS) but other prognostic factors have been reported by F Onida et al in 2002. In order to apply these prognostic factors to our series of patients (pts), we retrospectively analysed 113 CMML pts recruited between October 1991 and July 2005. Median age was 73 years (46−94), gender ratio was 44F/69M. 15 pts presented with hepatomegaly, and 23 pts with splenomegaly. 23 pts progressed to AML. The median overall survival was 19 months. LDH level was available for 39 pts and 27 were abnormal. Karyotypes were performed in 72 pts and 29 were abnormal, with trisomy 8 in 7 pts, −7/7q in 5 pts, 11q23 rearrangements in 5 pts, complex karyotypes in 3 pts, −X in 3 pts, −Y in 3 pts, −5/5q in 2 pts, 17p defects in 2 pts and trisomy 14 in 1 pt. IPSS could be evaluated in 71 pts (25 low risk, 28 intermediate1, 10 intermediate 2, 8 high risk), even for those with proliferative CMML. Univariate analysis showed that high intermediate2/high risk IPSS, hemoglobin level <10 g/dl, marrow blasts >10%, peripheral blasts >5%, monocytosis >4×109 /L and presence of circulating immature myeloid cells were poor prognostic
factors but not abnormal LDH level, white blood cell count >10×109 /L, platelets level <100×109 /L. In conclusion, the characteristics of our patients were similar to those published previously. The prognosis was strongly linked to IPSS. The other factors not involved in IPSS which could easily be used in routine practice are the percentage of peripheral blasts, monocytosis and the proportion of immature myeloid cells.
P116 Comparison of MDS patients with long survival to short survival patients. Analysis of cases with discrepancy between low IPSS and survival R. Neuwirtova1 ° , H. Krejcova, A. Smolikova, E. Polonyova, P. Kessler, A. Jonasova. Czech Cooperative MDS group. 1 1st Med. Dept., Charles University Hospital, Prague, Czech Republic *E-mail: [email protected] Introduction: Prognosis of majority MDS patients (pts) is determined by IPSS and some other parameters. Nevertheless there are cases where the course of disease is unexpected. We have analyzed pts with exceptionally long and short survival and have found some positive and negative prognostic markers. Material: We have collected data from 164 MDS pts. Seventy six lived >5 years including 21 pts living more then 10 years (group A), 68 pts died within 1 year (group B1) and 20 within 2 years (B2). We compare all groups by age, gender, MDS type, primary or secondary MDS, hematologic data, cytogenetics, IPSS and a course of disease. Results: Females predominated in the group A. Median age was 67 for group A, 74 for group B1 and 72 for group B2. In terms of diagnosis there were 75% RA and RARS, 3% RAEB, 6% CMML and 15% pts with thrombocytosis including 5q− pts in group A. In B1 group there were 46% RA and RARS and 42% high risk MDS. In B2 there were 40% low risk and 30% high risk pts. CMML was diagnosed in 10% in both groups. Thrombocytosis was found only in 4 pts in both B groups (all <500×109 /L). AML transformation was 7% in A, 37% in B1 and 30% in B2 group. The highest IPSS was 1.5 in A group, B groups had all range of IPSS. Cytogenetic analysis showed poor karyotype in 4% in A and 30% in both B groups. Secondary MDS was diagnosed in 4% A pts and 15% B pts. Among positive prognostic markers in A group belong good karyotype in all secondary MDS pts in contrast to poor karyotype in B sec. MDS pts. Only 4 A pts had thrombocytopenia <50×109 /L and 23 A pts had ANC <1.5×109 /L. But no one of these pts had thrombocytopenia together with low ANC. Further favorable markers for long survival were gender, low risk diagnosis RA, RARS and 5q− syndrome, younger age without polymorbidity and high platelet count.
6. Diagnostic and prognostic tools II – Prognostic factors and scoring systems In B group with low IPSS and good karyotype we found combination of thrombocytopenia with absolute neutropenia as negative prognostic marker for AML transformation. Frequent cause of short survival in this group was also infection complication for pts with low ANC, and non hematologic cause of short survival. Conclusion: Combination of thrombocytopenia and low ANC, polymorbidity, and higher age are the important negative prognostic markers for short living MDS pts with favorable IPSS. On the contrary good karyotype, absence of combination of thrombocytopenia and low ANC, thrombocytosis and the age below 70 are positive markers for long survival.
P117 Prevalence of cardiac disease among a US medicare population with myelodysplastic syndromes S.L. Goldberg1 , N. Mody-Patel2 , N. Warnock3 ° . 1 Cancer Center, Hackensack University Medical Center, 2 Novartis Pharmaceuticals, Florham Park, NJ, 3 Quorum Consulting, San Francisco, CA, USA *E-mail: [email protected] Background: The myelodysplastic syndromes (MDS) are a heterogeneous group of marrow failure syndromes frequently resulting in chronic anemia requiring red blood cell transfusions. It is known that iron overload resulting from chronic transfusion dependence contributes to cardiac diseases and other conditions. In a retrospective review, Malcovati (JCO 2005;23:7594) noted cardiac failure as the most common cause of non-leukemic death in MDS occurring in 51% of cases, and being more frequent among transfusion dependent patients. The aim of this analysis is to describe the prevalence of cardiac conditions in newly diagnosed MDS patients (pts) followed over a three year period compared to those without MDS in the Medicare population. Methods: The Medicare Standard Analytic File 5% (SAF5%) claims database was used to identify pts with a new primary MDS diagnosis code from Jan-Mar 2003 and followed till Dec 2005 or death to identify cardiac events including, congestive heart failure (CHF), myocardial infarctions (MI), arrhythmias, and other (other acute forms of ischemic heart disease, angina pectoris, conductions disorders, and cardiomyopathy). Pts with myeloid leukemia or anemias of known causes in the previous year were excluded. Results: Of the 1,713,502 pts in SAF5%, 705 (40 per 100,000) developed MDS from Jan-Mar 2003, including 159 with a previous history of unexplained anemia (23%), 43 chemotherapy or radiotherapy exposure (6%), and 503 de novo (71%). Mean age was 76 (range 29−98); 49% male, 90% Caucasian. During the 3-year study, 522 of the 705 MDS pts (74%) suffered a cardiac related event,
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including 142 MIs (20%), 344 CHF (48%), 374 arrhythmias (53%) and 415 other cardiac related events (58%). 46% of pts that developed MDS received blood transfusions and 6% received iron chelation therapy over the 3 years of follow up. 256 (79%) pts receiving transfusions were diagnosed with a cardiac event as compared with 175 (54%) that did not receive transfusions (p = 0.0001). Of interest, 383/705 MDS patients (54%) had no prior history of cardiac disease in 2002, and among this cohort 228 (60%) developed cardiac disease. For comparison, of the approximately 1.7 million individuals in this Medicare database, 726,936 (42.7%) were coded as having cardiac disease during the 3-year study, which was significantly less than the MDS cohort (74%; p = 0.002). Conclusions: Cardiac disease is a major co-morbid condition among elderly patients with MDS. Since chronic anemia causes myocardial ischemia and transfusional iron overload is also known to contribute to cardiac dysfunction, strategies to improve anemia and maintain adequate iron balance through the administration of iron chelation therapy are critical in MDS pts receiving blood transfusions.
P118 Detection of cardiac iron by T2* MRI in transfusion dependent patients with acquired anemias S. Deplano, A. Di Tucci, M. Pettinau, E. Usala, E. Angelucci ° . U.O. Ematologia e CTMO, Ospedale A. Businco, Cagliari, Italy *E-mail: [email protected] We measured cardiac MRI T2* in 21 consecutive transfusion dependent unchelated patients (14 males, 7 females) affected by myelodysplastic syndromes (13), myelofibrosis (6) and pure red cell aplasia (2), aged 46−82 years, (median age 68). They had received a median number of 61 (range16–225) packed red blood cell units equivalent to 3.2−45 (median12) grams of iron. Serum ferritin levels ranged from 1300 to 6241 mg/L (median value 2095). None of the patients presented signs or symptoms of cardiac failure at the time of the study. Cardiac MRI T2* values obtained ranged from 5.6 to 58.7 (median value 42.5) milliseconds. Pathologic cardiac T2* value (<20 ms) was detected in 3 patients (5.6, 12.4 and 8.5 ms, respectively). They had received 48, 101 and 225 units of red blood cell transfusion, corresponding to 9.6, 20 and 45 grams of iron, respectively. Genetic analysis was performed on the patient who had received 48 packed red blood cells transfusions and a condition of heterozygosis for the H63D mutation and homozygosis for V221 ferroportin gene mutation was found. This last mutation has been reported to be associated with clinical significant iron overload. All of the patients with a pathologic T2* value died within few months after the end of the study and in one case