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312 CLINICO-PATHOLOGIC AND CYTOGENETIC STUDY ON MYELODYSPLASTIC SYNDROMES (MDS) – A CASE SERIES FROM SOUTH INDIA
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
Results: 227 pts were analyzed, 139 TA and 88 DC. TA pts tended to be older (mean ± SD = 75.4± 9.8yr) at diagnosis, than DC pts (63.8±14.3yr, p>0.05), and had more cardiovascular diseases (56.8% vs 14.8%, p<0.001). Fewer cytopenias were found among TA pts (mean 1.67±0.82 vs 2.0±0.93 in DC, p=0.003). Hb, Hct, WBC, ANC, PLT, serum chemistry and ferritin, were not statistically different. Mean MCV was 94.3±9.9 Fl in TA pts and 100.5±15.3 Fl in DC (p<0.001). Bone marrow cellularity was similar in both groups. TA pts had more dysplasia: dyserythropoiesis (TA 79.9%, DC 71.3%, p=0.005); myelodysplasia (63.3% vs 52.9, p=0.003); dysmegakaryopoiesis (53.2% vs 40.2%, p=0.001). However, more TA pts had low blast count (<5%): 73.4% vs 50.6% (p=0.003). Accordingly, more TA pts (65%) were classified as early FAB types (RA/RARS) vs 40% in the DC group. Cyotgenetics was similar in both groups. IPSS was determined in 131 pts, 89 LR (low/Int-1), 42 HR (Int-2/high). TA pts were mostly LR (61 pts vs 28 pts). The cumulative 5 yr-survival (YS, Cox regression after neutralizing confounding effects) was 62% vs 55% (TA, DC, respectively). 5 YS according to FAB was 77% (TA) vs 65% (DC) for RA pts, and 43% (TA) vs 37% (DC) for more advanced FAB groups. Conclusions: Limitations include the retrospective nature, geographic, demographic and temporal differences between both populations, and transfusion-dependence of all TA pts. We find that pts today (TA) tend to be older, with more cardiovascular morbidities, fewer cytopenias and lower MCV. They tend to be classified as early disease (RA/RARS, LR-IPSS), and have slightly longer 5 YS. Hopefully, better biological tools and the novel therapeutic agents that have recently been introduced will result in a better outcome. 312 CLINICO-PATHOLOGIC AND CYTOGENETIC STUDY ON MYELODYSPLASTIC SYNDROMES (MDS) – A CASE SERIES FROM SOUTH INDIA T. Paul1, A. Tandon1, M. Uppin1, S. Uppin1, A. Narendra1, G. Sadashivudu1, V. Sreenivasan1, H. Swetha1, R. Jacob1 1 Pathology, Nizam’s Institute of Medical Sciences, Hyderabad, India Objectives: Myelodysplastic syndromes (MDSs) are a heterogenous group of clonal disorders, characterised by ineffective hematopoiesis and peripheral cytopenias. They have a high risk of progression to acute leukemias. This study was undertaken, as there are not many large series published from the Indian sub-continent. The aim was to study the clinico-pathologic and cytogenetic profile of all cases diagnosed as MDS at a tertiary care centre and look for any existing co-morbidities. Materials and Methods: Cases diagnosed as denovo MDS, following a morphologic study of the blood and bone marrow, were included, the study period being 2005 to 2014. Cases where other causes of anemia were detected, were excluded from the study. The clinical and follow-up data were obtained from the patients files. The morphology of each case was reviewed. Cytogenetic reports were obtained, wherever available. Results: During the study period, 188 cases of MDS were diagnosed, ranging from 21 to 88 years of age with a median age of 57 years. There were 125 males and 63 females with a M:F ratio of 1.98:1. Patients presented with varying ranges of cytopenias, with 28 patients having hemoglobin values < 4.0 gm/dL. The patients were classified as MDS-RA (70 cases), RT-(1), RCMD-(40), RARS-(15), RAEB-1 (28), RAEB-2 (28), MDS-U (3), MDS with isolated del(5q) (3). Of these, 7 tranformed to AML on follow-up. Due to financial constraints, only 91 cases (48%), had access to cytogenetic studies. The cytogenetic profile included- Normal karyotype- (57 cases), Trisomy 8 (9 cases), Monosomy 7 (16 cases), Isolated 5q- (3 cases), multiple- 2, and 3 cases with other abnormalities. There was a one case reported as 46,XX,t(3;12)(q26;p13) with an additional -7,
S155
which transformed to acute leukemia. The revised IPSS scores and categories was calculated for these 91 cases. Of the 188 cases, 28 were known diabetics on treatment and there were 11 cases of hypothyroidism. Conclusion: MDS is a serious problem in India. However, a large number of cases remain unrecognised. The median age at presentation was 57 years which is similar to that observed in other Asian countries.The number of male patients is almost double that of female patients, which could be due to a referral bias. Better and more affordable cytogenetic studies are necessary for a majority of the patients. More studies are required to know if Diabetes and hypothyroidism are co-incidental or actual comorbidities. 313 EVIDENCE FOR AN IMMUNOLOGIC ROLE IN THE PATHOGENESIS OF BENZENE-INDUCED MDS D. Pyatt1, P. Kerzic2 1 School of Public Health, University of Colorado, Denver, USA; 2 OEHHA, State of California, Los Angeles, USA Recent epidemiologic evidence has confirmed MDS as a rare but important consequence of occupational benzene exposures. In fact, MDS development seems to be one of the most sensitive toxicological manifestations of benzene exposures, with recent investigations indicating that it can occur at relatively low levels of exposure. MDS is a very diverse group of diseases, with various subtypes differing in diagnostic criteria, treatment, prognosis and likely etiology. Unfortunately, there is a paucity of relevant data; however, MDS cases identified in patients that have experienced excessive benzene exposures present with several common pathological characteristics but are difficult to classify per the WHO criteria. Recent advances in experimental and clinical hematology have led to the identification of subsets of patients with MDS presenting with clear evidence of immunologic dysregulation. The success of immunosuppressive therapy (IST) in MDS cases provide evidence that immune dysregulation can result in bone marrow dysplasia and MDS development. There is also pathologic evidence that immunologic dysfunction plays a role in the development of MDS subsequent to occupational benzene exposure. Further, benzene-induced MDS cases do not appear to present with a consistent set of clonal cytogenetic abnormalities, indicating a potential non-genotoxic or epigenetic mechanism. Herein, we present existing evidence supporting the hypothesis that immunologic dysregulation may play an important pathogenic role in the development of benzene-induced MDS. We believe this characterization will be useful in gaining a better understanding of benzene toxicology as well as inform regulatory and public health decision-making. 314 REFRACTORY CYTOPENIA OF CHILDHOOD AND ACQUIRED APLASTIC ANEMIA: A CLINICAL AND PATHOLOGICAL STUDY OF 128 CASES X. Qin1, M.Z. Yin2, I. Baumann3, J. Chen1, P. Shen2, J.F. Chen2, H.L. Xue1, S.H. Shen1, J. Chen1, C.Y. Luo1, C.J. Luo1, J.M. Wang1, W.T. Hu1, Y.J. Tang1 1 Department of Hematology and Oncology, Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of Pathology, Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; 3Department of Pathology, Boeblingen Hospital, Boeblingen, Germany Objective: Explore the clinical characteristics and histopathological morphology features of bone marrow biopsies between refractory
Results: 227 pts were analyzed, 139 TA and 88 DC. TA pts tended to be older (mean ± SD = 75.4± 9.8yr) at diagnosis, than DC pts (63.8±14.3yr, p>0.05), and had more cardiovascular diseases (56.8% vs 14.8%, p<0.001). Fewer cytopenias were found among TA pts (mean 1.67±0.82 vs 2.0±0.93 in DC, p=0.003). Hb, Hct, WBC, ANC, PLT, serum chemistry and ferritin, were not statistically different. Mean MCV was 94.3±9.9 Fl in TA pts and 100.5±15.3 Fl in DC (p<0.001). Bone marrow cellularity was similar in both groups. TA pts had more dysplasia: dyserythropoiesis (TA 79.9%, DC 71.3%, p=0.005); myelodysplasia (63.3% vs 52.9, p=0.003); dysmegakaryopoiesis (53.2% vs 40.2%, p=0.001). However, more TA pts had low blast count (<5%): 73.4% vs 50.6% (p=0.003). Accordingly, more TA pts (65%) were classified as early FAB types (RA/RARS) vs 40% in the DC group. Cyotgenetics was similar in both groups. IPSS was determined in 131 pts, 89 LR (low/Int-1), 42 HR (Int-2/high). TA pts were mostly LR (61 pts vs 28 pts). The cumulative 5 yr-survival (YS, Cox regression after neutralizing confounding effects) was 62% vs 55% (TA, DC, respectively). 5 YS according to FAB was 77% (TA) vs 65% (DC) for RA pts, and 43% (TA) vs 37% (DC) for more advanced FAB groups. Conclusions: Limitations include the retrospective nature, geographic, demographic and temporal differences between both populations, and transfusion-dependence of all TA pts. We find that pts today (TA) tend to be older, with more cardiovascular morbidities, fewer cytopenias and lower MCV. They tend to be classified as early disease (RA/RARS, LR-IPSS), and have slightly longer 5 YS. Hopefully, better biological tools and the novel therapeutic agents that have recently been introduced will result in a better outcome. 312 CLINICO-PATHOLOGIC AND CYTOGENETIC STUDY ON MYELODYSPLASTIC SYNDROMES (MDS) – A CASE SERIES FROM SOUTH INDIA T. Paul1, A. Tandon1, M. Uppin1, S. Uppin1, A. Narendra1, G. Sadashivudu1, V. Sreenivasan1, H. Swetha1, R. Jacob1 1 Pathology, Nizam’s Institute of Medical Sciences, Hyderabad, India Objectives: Myelodysplastic syndromes (MDSs) are a heterogenous group of clonal disorders, characterised by ineffective hematopoiesis and peripheral cytopenias. They have a high risk of progression to acute leukemias. This study was undertaken, as there are not many large series published from the Indian sub-continent. The aim was to study the clinico-pathologic and cytogenetic profile of all cases diagnosed as MDS at a tertiary care centre and look for any existing co-morbidities. Materials and Methods: Cases diagnosed as denovo MDS, following a morphologic study of the blood and bone marrow, were included, the study period being 2005 to 2014. Cases where other causes of anemia were detected, were excluded from the study. The clinical and follow-up data were obtained from the patients files. The morphology of each case was reviewed. Cytogenetic reports were obtained, wherever available. Results: During the study period, 188 cases of MDS were diagnosed, ranging from 21 to 88 years of age with a median age of 57 years. There were 125 males and 63 females with a M:F ratio of 1.98:1. Patients presented with varying ranges of cytopenias, with 28 patients having hemoglobin values < 4.0 gm/dL. The patients were classified as MDS-RA (70 cases), RT-(1), RCMD-(40), RARS-(15), RAEB-1 (28), RAEB-2 (28), MDS-U (3), MDS with isolated del(5q) (3). Of these, 7 tranformed to AML on follow-up. Due to financial constraints, only 91 cases (48%), had access to cytogenetic studies. The cytogenetic profile included- Normal karyotype- (57 cases), Trisomy 8 (9 cases), Monosomy 7 (16 cases), Isolated 5q- (3 cases), multiple- 2, and 3 cases with other abnormalities. There was a one case reported as 46,XX,t(3;12)(q26;p13) with an additional -7,
S155
which transformed to acute leukemia. The revised IPSS scores and categories was calculated for these 91 cases. Of the 188 cases, 28 were known diabetics on treatment and there were 11 cases of hypothyroidism. Conclusion: MDS is a serious problem in India. However, a large number of cases remain unrecognised. The median age at presentation was 57 years which is similar to that observed in other Asian countries.The number of male patients is almost double that of female patients, which could be due to a referral bias. Better and more affordable cytogenetic studies are necessary for a majority of the patients. More studies are required to know if Diabetes and hypothyroidism are co-incidental or actual comorbidities. 313 EVIDENCE FOR AN IMMUNOLOGIC ROLE IN THE PATHOGENESIS OF BENZENE-INDUCED MDS D. Pyatt1, P. Kerzic2 1 School of Public Health, University of Colorado, Denver, USA; 2 OEHHA, State of California, Los Angeles, USA Recent epidemiologic evidence has confirmed MDS as a rare but important consequence of occupational benzene exposures. In fact, MDS development seems to be one of the most sensitive toxicological manifestations of benzene exposures, with recent investigations indicating that it can occur at relatively low levels of exposure. MDS is a very diverse group of diseases, with various subtypes differing in diagnostic criteria, treatment, prognosis and likely etiology. Unfortunately, there is a paucity of relevant data; however, MDS cases identified in patients that have experienced excessive benzene exposures present with several common pathological characteristics but are difficult to classify per the WHO criteria. Recent advances in experimental and clinical hematology have led to the identification of subsets of patients with MDS presenting with clear evidence of immunologic dysregulation. The success of immunosuppressive therapy (IST) in MDS cases provide evidence that immune dysregulation can result in bone marrow dysplasia and MDS development. There is also pathologic evidence that immunologic dysfunction plays a role in the development of MDS subsequent to occupational benzene exposure. Further, benzene-induced MDS cases do not appear to present with a consistent set of clonal cytogenetic abnormalities, indicating a potential non-genotoxic or epigenetic mechanism. Herein, we present existing evidence supporting the hypothesis that immunologic dysregulation may play an important pathogenic role in the development of benzene-induced MDS. We believe this characterization will be useful in gaining a better understanding of benzene toxicology as well as inform regulatory and public health decision-making. 314 REFRACTORY CYTOPENIA OF CHILDHOOD AND ACQUIRED APLASTIC ANEMIA: A CLINICAL AND PATHOLOGICAL STUDY OF 128 CASES X. Qin1, M.Z. Yin2, I. Baumann3, J. Chen1, P. Shen2, J.F. Chen2, H.L. Xue1, S.H. Shen1, J. Chen1, C.Y. Luo1, C.J. Luo1, J.M. Wang1, W.T. Hu1, Y.J. Tang1 1 Department of Hematology and Oncology, Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; 2Department of Pathology, Shanghai Children’s Medical Center affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; 3Department of Pathology, Boeblingen Hospital, Boeblingen, Germany Objective: Explore the clinical characteristics and histopathological morphology features of bone marrow biopsies between refractory