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268 “BENIGN” CLONAL HEMATOPOIESIS IN APLASTIC ANEMIA
S134
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
for one week per month (1 week on and 3 weeks off). Response was assessed by International Working Group criteria. Results: The median age of the patients was 73,5 (55-86). There were 9 male and 5 female patients. 5 patients had RAEB-I, 4 patients had RAEB-II, 4 patients had RCMD and 1 patient had RCUD-RA according to World Health Organization classification. Among patients with MDS, 8 had intermediate-risk and 6 had high-risk disease according to IPSS-R criteria. Six patients received 8 cycles, 3 patients received 6 cycles, 4 patients received 4 cycles and 1 patient received 2 cycles of Azacitidine monotherapy. Complete response was observed in 1 (7 %) patient, complete marrow response was observed in 3 (21 %) patients and partial response was observed in 2 (14 %) patients following Azacitidine monotherapy. On the other hand, stable disease was observed in 4 patients (29%) and disease progression was seen in 4 (%29) patients. 4 patients required hospitalization for febrile neutropenia. 3 patients whose disease progressed despite therapy, died. The remaining patients are still being followed-up. Discussion: Due to its favorable tolerability profile, Azacitidine monotherapy is an important treatment option especially in elderly patients with intermediate to high risk MDS. Overall response to azacitidine monotherapy in the present cohort is consistent with the literature. Treatment and follow-up of patients are ongoing. 267 MONITORING OF CLONE SIZE BY FLUORESCENT IN SITU HYBRIDIZATION IN MYELODYSPLASTIC SYNDROME: IS IT CONSISTENT WITH TREATMENT RESPONSE OF INTERNATIONAL WORKING GROUP? D. Lee1, J.H. Park1, S.Y. Kim1, M.Y. Kim1 1 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea We examined whether fluorescence in situ hybridization (FISH) clone size at initial diagnosis is relevant to survival, and changes of clone size by FISH are concordant with the International Myelodysplastic Syndrome Working Group (IWG) response during follow-up. A tailored FISH panel (-5/5q-, -7/7q-, +8, -20/20q-, and +1/1q+) based on reported cytogenetic changes of Korean MDS was performed in 81 MDS cases at initial diagnosis and 28 cases at follow-up. Higher clonal cell % by G-banding and by FISH at initial diagnosis correlated with shorter AML-free survival (MannWhitney test, p=0.001, p=0.034, respectively). During follow-up, increases of FISH clone size by absolute ≥20% and relative ≥50% compared to previous specimens were related with acute myeloid leukemia (AML) transformation (P=0.001, P=0.002, respectively). Of 28 cases with abnormal FISH results at initial diagnosis, 7 (25.0%) showed discordance between FISH and IWG responses. Concordance between clone size by G-banding and interphase iFISH was higher in RCUD/RCMD group during follow-up, while the RAEB group showed higher correlation at initial diagnosis. We conclude that iFISH can provide additional prognostic information and can predict the response to therapy in MDS. Exploiting the synergism between G-banding and FISH assays would be beneficial. 268 “BENIGN” CLONAL HEMATOPOIESIS IN APLASTIC ANEMIA H. Leuva1, D. Townsley1, B. Dumitriu1, O. Rios1, P. Scheinberg2, N.S. Young1 1 Hematology Branch, National Institutes of Health National Heart Lung and Blood Institute, Bethesda, USA; 2Clinical Hematology, Antônio Ermírio de Moraes Cancer Center Hospital Saõ José and Beneficência Portuguesa, Saõ Paulo, Brazil Aplastic anemia (AA) is caused by immune-mediated destruction of hematopoietic stem cells (HSC). The majority of patients respond
Fig. 1. Survival curve (censored for death/HSCT/lost to follow-up).
to immunosuppressive therapy (IST) and the addition of HSC transplant have increased the survival rate to over 80% at 5 years. Long-term complication of AA is represented by development of myelodysplastic syndrome (MDS) and evolution to acute myeloid leukemia (AML), frequently associated with chromosomal abnormalities. Monosomy 7 and complex cytogenetics are the vast majority of the aneuploidies associated with clonal evolution in AA patients. Little data exists on the prognostic significance of other chromosomal abnormalities reported in AA patients, like del 13q, trisomy 8, and trisomy 6 despite considered nonMDS defining in AA patients in several reports. We reviewed all of the patients enrolled in protocols for either treatment naive or relapse/refractory severe AA at National Institutes of Health between 1990 and 2014. Twenty-four AA patients with initial normal cytogenetics have developed either a deletion of 13q (n=15), trisomy 8 (n=6), or trisomy 6 (n=3) as identified by metaphase karytotyping. Median age at identification of the aneuploidy was 55 years and it occurred after one course of IST in 63% of patients. Clones were transient in 21% (5/24). Leukemia or bone marrow dysplasia with increased myeloblasts were observed in 5 patients (3 del 13q, 1 trisomy 6, 1 trisomy 8). Trisomy 6 was seen transiently in a relapsed SAA patient and persistently in two of refractory SAA patients; one of them died of cytopenias. Time to evolution was more prolonged among the cases of trisomy 8. Trisomy 8 persisted on subsequent BM evaluation and although detected during hematologic response to IST, a history of relapse was frequent (5/6). Bone marrow dysplasia was usually absent (4/6). One patient with trisomy 8 died of cytopenic complications and one required HSCT for refractory cytopenias. Del 13q was found mostly in patients with either history of relapse (6/15) or at the time of relapse (4/15). Five other patients had refractory disease. Transformation to leukemia or increased myeloblasts was observed in 3 cases. Seven patients with del 13q underwent HSCT. Five patients with del 13q died; 2 post transplant, 2 due to cytopenic complications and 1 due to complications of PNH. Median survival of the cohort (n=24) is 5 years. Identification of these cytogenetic changes in AA, although not necessarily diagnostic of MDS/AML, is associated with poor overall survival due to relapsed/refractory disease.
Poster Presentations – 13th International Symposium on Myelodyspastic Syndromes / Leukemia Research 39 S1 (2015) S1–S166
for one week per month (1 week on and 3 weeks off). Response was assessed by International Working Group criteria. Results: The median age of the patients was 73,5 (55-86). There were 9 male and 5 female patients. 5 patients had RAEB-I, 4 patients had RAEB-II, 4 patients had RCMD and 1 patient had RCUD-RA according to World Health Organization classification. Among patients with MDS, 8 had intermediate-risk and 6 had high-risk disease according to IPSS-R criteria. Six patients received 8 cycles, 3 patients received 6 cycles, 4 patients received 4 cycles and 1 patient received 2 cycles of Azacitidine monotherapy. Complete response was observed in 1 (7 %) patient, complete marrow response was observed in 3 (21 %) patients and partial response was observed in 2 (14 %) patients following Azacitidine monotherapy. On the other hand, stable disease was observed in 4 patients (29%) and disease progression was seen in 4 (%29) patients. 4 patients required hospitalization for febrile neutropenia. 3 patients whose disease progressed despite therapy, died. The remaining patients are still being followed-up. Discussion: Due to its favorable tolerability profile, Azacitidine monotherapy is an important treatment option especially in elderly patients with intermediate to high risk MDS. Overall response to azacitidine monotherapy in the present cohort is consistent with the literature. Treatment and follow-up of patients are ongoing. 267 MONITORING OF CLONE SIZE BY FLUORESCENT IN SITU HYBRIDIZATION IN MYELODYSPLASTIC SYNDROME: IS IT CONSISTENT WITH TREATMENT RESPONSE OF INTERNATIONAL WORKING GROUP? D. Lee1, J.H. Park1, S.Y. Kim1, M.Y. Kim1 1 Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea We examined whether fluorescence in situ hybridization (FISH) clone size at initial diagnosis is relevant to survival, and changes of clone size by FISH are concordant with the International Myelodysplastic Syndrome Working Group (IWG) response during follow-up. A tailored FISH panel (-5/5q-, -7/7q-, +8, -20/20q-, and +1/1q+) based on reported cytogenetic changes of Korean MDS was performed in 81 MDS cases at initial diagnosis and 28 cases at follow-up. Higher clonal cell % by G-banding and by FISH at initial diagnosis correlated with shorter AML-free survival (MannWhitney test, p=0.001, p=0.034, respectively). During follow-up, increases of FISH clone size by absolute ≥20% and relative ≥50% compared to previous specimens were related with acute myeloid leukemia (AML) transformation (P=0.001, P=0.002, respectively). Of 28 cases with abnormal FISH results at initial diagnosis, 7 (25.0%) showed discordance between FISH and IWG responses. Concordance between clone size by G-banding and interphase iFISH was higher in RCUD/RCMD group during follow-up, while the RAEB group showed higher correlation at initial diagnosis. We conclude that iFISH can provide additional prognostic information and can predict the response to therapy in MDS. Exploiting the synergism between G-banding and FISH assays would be beneficial. 268 “BENIGN” CLONAL HEMATOPOIESIS IN APLASTIC ANEMIA H. Leuva1, D. Townsley1, B. Dumitriu1, O. Rios1, P. Scheinberg2, N.S. Young1 1 Hematology Branch, National Institutes of Health National Heart Lung and Blood Institute, Bethesda, USA; 2Clinical Hematology, Antônio Ermírio de Moraes Cancer Center Hospital Saõ José and Beneficência Portuguesa, Saõ Paulo, Brazil Aplastic anemia (AA) is caused by immune-mediated destruction of hematopoietic stem cells (HSC). The majority of patients respond
Fig. 1. Survival curve (censored for death/HSCT/lost to follow-up).
to immunosuppressive therapy (IST) and the addition of HSC transplant have increased the survival rate to over 80% at 5 years. Long-term complication of AA is represented by development of myelodysplastic syndrome (MDS) and evolution to acute myeloid leukemia (AML), frequently associated with chromosomal abnormalities. Monosomy 7 and complex cytogenetics are the vast majority of the aneuploidies associated with clonal evolution in AA patients. Little data exists on the prognostic significance of other chromosomal abnormalities reported in AA patients, like del 13q, trisomy 8, and trisomy 6 despite considered nonMDS defining in AA patients in several reports. We reviewed all of the patients enrolled in protocols for either treatment naive or relapse/refractory severe AA at National Institutes of Health between 1990 and 2014. Twenty-four AA patients with initial normal cytogenetics have developed either a deletion of 13q (n=15), trisomy 8 (n=6), or trisomy 6 (n=3) as identified by metaphase karytotyping. Median age at identification of the aneuploidy was 55 years and it occurred after one course of IST in 63% of patients. Clones were transient in 21% (5/24). Leukemia or bone marrow dysplasia with increased myeloblasts were observed in 5 patients (3 del 13q, 1 trisomy 6, 1 trisomy 8). Trisomy 6 was seen transiently in a relapsed SAA patient and persistently in two of refractory SAA patients; one of them died of cytopenias. Time to evolution was more prolonged among the cases of trisomy 8. Trisomy 8 persisted on subsequent BM evaluation and although detected during hematologic response to IST, a history of relapse was frequent (5/6). Bone marrow dysplasia was usually absent (4/6). One patient with trisomy 8 died of cytopenic complications and one required HSCT for refractory cytopenias. Del 13q was found mostly in patients with either history of relapse (6/15) or at the time of relapse (4/15). Five other patients had refractory disease. Transformation to leukemia or increased myeloblasts was observed in 3 cases. Seven patients with del 13q underwent HSCT. Five patients with del 13q died; 2 post transplant, 2 due to cytopenic complications and 1 due to complications of PNH. Median survival of the cohort (n=24) is 5 years. Identification of these cytogenetic changes in AA, although not necessarily diagnostic of MDS/AML, is associated with poor overall survival due to relapsed/refractory disease.