Contributions
Abstract: EP1248
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Patients with acute myeloid leukemia and 11p15/NUP98 gene rearrangement (NUP98-r AML) treated with chemotherapy alone generally show poor overall survival (OS) and prognosis, with less than 50% OS and leukemia-free survival; some reports with median OS of less than 1 year. In cases of NUP98-r AML with co-existing FLT3 mutation, treatment with chemotherapy alone has demonstrated poor prognosis, with only 28% of 3-year OS.
Aims
To study clinical outcome of patients with NUP98-r AML after allogeneic hematopoietic stem cell transplantation (HSCT).
Methods
We conducted retrospective assessment and outcome analysis in a cohort of 34 patients with NUP98-r AML treated with allogeneic HSCT at the Hebei Yanda Lu Daopei Hospital (from July 1, 2019 to February 1, 2021). Six types of NUP98 fusion gene partners were identified by PCR/FISH as follows: NSD1 (n=23), HOXA9 (n=5), KDM5A (n=4), HOXD13 (n=1), and LNP1 (n=1); 18 cases were identified with FT3 mutation. Median age was 16 years old (range from 1 to 61 years). Majority of patients underwent haplo-identical HSCT (n=31), while the rest received matched sibling donor HSCT (n=3). The conditioning regimens were based on Bu/Cy (n=31) and TBI/Cy (n=3). Patients received antithymocyte globulin, cyclosporine, mycophenolate mofetil, or methotrexate for graft-versus-host disease (GVHD) prophylaxis. Dosage of infused mononuclear cells and CD34+ cells were 10.5±3.2x108 /Kg and 5.5±2.3 x106 /Kg, respectively.
Results
In this study, the median follow-up time was 9 months (3-30). All 34 patients in this cohort achieved myeloid engraftment with median time for ANC above 0.5x109 /L on Day 14 (10-23). The median time for platelet count to exceed 20x109 /L was Day 13 (7-58) in 32 patients, with 2 patients remained thrombocytopenic. The incidence of acute GVHD (n=9) and chronic GVHD (n=7) was 26% and 20.5%, respectively. The average survival rate was 24±2 months (95% CI=19-27 months). Two-year OS and LFS were 75.9+7.5% and 75.6± 7.6%, respectively. In this cohort of NUP98-r AML patients, the subgroup with co-existing FLT3 mutation (n=18) has demonstrated an OS of 71.3 ± 10.9%, as compared to 81.3±9.8% in the subgroup without FLT3-mutation (n=16). Our data showed better survival of FLT3-positive patients in NUP98-rAML after allogeneic HSCT as compared to anecdotal survival data with chemotherapy alone. The OS of the subgroup without minimal residual disease (MRD negative, n=13) was 84.6±10.0%, versus 70.3±10.3% in the group with positive MRD (n=21). In this cohort of NUP98-r AML patients, the mortality rate within 100 days after HSCT was 11.7% (n=4). The causes of death (total of 8 patients) include relapse of disease (n=4), Grade IV GVHD (n=3), thrombotic microangiopathy (n=1) and subdural hemorrhage (n=1). Among the 5 patients developed relapse of disease, one with molecular relapse and responded well after chemotherapy and second allogeneic HSCT, while the other 4 relapsed patients expired.
Conclusion
This study has demonstrated encouraging clinical outcomes for NUP98-r AML patients after treatment with allogeneic HSCT, as compared to anecdotal data with chemotherapy alone in the literature, particularly in the clinical setting of coexisting FLT3 mutation. Larger clinical study is required to confirm this result.
Keyword(s): 11q23, AML, HSCT, NUP98
Abstract: EP1248
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Patients with acute myeloid leukemia and 11p15/NUP98 gene rearrangement (NUP98-r AML) treated with chemotherapy alone generally show poor overall survival (OS) and prognosis, with less than 50% OS and leukemia-free survival; some reports with median OS of less than 1 year. In cases of NUP98-r AML with co-existing FLT3 mutation, treatment with chemotherapy alone has demonstrated poor prognosis, with only 28% of 3-year OS.
Aims
To study clinical outcome of patients with NUP98-r AML after allogeneic hematopoietic stem cell transplantation (HSCT).
Methods
We conducted retrospective assessment and outcome analysis in a cohort of 34 patients with NUP98-r AML treated with allogeneic HSCT at the Hebei Yanda Lu Daopei Hospital (from July 1, 2019 to February 1, 2021). Six types of NUP98 fusion gene partners were identified by PCR/FISH as follows: NSD1 (n=23), HOXA9 (n=5), KDM5A (n=4), HOXD13 (n=1), and LNP1 (n=1); 18 cases were identified with FT3 mutation. Median age was 16 years old (range from 1 to 61 years). Majority of patients underwent haplo-identical HSCT (n=31), while the rest received matched sibling donor HSCT (n=3). The conditioning regimens were based on Bu/Cy (n=31) and TBI/Cy (n=3). Patients received antithymocyte globulin, cyclosporine, mycophenolate mofetil, or methotrexate for graft-versus-host disease (GVHD) prophylaxis. Dosage of infused mononuclear cells and CD34+ cells were 10.5±3.2x108 /Kg and 5.5±2.3 x106 /Kg, respectively.
Results
In this study, the median follow-up time was 9 months (3-30). All 34 patients in this cohort achieved myeloid engraftment with median time for ANC above 0.5x109 /L on Day 14 (10-23). The median time for platelet count to exceed 20x109 /L was Day 13 (7-58) in 32 patients, with 2 patients remained thrombocytopenic. The incidence of acute GVHD (n=9) and chronic GVHD (n=7) was 26% and 20.5%, respectively. The average survival rate was 24±2 months (95% CI=19-27 months). Two-year OS and LFS were 75.9+7.5% and 75.6± 7.6%, respectively. In this cohort of NUP98-r AML patients, the subgroup with co-existing FLT3 mutation (n=18) has demonstrated an OS of 71.3 ± 10.9%, as compared to 81.3±9.8% in the subgroup without FLT3-mutation (n=16). Our data showed better survival of FLT3-positive patients in NUP98-rAML after allogeneic HSCT as compared to anecdotal survival data with chemotherapy alone. The OS of the subgroup without minimal residual disease (MRD negative, n=13) was 84.6±10.0%, versus 70.3±10.3% in the group with positive MRD (n=21). In this cohort of NUP98-r AML patients, the mortality rate within 100 days after HSCT was 11.7% (n=4). The causes of death (total of 8 patients) include relapse of disease (n=4), Grade IV GVHD (n=3), thrombotic microangiopathy (n=1) and subdural hemorrhage (n=1). Among the 5 patients developed relapse of disease, one with molecular relapse and responded well after chemotherapy and second allogeneic HSCT, while the other 4 relapsed patients expired.
Conclusion
This study has demonstrated encouraging clinical outcomes for NUP98-r AML patients after treatment with allogeneic HSCT, as compared to anecdotal data with chemotherapy alone in the literature, particularly in the clinical setting of coexisting FLT3 mutation. Larger clinical study is required to confirm this result.
Keyword(s): 11q23, AML, HSCT, NUP98