Contributions
Abstract: PB2294
Type: Publication Only
Background
Myelodysplastic /myeloproliferative neoplasms, such as chronic myelomonocytic leukemia (CMML), and Philadelphia-chromosome negative chronic myeloproliferative neoplasms (MPNs) transformed to acute myeloid leukemia (AML) are associated with a poor response to available therapeutic options and a very dismal outcome, being only a minority of patients suitable for intensive chemotherapy and allogenic stem cell transplantation. Although a beneficial clinical activity by hypomethylating compounds have been suggested by some clinical studies, the role of these agents in this difficult setting has not been clearly established.
Aims
To report the outcome of 4 patients with AML transformation from essential thrombocytemia (1), polycythemia Vera (1) and JAK-2 positive CMML with bone marrow (BM) fibrosis, who were started on decitabine (25 mg/m2, 5 days every 4 weeks) at our institution between January 2015 and February 2018.
Methods
Clinical parameters, treatment and follow-up data were retrospectively collected and analyzed. There were 4 (3 male) patients with a median age of 71 (67-75). All patients were transfusion-dependent at the start of hypomethylating therapy. Abnormal karyotype (-7) were detected in one patients whereas the remaining three showed no cytogenetic abnormalities. Previous therapies included phlebotomy (1), hydroxyurea (3) and pipobroman (1); 1 patient was treatment-naïve. The time interval from the MPNs and CMML diagnoses to AML transformation was of 10 (2-27) years.The median number of decitabine courses was 14 (11-24). Other than expected therapy related cytopenias, which were well manageable with conventional measures, treatment was well-tolerated and no remarkable side effects were recorded. Broad spectrum antibacterial and anti-fungal agents were given according to the duration and the degree of neutropenia.
Results
Responses were assessed according to 2006 IWG criteria after almost 4 courses of decitabine, Out of the 4 patients, 2 (50%) achieved complete remission (CR) and 2 (50%) a partial remissions (PR); in one of latter PR patients, the disappearance of extramedullary (nodal and lung) AML involvements was observed by six cycles of epigenetic courses. After a median follow-up of 12 (11-28) months, 2 patients, both having obtained CR and including that presenting the -7 abnormal karyotype, are still alive: overall survivals from the start of decitabine were of 11,+15,18 and + 28 respectively. Two patients progressed from the achieved PR and deceased because of clinical complications of overt AML.
Conclusion
Despite the limited number of cases, our experience reflected a real-life treatment scenario with encouraging results, given that all patients responded to decitabine which was tolerable and efficacious in elderly, comorbid and pretreated AML patients with an unfavorable prognostic profile long disease history of chronic MPNs and CMML with BM fibrosis. The efficacy of decitabine in this difficult to treat setting, although not durable in our patients who have achieved a PR, may represent an useful clinical basis for potential applications of this agent with other clinically active synergistic compounds, such as JAK2 inhibitors, are needed to improve overall outcome into future clinical trials which should include molecular profiling tools for an accurate selection of suitable patients.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Acute Myeloid Leukemia, Decitabine, Myeloproliferative disorder
Abstract: PB2294
Type: Publication Only
Background
Myelodysplastic /myeloproliferative neoplasms, such as chronic myelomonocytic leukemia (CMML), and Philadelphia-chromosome negative chronic myeloproliferative neoplasms (MPNs) transformed to acute myeloid leukemia (AML) are associated with a poor response to available therapeutic options and a very dismal outcome, being only a minority of patients suitable for intensive chemotherapy and allogenic stem cell transplantation. Although a beneficial clinical activity by hypomethylating compounds have been suggested by some clinical studies, the role of these agents in this difficult setting has not been clearly established.
Aims
To report the outcome of 4 patients with AML transformation from essential thrombocytemia (1), polycythemia Vera (1) and JAK-2 positive CMML with bone marrow (BM) fibrosis, who were started on decitabine (25 mg/m2, 5 days every 4 weeks) at our institution between January 2015 and February 2018.
Methods
Clinical parameters, treatment and follow-up data were retrospectively collected and analyzed. There were 4 (3 male) patients with a median age of 71 (67-75). All patients were transfusion-dependent at the start of hypomethylating therapy. Abnormal karyotype (-7) were detected in one patients whereas the remaining three showed no cytogenetic abnormalities. Previous therapies included phlebotomy (1), hydroxyurea (3) and pipobroman (1); 1 patient was treatment-naïve. The time interval from the MPNs and CMML diagnoses to AML transformation was of 10 (2-27) years.The median number of decitabine courses was 14 (11-24). Other than expected therapy related cytopenias, which were well manageable with conventional measures, treatment was well-tolerated and no remarkable side effects were recorded. Broad spectrum antibacterial and anti-fungal agents were given according to the duration and the degree of neutropenia.
Results
Responses were assessed according to 2006 IWG criteria after almost 4 courses of decitabine, Out of the 4 patients, 2 (50%) achieved complete remission (CR) and 2 (50%) a partial remissions (PR); in one of latter PR patients, the disappearance of extramedullary (nodal and lung) AML involvements was observed by six cycles of epigenetic courses. After a median follow-up of 12 (11-28) months, 2 patients, both having obtained CR and including that presenting the -7 abnormal karyotype, are still alive: overall survivals from the start of decitabine were of 11,+15,18 and + 28 respectively. Two patients progressed from the achieved PR and deceased because of clinical complications of overt AML.
Conclusion
Despite the limited number of cases, our experience reflected a real-life treatment scenario with encouraging results, given that all patients responded to decitabine which was tolerable and efficacious in elderly, comorbid and pretreated AML patients with an unfavorable prognostic profile long disease history of chronic MPNs and CMML with BM fibrosis. The efficacy of decitabine in this difficult to treat setting, although not durable in our patients who have achieved a PR, may represent an useful clinical basis for potential applications of this agent with other clinically active synergistic compounds, such as JAK2 inhibitors, are needed to improve overall outcome into future clinical trials which should include molecular profiling tools for an accurate selection of suitable patients.
Session topic: 16. Myeloproliferative neoplasms - Clinical
Keyword(s): Acute Myeloid Leukemia, Decitabine, Myeloproliferative disorder