Davide Lazzarotto1, Anna Candoni2, Carla Filì2, Fabio Forghieri3, Livio Pagano4, Alessandro Busca5, Giuseppina Spinosa6, Maria Elena Zannier2, Erica Simeone2, Miriam Isola7, Erika Borlenghi8, Lorella Melillo9, Federico Mosna10, Federica Lessi11, Renato Fanin2. 1. Division of Hematology and Bone Marrow Transplantation, Azienda Sanitaria-Universitaria Integrata, University of Udine, Italy. Electronic address: davidelazzar8@gmail.com. 2. Division of Hematology and Bone Marrow Transplantation, Azienda Sanitaria-Universitaria Integrata, University of Udine, Italy. 3. Section of Hematology, Department of Surgical and Medical Sciences, University of Modena and Reggio Emilia, Italy. 4. Department of Hematology, Università Cattolica Sacro Cuore, Rome, Italy. 5. Division of Hematology, Ospedale S. Giovanni Battista, Torino, Italy. 6. Division of Hematology, Azienda Ospedaliera Universitaria Ospedali Riuniti di Foggia, Italy. 7. Department of Medical and Biological Sciences, Section of Statistics, University of Udine, Italy. 8. Division of Hematology, Azienda Ospedaliera Spedali Civili di Brescia, Italy. 9. Division of Hematology, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Italy. 10. Division of Hematology, Department of Specialty Medicine, Ospedale Ca' Foncello, Treviso, Italy. 11. Padua University School of Medicine, Department of Medicine, Hematology and Clinical Immunology, Italy.
Abstract
INTRODUCTION: Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease. PATIENTS AND RESULTS: we report the clinical characteristics and outcome of 48 histologically confirmed MS, diagnosed and treated in 9 Italian Hematological Centers in the last 10 years. The patient's median age was 46 years. There were 9/48 de novo extramedullary MS, 24/48 de novo AML-related MS and 15/48 were secondary AML-related MS. The most common extramedullary anatomic sites of disease were: skin, lymph nodes and soft tissues. Forty-three patients (90%) underwent a program of intensive chemotherapy including FLAI, HDAC-IDA, HyperCVAD and MEC schemes, with a DDI of 5% and a CR Rate of 45%. Twenty-two (46%) patients underwent Allogeneic SCT, 13 from a MUD, 8 from an HLA-identical sibling donor and 1 from an haploidentical donor. The median OS of the whole population (48 pts) was 16.7 months. The OS probability at 1, 2 and 5 years was 64%, 39% and 33%, respectively. The OS was better in patients that underwent an intensive therapeutic program (median OS: 18 months vs 5 months). Among the intensively treated patients, in univariate analysis, the OS was better in young patients (P=0,008), in patients that underwent Allo-SCT (P=0,009) and in patients that achieved a CR during treatment (P=0,001), and was worse in pts with secondary AML-related MS (P=0,007). Age, response to intensive chemotherapy and Allo-SCT were the only three variables that significantly influenced DFS (P=0,02, P=0,01 and P=0,04, respectively). In multivariable analysis, Allo-SCT and response to intensive chemotherapy remained significant in predicting a better OS (P=0,04 and P=0,001, respectively), and response to intensive chemotherapy was the only significant variable in predicting DFS (P=0,01). After Allo-SCT we observe a survival advantage in patients who achieved a pre-transplant CR (P=0,008) and in those who developed a chronic GvHD (P=0,05). CONCLUSIONS: Patients with MS, both with de novo and secondary forms, still have a very unfavorable outcome and require an intensive therapeutic program, that includes Allo-SCT whenever possible. The outcome after Allo-SCT is positively influenced by the development of chronic GvHD suggesting a Graft versus MS effect.
INTRODUCTION:Myeloid Sarcoma (MS) is a rare hematologic myeloid neoplasm that can involve any site of the body. It can occur as an exclusively extramedullary form or it can be associated with an acute myeloid leukemia (AML), a chronic myeloproliferative neoplasm (MPN) or a myelodysplastic syndrome (MDS) at onset or at relapse. The rarity of MS does not enable prospective clinical trials and therefore a specific multicenter register can be useful for the clinical and biological studies of this rare disease. PATIENTS AND RESULTS: we report the clinical characteristics and outcome of 48 histologically confirmed MS, diagnosed and treated in 9 Italian Hematological Centers in the last 10 years. The patient's median age was 46 years. There were 9/48 de novo extramedullary MS, 24/48 de novo AML-related MS and 15/48 were secondary AML-related MS. The most common extramedullary anatomic sites of disease were: skin, lymph nodes and soft tissues. Forty-three patients (90%) underwent a program of intensive chemotherapy including FLAI, HDAC-IDA, HyperCVAD and MEC schemes, with a DDI of 5% and a CR Rate of 45%. Twenty-two (46%) patients underwent Allogeneic SCT, 13 from a MUD, 8 from an HLA-identical sibling donor and 1 from an haploidentical donor. The median OS of the whole population (48 pts) was 16.7 months. The OS probability at 1, 2 and 5 years was 64%, 39% and 33%, respectively. The OS was better in patients that underwent an intensive therapeutic program (median OS: 18 months vs 5 months). Among the intensively treated patients, in univariate analysis, the OS was better in young patients (P=0,008), in patients that underwent Allo-SCT (P=0,009) and in patients that achieved a CR during treatment (P=0,001), and was worse in pts with secondary AML-related MS (P=0,007). Age, response to intensive chemotherapy and Allo-SCT were the only three variables that significantly influenced DFS (P=0,02, P=0,01 and P=0,04, respectively). In multivariable analysis, Allo-SCT and response to intensive chemotherapy remained significant in predicting a better OS (P=0,04 and P=0,001, respectively), and response to intensive chemotherapy was the only significant variable in predicting DFS (P=0,01). After Allo-SCT we observe a survival advantage in patients who achieved a pre-transplant CR (P=0,008) and in those who developed a chronic GvHD (P=0,05). CONCLUSIONS:Patients with MS, both with de novo and secondary forms, still have a very unfavorable outcome and require an intensive therapeutic program, that includes Allo-SCT whenever possible. The outcome after Allo-SCT is positively influenced by the development of chronic GvHD suggesting a Graft versus MS effect.