Myeloid Sarcoma or Extramedullary Acute Myeloid Leukemia: Experience in Managing Single-Centre Patients Cohort
Authors: Shatilova Aleksina , Budaeva Irina , Matvienko Yuliya , Mirolyubova Yuliya , Ryzhkova Darya , Grozov Roman , Bogdanov Konstantin , Lomaia Elza , Kulemina Olga , Badaev Renat , Shnalieva Nadezhda , Alexeeva Yulia , Ivanov Vladimir , Girshova Larisa 
Published: December 2024

Introduction. Myeloid sarcoma (MS) and extramedullary acute myeloid leukemia (eAML) are characterized by infiltration of leukemic cells occurring the extramedullary anatomical sites and can accompany AML or detect as isolated lesion. Due to the rarity of MS/eAML, some relevant issues continue to be discussed and remain unclear, including the role of new target agents and allogeneic stem cell transplantation (allo-SCT) in management of that patients and the best treatment strategy in case of isolated or relapsed disease.

Methods. We retrospectively analyzed the cohort of 39 patients with MS/eAML (24 were males and 15 were females) with median age of 40 years (13-84) who were treated in our institution from 2009 to 2024. Isolated MS were observed in 18% (7/39). Most patients (89,7%, 35/39) had MS/eAML at the onset of the disease. All patients received the AML-type induction chemotherapy (“7+3”, “HiDAC”, “FLAG+/-Ida” or low-intensity regimens). Gemtuzumab ozogamicin (GO) was administrated to 11 patients with relapsed or refractory disease, 13 patients received venetoclax-containing regiments (15,4% as first-line therapy) and 1 patient with persistent of extramedullary disease received gilteritinib. Allo-SCT was performed in 22 patients (56,4%).

Results. The most common affected sites were soft tissue (18.3%) and bones (12.7%), and 41% of patients (16/39) had multiorgan involvement. The prevalent genetic alterations in patients with MS/eAML were t(8;21)(q22;q22) (11,1%) or inv(16)(p13.1q22) (8,3%) and mutations in DNMT3A (R882) (30,8%), NPM1 (14,7%) and FLT3 (ITD) (8,8%). Patients with available cytogenetic and molecular data were stratified according to ELN-2022 into favorable (31,4%, 11/35), intermediate (34,3%, 12/35) and adverse (34.3%, 12/35) categories. Complete bone marrow response depended on ELN-2022 and was higher in favorable group (88.9% vs 45.5%, P=0.027), but extramedullary response (EMR) didn't (50% vs 78.3%, P&gt;0.05). Radiation therapy didn't influence on outcomes (P&gt;0.05).

Using consolidation with high-intensity regimens associated with decrease the early (during the first 12 months) relapse rate (26.7% vs 88.9%, P=0.014) and better overall survival (OS) (median wasn't reached vs. 6 months, P&lt;0.001). In patients with primary refractory disease or with persistent extramedullary lesion high-intensity treatment helped to achieve complete remission (CR) (92.3% vs. 33.3%, P=0.007) and complete EMR (85.2% vs. 0%, P=0.004). The overall response rate after GO adding or venetoclax administration was 63.6% (7/11) and 61.5% (8/13) respectively, including 4 and 3 patients in each group who achieve PET-negative EMR only after using the target agent. One patient with persistent extramedullary lesion after «7+3+midostaurin» reached CR after initiation of gilteritinib.

Patients with MS/eAML who underwent allo-SCT in their first CR experienced better relapse-free survival than patients who didn't undergo allo-SCT (47 months vs. 8 months, P=0.029). Furthermore, performing allo-SCT in first CR was associated with better median OS (not reached vs. 14.6 months, P=0.043) and relapse-free survival (not reached vs. 4.7 months, P=0.002) as well as with lower risk of early relapse (10% vs 86%, P=0.002) compared with allo-SCT in second CR or later.

Conclusions. According to our experience, the genetic profile of leukemic cells in bone marrow doesn't associate with response in extramedullary lesions, so further researches are needed to clarify the prognostic stratification according to genetic features of extramedullary mass. AML-type protocols remain the gold-standard for treatment MS/eAML and using regimens with high-dose cytarabine is essential for better results. Target agents such as GO, venetoclax and gilteritinib are perspective options and can effective eradicate the residual extramedullary mass after chemotherapy failure. Patients with MS/eAML have benefits in survival when allo-SCT is performed in their first CR.