Single-center experience with mitoxantrone hydrochloride liposome-based therapy for patients with myeloid sarcoma Free

Myeloid sarcoma (MS) accounts for 3% to 8% of acute myeloid leukemia (AML) cases and is characterized by an extramedullary tumor mass composed of myeloid blasts, with or without bone marrow involvement. The heterogeneity of MS clinical manifestations results in the determination that the optimal therapeutic approach for MS remains uncertain. Previous studies have indicated that intensified chemotherapy is associated with a better prognosis compared to low-dose chemotherapy or local therapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been regarded as a potential curative strategy for MS. Mitoxantrone hydrochloride liposome (Lipo-MIT) is considered to have strong penetrability to extramedullary sites. Therefore, we report the characteristics and outcomes of MS patients who were treated with a Lipo-MIT-based strategy at a single center.

We retrospectively analyzed six patients with MS who were treated with Lipo-MIT at the Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, from June 2022 to January 2024, excluding 1 patient due to insufficient clinical data. The diagnosis of myeloid sarcoma was made according to the 2022 World Health Organization (WHO) criteria, and all six patients were confirmed to have MS by histopathological biopsy. Lipo-MIT was administered on day 1 at a median dose of 23.9 mg/m^2 (range 19.6-31.1), in combination with other chemotherapy drugs in a 28-day cycle for up to two cycles. Data regarding age, sex, involved sites, disease type, treatment, outcomes, and follow-up of the six patients were collected. The response criteria for MS were evaluated through bone marrow (BM) analysis, physical examination, and radiological investigations.

Results The median age of the six patients was 44 years (range 16-58), with 50% being male. Among them, three patients had de novo isolated MS without BM involvement, one patient had de novo leukemic MS occurring synchronously with AML, and two patients experienced relapses from previously diagnosed AML or isolated MS. The most common sites for MS in our study were the lymph nodes, observed in three patients, followed by soft tissue in two patients, and breast and spinal canal involvement in one patient each. Five patients had more than one site involved.

The median duration from initial diagnosis of MS to Lipo-MIT-based induction treatment was 4.1 months (range 0.1-22.4).

• For the three patients with de novo isolated MS, the induction treatment consisted of Lipo-MIT and cytarabine (MA). After the first induction, all three patients showed significant reductions in tumor burden without evidence of new lesions. At the end of the induction treatment, one patient achieved complete remission (CR), while two patients achieved partial remission (PR). Two of these patients subsequently received allo-HSCT and remain alive without evidence of AML. Another patient experienced a recurrence after consolidation treatment and died due to complications following CAR-T and allo-HSCT therapy.

• Two patients with relapsed MS (with or without BM involvement) were treated with Lipo-MIT, cytarabine, and etoposide (MAE) ± PD-1. Both of them failed toachieve remission; one showed significant reduction in MS mass after the first cycle but developed new lesions at the second cycle, and finally died due to AML progression, while the other failed to reduce BM blasts to less than 5%.

• One patient with leukemic MS, secondary to chronic myeloid leukemia (CML), exhibited both myeloid and lymphoid characteristics. After one cycle of treatment with the VMCP (vindesine, Lipo-MIT, cyclophosphamide and dexamethasone) regimen, both BM and extramedullary sites were assessed as CR, with negative minimal residual disease (MRD) detected by flow cytometry. This patient subsequently received allo-HSCT but died from severe pneumonia seven months later.

The most frequently reported adverse events included hematological toxicity, pulmonary infections, and fever. All adverse events were manageable and improved through supportive treatment.

Our results indicated the initial efficacy of Lipo-MIT for de novo MS, demonstrated by its ability to reduce or eliminate tumor burden within two cycles. Sequential allo-HSCT following remission could extend survival duration. Further large-sample analyses are anticipated to comprehensively elucidate the efficacy and safety of the Lipo-MIT-based regimen.