Gemtuzumab

Core binding factor-acute myeloid leukemia (CBF-AML), a subtype that represents almost 25% of de novo AML pediatric cases with a survival rate nearing 85%, has not been extensively described in the setting of AML-post-cytotoxic therapy (pCT).Despite the known favorable prognosis associated with CBF in de novo pediatric AML, AML-pCT portends a poorer prognosis in adult patients, often requiring hematopoietic stem cell transplantation (HSCT).A 10-yr-old African American girl with a history of a right ovarian dysgerminoma was treated with two cycles of cisplatin, etoposide, and bleomycin followed by a right salpingooophorectomy with total resection of the right ovarian mass.This was followed by two further cycles of the previous chemotherapy.Nineteen months following completion of therapy, the patient was found to have 26% blasts on a complete blood count.Flow cytometry anal. of the bone marrow showed 34% blasts with 93% cells pos. for CD33. Polymerase chain reaction (PCR) anal. showed CBFB-MYH11 fusion transcript to ABL1 and fluorescence in situ hybridization confirmed the inversion of chromosome 16 (inv16)(p13.1q22) as well as the presence of CBFB rearrangement in nearly 54% of analyzed cells.GO, a monoclonal antibody-drug conjugate directed against CD33 expressed on AML cells, has shown a 20% survival benefit in adults with de novo CBF-AML.In adult patients with AML, including AML-pCT, the addition of GO to 7+3 led to significantly better rates of complete remission compared with those receiving 7+3 only (82 vs. 55%, p = 0.019, resp.).Currently, there are no data that demonstrate the role of allogeneic HSCT to induce long term remission in pediatric patients with CBF-AML-pCT.We demonstrate that the aggressive treatment of CBF-AML-pCT with a regimen consisting of GO followed by HSCT may represent an effective method to inducing a deep and durable remission.Due to a promising prognosis, de novo CBF in children and adolescents with AML is largely treated with chemotherapy only and AML-pCT is generally treated with chemotherapy followed by HSCT due to a poor prognosis.

Paediatric acute myeloid leukemia (AML) is a heterogeneous hematological malignancy still heavily reliant on traditional chemotherapeutic approaches. Combination treatments have shown to be a superior approach, but their success is often hindered by side effects and different drugs' pharmacokinetics. Here, we investigated ABT-737 and Purvalanol A as a potential drug pairing for pediatric AML and described the development of CD33-targeted polymeric nanoparticles (NPs) to enable their simultaneous targeted codelivery. Separate drug encapsulation within poly(lactic-co-glycolic acid) (PLGA) NPs was optimized prior to coencapsulation of both drugs at a synergistic ratio in PEGylated PLGA NPs. The therapeutic effects of formulations were evaluated in a panel of pediatric AML cells, and dual drug-loaded NPs (dual NPs) demonstrated significantly enhanced apoptotic cell death. Moreover, conjugation to gemtuzumab resulted in improved NP binding and internalization in CD33-positive cells. Finally, CD33-targeted dual-loaded NPs showed enhanced cytotoxicity to CD33-positive AML cells via CD33-mediated targeted drug delivery.