Optimizing Autologous Hematopoietic Stem Cell Transplantation for Acute Leukemia

Pang, Aiming; Huo, Yingying; Shen, Biao; Zheng, Yawei; Jiang, Erlie; Feng, Sizhou; Han, Mingzhe

doi:10.1002/sctm.21-0176

Cited by 7 publications

(3 citation statements)

References 61 publications

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“…To address the risk of graft contamination with acute leukemia cells when using autologous peripheral blood stem cells (PBSC) for transplantation [ 51 ], we investigated the efficiency of Val-ILs in eradicating leukemia cells. This is particularly crucial for securing transplantation, and CD34 + tissue purging can be an effective method for eliminating malignant cells from the graft [ 51 ]. B-ALL cells from PDX #1 and #2 were transduced with a lentivirus to express a green fluorescent protein (GFP).…”

Section: Resultsmentioning

confidence: 99%

Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers

Georgievski,

Bellaye,

Tournier

et al. 2024

Cell Death Dis

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We created valrubicin-loaded immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analog of daunorubicin. Being lipophilic, valrubicin readily incorporated Val-lLs that were loaded with specific antibodies. Val-ILs injected intravenously rapidly reached the bone marrow and spleen, indicating their potential to effectively target cancer cells in these areas. Following the transplantation of human pediatric B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), or acute myeloid leukemia (AML) in immunodeficient NSG mice, we generated patient-derived xenograft (PDX) models, which were treated with Val-ILs loaded with antibodies to target CD19, CD7 or CD33. Only a small amount of valrubicin incorporated into Val-ILs was needed to induce leukemia cell death in vivo, suggesting that this approach could be used to efficiently treat acute leukemia cells. We also demonstrated that Val-ILs could reduce the risk of contamination of CD34+ hematopoietic stem cells by acute leukemia cells during autologous peripheral blood stem cell transplantation, which is a significant advantage for clinical applications. Using EL4 lymphoma cells on immunocompetent C57BL/6 mice, we also highlighted the potential of Val-ILs to target immunosuppressive cell populations in the spleen, which could be valuable in impairing cancer cell expansion, particularly in lymphoma cases. The most efficient Val-ILs were found to be those loaded with CD11b or CD223 antibodies, which, respectively, target the myeloid-derived suppressor cells (MDSC) or the lymphocyte-activation gene 3 (LAG-3 or CD223) on T4 lymphocytes. This study provides a promising preclinical demonstration of the effectiveness and ease of preparation of Val-ILs as a novel nanoparticle technology. In the context of hematological cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.

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Section: Resultsmentioning

confidence: 99%

Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers

Georgievski,

Bellaye,

Tournier

et al. 2024

Cell Death Dis

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“…Advances in testing techniques and treatments have led to using measurable residual disease (MRD) as a prognostic indicator for leukemia. As a result, the positioning of autologous SCT for acute leukemia has changed [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Autologous peripheral blood stem cell transplantation for Philadelphia chromosome‐positive acute lymphoblastic leukemia is safe but poses challenges for long‐term maintenance of molecular remission: Results of the Auto‐Ph17 study

Nishiwaki

Sugiura

Sato

et al. 2023

eJHaem

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Autologous hematopoietic stem cell transplantation (SCT) is not a standard treatment option for Philadelphia chromosome‐positive acute lymphoblastic leukemia (Ph+ALL); however, its position has been reassessed since the introduction of tyrosine kinase inhibitors (TKIs). We prospectively analyzed the efficacy and safety of autologous peripheral blood SCT (auto‐PBSCT) for Ph+ALL patients aged between 55 and 70 years who had achieved complete molecular remission. Melphalan, cyclophosphamide, etoposide, and dexamethasone were used for conditioning. A total of 12 courses of maintenance therapy, including dasatinib, were performed. The required number of CD34+ cells was harvested in all five patients. No patient died within 100 days after auto‐PBSCT, and no unexpected serious adverse events were observed. Although 1‐year event‐free survival was 100%, hematological relapse was observed in three patients at a median of 801 days (range, 389–1088 days) after auto‐PBSCT. Molecular progressive disease was observed in the other two patients, although they maintained their first hematological remission at the last visit. Auto‐PBSCT can be safely performed for Ph+ALL with TKIs. A limitation of auto‐PBSCT was suggested, despite the increase in the intensity of a single treatment. The development of long‐term therapeutic strategies by including new molecular targeted drugs is warranted to maintain long‐term molecular remission.

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“…However, the lack of HLA matched sibling donor and high nonrelapse mortality (NRM) limit its application. Autologous hematopoietic stem cell transplantation (auto-HSCT) may offer lower transplantationrelated mortality (TRM) compared with allogeneic HSCT and lower relapse rate comparing to chemotherapy [5][6][7][8][9]. Therefore, auto-HSCT is a promising treatment for patients with favorable-risk AML as it may improve survival with relatively low TRM.…”

Section: Introductionmentioning

confidence: 99%

Outcome of autologous stem cell transplantation in patients with favorable-risk acute myeloid leukemia in first remission

Chen

Liu

et al. 2022

Cancer Cell Int

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Objective To evaluate the efficacy of autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with favorable-risk acute myeloid leukemia in first remission. Method Twenty patients who received auto-HSCT at our center between January 2014 and January 2021 were retrospectively reviewed. Results Until last follow-up, three patients in the cohort were dead due to relapse. The estimated 1-year and 5-year overall survival were 95.00% ± 4.87% and 83.82% ± 8.58%, respectively. The estimated 5-year RFS and CIR (cumulative incidence of relapse) were 85.00% ± 7.98% and 15.00% ±7.98%, respectively. Conclusion The outcome of auto-HSCT in patients with favorable-risk acute myeloid leukemia in first remission was excellent and auto-HSCT could be an effective treatment for these patients.

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Optimizing Autologous Hematopoietic Stem Cell Transplantation for Acute Leukemia

Cited by 7 publications

References 61 publications

Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers

Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers

Autologous peripheral blood stem cell transplantation for Philadelphia chromosome‐positive acute lymphoblastic leukemia is safe but poses challenges for long‐term maintenance of molecular remission: Results of the Auto‐Ph17 study

Outcome of autologous stem cell transplantation in patients with favorable-risk acute myeloid leukemia in first remission

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