HLA-Mismatched Stem-Cell Microtransplantation As Postremission Therapy for Acute Myeloid Leukemia: Long-Term Follow-Up

Abstract

Microtransplantation as a postremission therapy may improve outcomes and avoid GVHD in patients with AML-CR1.

Cooperation of CD4+ T cells and CD8+ T cells and release of IFN-γ are critical for antileukemia responses of recipient mice treated by microtransplantation

“…Microtransplantation was reported to have antileukemic effects and promoted hematopoietic recovery. For AML patients aged <65, the 6-year OS rate for low-and medium-risk patients reached 89.5 and 65.2%, respectively, when microtransplantation was added to chemotherapy (9). These results indicated that microtransplantation utilized as a postremission therapy may improve outcomes and prevent GVHD in patients with AML at any age.…”

“…Therefore, it was inferred that IL-2 may strengthen this effect by increasing the number and function of CD4 + and CD8 + T cells. In 2011 and 2012, Guo et al (7,9) reported the largest clinical trial with high efficacy of HLA haploidentical peripheral blood stem cell infusions in combination with chemotherapy for patients with AML and myelodysplastic syndrome. The failure to observe T-cell engraftment makes it unlikely that the increased responses observed in the above study were associated with a 'classical' GVL response.…”

Treatment of acute mixed-cell leukemia with autologous hematopoietic SCT followed by allogeneic hematopoietic stem cell micro-transplantation

“…5 Its effectiveness has been further demonstrated in young patients with AML. 7 However, its effects in patients with ALL or AMAL have not previously been reported. We supposed that G-CSF-mobilized donor PMNCs may be beneficial in this patient with AMAL, as confirmed by the prolonged disease-free survival (nearly 2 years) without allo-HSCT, the disappearance of clusters of immature precursor cells in BM biopsy, and the change from WT1-positive to negative status following micro-transplantation.…”

Adoptive immunotherapy for myeloid malignancies

“…Previous work has shown the infusion of allogeneic matched and haploidentical peripheral blood stem cells with minimal conditioning can result in durable responses for patients with refractory leukemia/lymphoma in the absence of engraftment. [1][2][3][4] Furthermore, responders to therapy demonstrated a robust cytokine release syndrome that is similar to that seen in chimeric antigen receptor-modified T cells in its involvement of the release of interferon-γ (IFN-α) and interleukin-6 (IL-6). 2,5 Based on the loss of chimerism in responders, we hypothesize that the mechanism of action behind response is via the generation of a host versus tumor and not a graft versus tumor response.…”

“…Previous work has shown the infusion of allogeneic matched and haploidentical peripheral blood stem cells with minimal conditioning can result in durable responses for patients with refractory leukemia/lymphoma in the absence of engraftment. [1][2][3][4] Furthermore, responders to therapy demonstrated a robust cytokine release syndrome that is similar to that seen in chimeric antigen receptor-modified T cells in its involvement of the release of interferon-γ (IFN-α) and interleukin-6 (IL-6).2,5 Based on the loss of chimerism in responders, we hypothesize that the mechanism of action behind response is via the generation of a host versus tumor and not a graft versus tumor response.Our current cellular therapy protocol seeks to further develop cellular infusion as a form of immunotherapy for refractory hematological malignancies. 6 Patients are enrolled in an already FDA and institutional review board-approved trial that utilizes peripheral blood mononuclear cells (PBMNC) collected from human leukocyte antigen-haploidentical donors.…”