HLA-partially matched cellular therapy (stem-cell microtransplantation) for acute myeloid leukaemia: description of four cases

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

“…WEHI-3 cells were administered through the tail vein on day 5 prior to transplantation (1x10 6 /mouse). The recipients were treated with a chemotherapy regimen including mitoxantrone (MA; 4 mg/kg) on day 4 and cytarabine (200 mg/kg) (both from Pfizer, Inc., New York, NY, USA) on days 3-1.…”

“…Afterwards, the cells were counted and the cell concentration was adjusted. Donor-derived sMNC (6x10 6 /mouse) were infused into recipients on day 0 within 8 h after the last dose of chemotherapy. The control group received the same volume of saline solution.…”

“…As the incidence of acute myeloid leukemia (AML) increases with age, the majority of AML patients have numerous types of comorbidities and are less tolerant to high-intensity consolidation and allo-SCT, leading to a significantly worse prognosis. Microtransplantation, also known as human leucocyte antigen (HLA)-partially matched donor leucocyte infusion (DLI), is a fractional infusion of small amounts of allogeneic hematopoietic stem cells and has rapidly developed in recent years (2)(3)(4)(5)(6). In 2011, Guo et al (7) as well as Mackinnon and Chakraverty (8) first reported that the 2-year overall survival (OS) rate in elderly patients with AML increased from 11 to 39% with microtransplantation following chemotherapy.…”

Harnessing the power of alloreactivity without triggering graft-versus-host disease: how non-engrafting alloreactive cellular therapy might change the landscape of acute myeloid leukemia treatment

“…We call this approach NEACT to emphasize that recipient hematopoiesis remains dominant. Moreover, NEACT must not be confused with synonyms that might include autologous T cell, NK cell and DC therapy (e.g., "nonengraftment cellular therapy" [4]) or natural fetal-maternal microchimerism [2,3], or misleadingly suggest a goal of sustainable engraftment ("microtransplantation" [5]). The early laboratory work leading to this approach has been reviewed by Reagan and colleagues [4,41].…”

“…Others have used the terms "nonengraftment cellular therapy," "microchimerism" and "microtransplantation" [2][3][4][5]. Their common features include a focus on HLA-mismatched T or NK cell transfer to mediate strong alloreactivity in order to bring about immediate anti-neoplastic effects in recipients who are not profoundly immunosuppressed as well as the intentional rejection of donor cells such that long-term hematopoiesis overwhelmingly, if not entirely, derives from the recipient's native marrow.…”