Microtransplantation for Elderly Acute Myeloid Leukemia - Current and Future

The outcome of acute myeloid leukemia in elderly acute myeloid leukemia (EAML) patients is still unsatisfactory with a low complete remission (CR) rate and a poor overall survival due to prolonged pancytopenia and intrinsic resistance of leukemic blasts to therapeutic. The high/standard induction chemotherapy improved CR rate but remission is usually transient. Non-myeloablative stem cells transplantation or reduced-intensity conditioning transplantation shows curative effects but severe graft-versus-host disease (GVHD) still exists. Our clinical studies revealed that the microtransplantation (MST) could improve outcome and without GVHD in EAML. Recently, other centers worldwide used microtransplantation to young AML patients, MDS, non-Hodgkin's lymphoma and others. Here we introduce some important developments and in future directions about MST.

1. Microtransplantation is effective for EAML

A seminal randomized study with 58 cases of EAML by Beijing group reported that MST result in a significantly higher CR rate and higher 2-year OS compared to chemotherapy. Another randomized muti-centres study with MST for EAML in China and USA is ongoing. Total of the fifteen EAML patients including 8 in chemotherapy-group and 7 in MST-group were registered with primary much better outcomes. Otherwise, another enlargement study about MST for EAML in China MST Cooperative Group showed overall CR rate was 77.1% which was no significantly difference among the patients with 60-65 years, 66-75 years or more. Fores reported three EAML patients get CR after MST. Gottlieb reported two EAML achieved CR. Otherwise, high CR rates (70-86%) was also found in other as-yet unpublished series of data included 5 cases of EAML from the University of Duke and 9 patients from the University of South California.

2. Microtransplantation is safe and hardly no GVHD

From Ai, thirty EAML and 101 young AML patients did not develop GVHD. However, Ai reported one patient who developed a severe acute GVHD. No cytomegalovirus pneumocystis was reported.

3. Microtransplantation is no limit to donors

Most patients received HLA partial/full-mismatched related/unrelated donor, which suggested that MST could overcome MHC barrier and without limitation of donors.

4. Microtransplantation mechanism study is ongoing

Donor micro-chimerism has been detected by using Sry gene, HLA loci and G-6PD isoenzyme detected. Micro-chimerism generally becomes undetectable after weeks and months by a single infusion, and rarely persists beyond two or three years after several infusions.

Other important experiment studies including: 1) Distribution, evolution and persistence of donor micro-chimerism was observed by molecular imaging in mouse. 2) Donor micro vesicle was found in host lymphocyte, who received mv from G-CSF mobilization donor mouse spleen cells infusion.

5. Anti-leukemia effects

In addition to induce Graft-versus-leukemia effects, MST mediated recipient-versus-leukemia effects which may involve in host B-cell antibody synthesis and T/NK cytotoxicity. IL-2, Il-6, TNF and IL-10 are significantly increase in mouse leukemia model.

In the future, Microtransplantation offers the benefit of allo-reactivity and hardly any GVHD. Further studies will focus on the mechanism of microtransplantation and multicentre cooperation study. It may become a standard weapon for EAML infuture.