Hematopoietic stem cell microtransplantation in patients aged over 70 with acute myeloid leukemia: a multicenter study

Abstract

In the era of molecular targeted drugs, elderly patients with acute myeloid leukemia (AML) are still very difficult to treat, especially those older than 70 years. The decline in immune function leads to serious infection and disease recurrence. The microtransplant treatment regimen (MST) chemotherapy combined with allogeneic hematopoietic stem cell infusion is a new cell therapy regimen. The aim of this MST study was to improve the survival of elderly patients by graft versus leukemia action and improving T-cell immune function. From May 2012 to July 2020, one hundred and eleven patients aged 70 to 88 years with de novo AML were analyzed retrospectively. After induction chemotherapy, patients whom complete remission (CR) was achieved were given another 2 cycles of postremission therapy. The MST groups were given allogeneic stem cell infusion after each chemotherapy cycle. CR, leukemia-free survival, and overall survival (OS) were compared between groups. Additionally, the immune function and the T cell receptor (TCR) library of T cells were detected and analyzed. The MST group exhibited an encouragingly high CR rate (63.8%), even in high-risk patients (54%), and this rate was significantly higher than that in the chemotherapy alone group. The 1-year OS of MST patients was 57.7%, and it was 55.9% in the high-risk group. It was only 37.3% in the chemotherapy alone group. Higher numbers of naive T cells were found in the MST population than in the chemotherapy alone group. More updated T-cell clones were observed in MST patients by T-cell receptor repertoire analysis with a next-generation sequencing methodology. These results suggest that MST is a safe and practical regimen conducive to longer-term survival in patients of a highly advanced age with AML. Furthermore, it has broad clinical value in the recovery of immune function in elderly patients.

Keywords: Acute myeloid leukemia; T cell receptor repertoire; elderly patients; hematopoietic stem cell; micro-transplantation.

Figure 1

A, B. The probabilities of LFS and OS in the high-risk MST group compared with the standard MST group. The mean months: LFS, 10±1.2 vs. 10±1.5 months, P=0.784; OS, 13±2 months vs. 13±1.2 months, P=0.227. C, D. The probabilities of LFS and OS in all of the MST patients compared with the chemotherapy alone patients. The mean months: LFS, 10±1.1 vs. 5±2.8 months, P=0.365; OS, 13±0.7 months vs. 6±2.6 months, P=0.043.

Figure 2

Enumeration of T-cell subsets by flow cytometry. MST-CR, patients with complete remission (CR) after MST; MST-NCR, patients with non-CR after MST; chemo-CR, patients with CR after chemotherapy alone; normal, normal population aged over 70. * indicates a statistically significant different (P<0.05).

Figure 3

A. Comparative diagram of subcloning of the top 50 VJ genes of samples. Group 1 was the chemotherapy alone group, and group 2 was the MST group. The changes in color from blue to red indicate increased expression of subclones. The left and upper cluster lines indicate the closeness of different subclones. MST 1, MST 2, chemo 1 and chemo 2 mean 4 cases by MST or chemotherapy alone. The Pre means results before treatment; Y, one year; HY, half a year. B. Comparison diagram of subclone update frequency. Results showed that 90.4% and 92.3% subclones of two patients were updated half a year following the treatment, compared with the number before MST. Moreover, 80.6% and 90.3% of the clones continued updating 1 year following the treatment, a sharp contrast with the result half a year after treatment. For the two patients in the chemotherapy alone group, only 75% of the clones were updated half a year after the treatment, compared with the number before the treatment. A significant difference was detected between the two groups, P=0.004.