HLA-mismatched stem-cell microtransplantation as postremission therapy for acute myeloid leukemia: long-term follow-up.

Abstract

PURPOSE:

Despite best current therapies, approximately half of patients with acute myeloid leukemia in first complete remission (AML-CR1) with no HLA-identical donors experience relapse. Whether HLA-mismatched stem-cell microtransplantation as a novel postremission therapy in these patients will improve survival and avoid graft-versus-host disease (GVHD) is still unknown.

PATIENTS AND METHODS:

One hundred one patients with AML-CR1 (9 to 65 years old) from four treatment centers received programmed infusions of G-CSF-mobilized HLA-mismatched donor peripheral-blood stem cells after each of three cycles of high-dose cytarabine conditioning without GVHD prophylaxis. Donor chimerism and microchimerism and WT1+CD8+ T cells were analyzed.

RESULTS:

The 6-year leukemia-free survival (LFS) and overall survival (OS) rates were 84.4% and 89.5%, respectively, in the low-risk group, which were similar to the rates in the intermediate-risk group (59.2% and 65.2%, respectively; P=.272 and P=.308). The 6-year LFS and OS were 76.4% and 82.1%, respectively, in patients who received a high dose of donor CD3+ T cells (≥1.1×10(8)/kg) in each infusion, which were significantly higher than the LFS and OS in patients who received a lower dose (<1.1×10(8)/kg) of donor CD3+ T cells (49.5% and 55.3%, respectively; P=.091 and P=.041). No GVHD was observed in any of the patients. Donor microchimerism (2 to 1,020 days) was detected in 20 of the 23 female patients who were available for Y chromosome analysis. A significant increase in WT1+CD8+ T cells (from 0.2% to 4.56%) was observed in 33 of 39 patients with positive HLA-A*02:01 antigen by a pentamer analysis.

CONCLUSION:

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

• Authors: Mei Guo, Kai-Xun Hu, Guang-Xian Liu, Chang-Lin Yu, Jian-Hui Qiao, Qi-Yun Sun, Jun-Xiao Qiao, Zheng Dong, Wan-Jun Sun, Xue-Dong Sun, Hong-Li Zuo, Qiu-Hong Man, Zhi-Qing Liu, Tie-Qiang Liu, Hong-Xia Zhao, Ya-Jing Huang, Li Wei, Bing Liu, Juan Wang, Xu-Liang Shen, Hui-Sheng Ai
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 30 Issue 33 Pg. 4084-90 (Nov 20 2012) ISSN: 1527-7755 [Electronic] United States
• PMID: 23045576 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• HLA-A*02 antigen
• HLA-A2 Antigen
• Granulocyte Colony-Stimulating Factor

Topics

• Adolescent
• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Blood Component Removal (methods)
• Child
• Combined Modality Therapy
• Disease-Free Survival
• Female
• Follow-Up Studies
• Graft vs Host Disease (etiology, immunology)
• Granulocyte Colony-Stimulating Factor (administration & dosage)
• HLA-A2 Antigen (immunology)
• Hematopoietic Stem Cell Transplantation (adverse effects, methods)
• Humans
• Leukemia, Myeloid, Acute (drug therapy, immunology, surgery)
• Male
• Middle Aged
• Remission Induction
• Tissue Donors
• Transplantation Chimera
• Young Adult