General AML

DAC plus ID-AraC followed by HLA-mismatched peripheral blood stem cells infusion in older AML patients

Infusions of HLA-mismatched Granulocyte Colony-Stimulating Factor (G-CSF)-mobilized Peripheral Donor Blood Stem Cells (GPBSCs) in combination with chemotherapy have been reported to result in a high Complete Remission (CR) rate, a longer survival time, and a shorter duration of pancytopenia than conventional chemotherapy alone in elderly Acute Myeloid Leukemia (AML) patients.1 However, the optimal cytoreductive therapy in combination with GPBSCs is not well understood yet.

In an article published in Leukemia & Lymphoma, Wei-Yang Li et al. from the Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China, discussed results from their retrospective study which assessed the safety and efficacy of decitabine (DAC) in combination with intermediate-dose cytarabine (ID-Arac) followed by GPBSCs as consolidation treatment in older AML patients in CR1.

In total, 42 consecutive AML patients (median age = 63 years, range, 60–74 years) who were enrolled in this study. Twenty-three patients received DAC and ID-AraC followed by GPBSCs (D-GPBSCs group) while the remaining 19 patients received ID-AraC alone (chemo group).

The key findings were:
  • Safety
    • No significant difference in grade 3–4 non-hematologic toxicities between the D-GPBSCs and chemo group; 39% (9/23) vs 26.8% (7/19), P = 0.879
    • No definite graft versus host disease was recorded in both the D-GPBSCs and chemo groups
    • Median time for neutrophil recovery to > 0.5 x 109/L in the D-GPBSCs and chemo group; 12 vs 14 days respectively, P = 0.046
    • Median time for platelet recovery to > 20 x 109/L in the D-GPBSCs and chemo group; 14 vs 16 days respectively, P = 0.022
  • Survival in the D-GPBSCs and chemo group respectively
    • 2-year Leukemia Free survival; 51.6% vs 27.1%, P = 0.047
    • 2-year Overall Survival; 55.4% vs 34.2%, P = 0.056
  • Low-level minimal residual disease (< 1 x 10-3) was more frequent in the D-GPBSCs group than the chemo group; 14/23 vs 5/19, P = 0.025

In summary, DAC plus ID-AraC followed by subsequent GPBSCs was well tolerated and improved the survival of elderly AML patients. Key limitations of this study include its retrospective nature and small size.

The authors concluded by suggesting that a prospective study optimizing the schedule, dosing and timing of DAC plus ID-AraC followed by GPBSCS is warranted as this regimen might be a promising possibility for elderly AML patients.

 

Abstract

This retrospective study tested the feasibility of decitabine (DAC) plus intermediate-dose cytarabine (ID-AraC) followed by HLA-mismatched granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral donor blood stem cells (GPBSCs) infusion as consolidation treatment for older patients with acute myeloid leukemia (AML) in first complete remission (CR). A total of 23 patients received this regimen for 3 cycles (D-GPBSCs group), and the outcome was compared with that of 19 patients treated with repeated cycles of ID-AraC chemotherapy (chemo group). The two regimens were well tolerated. The median recovery times for neutrophils and platelets were shorter in D-GPBSCs group than in chemo group (p<.05). No graft-versus-host disease (GVHD) was observed in D-GPBSCs group. The 2-year leukemia-free survival (LFS) and overall survival (OS) were better in D-GPBSCs group (51.6 and 55.4%) than in chemo group (27.1 and 34.2%) (p = .047 and p = .056). These data suggest that DAC and ID-AraC followed by GPBSCs as a consolidation regimen may be a safe and promising option for older patients with AML.

References
  1. Guo M. et al. Infusion of HLA-mismatched peripheral blood stem cells improves the outcome of chemotherapy for acute myeloid leukemia in elderly patients. Blood. 2011 Jan 20; 117(3): 936–41. DOI: 10.1182/blood-2010-06-288506.
  2. Li W.Y. et al. Consolidation therapy with decitabine and intermediate-dose cytarabine followed by HLA-mismatched peripheral blood stem cells infusion for older patients with acute myeloid leukemia in first remission. Leuk Lymphoma. 2017 Oct 18:1-7. DOI: 10.1080/10428194.2017.1390235.