General AML

Decitabine before low-dose cytarabine in combination with stem cell microtransplantation in elderly AML patients – a Chinese study

HLA-mismatched Stem Cell (SC) Microtransplantation (MST) has been reported to improve the outcomes of elderly patients with Acute Myeloid Leukemia (AML).1 Additionally, decitabine plus Granulocyte-Colony Stimulating Factor priming, low-dose aclarubicin, and cytarabine (DCAG) chemotherapy regimen improved the Complete Remission (CR) rate and survival of elderly AML patients.2 However, the combination of SC-MST and DCAG regimen in elderly AML patients have not been explored yet.

Yu Zhu and colleagues from the Nanjing Medical University, Nanjing, China, discuss results from their phase II prospective study, which investigated the efficacy and safety of DCAG in combination with SC-MST in newly diagnosed elderly AML patients. The results of the study were published in Biology of Blood and Marrow Transplantation.3

Twenty-three adult AML patients (median age = 68 years) were enrolled in this study between July 2013 and July 2015. Patients were administered DCAG combined with SC-MST without Graft versus Host Disease (GvHD) prophylaxis. Response assessment was available for twenty-two patients.

The key results were:
  • After the first cycle of DCAG-SC-MST regimen, the Overall Response (OR) and Complete Remission (CR) rates were 86.4% and 81.8%, respectively
  • 91% (10/11) of patients with normal karyotype and 80.0% (4/5) of patients with unfavorable karyotype at base line achieved CR
  • Median Overall Survival (OS) and Disease Free Survival (DFS) in all patients were 17 and 13 months, respectively
  • Median OS was significantly longer in patients who received ≥ 3 cycles of SC-MST than those who received 1 or 2 cycles of treatment; P = 0.009
  • Most frequent Adverse Events (AEs) were thrombocytopenia and neutropenia with no GvHD observed
  • 4-week mortality in all patients was 4.3%

In summary, “DCAG SC-MST may have a clinical benefit for newly diagnosed elderly AML patients”.

Abstract

The optimal treatment for elderly patients with acute myeloid leukemia (AML) remains a great challenge. Establishing a more feasible, acceptable, accessible and safe treatment strategy for elderly patients is urgently needed. We conducted a prospective study of 23 elderly patients (median age, 68 years; range, 60 to 87 years) with newly diagnosed AML to evaluate the efficacy and toxicity of decitabine plus granulocyte colony–stimulating factor priming, low-dose aclarubicin, and cytarabine (DCAG) chemotherapy combined with HLA-mismatched stem cell microtransplantation (SC-MST) without graft-versus-host disease (GVHD) prophylaxis. After the first cycle, the overall response and the complete remission (CR) rates were 86.4% and 81.8%, respectively. CR was achieved in 90.9% of the normal karyotype group and in 80.0% of patients with unfavorable karyotypes at baseline. The median overall survival (OS) and disease-free survival rates were 17 and 13 months, respectively, with a 2-year OS of 34.8%. The median OS of the patients who received ≥3 cycles of SC-MST was significantly longer than those who received only 1 or 2 cycles of treatment. The regimen was well tolerated with a 4-week mortality of 4.3%, and no GVHD was observed. The most common adverse events were hematologic toxicities. Our data suggest that the innovative combination of DCAG with SC-MST may optimize the clinical strategy for elderly patients with newly diagnosed AML.

References
  1.  Ai H. et al. Microtransplantation for Elderly Acute Myeloid Leukemia - Current and Future. Blood. 2015; 123: 4941.
  2. Li H. et al. Efficacy and safety of decitabine in combination with G-CSF, low-dose cytarabine and aclarubicin in newly diagnosed elderly patients with acute myeloid leukemia. Oncotarget. 2015 Mar 20; 6(8): 6448–6458. DOI: 10.18632/oncotarget.3361. Epub 2015 Jan 31.
  3. Zhu Y. et al. Decitabine before Low-Dose Cytarabine-Based Chemotherapy Combined with Human Leukocyte Antigen-Mismatched Stem Cell Microtransplantation Improved Outcomes in Elderly Patients with Newly Diagnosed Acute Myeloid Leukemia. Biol Blood Marrow Transplant. 2017 May; 23(5): 830–835. DOI: 10.1016/j.bbmt.2017.01.085. Epub 2017 Feb 8.