In July 2018, a study led by Professor Zhengzheng Fu from the First Affiliated Hospital of Soochow University was published in the international academic journal ——Leuk Lymphoma. The title of the study is “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“. This study contributes to the growing body of evidence seeking to enhance treatment paradigms for AML, particularly in older patients who have historically faced limited options and poor prognoses.
Acute myeloid leukemia (AML) represents a significant challenge in the field of hematology, particularly among older patients. The incidence of AML escalates with age, presenting a complex therapeutic dilemma due to the aggressive nature of the disease and the diminished tolerance of elderly patients to intensive chemotherapy. Despite advancements in treatment strategies, the prognosis for these patients remains bleak. Induction therapy can achieve complete remission (CR) in a notable fraction of cases, ranging from 50% to 60%. However, this success is overshadowed by a high relapse rate, culminating in a disheartening 2-year overall survival (OS) rate of merely 15% to 25%.
Current post-remission therapeutic strategies predominantly revolve around repeated cycles of modest consolidation chemotherapy, which have shown limited success. Allogeneic stem cell transplantation (allo-HSCT) offers a potential cure but is marred by significant risks such as graft-versus-host disease (GVHD) and other life-threatening complications. In this context, innovative treatment paradigms are urgently needed. Recent studies have highlighted the potential of HLA-mismatched granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral donor blood stem cells (GPBSCs) following chemotherapy to elicit anti-leukemia effects while circumventing the development of GVHD. Moreover, the integration of hypomethylating agents (HMAs) like decitabine (DAC) and azacitidine with chemotherapeutic agents has shown promise in enhancing treatment efficacy, as evidenced by in vitro research and preliminary clinical trials.
The focal point of this retrospective study is to scrutinize the viability of a novel consolidation therapy comprising decitabine (DAC) combined with intermediate-dose cytarabine (ID-AraC), succeeded by an infusion of HLA-mismatched GPBSCs, for treating older AML patients who have achieved first complete remission (CR1). This investigation is driven by the pressing need for more effective post-remission therapies that can mitigate the high relapse rates and improve overall survival in this patient population.
This study encompasses a cohort of 42 patients, segmented into two groups. The first group, consisting of 23 patients, underwent three cycles of the DAC-ID-AraC-GPBSC regimen (referred to as the D-GPBSCs group). In contrast, the second group, comprising 19 patients, received repeated cycles of ID-AraC chemotherapy alone (termed the chemo group). The evaluation metrics for this study were meticulously chosen to encompass safety, tolerability, and the therapeutic efficacy of the regimens, with a particular emphasis on hematologic recovery times, incidence of GVHD, leukemia-free survival (LFS), and overall survival (OS).
The comparative analysis revealed that both regimens were well tolerated among the study participants, with no instances of graft-versus-host disease observed in the D-GPBSCs group. Notably, the D-GPBSCs regimen was associated with significantly shorter median recovery times for both neutrophils and platelets. Furthermore, the 2-year leukemia-free survival (LFS) and overall survival (OS) rates were markedly improved in the D-GPBSCs group compared to the chemo group. These findings suggest that the combination of DAC and ID-AraC chemotherapy followed by GPBSCs infusion constitutes a viable and efficacious consolidation therapy for older AML patients in CR1.
This retrospective study has illuminated the potential of a novel consolidation therapy regimen comprising decitabine (DAC) plus intermediate-dose cytarabine (ID-AraC), followed by an infusion of HLA-mismatched granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral donor blood stem cells (GPBSCs), for older patients with AML in first complete remission (CR1). The findings underscore the regimen’s safety, tolerability, and efficacy, evidenced by shorter median recovery times for neutrophils and platelets, and superior 2-year leukemia-free survival (LFS) and overall survival (OS) rates compared to those treated with repeated cycles of ID-AraC chemotherapy alone.
The study’s outcomes suggest that the DAC-ID-AraC-GPBSC regimen represents a promising consolidation therapy alternative for older AML patients, potentially improving survival outcomes and offering a viable option beyond conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). Given the promising nature of these preliminary findings, further prospective, multicenter studies are warranted to validate these results, explore the mechanistic underpinnings of the observed benefits, and assess the long-term impact of this therapy on the quality of life and survival of AML patients.
Ultimately, this study contributes to the growing body of evidence seeking to enhance treatment paradigms for AML, particularly in older patients who have historically faced limited options and poor prognoses. The integration of novel therapeutic strategies such as hypomethylating agents and cell therapy into the AML treatment landscape holds the potential to redefine standard care, offering hope for improved outcomes in this challenging patient population.
