Viewpoint: What is the role of allogeneic haematopoietic cell transplantation in the era of reduced-intensity conditioning – is there still an upper age limit? A focus on myeloid neoplasia

Abstract

Allogeneic haematopoietic cell transplantation (HCT) is the most effective curative therapy in acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Incidence of AML and MDS increases with age, peaking in the seventh decade. Despite improved Ara-C and anthracyclin-based chemotherapy regimens, the prognosis of AML in patients beyond 60 years of age is dismal. The introduction of peripheral bloodderived stem cell grafts into allogeneic HCT and the known antileukaemic effect of donor lymphocyte infusions paved the way for reduced-intensity conditioning (RIC) allogeneic stem-cell transplantation, which makes transplant in advanced age possible and significantly reduces transplant-related organ toxicity and mortality. The success of RIC HCT relies on the alloreactivity of the donor immune system and the graft-versusleukaemia effect. We try to answer the following questions in this paper: who should receive RIC HCT? when and how should the transplant be performed? is there an upper age limit and what is the future of RIC HCT?

Comparative analysis of remission induction therapy for high-risk MDS and AML progressed from MDS in the MDS200 study of Japan Adult Leukemia Study Group

“…Allogeneic hematopoietic cell transplantation (allo-HCT) is the most effective curative therapy for acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) [4]. However, for patients with high-risk MDS (those with refractory anemia with excess of blasts in transformation (RAEB)-t and some patients with RAEB) and patients with acute myeloid leukemia progressed from MDS (MDS-AML), chemotherapy aimed at remission is being used.…”

“…Common antineoplastic agents used in low-dose chemotherapy include cytosine arabinoside (Ara-C), aclarubicin (ACR), melphalan and etoposide. Nevertheless, despite improved Ara-C and regimens, the prognosis of AML in patients beyond 60 years of age remains dismal [4]. Low-dose antineoplastic drug therapy is still being used in some patients with MDS, which is common in elderly people, especially when the patient is at risk due to poor general condition or organ disorder [12].…”

Reduced-Intensity Conditioning Regimen Combined with Low-Dose Total Body Irradiation in the Treatment of Myelodysplastic Syndrome

“…Recently, in view of these issues, RIC-SCT has been widely applied. Various RIC regimens have been developed by different investigators since the early 1990s [16,17,18]. RIC-SCT is beneficial for elderly patients and patients with comorbidities who are not candidates for MAC-SCT, since it is less toxic to bone marrow and other organs and tissues [19].…”

Reduced intensity conditioning prior to allogeneic stem cell transplantation in first complete remission is effective in patients with acute myeloid leukemia and an intermediate-risk karyotype

“…Reduced intensity conditioning (RIC-alloSCT) expands potentially curative therapy to AML patients ineligible to transplantation following standard MAC due to advanced age, a history of severe infectious complications, or major organ dysfunction [9][10][11][12][13][14][15]. However, in many situations, the lower anti-leukemic activity of RIC may result in an increased relapse rate [14][15][16].…”

“…However, in many situations, the lower anti-leukemic activity of RIC may result in an increased relapse rate [14][15][16]. This may be particularly relevant in patients with active or advanced disease at the time of transplantation.…”