Allogeneic HCT

Allogeneic HCT, even with minimal conditioning chemotherapy, results in the lowest incidence of leukemic relapse, even when compared with HCT from an identical twin (syngeneic HCT). This finding led to the concept of an immunologic graft-versus-leukemia effect, similar to (and related to) graft-versus-host disease. The improvement in freedom from relapse using allogeneic HCT as the primary consolidation therapy is offset, at least in part, by the increased morbidity and mortality caused by graft-versus-host disease, veno-occlusive disease of the liver, and infection. The DFS rates using allogeneic transplant in first complete remission have ranged from 45% to 60%.[21-24]

The use of allogeneic HCT in adults requires either a HLA-matched sibling donor, an HLA-matched unrelated donor, a haploidentical donor (“half HLA-matched”), or two well-matched umbilical cord blood units. Including patients who underwent HCT from 2007 to 2017, the 3-year probabilities of survival after HLA-matched sibling transplant were 59% (±1%) for patients with early disease, 53% (±1%) for patients with intermediate disease, and 29% (±1%) for patients with advanced disease, according to the Center for International Blood and Marrow Transplant Research registry.[24] The probabilities of survival after an unrelated donor transplant were 53% (±1%) for patients with early disease, 50% (±1%) for intermediate disease, and 27% (±1%) for patients with advanced disease. [Level of evidence C1]

Because HCT can cure more than 30% of patients who experience relapse after chemotherapy, some investigators suggested that allogeneic bone marrow transplant (BMT) can be reserved for early first relapse or second CR without compromising the number of patients who are ultimately cured.[25] Clinical and cytogenetic information can define certain subsets of patients with predictable better or worse prognoses according to favorable- and adverse-risk factors in those using consolidation chemotherapy.[26]

A common clinical trial design used to evaluate the benefit of allogeneic transplant as consolidation therapy for AML in first remission is the so-called donor-no donor comparison. In this design, newly diagnosed AML patients who achieve a CR are deemed medically eligible for allogeneic transplant and undergo HLA typing. If a matched sibling or matched unrelated donor is identified, the patient is allocated to the transplant arm. Analysis of outcome is by intention to treat; that is, patients assigned to the donor arm who do not receive a transplant are grouped in the analysis with the patients who did actually receive a transplant. RFS is the usual end point for this type of trial. OS from the time of diagnosis is less frequently reported in these trials.

Investigators attempted to address this issue with a meta-analysis using data from 18 separate prospective trials of AML patients using the donor-no donor design, with data from an additional six trials included for sensitivity analysis.[28] The trials included in this meta-analysis enrolled adult patients aged 60 years and younger from 1982 to 2006. Median follow-up ranged from 42 months to 142 months. Preparative regimens were similar among the different trials. Allogeneic transplant was compared with autologous transplant (six trials) or with a variety of consolidation chemotherapy regimens, with high-dose cytarabine being the most common.

Most physicians who treat patients with leukemia agree that transplant should be offered to AML patients in first CR in the setting of adverse-risk cytogenetics and should not be offered to patients in first CR with favorable-risk cytogenetics.[26] However, older patients with favorable-risk AML who are unlikely to tolerate intensive cytarabine-based consolidation therapy can be considered for allogeneic HCT as consolidation therapy.[29]