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HCT superior in patients with AML in second complete remission
Allogeneic hematopoietic cell transplantation may still be valuable for patients with acute myeloid leukemia in first relapse or primary induction failure, despite producing superior outcomes for patients in second complete remission, according to findings published in Cancer.
“For patients with AML who fail to achieve complete remission or those in relapse after first complete remission, allogeneic hematopoietic cell transplantation can produce leukemia control and extended survival,” Daniel J. Weisdorf, MD, professor of medicine in the division of hematology, oncology and transplantation at the University of Minnesota Medical Center, Minneapolis, and colleagues wrote. “Some reports suggest that immediate transplantation, if an available donor can be quickly identified, is a best strategy for primary induction failure or at first relapse. Other data argue that additional therapy to achieve remission yields favorable outcomes and superior survival, noting that achieving complete remission may indicate intrinsically more responsive leukemia.”
The researchers analyzed survival of 4,682 patients who received HCT, organized by disease status: primary induction failure (n = 1,440) first relapse (n = 1,256) and second complete remission (n = 1,986).
Patient characteristics, as well as disease and transplantation characteristics, were similar across groups, except that patients in second complete remission more frequently had performance scores ranging from 90% to 100%, de novo AML and longer duration of first complete remission. Patients who experienced primary induction failure had adverse cytogenetics more commonly than other groups.
The adjusted 5-year survival rate — which accounted for performance score, cytogenetic risk and donor type — was 39% (95% CI, 37-41) for second complete remission, compared with 18% (95% CI, 16-20) for HCT in first relapse and 21% (95% CI, 19-23) in primary induction failure (P < .0001).
“Allogeneic transplantation in later stage AML can still yield long-term disease control and improved survival for sizable fractions of patients, but the current analysis strongly suggests that transplantation during second complete remission is preferred over other approaches, including transplantation in first relapse or primary induction therapy,” the researchers wrote.
Weisdorf and colleagues acknowledged that the study was limited by an “unquantifiable selection bias,” because it included only patients who were considered fit for HCT during relapse.
“Nonetheless, the large numbers of patients,” they wrote, “the multivariable regression adjustments and the international experience likely represent valid outcomes for patients who undergo transplantation in these three clinical situations who are selected for HCT.” – by Andy Polhamus
Disclosure: Weisdorf reports grants from Alexion, personal fees from Enlivex and Kadmon and additional grants from Sunesis Pharmaceuticals. Please see the full study for a list of all other researchers’ relevant financial disclosures.
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Survival after allogeneic hematopoietic stem cell transplantation (HCT) is superior for patients with acute myeloid leukemia (AML) who are in a second complete remission than for patients who have primary induction failure or have active disease in first relapse, according to a large analysis of data from the Center for International Blood and Marrow Transplant Research.
Weisdorf et al. performed an analysis of 4,682 patients with AML in second complete remission, primary induction failure, or first relapse who underwent HCT. Five-year OS adjusted for performance status, cytogenetic risk, and donor type was 39% (95% CI, 37-41) for second complete remission, compared with 21% (95% CI 19-23) for primary induction failure and 18% (95% CI, 16-20) for first relapse (P < 0.0001). Recurrent leukemia was the most common cause of death for all patients. Researchers applied a previously established scoring system using risk factors to predict relapse after HCT for AML with active disease to patients with primary induction failure and first relapse, and found survival to be inferior in patients with short initial remission, circulating blasts, donors other than HLA–identical siblings, lower performance scores, and poor-risk cytogenetics. Persistent AML before day 100 was common in primary induction failure (49%) and first relapse (46%). A landmark analysis of patients alive and in CR at day 100 showed nonrelapse mortality rates of 23% (95% CI, 21-25) for second complete remission, 28% (95% CI, 24-32) for first relapse, and 25% (95% CI, 21-29) for primary induction failure. The risk for relapse after day 100 appeared lower in second complete remission than primary induction failure and first relapse.
The decision to proceed with HCT versus additional salvage chemotherapy in patients with primary induction failure and first relapse can be difficult. This analysis describes clinical outcomes in a very large cohort of patients with high-risk disease, which only a registry study such as this could provide. The authors recognize the unavoidable selection bias, where patients who never underwent HCT are not included in the analysis; however, it is recognized that these patients, ultimately, do poorly. Moreover, these outcomes reflect real world experiences where patients are carefully selected for HCT, and are generalizable to clinical practice. ,It is likely that the superior outcomes for patients in second complete remission compared with primary induction failure and first relapse reflect underlying biology of these leukemias, where remission may be easier to achieve for certain patients. This is supported by the fact that patients with favorable-risk cytogenetics and longer second complete remission duration before relapse had better outcomes. This study provides important data to be used in counseling patients regarding risks and benefits of HCT in these clinical settings, and can aid in the difficult, case-by-case decisions regarding HCT in this high-risk patient population.