Abstract
For allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, preemptive interferon-α (IFN-α) therapy is considered as a useful method to eliminate the minimal residual disease (MRD). Our purpose is to assess the long-term efficacy of preemptive IFN-α therapy in acute myeloid leukemia (AML) patients following allo-HSCT based on two registry studies (#NCT02185261 and #NCT02027064). We would present the final data and unpublished results of long-term clinical outcomes with extended follow-up. We adopted polymerase chain reaction (PCR) and multiparameter flow cytometry (MFC) to monitor MRD, and a positive result of bone marrow specimen examined by either of them would be identified as the MRD-positive status. Subcutaneous injections of recombinant human IFN-α-2b were performed for 6 cycles, and prolonged IFN-α therapy could be permitted at the request of patients. The median cycles were 3.5 (range, 0.5–30.5) cycles. A total of 9 patients suffered from grade ≥3 toxicities (i.e., infectious: n = 6; hematologic: n = 3). The 6-year cumulative incidences of relapse and non-relapse mortality following IFN-α therapy were 13.0% (95% confidence interval [CI], 5.4–20.6%) and 3.9% (95%CI, 0.0–17.6%), respectively. The probability of disease-free survival at 6 years following IFN-α therapy was 83.1% (95%CI, 75.2–91.9%). The probability of overall survival at 6 years following IFN-α therapy was 88.3% (95%CI, 81.4–95.8%). The cumulative incidences of total chronic graft-versus-host disease (cGVHD) and severe cGVHD at 6 years following IFN-α therapy were 66.2% (95%CI, 55.5–77.0%) and 10.4% (95%CI, 3.6–17.2%), respectively. Multivariable analysis showed that an alternative donor was associated with a lower risk of relapse and the better disease-free survival. Thus, preemptive IFN-α therapy could clear MRD persistently, prevent relapse truly, and improve long-term survival in AML patients following allo-HSCT.
Highlights
In acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation, relapse is the most important cause for transplant failure [1, 2]
The characteristics of 77 AML patients after preemptive IFN-a therapy following allo-HSCT are summarized in Table 1 and Figure 3
Numerous studies have suggested that IFN-a could play a role in inducing anti-leukemic responses in vivo [20]; only single case reports or studies with small sample sizes have supported that IFN-a could be a treatment choice for AML [22, 49,50,51]
Summary
In acute myeloid leukemia (AML) patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT), relapse is the most important cause for transplant failure [1, 2]. Patients who still suffer from the disease while cannot be detected by morphological analysis can be identified by the minimal residual disease (MRD) monitoring [3]. Polymerase chain reaction (PCR) assays based on detecting genetic abnormalities associated with leukemia and multiparameter flow cytometry (MFC) based on detecting leukemia-associated immunophenotypes (LAIPs) can be employed to monitor MRD. Many studies provided evidence that MRD monitoring could predict forthcoming relapse after allo-HSCT [3,4,5,6]. Patients who have MRD receiving preemptive interventions are reasonable. Unlike maintenance or phylactic treatments, MRDdirected preemptive treatments can help risk stratification and spare some patients in remission from further therapy
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