interferon-α prevents leukemia relapse of aml patients after transplantation

Conditions: Interferon-A-2B; Relapse; Prevention; Hematopietic Stem Cell Transplantation

Summary: allogeneic stem cell transplantation (sct) remains a powerful therapeutic modality for patients with acute myeloid leukemia (aml).the superior clinical outcomes of allogeneic human sct versus chemotherapy alone as post-remission treatment could be related to the graft-versus-leukemia (gvl) effects of recovered donor t cells. our previous study investigated both the association of mrd status with transplant outcomes in haplo-sct and matched sibling donor transplantation(msdt)， and also possible differences in the transplant outcomes of patients with positive pre-mrd (as determined by mfc) who underwent haplo-sct versus msdt. it provided new evidence that unmanipulated haplo-sct is superior to matched sibling donor transplantation in eradicating pre-transplantation mrd, indicating that unmanipulated haploidentical allografts have stronger gvl effects.as to the aml patients in standard-risk, who have a positive mrd before msdt, whether these patients should be given any relapse prevention is the question to be answered in this study. interferon α-2b exerts a relatively strong immunomodulatory effect. it can kill al cells by regulating t-cell and/or natural killer cell functions.consequently, interferon α-2b may have potential value for high-risk al patients after transplantation. the study hypothesis: using interferon α-2b following hematopoietic stem cell transplantation in patients with standard-risk aml can further reduce relapse rate and improve leukemia-free survival.

the standard-risk aml patients (18-60 years) receiving hla-identical allogeneic stem cell transplantation in peking university institute of hematology will be enrolled in this study if their mrd were positive before sct, in cr1/cr2, remain in cr and mrd negative in the first two months after transplantation. the patients in this study will be treated with interferon-alpha injection twice a week (3 million units / time, ih) since the third month posttransplant. if the patients were well tolerated, the interferon-alpha treatment will continue 6 months. all the enrolled patients will undergo mrd monitoring after sct as the same as the routine procedure. bone marrow examination will be performed at the regular time points (+1, 2,3, 4, 5, 6, 9, 12 month) and 8-colour flow cytometry and rq-pcr-based wt1 examination will be empolyed to evaluate mrd and disease status. based on the statistical calculation, in order to reduce the incidence of relapse from 40% (previous data) to 15% (the cumulative incidence of relapse in pre-mrd- aml patients), total 29 patients will be enrolled. the main side effects might related to interferon-alpha include induction of severe gvhd, hematological toxicity and flu - like symptoms. if the patients met the following criteria, they will withdraw from the trial: 1）met the combined criteria for positive mrd (mrdco+) which was defined as 2 consecutive fcm+ or wt1+ results or both fcm+ and wt1+ in a single sample within 1 year after transplantation; 2）hematological relapse; 3) grade iii or iv acute gvhd, or moderate/ severe chronic gvhd; 4) severe infection; 5) grade iv hematological toxicity; 6) organ failure; 7) death; 8) patients refuse to continue the interferon-alpha treatment. the main end point of the study is one-year cumulative incidence of relapse. the second end points include os, nrm, dfs, mrd, gvhd, infection and hematological toxicity.

Eligibility criteria:
inclusion criteria: * standard-risk aml in cr1/cr2 * without t(9;22) and t(15;17) * receive hla-identical transplantation * with positive mrd before transplantation (measured by flow cytometry) * cr within the first two months posttransplantation and mrd is negative * between 18-60 years exclusion criteria: * uncontrolled gvhd * be in myelosuppression (wbc\<1.5x10\^9/l, anc\<0.5×10\^9/l，plt\<25×10\^9/l,hb\<65g/l) * severe infection * organ failure * the patients do not agree to participate in the study

Keywords: interferon-alpha relapse prevention hematopietic stem cell transplantation acute myeloid leukemia