Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation
Xiaodong Mo, Xiaohui Zhang, Lanping Xu, Yu Wang, Chenhua Yan, Huan Chen, Yuhong Chen, Wei Han, Fengrong Wang, Jingzhi Wang, Kaiyan Liu, Xiaojun Huang
Interferon-α salvage treatment is effective for patients with acute leukemia/myelodysplastic syndrome with unsatisfactory response to minimal residual disease-directed donor lymphocyte infusion after allogeneic hematopoietic stem cell transplantation
The efficacy of salvage interferon-α (IFN-α) treatment was investigated in patients with unsatisfactory response to minimal residual disease (MRD)-directed donor lymphocyte infusion (DLI) (n=24). Patients who did not become MRD-negative at 1 month after DLI were those with unsatisfactory response and were eligible to receive salvage IFN-α treatment within 3 months of DLI. Recombinant human IFN-α-2b injections were subcutaneously administered 2–3 times a week for 6 months. Nine (37.5%), 6 (25.0%), and 3 (12.5%) patients became MRD-negative at 1, 2, and>2 months after the salvage IFN-α treatment, respectively. Two-year cumulative incidences of relapse and non-relapse mortality were 35.9% and 8.3%, respectively. Two-year probabilities of event-free survival, disease-free survival, and overall survival were 51.6%, 54.3%, and 68.0%, respectively. Outcomes of patients subjected to salvage IFN-α treatment after DLI were significantly better than those with persistent MRD without IFN-α treatment. Moreover, clinical outcomes were comparable between the salvage DLI and IFN-α treatment groups. Thus, salvage IFN-α treatment may help improve the outcome of patients with unsatisfactory responses to MRD-directed DLI and could be a potential salvage treatment for these patients after allogeneic hematopoietic stem cell transplantation.
interferon-α / hematopoietic stem cell transplantation / minimal residual disease / donor lymphocyte infusion
[1] |
Tsirigotis P, Byrne M, Schmid C, Baron F, Ciceri F, Esteve J, Gorin NC, Giebel S, Mohty M, Savani BN, Nagler A. Relapse of AML after hematopoietic stem cell transplantation: methods of monitoring and preventive strategies. A review from the ALWP of the EBMT. Bone Marrow Transplant 2016; 51(11): 1431–1438
CrossRef
Pubmed
Google scholar
|
[2] |
Tsirigotis P, Liga M, Gkirkas K, Stamouli M, Triantafyllou E, Marangos M, Pessach I, Sarantopoulos A, Spyridis N, Spyridonidis A. Low-dose alemtuzumab for GvHD prevention followed by prophylactic donor lymphocyte infusions in high-risk leukemia. Bone Marrow Transplant 2017; 52(3): 445–451
CrossRef
Pubmed
Google scholar
|
[3] |
Dominietto A, Pozzi S, Miglino M, Albarracin F, Piaggio G, Bertolotti F, Grasso R, Zupo S, Raiola AM, Gobbi M, Frassoni F, Bacigalupo A. Donor lymphocyte infusions for the treatment of minimal residual disease in acute leukemia. Blood 2007; 109(11): 5063–5064
CrossRef
Pubmed
Google scholar
|
[4] |
Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, Han W, Wang Y, Qin YZ, Huang XJ. Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood 2012; 119(14): 3256–3262
CrossRef
Pubmed
Google scholar
|
[5] |
Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Salvage chemotherapy followed by granulocyte colony-stimulating factor-primed donor leukocyte infusion with graft-vs.-host disease control for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation: prognostic factors and clinical outcomes. Eur J Haematol 2016; 96(3): 297–308
CrossRef
Pubmed
Google scholar
|
[6] |
McSweeney EN, Worman CP, Tsakona CP, Jewel AP, Hoffbrand AV, Milligan DW, Burnett AK, Lewis ML, Goldstone AH. Low-dose recombinant alfa-2a-interferon: a feasible maintenance therapy in acute myeloid leukaemia in the older patient. Acta Haematol 1993; 89(1): 1–5
Pubmed
|
[7] |
Smits EL, Anguille S, Berneman ZN. Interferon α may be back on track to treat acute myeloid leukemia. OncoImmunology 2013; 2(4): e23619
CrossRef
Pubmed
Google scholar
|
[8] |
Anguille S, Lion E, Willemen Y, Van Tendeloo VF, Berneman ZN, Smits EL. Interferon-α in acute myeloid leukemia: an old drug revisited. Leukemia 2011; 25(5): 739–748
CrossRef
Pubmed
Google scholar
|
[9] |
Singhal S, Powles R, Treleaven J, Mehta J. Sensitivity of secondary acute myeloid leukemia relapsing after allogeneic bone marrow transplantation to immunotherapy with interferon-α2b. Bone Marrow Transplant 1997; 19(11): 1151–1153
CrossRef
Pubmed
Google scholar
|
[10] |
Gesundheit B, Shapira MY, Resnick IB, Amar A, Kristt D, Dray L, Budowski E, Or R. Successful cell-mediated cytokine-activated immunotherapy for relapsed acute myeloid leukemia after hematopoietic stem cell transplantation. Am J Hematol 2009; 84(3): 188–190
CrossRef
Pubmed
Google scholar
|
[11] |
Tang X, Song YH, Sun A, Zhu X, Ruan C, Wu D. Successful treatment of relapsed acute myeloid leukemia without chemotherapy. J Clin Oncol 2016; 34(13): e117–e119
CrossRef
Pubmed
Google scholar
|
[12] |
Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Interferon-α: a potentially effective treatment for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 2015; 21(11): 1939–1947
CrossRef
Pubmed
Google scholar
|
[13] |
Mo X, Zhao X, Xu L, Liu D, Zhang X, Chen H, Wang Y, Huang X. Interferon α: the salvage therapy for patients with unsatisfactory response to minimal residual disease-directed modified donor lymphocyte infusion. Chin Med J (Engl) 2014; 127(14): 2583–2587
Pubmed
|
[14] |
Huang XJ, Xu LP, Liu KY, Liu DH, Wang Y, Chen H, Chen YH, Han W, Wang JZ, Chen Y, Zhang XH, Shi HX, Wang FR, Tang FF. Partially matched related donor transplantation can achieve outcomes comparable with unrelated donor transplantation for patients with hematologic malignancies. Clin Cancer Res 2009; 15(14): 4777–4783
CrossRef
Pubmed
Google scholar
|
[15] |
Wang Y, Liu QF, Xu LP, Liu KY, Zhang XH, Ma X, Fan ZP, Wu DP, Huang XJ. Haploidentical vs. identical-sibling transplant for AML in remission: a multicenter, prospective study. Blood 2015; 125(25): 3956–3962
CrossRef
Pubmed
Google scholar
|
[16] |
Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Wang JZ, Gao ZY, Zhang YC, Jiang Q, Shi HX, Lu DP. Haploidentical hematopoietic stem cell transplantation without in vitro T-cell depletion for the treatment of hematological malignancies. Bone Marrow Transplant 2006; 38(4): 291–297
CrossRef
Pubmed
Google scholar
|
[17] |
Huang XJ, Liu DH, Liu KY, Xu LP, Chen H, Han W, Chen YH, Zhang XH, Lu DP. Treatment of acute leukemia with unmanipulated HLA-mismatched/haploidentical blood and bone marrow transplantation. Biol Blood Marrow Transplant 2009; 15(2): 257–265
CrossRef
Pubmed
Google scholar
|
[18] |
Zhao XS, Liu YR, Zhu HH, Xu LP, Liu DH, Liu KY, Huang XJ. Monitoring MRD with flow cytometry: an effective method to predict relapse for ALL patients after allogeneic hematopoietic stem cell transplantation. Ann Hematol 2012; 91(2): 183–192
CrossRef
Pubmed
Google scholar
|
[19] |
Zhu HH, Zhang XH, Qin YZ, Liu DH, Jiang H, Chen H, Jiang Q, Xu LP, Lu J, Han W, Bao L, Wang Y, Chen YH, Wang JZ, Wang FR, Lai YY, Chai JY, Wang LR, Liu YR, Liu KY, Jiang B, Huang XJ. MRD-directed risk stratification treatment may improve outcomes of t(8;21) AML in the first complete remission: results from the AML05 multicenter trial. Blood 2013; 121(20): 4056–4062
CrossRef
Pubmed
Google scholar
|
[20] |
Wang Y, Wu DP, Liu QF, Qin YZ, Wang JB, Xu LP, Liu YR, Zhu HH, Chen J, Dai M, Huang XJ. In adults with t(8;21)AML, posttransplant RUNX1/RUNX1T1-based MRD monitoring, rather than c-KIT mutations, allows further risk stratification. Blood 2014; 124(12): 1880–1886
CrossRef
Pubmed
Google scholar
|
[21] |
Zhao XS, Jin S, Zhu HH, Xu LP, Liu DH, Chen H, Liu KY, Huang XJ. Wilms’ tumor gene 1 expression: an independent acute leukemia prognostic indicator following allogeneic hematopoietic SCT. Bone Marrow Transplant 2012; 47(4): 499–507
CrossRef
Pubmed
Google scholar
|
[22] |
Zhao XS, Yan CH, Liu DH, Xu LP, Liu YR, Liu KY, Qin YZ, Wang Y, Huang XJ. Combined use of WT1 and flow cytometry monitoring can promote sensitivity of predicting relapse after allogeneic HSCT without affecting specificity. Ann Hematol 2013; 92(8): 1111–1119
CrossRef
Pubmed
Google scholar
|
[23] |
Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Comparison of outcomes after donor lymphocyte infusion with or without prior chemotherapy for minimal residual disease in acute leukemia/myelodysplastic syndrome after allogeneic hematopoietic stem cell transplantation. Ann Hematol 2017; 96(5): 829–838
CrossRef
Pubmed
Google scholar
|
[24] |
Dignan FL, Clark A, Amrolia P, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Hadzic N, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of acute graft-versus-host disease. Br J Haematol 2012; 158(1): 30–45
CrossRef
Pubmed
Google scholar
|
[25] |
Dignan FL, Amrolia P, Clark A, Cornish J, Jackson G, Mahendra P, Scarisbrick JJ, Taylor PC, Shaw BE, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. Diagnosis and management of chronic graft-versus-host disease. Br J Haematol 2012; 158(1): 46–61
CrossRef
Pubmed
Google scholar
|
[26] |
Armand P, Gibson CJ, Cutler C, Ho VT, Koreth J, Alyea EP, Ritz J, Sorror ML, Lee SJ, Deeg HJ, Storer BE, Appelbaum FR, Antin JH, Soiffer RJ, Kim HT. A disease risk index for patients undergoing allogeneic stem cell transplantation. Blood 2012; 120(4): 905–913
CrossRef
Pubmed
Google scholar
|
[27] |
Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant 1995; 15(6): 825–828
Pubmed
|
[28] |
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, Martin P, Chien J, Przepiorka D, Couriel D, Cowen EW, Dinndorf P, Farrell A, Hartzman R, Henslee-Downey J, Jacobsohn D, McDonald G, Mittleman B, Rizzo JD, Robinson M, Schubert M, Schultz K, Shulman H, Turner M, Vogelsang G, Flowers ME. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant 2005; 11(12): 945–956
CrossRef
Pubmed
Google scholar
|
[29] |
Gooley TA, Leisenring W, Crowley J, Storer BE. Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 1999; 18(6): 695–706
CrossRef
Pubmed
Google scholar
|
[30] |
Rohatiner AZ. Growth inhibitory effects of interferon on blast cells from patients with acute myelogenous leukaemia. Br J Cancer 1984; 49(6): 805–807
CrossRef
Pubmed
Google scholar
|
[31] |
Morecki S, Revel-Vilk S, Nabet C, Pick M, Ackerstein A, Nagler A, Naparstek E, Ben Shahar M, Slavin S. Immunological evaluation of patients with hematological malignancies receiving ambulatory cytokine-mediated immunotherapy with recombinant human interferon-alpha 2a and interleukin-2. Cancer Immunol Immunother 1992; 35(6): 401–411
CrossRef
Pubmed
Google scholar
|
[32] |
Mo XD, Zhang XH, Xu LP, Wang Y, Yan CH, Chen H, Chen YH, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. IFN-α is effective for treatment of minimal residual disease in patients with acute leukemia after allogeneic hematopoietic stem cell transplantation: results of a registry study. Biol Blood Marrow Transplant 2017; 23(8): 1303–1310
CrossRef
Pubmed
Google scholar
|
[33] |
Kolb HJ, Mittermüller J, Clemm C, Holler E, Ledderose G, Brehm G, Heim M, Wilmanns W. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990; 76(12): 2462–2465
Pubmed
|
[34] |
Grigg A, Kannan K, Schwarer AP, Spencer A, Szer J. Chemotherapy and granulocyte colony stimulating factor-mobilized blood cell infusion followed by interferon-α for relapsed malignancy after allogeneic bone marrow transplantation. Intern Med J 2001; 31(1): 15–22
CrossRef
Pubmed
Google scholar
|
[35] |
Baron F, Labopin M, Niederwieser D, Vigouroux S, Cornelissen JJ, Malm C, Vindelov LL, Blaise D, Janssen JJ, Petersen E, Socié G, Nagler A, Rocha V, Mohty M. Impact of graft-versus-host disease after reduced-intensity conditioning allogeneic stem cell transplantation for acute myeloid leukemia: a report from the Acute Leukemia Working Party of the European group for blood and marrow transplantation. Leukemia 2012; 26(12): 2462–2468
CrossRef
Pubmed
Google scholar
|
[36] |
Mo XD, Xu LP, Zhang XH, Liu DH, Wang Y, Chen H, Yan CH, Chen YH, Han W, Wang FR, Wang JZ, Liu KY, Huang XJ. Chronic GVHD induced GVL effect after unmanipulated haploidentical hematopoietic SCT for AML and myelodysplastic syndrome. Bone Marrow Transplant 2015; 50(1): 127–133
CrossRef
Pubmed
Google scholar
|
[37] |
Schroeder T, Czibere A, Platzbecker U, Bug G, Uharek L, Luft T, Giagounidis A, Zohren F, Bruns I, Wolschke C, Rieger K, Fenk R, Germing U, Haas R, Kröger N, Kobbe G. Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia 2013; 27(6): 1229–1235
CrossRef
Pubmed
Google scholar
|
[38] |
Platzbecker U, Wermke M, Radke J, Oelschlaegel U, Seltmann F, Kiani A, Klut IM, Knoth H, Röllig C, Schetelig J, Mohr B, Graehlert X, Ehninger G, Bornhäuser M, Thiede C. Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia 2012; 26(3): 381–389
CrossRef
Pubmed
Google scholar
|
[39] |
Choi I, Yoon SR, Park SY, Kim H, Jung SJ, Jang YJ, Kang M, Yeom YI, Lee JL, Kim DY, Lee YS, Kang YA, Jeon M, Seol M, Lee JH, Lee JH, Kim HJ, Yun SC, Lee KH. Donor-derived natural killer cells infused after human leukocyte antigen-haploidentical hematopoietic cell transplantation: a dose-escalation study. Biol Blood Marrow Transplant 2014; 20(5): 696–704
CrossRef
Pubmed
Google scholar
|
[40] |
Cruz CR, Micklethwaite KP, Savoldo B, Ramos CA, Lam S, Ku S, Diouf O, Liu E, Barrett AJ, Ito S, Shpall EJ, Krance RA, Kamble RT, Carrum G, Hosing CM, Gee AP, Mei Z, Grilley BJ, Heslop HE, Rooney CM, Brenner MK, Bollard CM, Dotti G. Infusion of donor-derived CD19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood 2013; 122(17): 2965–2973
CrossRef
Pubmed
Google scholar
|
[41] |
Chen YB, Li S, Lane AA, Connolly C, Del Rio C, Valles B, Curtis M, Ballen K, Cutler C, Dey BR, El-Jawahri A, Fathi AT, Ho VT, Joyce A, McAfee S, Rudek M, Rajkhowa T, Verselis S, Antin JH, Spitzer TR, Levis M, Soiffer R. Phase I trial of maintenance sorafenib after allogeneic hematopoietic stem cell transplantation for fms-like tyrosine kinase 3 internal tandem duplication acute myeloid leukemia. Biol Blood Marrow Transplant 2014; 20(12): 2042–2048
CrossRef
Pubmed
Google scholar
|
[42] |
Klingemann HG, Grigg AP, Wilkie-Boyd K, Barnett MJ, Eaves AC, Reece DE, Shepherd JD, Phillips GL. Treatment with recombinant interferon (alpha-2b) early after bone marrow transplantation in patients at high risk for relapse [corrected]. Blood 1991; 78(12): 3306–3311 (corrected)
Pubmed
|
[43] |
Yan C, Xu L, Liu D, Chen H, Wang Y, Liu K, Huang X. Immunosuppression for 6-8 weeks after modified donor lymphocyte infusion reduced acute graft-versus-host disease without influencing graft-versus-leukemia effect in haploidentical transplant. Chin Med J (Engl) 2014; 127(20): 3602–3609
Pubmed
|
/
〈 | 〉 |