Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Roux, C; Tifratene, K; Socié, Get al.
2017 • In Bone Marrow Transplantation, 52, p. 678-682
[en] Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent ten-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted in chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and DLI (n=30), or isolated reinfusion of donor lymphocytes (DLI) (n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy = 385 d, second allograft = 391d, chemotherapy = 174d, DLI alone = 140d, palliative care = 43d. A second SCT or a combination of chemotherapy and donor lymphocytes infusion yielded similar outcome (HR=0.85, p=0.53) unlike chemotherapy alone (HR 1.43 p=0.04), palliative care (HR=4.24, p<0.0001) or isolated DLI (HR=1,94, p<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML.
Disciplines :
Hematology
Author, co-author :
Roux, C
Tifratene, K
Socié, G
Galambrun, C
Bertrand, Y
Rialland, F
Jubert, C
Pochon, C
Paillard, C
Sirvent, A
Nelken, B
Vannier, J-P
Freycon, C
BEGUIN, Yves ; Centre Hospitalier Universitaire de Liège - CHU > Service d'hématologie clinique
Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)
Frassoni F, Barrett AJ, Granena A, Ernst P, Garthon G, Kolb HJ et al. Relapse after allogeneic bone marrow transplantation for acute leukaemia: a survey by the E.B.M.T. of 117 cases. Br J Haematol 1988; 70: 317-320.
Mortimer J, Blinder MA, Schulman S, Schulman S, Appelbaum FR, Buckner CD et al. Relapse of acute leukemia after marrow transplantation: natural history and results of subsequent therapy. J Clin Oncol 1989; 7: 50-57.
Radich JP, Sanders JE, Buckner CD, Martin PJ, Petersen FB, Bensinger W et al. Second allogeneic marrow transplantation for patients with recurrent leukemia after initial transplant with total body irradiation containing regimens. J Clin Oncol 1993; 11: 304-313.
Barrett AJ, Locatelli F, Treleaven JG, Gratwohl A, Szydlo R, Zwaan FE. Second transplants for leukaemic relapse after bone marrow transplantation: high early mortality but favourable effect of chronic GVHD on continued remission. A report by the EBMT Leukaemia Working Party. Br J Haematol 1991; 79: 567-574.
Michallet M, Tanguy ML, Socie G, Thiébaut A, Belhabri A, Milpied N et al. Second allogeneic haematopoietic stem cell trans-plantation in relapsed acute and chronic leukaemias for patients who underwent a first allogeneic bone marrow transplantation: a survey of the Societe Francaise de Greffe de moelle (SFGM). Br J Haematol 2000; 108: 400-407.
Eapen M, Giralt SA, Horowitz MM, Klein JP, Wagner JE, Zhang MJ et al. Second transplant for acute and chronic leukemia relapsing after first HLA-identical sibling transplant. Bone Marrow Transplant 2004; 34: 721-727.
Bosi A, Laszlo D, Labopin M, Reffeirs J, Michallet M, Gluckman E et al. Second allogeneic bone marrow transplantation in acute leukemia: results of a survey by the European Cooperative Group for Blood and Marrow Transplantation. J Clin Oncol 2001; 19: 3675-3684.
Hosing C, Saliba RM, Shahjahan M, Estey EH, Couriel D, Giralt S et al. Disease burden may identify patients more likely to benefit from second allogeneic hematopoietic stemcell transplantation to treat relapsed acute myelogenous leukemia. Bone Marrow Transplant 2005; 36: 157-162.
Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W et al. Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients: European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia. Blood 1995; 86: 2041-2050.
Porter DL, Roth MS, Lee SJ, McGarigle C, Ferrara JL, Antin JH. Adoptive immunotherapy with donor mononuclear cell infusions to treat relapse of acute leukemia or myelodysplasia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1996; 18: 975-980.
Collins RH Jr., Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al. Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 1997; 15: 433-444.
Levine JE, Braun T, Penza SL, Beatty P, Cornetta K, Martino R et al. Prospective trial of chemotherapy and donor leukocyte infusions for relapse of advanced myeloid malignancies after allogeneic stem-cell transplantation. J Clin Oncol 2002; 20: 405-412.
Schmid C, Labopin M, Nagler A, Bornhäuser M, Finke J, Fassas A et al. Donor lymphocyte infusion in the treatment of first hematological relapse after allogeneic stem-cell transplantation in adults with acute myeloid leukemia: a retrospective risk factors analysis and comparison with other strategies by the EBMT Acute Leukemia Working Party. J Clin Oncol 2007; 25: 4938-4945.
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53: 457-481.
Rubin D. Multiple Imputation for Nonresponse in Surveys. Wiley: New York, NY, USA, 1987.
Meshinchi S, Leisenring WM, Carpenter PA, Woolfrey AE, Sievers EL, Radich JP et al. Survival after second hematopoietic stem cell transplantation for recurrent pediatric acute myeloid leukemia. Biol Blood Marrow Transplant 2003; 9: 706-713.
Von Stackelberg A, Völzke E, Kühl JS, Seeger K, Schrauder A, Escherich G et al. ALLREZ BFM Study Group Outcome of children and adolescents with relapsed acute lymphoblastic leukaemia and non-response to salvage protocol therapy: a retrospective analysis of the ALL-REZ BFM Study Group. Eur J Cancer 2011; 47: 90-97.
Schroeder T, Czibere A, Platzbecker U, Bug G, Uharek L, Luft T et al. Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia 2013; 27: 1229-1235.
Bader P, Kreyenberg H, Henze GH, Eckert C, Reising M, Willasch A et al. Prognostic value of minimal residual disease quantification before allogeneic stem-cell transplantation in relapsed childhood acute lymphoblastic leukemia: the ALL-REZ BFM Study Group. J Clin Oncol 2009; 27: 377-384.
Van der Velden VH, van der Sluijs-Geling A, Gibson BE, te Marvelde JG, Hoogeveen PG, Hop WC et al. Clinical significance of flow cytometric minimal residual disease detection in pediatric acute myeloid leukemia patients treated according to the DCOG AnLL97/MRC AML12 protocol. Leukemia 2010; 24: 1599-1606.
Rubnitz JE, Inaba H. Childhood acute myeloid leukaemia. Br J Haematol 2012; 159: 259-276.
Zugmaier G, Gökbuget N, Klinger M, Bargou RC, Topp MS et al. Long-term survival and T-cell kinetics in relapsed/refractory ALL patients who achieved MRD response after blinatumomab treatment. Blood 2015; 126: 2578-2584.
Schlegel P, Lang P, Zugmaier G, Feuchtinger T, Handgretinger R. Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab. Haematologica 2014; 99: 1212-1219.
Zhang T, Cao L, Xie J, Shi N, Zhang Z, Luo Z et al. Efficiency of CD19 chimeric antigen receptor-modified T cells for treatment of B cell malignancies in phase I clinical trials: a meta-Analysis. Oncotarget 2015; 6: 33961-33971.
Van der Stegen SJ, Hamieh M, Sadelain M. The pharmacology of second-generation chimeric antigen receptors. Nat Rev Drug Discov 2015; 14: 499-509.
