Skip to main content
Top
Published in: Annals of Hematology 9/2020

01-09-2020 | Myelodysplastic Syndrome | Review Article

The FLAMSA concept—past and future

Authors: Hans-Jochem Kolb, Christoph Schmid

Published in: Annals of Hematology | Issue 9/2020

Login to get access

Abstract

The FLAMSA reduced intensity (RIC) concept, also known as “sequential therapy”, is a conceptual platform for the treatment of leukemia separated in several parts: induction therapy, a sequence of antileukemic and immunosuppressive conditioning for allogeneic stem cell transplantation, and immune restitution supported by donor lymphocyte transfusions. The antileukemic part consists of fludarabine, cytosine arabinoside, and amsacrine (FLAMSA); non-cross reactive agents like fludarabine and amsacrine have been successfully used in cases of refractoriness and relapse. Immunosuppressive conditioning and transplantation follow after only 3 days of rest. This way, the toxicity of allogeneic transplantation could be reduced and the anti-leukemia effects by using allogeneic immune cells could be optimized. This review summarizes available data on efficacy and toxicity of this approach. Further, possible strategies for improvements are discussed in order to provide better chances for elderly and frail patients and patients with advanced and high-risk disease. Among others, several new agents are available that target molecular changes of leukemia for induction of remission and allow for bridging the time after transplantation until adoptive immunotherapy becomes safe and effective.
Literature
1.
go back to reference Thomas ED, Lochte HL Jr, Cannon JH, Sahler OD, Ferrebee JW (1959) Supralethal whole body irradiation and isologous marrow transplantation in man. J Clin Invest 38:1709–1716PubMedPubMedCentralCrossRef Thomas ED, Lochte HL Jr, Cannon JH, Sahler OD, Ferrebee JW (1959) Supralethal whole body irradiation and isologous marrow transplantation in man. J Clin Invest 38:1709–1716PubMedPubMedCentralCrossRef
2.
go back to reference Mathe G, Amiel JL, Schwarzenberg L, Cattan A, Schneider M (1965) Adoptive immunotherapy of acute leukemia: experimental and clinical results. Cancer Res 25(9):1525–1531PubMed Mathe G, Amiel JL, Schwarzenberg L, Cattan A, Schneider M (1965) Adoptive immunotherapy of acute leukemia: experimental and clinical results. Cancer Res 25(9):1525–1531PubMed
3.
go back to reference Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE et al (1975) Bone-marrow transplantation (first of two parts). N Engl J Med 292(16):832–843PubMedCrossRef Thomas E, Storb R, Clift RA, Fefer A, Johnson FL, Neiman PE et al (1975) Bone-marrow transplantation (first of two parts). N Engl J Med 292(16):832–843PubMedCrossRef
4.
go back to reference Kolb HJ, Rieder I, Rodt H, Netzel B, Grosse Wilde H, Scholz S et al (1979) Antilymphocytic antibodies and marrow transplantation. VI. Graft- versus-host tolerance in DLA-incompatible dogs after in vitro treatment of bone marrow with absorbed antithymocyte globulin. Transplantation 27:242–245PubMedCrossRef Kolb HJ, Rieder I, Rodt H, Netzel B, Grosse Wilde H, Scholz S et al (1979) Antilymphocytic antibodies and marrow transplantation. VI. Graft- versus-host tolerance in DLA-incompatible dogs after in vitro treatment of bone marrow with absorbed antithymocyte globulin. Transplantation 27:242–245PubMedCrossRef
5.
go back to reference Rodt H, Kolb HJ, Netzel B, Rieder I, Janka G, Belohradsky B et al (1979) GVHD suppression by incubation of bone marrow grafts with anti-T- cell globulin: effect in the canine model and application to clinical bone marrow transplantation. TransplantProc. 11:962–966 Rodt H, Kolb HJ, Netzel B, Rieder I, Janka G, Belohradsky B et al (1979) GVHD suppression by incubation of bone marrow grafts with anti-T- cell globulin: effect in the canine model and application to clinical bone marrow transplantation. TransplantProc. 11:962–966
6.
go back to reference Waldmann H, Polliak A, Hale G, Or R, Cividalli G, Weiss L et al (1984) Elimination of graft-versus-host disease by in-vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (Campath 1). Lancet II:483–486CrossRef Waldmann H, Polliak A, Hale G, Or R, Cividalli G, Weiss L et al (1984) Elimination of graft-versus-host disease by in-vitro depletion of alloreactive lymphocytes with a monoclonal rat anti-human lymphocyte antibody (Campath 1). Lancet II:483–486CrossRef
7.
go back to reference Goldman JM, Gale RP, Horowitz MM, Biggs JC, Champlin RE, Gluckman E et al (1988) Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T-cell depletion. AnnInternMed. 108:806–814 Goldman JM, Gale RP, Horowitz MM, Biggs JC, Champlin RE, Gluckman E et al (1988) Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk of relapse associated with T-cell depletion. AnnInternMed. 108:806–814
8.
go back to reference Kolb HJ, Gunther W, Schumm M, Holler E, Wilmanns W, Thierfelder S (1997) Adoptive immunotherapy in canine chimeras. Transplantation. 63(3):430–436PubMedCrossRef Kolb HJ, Gunther W, Schumm M, Holler E, Wilmanns W, Thierfelder S (1997) Adoptive immunotherapy in canine chimeras. Transplantation. 63(3):430–436PubMedCrossRef
9.
go back to reference Apperley JF, Jones L, Hale G, Waldmann H, Hows J, Rombos Y, Tsatalas C, Marcus RE, Goolden AW, Gordon-Smith EC (1986) Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse. Bone Marrow Transplant 1(1):53–66PubMed Apperley JF, Jones L, Hale G, Waldmann H, Hows J, Rombos Y, Tsatalas C, Marcus RE, Goolden AW, Gordon-Smith EC (1986) Bone marrow transplantation for patients with chronic myeloid leukaemia: T-cell depletion with Campath-1 reduces the incidence of graft-versus-host disease but may increase the risk of leukaemic relapse. Bone Marrow Transplant 1(1):53–66PubMed
10.
go back to reference Kolb HJ, Beisser K, Mittermueller J, Clemm C, Schumm M, Ledderose G et al (1992) Adoptive immunotherapy in human and canine chimeras. In: Hiddemann W, Büchner T, Plunkett W, Keating M, Wörmann B, Andreeff M (eds) Acute Leukemias - Pharmakokinetics. Springer, Berlin, pp 595–600CrossRef Kolb HJ, Beisser K, Mittermueller J, Clemm C, Schumm M, Ledderose G et al (1992) Adoptive immunotherapy in human and canine chimeras. In: Hiddemann W, Büchner T, Plunkett W, Keating M, Wörmann B, Andreeff M (eds) Acute Leukemias - Pharmakokinetics. Springer, Berlin, pp 595–600CrossRef
11.
go back to reference Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G, Heim M, Wilmanns W (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 76(12):2462–2465PubMedCrossRef Kolb HJ, Mittermuller J, Clemm C, Holler E, Ledderose G, Brehm G, Heim M, Wilmanns W (1990) Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 76(12):2462–2465PubMedCrossRef
12.
go back to reference Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, Ljungman P, Ferrant A, Verdonck L, Niederwieser D, van Rhee F, Mittermueller J, de Witte T, Holler E, Ansari H, European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia (1995) Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients 397. Blood. 86(5):2041–2050PubMedCrossRef Kolb HJ, Schattenberg A, Goldman JM, Hertenstein B, Jacobsen N, Arcese W, Ljungman P, Ferrant A, Verdonck L, Niederwieser D, van Rhee F, Mittermueller J, de Witte T, Holler E, Ansari H, European Group for Blood and Marrow Transplantation Working Party Chronic Leukemia (1995) Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients 397. Blood. 86(5):2041–2050PubMedCrossRef
13.
go back to reference Collins RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al (1997) Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 15:433–444PubMedCrossRef Collins RH, Shpilberg O, Drobyski WR, Porter DL, Giralt S, Champlin R et al (1997) Donor leukocyte infusions in 140 patients with relapsed malignancy after allogeneic bone marrow transplantation. J Clin Oncol 15:433–444PubMedCrossRef
14.
go back to reference Shiobara S, Nakao S, Ueda M, Yamazaki H, Takahashi S, Asano S, Yabe H, Kato S, Imoto S, Maruta A, Yoshida T, Gondo H, Morishima Y, Kodera Y (2000) Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: lower incidence of acute graft-versus-host disease and improved outcome. Bone Marrow Transplant 26(7):769–774PubMedCrossRef Shiobara S, Nakao S, Ueda M, Yamazaki H, Takahashi S, Asano S, Yabe H, Kato S, Imoto S, Maruta A, Yoshida T, Gondo H, Morishima Y, Kodera Y (2000) Donor leukocyte infusion for Japanese patients with relapsed leukemia after allogeneic bone marrow transplantation: lower incidence of acute graft-versus-host disease and improved outcome. Bone Marrow Transplant 26(7):769–774PubMedCrossRef
15.
go back to reference McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG et al (2001) Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 97(11):3390–3400PubMedCrossRef McSweeney PA, Niederwieser D, Shizuru JA, Sandmaier BM, Molina AJ, Maloney DG et al (2001) Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood. 97(11):3390–3400PubMedCrossRef
16.
go back to reference Giralt S, Khouri I, Champlin R (1999) Non myeloablative "mini transplants". Cancer Treat Res 101:97–108PubMedCrossRef Giralt S, Khouri I, Champlin R (1999) Non myeloablative "mini transplants". Cancer Treat Res 101:97–108PubMedCrossRef
17.
go back to reference Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ (2005) Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 23(24):5675–5687PubMedCrossRef Schmid C, Schleuning M, Ledderose G, Tischer J, Kolb HJ (2005) Sequential regimen of chemotherapy, reduced-intensity conditioning for allogeneic stem-cell transplantation, and prophylactic donor lymphocyte transfusion in high-risk acute myeloid leukemia and myelodysplastic syndrome. J Clin Oncol 23(24):5675–5687PubMedCrossRef
18.
go back to reference Gandhi V, Estey E, Keating MJ, Plunkett W (1993) Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol 11(1):116–124PubMedCrossRef Gandhi V, Estey E, Keating MJ, Plunkett W (1993) Fludarabine potentiates metabolism of cytarabine in patients with acute myelogenous leukemia during therapy. J Clin Oncol 11(1):116–124PubMedCrossRef
19.
go back to reference Legha SS, Keating MJ, Zander AR, McCredie KB, Bodey GP, Freireich EJ (1980) 4′-(9-Acridinylamino) methanesulfon-m-anisidide (AMSA): a new drug effective in the treatment of adult acute leukemia. Ann Intern Med 93(1):17–21PubMedCrossRef Legha SS, Keating MJ, Zander AR, McCredie KB, Bodey GP, Freireich EJ (1980) 4′-(9-Acridinylamino) methanesulfon-m-anisidide (AMSA): a new drug effective in the treatment of adult acute leukemia. Ann Intern Med 93(1):17–21PubMedCrossRef
20.
go back to reference Arlin ZA, Feldman EJ, Mittelman A, Ahmed T, Puccio C, Chun HG, Cook P, Baskind P, Marboe C, Mehta R (1991) Amsacrine is safe and effective therapy for patients with myocardial dysfunction and acute leukemia. Cancer. 68(6):1198–1200PubMedCrossRef Arlin ZA, Feldman EJ, Mittelman A, Ahmed T, Puccio C, Chun HG, Cook P, Baskind P, Marboe C, Mehta R (1991) Amsacrine is safe and effective therapy for patients with myocardial dysfunction and acute leukemia. Cancer. 68(6):1198–1200PubMedCrossRef
21.
go back to reference Mohty M, Malard F, Blaise D, Milpied N, Socie G, Huynh A et al (2017) Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia. Haematologica. 102(1):184–191PubMedPubMedCentralCrossRef Mohty M, Malard F, Blaise D, Milpied N, Socie G, Huynh A et al (2017) Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia. Haematologica. 102(1):184–191PubMedPubMedCentralCrossRef
22.
go back to reference Santos GW, Tutschka P, Brookmeyer R et al (1983) Marrow transplantation for acute non-lymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 309:1347–1353PubMedCrossRef Santos GW, Tutschka P, Brookmeyer R et al (1983) Marrow transplantation for acute non-lymphocytic leukemia after treatment with busulfan and cyclophosphamide. N Engl J Med 309:1347–1353PubMedCrossRef
23.
go back to reference Kolb HJ, Guenther W, Gyurkocza B, Hoetzl F, Simoes B, Falk C, Schleuning M, Ledderose G (2003) Tolerance and chimerism. Transplantation. 75(9 Suppl):26S–31SPubMedCrossRef Kolb HJ, Guenther W, Gyurkocza B, Hoetzl F, Simoes B, Falk C, Schleuning M, Ledderose G (2003) Tolerance and chimerism. Transplantation. 75(9 Suppl):26S–31SPubMedCrossRef
24.
go back to reference Anderlini P, Wu J, Gersten I, Ewell M, Tolar J, Antin JH, Adams R, Arai S, Eames G, Horwitz ME, McCarty J, Nakamura R, Pulsipher MA, Rowley S, Leifer E, Carter SL, DiFronzo NL, Horowitz MM, Confer D, Deeg HJ, Eapen M (2015) Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. Lancet Haematol 2(9):e367–e375PubMedPubMedCentralCrossRef Anderlini P, Wu J, Gersten I, Ewell M, Tolar J, Antin JH, Adams R, Arai S, Eames G, Horwitz ME, McCarty J, Nakamura R, Pulsipher MA, Rowley S, Leifer E, Carter SL, DiFronzo NL, Horowitz MM, Confer D, Deeg HJ, Eapen M (2015) Cyclophosphamide conditioning in patients with severe aplastic anaemia given unrelated marrow transplantation: a phase 1-2 dose de-escalation study. Lancet Haematol 2(9):e367–e375PubMedPubMedCentralCrossRef
25.
go back to reference Weisser M, Schleuning M, Ledderose G, Rolf B, Schnittger S, Schoch C, Schwerdtfeger R, Kolb HJ (2004) Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide and ATG in elderly CML patients provides excellent results especially when performed in the early course of the disease. Bone Marrow Transplant 34(12):1083–1088PubMedCrossRef Weisser M, Schleuning M, Ledderose G, Rolf B, Schnittger S, Schoch C, Schwerdtfeger R, Kolb HJ (2004) Reduced-intensity conditioning using TBI (8 Gy), fludarabine, cyclophosphamide and ATG in elderly CML patients provides excellent results especially when performed in the early course of the disease. Bone Marrow Transplant 34(12):1083–1088PubMedCrossRef
26.
go back to reference Kimler BF, Park CH, Yakar D, Mies RM (1985) Radiation response of human normal and leukemic hemopoietic cells assayed by in vitro colony formation. Int J Radiat Oncol Biol Phys 11(4):809–816PubMedCrossRef Kimler BF, Park CH, Yakar D, Mies RM (1985) Radiation response of human normal and leukemic hemopoietic cells assayed by in vitro colony formation. Int J Radiat Oncol Biol Phys 11(4):809–816PubMedCrossRef
27.
go back to reference Pfeiffer T, Schleuning M, Mayer J, Haude KH, Tischer J, Buchholz S, Bunjes D, Bug G, Holler E, Meyer RG, Greinix H, Scheid C, Christopeit M, Schnittger S, Braess J, Schlimok G, Spiekermann K, Ganser A, Kolb HJ, Schmid C (2013) Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse. Haematologica. 98(4):518–525PubMedPubMedCentralCrossRef Pfeiffer T, Schleuning M, Mayer J, Haude KH, Tischer J, Buchholz S, Bunjes D, Bug G, Holler E, Meyer RG, Greinix H, Scheid C, Christopeit M, Schnittger S, Braess J, Schlimok G, Spiekermann K, Ganser A, Kolb HJ, Schmid C (2013) Influence of molecular subgroups on outcome of acute myeloid leukemia with normal karyotype in 141 patients undergoing salvage allogeneic stem cell transplantation in primary induction failure or beyond first relapse. Haematologica. 98(4):518–525PubMedPubMedCentralCrossRef
28.
go back to reference Heinicke T, Labopin M, Schmid C, Polge E, Socie G, Blaise D et al (2018) Reduced relapse incidence with FLAMSA-RIC compared with busulfan/fludarabine for acute myelogenous leukemia patients in first or second complete remission: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 24(11):2224–2232PubMedCrossRef Heinicke T, Labopin M, Schmid C, Polge E, Socie G, Blaise D et al (2018) Reduced relapse incidence with FLAMSA-RIC compared with busulfan/fludarabine for acute myelogenous leukemia patients in first or second complete remission: a study from the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant 24(11):2224–2232PubMedCrossRef
29.
go back to reference Holtick U, Herling M, Pflug N, Chakupurakal G, Leitzke S, Wolf D, Hallek M, Scheid C, Chemnitz JM (2017) Similar outcome after allogeneic stem cell transplantation with a modified FLAMSA conditioning protocol substituting 4 Gy TBI with treosulfan in an elderly population with high-risk AML. Ann Hematol 96(3):479–487PubMedCrossRef Holtick U, Herling M, Pflug N, Chakupurakal G, Leitzke S, Wolf D, Hallek M, Scheid C, Chemnitz JM (2017) Similar outcome after allogeneic stem cell transplantation with a modified FLAMSA conditioning protocol substituting 4 Gy TBI with treosulfan in an elderly population with high-risk AML. Ann Hematol 96(3):479–487PubMedCrossRef
30.
go back to reference Craddock C, Jackson AE, Malladi RK, Gilleece MH, Peniket A, Salim R, Tholouli E, Potter V, Crawley CR, Protheroe RE, Anne Parker A, Wilson K, Pavlu J, Nagra Siddique S, Hodgkinson A, Mason J, Wheatley K, Russell NH, Freeman SD (2019) The sequential FLAMSA-Bu conditioning regimen does not improve outcome in patients allografted for high risk acute myeloid and myelodysplasia irrespective of pre-transplant MRD status: results of the UK NCRI Figaro Trial. Blood. 134(Suppl 1) Craddock C, Jackson AE, Malladi RK, Gilleece MH, Peniket A, Salim R, Tholouli E, Potter V, Crawley CR, Protheroe RE, Anne Parker A, Wilson K, Pavlu J, Nagra Siddique S, Hodgkinson A, Mason J, Wheatley K, Russell NH, Freeman SD (2019) The sequential FLAMSA-Bu conditioning regimen does not improve outcome in patients allografted for high risk acute myeloid and myelodysplasia irrespective of pre-transplant MRD status: results of the UK NCRI Figaro Trial. Blood. 134(Suppl 1)
31.
go back to reference Sheth V, Labopin M, Canaani J, Volin L, Brecht A, Ganser A, et al. (2018) Comparison of FLAMSA-based reduced intensity conditioning with treosulfan/fludarabine conditioning for patients with acute myeloid leukemia: an ALWP/EBMT analysis. Bone Marrow Transplant Sheth V, Labopin M, Canaani J, Volin L, Brecht A, Ganser A, et al. (2018) Comparison of FLAMSA-based reduced intensity conditioning with treosulfan/fludarabine conditioning for patients with acute myeloid leukemia: an ALWP/EBMT analysis. Bone Marrow Transplant
32.
go back to reference Deeg HJ, Stevens EA, Salit RB, Ermoian RP, Fang M, Gyurkocza B, Sorror ML, Fatobene G, Baumgart J, Burroughs LM, Delaney C, Doney K, Egan DN, Flowers MED, Milano F, Radich JP, Scott BL, Sickle EJ, Wood BL, Yeung C, Storer BE (2018) Transplant conditioning with treosulfan/fludarabine with or without total body irradiation: a randomized phase II trial in patients with myelodysplastic syndrome and acute myeloid leukemia. Biol Blood Marrow Transplant 24(5):956–963PubMedCrossRef Deeg HJ, Stevens EA, Salit RB, Ermoian RP, Fang M, Gyurkocza B, Sorror ML, Fatobene G, Baumgart J, Burroughs LM, Delaney C, Doney K, Egan DN, Flowers MED, Milano F, Radich JP, Scott BL, Sickle EJ, Wood BL, Yeung C, Storer BE (2018) Transplant conditioning with treosulfan/fludarabine with or without total body irradiation: a randomized phase II trial in patients with myelodysplastic syndrome and acute myeloid leukemia. Biol Blood Marrow Transplant 24(5):956–963PubMedCrossRef
33.
go back to reference Drobyski WR, Keever CA, Roth MS, Koethe S, Hanson G, McFadden P, Gottschall JL, Ash RC, van Tuinen P, Horowitz MM (1993) Salvage immunotherapy using donor leukocyte infusions as treatment for relpased chronic myelogenous leukemia after bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood. 82:2310–2318PubMedCrossRef Drobyski WR, Keever CA, Roth MS, Koethe S, Hanson G, McFadden P, Gottschall JL, Ash RC, van Tuinen P, Horowitz MM (1993) Salvage immunotherapy using donor leukocyte infusions as treatment for relpased chronic myelogenous leukemia after bone marrow transplantation: efficacy and toxicity of a defined T-cell dose. Blood. 82:2310–2318PubMedCrossRef
34.
go back to reference Johnson BD, Becker EE, LaBelle JL, Truitt RL (1999) Role of immunoregulatory donor T cells in suppression of graft-versus-host disease following donor leukocyte infusion therapy. JImmunol. 163(12):6479–6487 Johnson BD, Becker EE, LaBelle JL, Truitt RL (1999) Role of immunoregulatory donor T cells in suppression of graft-versus-host disease following donor leukocyte infusion therapy. JImmunol. 163(12):6479–6487
35.
go back to reference Kolb HJ, Rank A, Chen X (2004) In-vivo generation of leukaemia-derived dendritic cells. . p. 439–51 Kolb HJ, Rank A, Chen X (2004) In-vivo generation of leukaemia-derived dendritic cells. . p. 439–51
36.
go back to reference Mackinnon S, Papadopoulos EB, Carabasi MH, Reich L, Collins NH, Boulad F, Castro-Malaspina H, Childs BH, Gillio AP, Kernan NA (1995) Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood. 86:1261–1268PubMedCrossRef Mackinnon S, Papadopoulos EB, Carabasi MH, Reich L, Collins NH, Boulad F, Castro-Malaspina H, Childs BH, Gillio AP, Kernan NA (1995) Adoptive immunotherapy evaluating escalating doses of donor leukocytes for relapse of chronic myeloid leukemia after bone marrow transplantation: separation of graft-versus-leukemia responses from graft-versus-host disease. Blood. 86:1261–1268PubMedCrossRef
37.
go back to reference Dazzi F, Szydlo RM, Craddock C, Cross NC, Kaeda J, Chase A et al (2000) Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood. 95(1):67–71PubMedCrossRef Dazzi F, Szydlo RM, Craddock C, Cross NC, Kaeda J, Chase A et al (2000) Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood. 95(1):67–71PubMedCrossRef
38.
go back to reference Schmid C, Schleuning M, Aschan J, Ringden O, Hahn J, Holler E et al (2004) Low-dose ARAC, donor cells, and GM-CSF for treatment of recurrent acute myeloid leukemia after allogeneic stem cell transplantation. Leukemia. 18(8):1430–1433PubMedCrossRef Schmid C, Schleuning M, Aschan J, Ringden O, Hahn J, Holler E et al (2004) Low-dose ARAC, donor cells, and GM-CSF for treatment of recurrent acute myeloid leukemia after allogeneic stem cell transplantation. Leukemia. 18(8):1430–1433PubMedCrossRef
39.
go back to reference Jedlickova Z, Schmid C, Koenecke C, Hertenstein B, Baurmann H, Schwerdtfeger R, Tischer J, Kolb HJ, Schleuning M (2016) Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation. Bone Marrow Transplant 51(5):663–667PubMedCrossRef Jedlickova Z, Schmid C, Koenecke C, Hertenstein B, Baurmann H, Schwerdtfeger R, Tischer J, Kolb HJ, Schleuning M (2016) Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation. Bone Marrow Transplant 51(5):663–667PubMedCrossRef
40.
go back to reference Schumm M, Günther W, Kolb HJ, Rieber P, Büttner M, Voss C et al (1994) Prevention of graft-versus-host disease in DLA-haplotype mismatched dogs and hemopoietic engraftment of CD6-depleted marrow with and without cG-CSF treatment after transplantation. Tissue Antigens 43:170–178PubMedCrossRef Schumm M, Günther W, Kolb HJ, Rieber P, Büttner M, Voss C et al (1994) Prevention of graft-versus-host disease in DLA-haplotype mismatched dogs and hemopoietic engraftment of CD6-depleted marrow with and without cG-CSF treatment after transplantation. Tissue Antigens 43:170–178PubMedCrossRef
41.
go back to reference Kernan NA, Collins NJ, Juliano L, Cartagena T, Dupont B, Oreilly RJ (1986) Clonable T-lymphocytes in T-depleted bone marrow transplants correlate with development of graft-versus-host disease. Blood 68:770PubMedCrossRef Kernan NA, Collins NJ, Juliano L, Cartagena T, Dupont B, Oreilly RJ (1986) Clonable T-lymphocytes in T-depleted bone marrow transplants correlate with development of graft-versus-host disease. Blood 68:770PubMedCrossRef
42.
go back to reference Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A, Clark FJ, Hunt L, Yin J, Fuller S, Vandenberghe E, Marsh J, Littlewood T, Smith GM, Culligan D, Hunter A, Chopra R, Davies A, Towlson K, Williams CD (2002) The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood. 100(9):3108–3114PubMedCrossRef Marks DI, Lush R, Cavenagh J, Milligan DW, Schey S, Parker A, Clark FJ, Hunt L, Yin J, Fuller S, Vandenberghe E, Marsh J, Littlewood T, Smith GM, Culligan D, Hunter A, Chopra R, Davies A, Towlson K, Williams CD (2002) The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood. 100(9):3108–3114PubMedCrossRef
43.
go back to reference Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, Patel Y, Bhudia N, Farah H, Mason J, Wall K, Akiki S, Griffiths M, Solomon E, McCaughan F, Linch DC, Gale RE, Vyas P, Freeman SD, Russell N, Burnett AK, Grimwade D, UK National Cancer Research Institute AML Working Group (2016) Assessment of minimal residual disease in standard-risk AML. N Engl J Med 374(5):422–433PubMedCrossRef Ivey A, Hills RK, Simpson MA, Jovanovic JV, Gilkes A, Grech A, Patel Y, Bhudia N, Farah H, Mason J, Wall K, Akiki S, Griffiths M, Solomon E, McCaughan F, Linch DC, Gale RE, Vyas P, Freeman SD, Russell N, Burnett AK, Grimwade D, UK National Cancer Research Institute AML Working Group (2016) Assessment of minimal residual disease in standard-risk AML. N Engl J Med 374(5):422–433PubMedCrossRef
44.
go back to reference Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A et al (2018) Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med 378(13):1189–1199PubMedCrossRef Jongen-Lavrencic M, Grob T, Hanekamp D, Kavelaars FG, Al Hinai A, Zeilemaker A et al (2018) Molecular minimal residual disease in acute myeloid leukemia. N Engl J Med 378(13):1189–1199PubMedCrossRef
45.
go back to reference Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, Han W, Wang Y, Qin YZ, Huang XJ (2012) Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 119(14):3256–3262PubMedCrossRef Yan CH, Liu DH, Liu KY, Xu LP, Liu YR, Chen H, Han W, Wang Y, Qin YZ, Huang XJ (2012) Risk stratification-directed donor lymphocyte infusion could reduce relapse of standard-risk acute leukemia patients after allogeneic hematopoietic stem cell transplantation. Blood. 119(14):3256–3262PubMedCrossRef
46.
go back to reference Yan CH, Liu QF, Wu DP, Zhang X, Xu LP, Zhang XH et al (2017) Prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease and graft-versus-host disease-guided multiple DLIs could improve outcomes after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapsed acute leukemia. Biol Blood Marrow Transplant 23(8):1311–1319PubMedCrossRef Yan CH, Liu QF, Wu DP, Zhang X, Xu LP, Zhang XH et al (2017) Prophylactic donor lymphocyte infusion (DLI) followed by minimal residual disease and graft-versus-host disease-guided multiple DLIs could improve outcomes after allogeneic hematopoietic stem cell transplantation in patients with refractory/relapsed acute leukemia. Biol Blood Marrow Transplant 23(8):1311–1319PubMedCrossRef
47.
go back to reference Dazzi F, Raanani P, van Rhee F, Olavarria E, Szydlo RM, Apperley JF, et al. (1997) RT-PCR for bcr-abl transcripts in CML patients receiving DLI as treatment for relapse after BMT: differing pattern of molecular response. Bone Marrow Transplant. 19(Suppl 1):S32-S Dazzi F, Raanani P, van Rhee F, Olavarria E, Szydlo RM, Apperley JF, et al. (1997) RT-PCR for bcr-abl transcripts in CML patients receiving DLI as treatment for relapse after BMT: differing pattern of molecular response. Bone Marrow Transplant. 19(Suppl 1):S32-S
48.
go back to reference Chen X, Regn S, Kolb HJ, Roskrow M (1999) The generation of leukemic dendritic cells from patients with chronic myeloid leukemia (CML) using the combination of interferon-à and GM-CSF. Blood. 94(10 Suppl 1):529a-a Chen X, Regn S, Kolb HJ, Roskrow M (1999) The generation of leukemic dendritic cells from patients with chronic myeloid leukemia (CML) using the combination of interferon-à and GM-CSF. Blood. 94(10 Suppl 1):529a-a
49.
go back to reference Chen X, Regn S, Raffegerst S, Kolb HJ, Roskrow M (2000) Interferon alpha in combination with GM-CSF induces the differentiation of leukaemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukaemic cytotoxic T-cell response from patients with chronic myeloid leukaemia. Br J Haematol 111(2):596–607PubMed Chen X, Regn S, Raffegerst S, Kolb HJ, Roskrow M (2000) Interferon alpha in combination with GM-CSF induces the differentiation of leukaemic antigen-presenting cells that have the capacity to stimulate a specific anti-leukaemic cytotoxic T-cell response from patients with chronic myeloid leukaemia. Br J Haematol 111(2):596–607PubMed
50.
go back to reference Woiciechowsky A, Regn S, Kolb HJ, Roskrow M (2001) Leukemic dendritic cells generated in the presence of FLT3 ligand have the capacity to stimulate an autologous leukaemia-specific cytotoxic T cell response from patients with acute myeloid leukaemia. Leukemia. 15:246–255PubMedCrossRef Woiciechowsky A, Regn S, Kolb HJ, Roskrow M (2001) Leukemic dendritic cells generated in the presence of FLT3 ligand have the capacity to stimulate an autologous leukaemia-specific cytotoxic T cell response from patients with acute myeloid leukaemia. Leukemia. 15:246–255PubMedCrossRef
51.
go back to reference Schmetzer HM, Kremser A, Loibl J, Kroell T, Kolb HJ (2007) Quantification of ex vivo generated dendritic cells (DC) and leukemia-derived DC contributes to estimate the quality of DC, to detect optimal DC-generating methods or to optimize DC-mediated T-cell-activation-procedures ex vivo or in vivo 9. Leukemia. 21(6):1338–1341PubMedCrossRef Schmetzer HM, Kremser A, Loibl J, Kroell T, Kolb HJ (2007) Quantification of ex vivo generated dendritic cells (DC) and leukemia-derived DC contributes to estimate the quality of DC, to detect optimal DC-generating methods or to optimize DC-mediated T-cell-activation-procedures ex vivo or in vivo 9. Leukemia. 21(6):1338–1341PubMedCrossRef
52.
go back to reference Anguille S, Lion E, Willemen Y, Van Tendeloo VF, Berneman ZN, Smits EL (2011) Interferon-alpha in acute myeloid leukemia: an old drug revisited. Leukemia. 25(5):739–748PubMedCrossRef Anguille S, Lion E, Willemen Y, Van Tendeloo VF, Berneman ZN, Smits EL (2011) Interferon-alpha in acute myeloid leukemia: an old drug revisited. Leukemia. 25(5):739–748PubMedCrossRef
53.
go back to reference 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 (2013) Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia. 27(6):1229–1235PubMedCrossRef 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 (2013) Azacitidine and donor lymphocyte infusions as first salvage therapy for relapse of AML or MDS after allogeneic stem cell transplantation. Leukemia. 27(6):1229–1235PubMedCrossRef
54.
go back to reference Zeiser R, Beelen DW, Bethge W, Bornhauser M, Bug G, Burchert A et al (2019) Biology-driven approaches to prevent and treat relapse of myeloid Neoplasia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 25(4):e128–ee40PubMedCrossRef Zeiser R, Beelen DW, Bethge W, Bornhauser M, Bug G, Burchert A et al (2019) Biology-driven approaches to prevent and treat relapse of myeloid Neoplasia after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant 25(4):e128–ee40PubMedCrossRef
55.
go back to reference Zeiser R, Vago L (2019) Mechanisms of immune escape after allogeneic hematopoietic cell transplantation. Blood. 133(12):1290–1297PubMedCrossRef Zeiser R, Vago L (2019) Mechanisms of immune escape after allogeneic hematopoietic cell transplantation. Blood. 133(12):1290–1297PubMedCrossRef
56.
go back to reference Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT et al (2009) Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med 361(5):478–488PubMedCrossRef Vago L, Perna SK, Zanussi M, Mazzi B, Barlassina C, Stanghellini MT et al (2009) Loss of mismatched HLA in leukemia after stem-cell transplantation. N Engl J Med 361(5):478–488PubMedCrossRef
57.
go back to reference Christopher MJ, Petti AA, Rettig MP, Miller CA, Chendamarai E, Duncavage EJ, et al. (2018) Immune escape of relapsed aml cells after allogeneic transplantation. N Engl J Med Christopher MJ, Petti AA, Rettig MP, Miller CA, Chendamarai E, Duncavage EJ, et al. (2018) Immune escape of relapsed aml cells after allogeneic transplantation. N Engl J Med
58.
go back to reference Toffalori C, Zito L, Gambacorta V, Riba M, Oliveira G, Bucci G, Barcella M, Spinelli O, Greco R, Crucitti L, Cieri N, Noviello M, Manfredi F, Montaldo E, Ostuni R, Naldini MM, Gentner B, Waterhouse M, Zeiser R, Finke J, Hanoun M, Beelen DW, Gojo I, Luznik L, Onozawa M, Teshima T, Devillier R, Blaise D, Halkes CJM, Griffioen M, Carrabba MG, Bernardi M, Peccatori J, Barlassina C, Stupka E, Lazarevic D, Tonon G, Rambaldi A, Cittaro D, Bonini C, Fleischhauer K, Ciceri F, Vago L (2019) Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation. Nat Med 25(4):603–611PubMedCrossRef Toffalori C, Zito L, Gambacorta V, Riba M, Oliveira G, Bucci G, Barcella M, Spinelli O, Greco R, Crucitti L, Cieri N, Noviello M, Manfredi F, Montaldo E, Ostuni R, Naldini MM, Gentner B, Waterhouse M, Zeiser R, Finke J, Hanoun M, Beelen DW, Gojo I, Luznik L, Onozawa M, Teshima T, Devillier R, Blaise D, Halkes CJM, Griffioen M, Carrabba MG, Bernardi M, Peccatori J, Barlassina C, Stupka E, Lazarevic D, Tonon G, Rambaldi A, Cittaro D, Bonini C, Fleischhauer K, Ciceri F, Vago L (2019) Immune signature drives leukemia escape and relapse after hematopoietic cell transplantation. Nat Med 25(4):603–611PubMedCrossRef
59.
go back to reference Spinner MA, Advani RH, Connors JM, Azzi J, Diefenbach C (2018) New treatment algorithms in Hodgkin lymphoma: too much or too little? Am Soc Clin Oncol Educ Book 38:626–636PubMedCrossRef Spinner MA, Advani RH, Connors JM, Azzi J, Diefenbach C (2018) New treatment algorithms in Hodgkin lymphoma: too much or too little? Am Soc Clin Oncol Educ Book 38:626–636PubMedCrossRef
60.
go back to reference Zhou J, Bashey A, Zhong R, Corringham S, Messer K, Pu M, Ma W, Chut T, Soiffer R, Mitrovich RC, Lowy I, Ball ED (2011) CTLA-4 blockade following relapse of malignancy after allogeneic stem cell transplantation is associated with T cell activation but not with increased levels of T regulatory cells. Biol Blood Marrow Transplant 17(5):682–692PubMedCrossRef Zhou J, Bashey A, Zhong R, Corringham S, Messer K, Pu M, Ma W, Chut T, Soiffer R, Mitrovich RC, Lowy I, Ball ED (2011) CTLA-4 blockade following relapse of malignancy after allogeneic stem cell transplantation is associated with T cell activation but not with increased levels of T regulatory cells. Biol Blood Marrow Transplant 17(5):682–692PubMedCrossRef
61.
go back to reference Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, LeBoeuf N, Rooney MS, Bowden M, Zhou CW, Granter SR, Hornick JL, Rodig SJ, Hirakawa M, Severgnini M, Hodi FS, Wu CJ, Ho VT, Cutler C, Koreth J, Alyea EP, Antin JH, Armand P, Streicher H, Ball ED, Ritz J, Bashey A, Soiffer RJ, Leukemia and Lymphoma Society Blood Cancer Research Partnership (2016) Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med 375(2):143–153PubMedPubMedCentralCrossRef Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, Lukez AP, Avigan D, Chen YB, McSweeney P, LeBoeuf N, Rooney MS, Bowden M, Zhou CW, Granter SR, Hornick JL, Rodig SJ, Hirakawa M, Severgnini M, Hodi FS, Wu CJ, Ho VT, Cutler C, Koreth J, Alyea EP, Antin JH, Armand P, Streicher H, Ball ED, Ritz J, Bashey A, Soiffer RJ, Leukemia and Lymphoma Society Blood Cancer Research Partnership (2016) Ipilimumab for patients with relapse after allogeneic transplantation. N Engl J Med 375(2):143–153PubMedPubMedCentralCrossRef
62.
go back to reference Chang YJ, Wang Y, Liu YR, Xu LP, Zhang XH, Chen H, Chen YH, Wang FR, Han W, Sun YQ, Yan CH, Tang FF, Mo XD, Liu KY, Huang XJ (2017) Haploidentical allograft is superior to matched sibling donor allograft in eradicating pre-transplantation minimal residual disease of AML patients as determined by multiparameter flow cytometry: a retrospective and prospective analysis. J Hematol Oncol 10(1):134PubMedPubMedCentralCrossRef Chang YJ, Wang Y, Liu YR, Xu LP, Zhang XH, Chen H, Chen YH, Wang FR, Han W, Sun YQ, Yan CH, Tang FF, Mo XD, Liu KY, Huang XJ (2017) Haploidentical allograft is superior to matched sibling donor allograft in eradicating pre-transplantation minimal residual disease of AML patients as determined by multiparameter flow cytometry: a retrospective and prospective analysis. J Hematol Oncol 10(1):134PubMedPubMedCentralCrossRef
63.
go back to reference 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 (2012) Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia. 26(3):381–389PubMedCrossRef 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 (2012) Azacitidine for treatment of imminent relapse in MDS or AML patients after allogeneic HSCT: results of the RELAZA trial. Leukemia. 26(3):381–389PubMedCrossRef
64.
go back to reference Goodyear O, Agathanggelou A, Novitzky-Basso I, Siddique S, McSkeane T, Ryan G, Vyas P, Cavenagh J, Stankovic T, Moss P, Craddock C (2010) Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood. 116(11):1908–1918PubMedCrossRef Goodyear O, Agathanggelou A, Novitzky-Basso I, Siddique S, McSkeane T, Ryan G, Vyas P, Cavenagh J, Stankovic T, Moss P, Craddock C (2010) Induction of a CD8+ T-cell response to the MAGE cancer testis antigen by combined treatment with azacitidine and sodium valproate in patients with acute myeloid leukemia and myelodysplasia. Blood. 116(11):1908–1918PubMedCrossRef
65.
go back to reference de Lima M, Giralt S, Thall PF, de Padua SL, Jones RB, Komanduri K et al (2010) Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer. 116(23):5420–5431PubMedCrossRef de Lima M, Giralt S, Thall PF, de Padua SL, Jones RB, Komanduri K et al (2010) Maintenance therapy with low-dose azacitidine after allogeneic hematopoietic stem cell transplantation for recurrent acute myelogenous leukemia or myelodysplastic syndrome: a dose and schedule finding study. Cancer. 116(23):5420–5431PubMedCrossRef
66.
go back to reference Craddock C, Labopin M, Robin M, Finke J, Chevallier P, Yakoub-Agha I, Bourhis JH, Sengelov H, Blaise D, Luft T, Hallek M, Kroger N, Nagler A, Mohty M (2016) Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica. 101(7):879–883PubMedPubMedCentralCrossRef Craddock C, Labopin M, Robin M, Finke J, Chevallier P, Yakoub-Agha I, Bourhis JH, Sengelov H, Blaise D, Luft T, Hallek M, Kroger N, Nagler A, Mohty M (2016) Clinical activity of azacitidine in patients who relapse after allogeneic stem cell transplantation for acute myeloid leukemia. Haematologica. 101(7):879–883PubMedPubMedCentralCrossRef
67.
go back to reference de Lima M, Oran B, Champlin RE, Papadopoulos EB, Giralt SA, Scott BL, William BM, Hetzer J, Laille E, Hubbell B, Skikne BS, Craddock C (2018) CC-486 maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes. Biol Blood Marrow Transplant 24(10):2017–2024PubMedCrossRefPubMedCentral de Lima M, Oran B, Champlin RE, Papadopoulos EB, Giralt SA, Scott BL, William BM, Hetzer J, Laille E, Hubbell B, Skikne BS, Craddock C (2018) CC-486 maintenance after stem cell transplantation in patients with acute myeloid leukemia or myelodysplastic syndromes. Biol Blood Marrow Transplant 24(10):2017–2024PubMedCrossRefPubMedCentral
68.
go back to reference Sommer S, Cruijsen M, Claus R, Bertz H, Wasch R, Marks R et al (2018) Decitabine in combination with donor lymphocyte infusions can induce remissions in relapsed myeloid malignancies with higher leukemic burden after allogeneic hematopoietic cell transplantation. Leuk Res 72:20–26PubMedCrossRef Sommer S, Cruijsen M, Claus R, Bertz H, Wasch R, Marks R et al (2018) Decitabine in combination with donor lymphocyte infusions can induce remissions in relapsed myeloid malignancies with higher leukemic burden after allogeneic hematopoietic cell transplantation. Leuk Res 72:20–26PubMedCrossRef
69.
go back to reference Metzelder S, Wang Y, Wollmer E, Wanzel M, Teichler S, Chaturvedi A, et al. (2009) Compassionate-use of sorafenib in Flt3-ITD positive acute myeloid leukemia: sustained regression prior and post allogenic stem cell transplantation 1. Blood Metzelder S, Wang Y, Wollmer E, Wanzel M, Teichler S, Chaturvedi A, et al. (2009) Compassionate-use of sorafenib in Flt3-ITD positive acute myeloid leukemia: sustained regression prior and post allogenic stem cell transplantation 1. Blood
70.
go back to reference Metzelder SK, Schroeder T, Lubbert M, Ditschkowski M, Gotze K, Scholl S et al (2017) Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation. Eur J Cancer 86:233–239PubMedCrossRef Metzelder SK, Schroeder T, Lubbert M, Ditschkowski M, Gotze K, Scholl S et al (2017) Long-term survival of sorafenib-treated FLT3-ITD-positive acute myeloid leukaemia patients relapsing after allogeneic stem cell transplantation. Eur J Cancer 86:233–239PubMedCrossRef
71.
go back to reference Brunner AM, Li S, Fathi AT, Wadleigh M, Ho VT, Collier K, Connolly C, Ballen KK, Cutler CS, Dey BR, el-Jawahri A, Nikiforow S, McAfee SL, Koreth J, Deangelo DJ, Alyea EP, Antin JH, Spitzer TR, Stone RM, Soiffer RJ, Chen YB (2016) Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission. Br J Haematol 175(3):496–504PubMedPubMedCentralCrossRef Brunner AM, Li S, Fathi AT, Wadleigh M, Ho VT, Collier K, Connolly C, Ballen KK, Cutler CS, Dey BR, el-Jawahri A, Nikiforow S, McAfee SL, Koreth J, Deangelo DJ, Alyea EP, Antin JH, Spitzer TR, Stone RM, Soiffer RJ, Chen YB (2016) Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission. Br J Haematol 175(3):496–504PubMedPubMedCentralCrossRef
72.
go back to reference Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H (2017) Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 377(5):454–464PubMedPubMedCentralCrossRef Stone RM, Mandrekar SJ, Sanford BL, Laumann K, Geyer S, Bloomfield CD, Thiede C, Prior TW, Döhner K, Marcucci G, Lo-Coco F, Klisovic RB, Wei A, Sierra J, Sanz MA, Brandwein JM, de Witte T, Niederwieser D, Appelbaum FR, Medeiros BC, Tallman MS, Krauter J, Schlenk RF, Ganser A, Serve H, Ehninger G, Amadori S, Larson RA, Döhner H (2017) Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 377(5):454–464PubMedPubMedCentralCrossRef
73.
go back to reference Stone RM (2018) What FLT3 inhibitor holds the greatest promise? Best Pract Res Clin Haematol 31(4):401–404PubMedCrossRef Stone RM (2018) What FLT3 inhibitor holds the greatest promise? Best Pract Res Clin Haematol 31(4):401–404PubMedCrossRef
74.
go back to reference Mathew NR, Baumgartner F, Braun L, O'Sullivan D, Thomas S, Waterhouse M, Müller TA, Hanke K, Taromi S, Apostolova P, Illert AL, Melchinger W, Duquesne S, Schmitt-Graeff A, Osswald L, Yan KL, Weber A, Tugues S, Spath S, Pfeifer D, Follo M, Claus R, Lübbert M, Rummelt C, Bertz H, Wäsch R, Haag J, Schmidts A, Schultheiss M, Bettinger D, Thimme R, Ullrich E, Tanriver Y, Vuong GL, Arnold R, Hemmati P, Wolf D, Ditschkowski M, Jilg C, Wilhelm K, Leiber C, Gerull S, Halter J, Lengerke C, Pabst T, Schroeder T, Kobbe G, Rösler W, Doostkam S, Meckel S, Stabla K, Metzelder SK, Halbach S, Brummer T, Hu Z, Dengjel J, Hackanson B, Schmid C, Holtick U, Scheid C, Spyridonidis A, Stölzel F, Ordemann R, Müller LP, Sicre-de-Fontbrune F, Ihorst G, Kuball J, Ehlert JE, Feger D, Wagner EM, Cahn JY, Schnell J, Kuchenbauer F, Bunjes D, Chakraverty R, Richardson S, Gill S, Kröger N, Ayuk F, Vago L, Ciceri F, Müller AM, Kondo T, Teshima T, Klaeger S, Kuster B, Kim D(DH), Weisdorf D, van der Velden W, Dörfel D, Bethge W, Hilgendorf I, Hochhaus A, Andrieux G, Börries M, Busch H, Magenau J, Reddy P, Labopin M, Antin JH, Henden AS, Hill GR, Kennedy GA, Bar M, Sarma A, McLornan D, Mufti G, Oran B, Rezvani K, Shah O, Negrin RS, Nagler A, Prinz M, Burchert A, Neubauer A, Beelen D, Mackensen A, von Bubnoff N, Herr W, Becher B, Socié G, Caligiuri MA, Ruggiero E, Bonini C, Häcker G, Duyster J, Finke J, Pearce E, Blazar BR, Zeiser R (2018) Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med 24(3):282–291PubMedPubMedCentralCrossRef Mathew NR, Baumgartner F, Braun L, O'Sullivan D, Thomas S, Waterhouse M, Müller TA, Hanke K, Taromi S, Apostolova P, Illert AL, Melchinger W, Duquesne S, Schmitt-Graeff A, Osswald L, Yan KL, Weber A, Tugues S, Spath S, Pfeifer D, Follo M, Claus R, Lübbert M, Rummelt C, Bertz H, Wäsch R, Haag J, Schmidts A, Schultheiss M, Bettinger D, Thimme R, Ullrich E, Tanriver Y, Vuong GL, Arnold R, Hemmati P, Wolf D, Ditschkowski M, Jilg C, Wilhelm K, Leiber C, Gerull S, Halter J, Lengerke C, Pabst T, Schroeder T, Kobbe G, Rösler W, Doostkam S, Meckel S, Stabla K, Metzelder SK, Halbach S, Brummer T, Hu Z, Dengjel J, Hackanson B, Schmid C, Holtick U, Scheid C, Spyridonidis A, Stölzel F, Ordemann R, Müller LP, Sicre-de-Fontbrune F, Ihorst G, Kuball J, Ehlert JE, Feger D, Wagner EM, Cahn JY, Schnell J, Kuchenbauer F, Bunjes D, Chakraverty R, Richardson S, Gill S, Kröger N, Ayuk F, Vago L, Ciceri F, Müller AM, Kondo T, Teshima T, Klaeger S, Kuster B, Kim D(DH), Weisdorf D, van der Velden W, Dörfel D, Bethge W, Hilgendorf I, Hochhaus A, Andrieux G, Börries M, Busch H, Magenau J, Reddy P, Labopin M, Antin JH, Henden AS, Hill GR, Kennedy GA, Bar M, Sarma A, McLornan D, Mufti G, Oran B, Rezvani K, Shah O, Negrin RS, Nagler A, Prinz M, Burchert A, Neubauer A, Beelen D, Mackensen A, von Bubnoff N, Herr W, Becher B, Socié G, Caligiuri MA, Ruggiero E, Bonini C, Häcker G, Duyster J, Finke J, Pearce E, Blazar BR, Zeiser R (2018) Sorafenib promotes graft-versus-leukemia activity in mice and humans through IL-15 production in FLT3-ITD-mutant leukemia cells. Nat Med 24(3):282–291PubMedPubMedCentralCrossRef
75.
go back to reference Bug G, Burchert A, Wagner EM, Kroger N, Berg T, Guller S et al (2017) Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial). Leukemia. 31(11):2523–2525PubMedPubMedCentralCrossRef Bug G, Burchert A, Wagner EM, Kroger N, Berg T, Guller S et al (2017) Phase I/II study of the deacetylase inhibitor panobinostat after allogeneic stem cell transplantation in patients with high-risk MDS or AML (PANOBEST trial). Leukemia. 31(11):2523–2525PubMedPubMedCentralCrossRef
76.
go back to reference Choi SW, Braun T, Chang L, Ferrara JL, Pawarode A, Magenau JM et al (2014) Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. Lancet Oncol 15(1):87–95PubMedCrossRef Choi SW, Braun T, Chang L, Ferrara JL, Pawarode A, Magenau JM et al (2014) Vorinostat plus tacrolimus and mycophenolate to prevent graft-versus-host disease after related-donor reduced-intensity conditioning allogeneic haemopoietic stem-cell transplantation: a phase 1/2 trial. Lancet Oncol 15(1):87–95PubMedCrossRef
77.
go back to reference Buchner T, Schlenk RF, Schaich M, Dohner K, Krahl R, Krauter J et al (2012) Acute myeloid leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML intergroup. J Clin Oncol 30(29):3604–3610PubMedCrossRef Buchner T, Schlenk RF, Schaich M, Dohner K, Krahl R, Krauter J et al (2012) Acute myeloid leukemia (AML): different treatment strategies versus a common standard arm--combined prospective analysis by the German AML intergroup. J Clin Oncol 30(29):3604–3610PubMedCrossRef
78.
go back to reference Estey EH (2018) Acute myeloid leukemia: 2019 update on risk-stratification and management. Am J Hematol 93(10):1267–1291PubMedCrossRef Estey EH (2018) Acute myeloid leukemia: 2019 update on risk-stratification and management. Am J Hematol 93(10):1267–1291PubMedCrossRef
79.
go back to reference Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK et al (2007) A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 109(6):1114–1124PubMedCrossRef Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK et al (2007) A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer. 109(6):1114–1124PubMedCrossRef
80.
go back to reference Tilly H, Castaigne S, Bordessoule D, Casassus P, Le Prise PY, Tertian G et al (1990) Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol 8(2):272–279PubMedCrossRef Tilly H, Castaigne S, Bordessoule D, Casassus P, Le Prise PY, Tertian G et al (1990) Low-dose cytarabine versus intensive chemotherapy in the treatment of acute nonlymphocytic leukemia in the elderly. J Clin Oncol 8(2):272–279PubMedCrossRef
81.
go back to reference Kadia TM, Cortes J, Ravandi F, Jabbour E, Konopleva M, Benton CB, Burger J, Sasaki K, Borthakur G, DiNardo CD, Pemmaraju N, Daver N, Ferrajoli A, Wang X, Patel K, Jorgensen JL, Wang S, O'Brien S, Pierce S, Tuttle C, Estrov Z, Verstovsek S, Garcia-Manero G, Kantarjian H (2018) Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. Lancet Haematol 5(9):e411–ee21PubMedPubMedCentralCrossRef Kadia TM, Cortes J, Ravandi F, Jabbour E, Konopleva M, Benton CB, Burger J, Sasaki K, Borthakur G, DiNardo CD, Pemmaraju N, Daver N, Ferrajoli A, Wang X, Patel K, Jorgensen JL, Wang S, O'Brien S, Pierce S, Tuttle C, Estrov Z, Verstovsek S, Garcia-Manero G, Kantarjian H (2018) Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. Lancet Haematol 5(9):e411–ee21PubMedPubMedCentralCrossRef
82.
go back to reference Bose P, Vachhani P, Cortes JE (2017) Treatment of relapsed/refractory acute myeloid leukemia. Curr Treat Options in Oncol 18(3):17CrossRef Bose P, Vachhani P, Cortes JE (2017) Treatment of relapsed/refractory acute myeloid leukemia. Curr Treat Options in Oncol 18(3):17CrossRef
83.
go back to reference Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC (2018) CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol 36(26):2684–2692PubMedPubMedCentralCrossRef Lancet JE, Uy GL, Cortes JE, Newell LF, Lin TL, Ritchie EK, Stuart RK, Strickland SA, Hogge D, Solomon SR, Stone RM, Bixby DL, Kolitz JE, Schiller GJ, Wieduwilt MJ, Ryan DH, Hoering A, Banerjee K, Chiarella M, Louie AC, Medeiros BC (2018) CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol 36(26):2684–2692PubMedPubMedCentralCrossRef
84.
go back to reference DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS et al (2019) Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 133(1):7–17PubMedPubMedCentralCrossRef DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS et al (2019) Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 133(1):7–17PubMedPubMedCentralCrossRef
85.
go back to reference DiNardo CD, Rausch CR, Benton C, Kadia T, Jain N, Pemmaraju N et al (2018) Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Am J Hematol 93(3):401–407PubMedCrossRef DiNardo CD, Rausch CR, Benton C, Kadia T, Jain N, Pemmaraju N et al (2018) Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies. Am J Hematol 93(3):401–407PubMedCrossRef
86.
go back to reference Wei AH, Tiong IS (2017) Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. Blood. 130(23):2469–2474PubMedCrossRef Wei AH, Tiong IS (2017) Midostaurin, enasidenib, CPX-351, gemtuzumab ozogamicin, and venetoclax bring new hope to AML. Blood. 130(23):2469–2474PubMedCrossRef
Metadata
Title
The FLAMSA concept—past and future
Authors
Hans-Jochem Kolb
Christoph Schmid
Publication date
01-09-2020
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 9/2020
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-020-04131-1

Other articles of this Issue 9/2020

Annals of Hematology 9/2020 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.