Salvage regimens using conventional chemotherapy agents for relapsed/refractory adult AML patients: a systematic literature review

1.

Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, Dombret H, Ebert BL, Fenaux P, Larson RA, Levine RL, Lo-Coco F, Naoe T, Niederwieser D, Ossenkoppele GJ, Sanz M, Sierra J, Tallman MS, Tien HF, Wei AH, Löwenberg B, Bloomfield CD (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–427PubMedPubMedCentralCrossRef

2.

Walter RB, Othus M, Burnett AK, Lowenberg B, Kantarjian HM, Ossenkoppele GJ, Hills RK, Ravandi F, Pabst T, Evans A, Pierce SR, Vekemans MC, Appelbaum FR, Estey EH (2014) Resistance prediction in aml: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOC and MD Anderson Cancer Center. Leukemia 29(2):312–320PubMedPubMedCentralCrossRef

3.

Keating MJ, Kantarjian H, Smith TL, Estey E, Walters R, Andersson B, Beran M, McCredie KB, Freireich EJ (1989) Response to salvage therapy and survival after relapse in acute myelogenous leukemia. J Clin Oncol 7(8):1071–1080PubMedCrossRef

4.

Sternberg DW, Aird W, Neuberg D, Thompson L, MacNeill K, Amrein P, Shulman LN (2000) Treatment of patients with recurrent and primary refractory acute myelogenous leukemia using mitoxantrone and intermediate-dose cytarabine: a pharmacologically based regimen. Cancer 88(9):2037–2041PubMedCrossRef

5.

Kern W, Aul C, Maschmeyer G, Schönrock-Nabulsi R, Ludwig WD, Bartholomäus A, Bettelheim P, Wörmann B, Büchner T, Hiddemann W (1998) Superiority of high-dose over intermediate-dose cytosine arabinoside in the treatment of patients with high-risk acute myeloid leukemia: results of an age-adjusted prospective randomized comparison. Leukemia 12(7):1049–1055PubMedCrossRef

6.

Rees JK, Gray RG, Swirsky D, Hayhoe FG (1986) Principal results of the Medical Research Council’s 8th acute myeloid leukaemia trial. Lancet 2(8518):1236–1241PubMedCrossRef

7.

Tavernier E, Le QH, Elhamri M, Thomas X (2003) Salvage therapy in refractory acute myeloid leukemia: prediction of outcome based on analysis of prognostic factors. Leuk Res 27(3):205–214PubMedCrossRef

8.

Estey E, Plunkett W, Gandhi V, Rios MB, Kantarjian H, Keating MJ (1993) Fludarabine and arabinosylcytosine therapy of refractory and relapsed acute myelogenous leukemia. Leuk Lymphoma 9(4–5):343–350PubMedCrossRef

9.

Thalhammer F, Geissler K, Jager U, Kyrle PA, Pabinger I, Mitterbauer M, Gisslinger H, Knöbl P, Laczika K, Schneider B, Haas OA, Lechner K (1996) Duration of second complete remission in patients with acute myeloid leukemia treated with chemotherapy: a retrospective single-center study. Ann Hematol 72(4):216–222PubMedCrossRef

10.

Wheatley K, Burnett AK, Goldstone AH, Gray RG, Hann IM, Harrison CJ, Rees JK, Stevens RF, Walker H (1999) A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial. United Kingdom Medical Research Council’s Adult and Childhood Leukaemia Working Parties. Br J Haematol 107(1):69–79PubMedCrossRef

11.

Weltermann A, Fonatsch C, Haas OA, Greinix HT, Kahls P, Mitterbauer G, Jäger U, Kainz B, Geissler K, Valent P, Sperr WR, Knöbl P, Schwarzinger I, Gleiss A, Lechner K (2004) Impact of cytogenetics on the prognosis of adults with de novo AML in first relapse. Leukemia 18(2):293–302PubMedCrossRef

12.

Kern W, Haferlach T, Schnittger S, Ludwig WD, Hiddemann W, Schoch C (2002) Karyotype instability between diagnosis and relapse in 117 patients with acute myeloid leukemia: implications for resistance against therapy. Leukemia 16(10):2084–2091PubMedCrossRef

13.

Zittoun R, Jehn U, Fière D, Haanen C, Löwenberg B, Willemze R, Abels J, Bury J, Peetermans M, Hayat M et al (1989) Alternating v repeated postremission treatment in adult acute myelogenous leukemia: a randomized phase III study (AML6) of the EORTC Leukemia Cooperative Group. Blood 73(4):896–906PubMed

14.

Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gøtzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700PubMedPubMedCentralCrossRef

15.

Herzig RH, Lazarus HM, Wolff SN, Phillips GL, Herzig GP (1985) High-dose cytosine arabinoside therapy with and without anthracycline antibiotics for remission reinduction of acute nonlymphoblastic leukemia. J Clin Oncol 3(7):992–997PubMedCrossRef

16.

Capizzi RL, Davis R, Powell B, Cuttner J, Ellison RR, Cooper MR, Dillman R, Major WB, Dupre E, McIntyre OR (1988) Synergy between high-dose cytarabine and asparaginase in the treatment of adults with refractory and relapsed acute myelogenous leukemia—a Cancer and Leukemia Group B Study. J Clin Oncol 6(3):499–508PubMedCrossRef

17.

Estey EH, Plunkett W, Kantarjian H, Rios MB, Keating MJ (1993) Treatment of relapsed or refractory AML with intermediate-dose arabinosylcytosine (ara-C): confirmation of the importance of ara-C triphosphate formation in mediating response to ara-C. Leuk Lymphoma 10(Suppl):115–121PubMedCrossRef

18.

Vogler WR, McCarley DL, Stagg M, Bartolucci AA, Moore J, Martelo O, Omura GA (1994) A phase III trial of high-dose cytosine arabinoside with or without etoposide in relapsed and refractory acute myelogenous leukemia. A Southeastern Cancer Study Group trial. Leukemia 8(11):1847–1853PubMed

19.

Karanes C, Kopecky KJ, Head DR, Grever MR, Hynes HE, Kraut EH, Vial RH, Lichtin A, Nand S, Samlowski WE, Appelbaum FR (1999) A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study. Leuk Res 23(9):787–794PubMedCrossRef

20.

Giles F, Vey N, DeAngelo D, Seiter K, Stock W, Stuart R, Boskovic D, Pigneux A, Tallman M, Brandwein J, Kell J, Robak T, Staib P, Thomas X, Cahill A, Albitar M, O'Brien S (2009) Phase 3 randomized, placebo-controlled, double-blind study of high-dose continuous infusion cytarabine alone or with laromustine (VNP40101M) in patients with acute myeloid leukemia in first relapse. Blood 114(19):4027–4033PubMedCrossRef

21.

Faderl S, Wetzler M, Rizzieri D, Schiller G, Jagasia M, Stuart R, Ganguly S, Avigan D, Craig M, Collins R, Maris M, Kovacsovics T, Goldberg S, Seiter K, Hari P, Greiner J, Vey N, Recher C, Ravandi F, Wang ES, Vasconcelles M, Huebner D, Kantarjian HM (2012) Clofarabine plus cytarabine compared with cytarabine alone in older patients with relapsed or refractory acute myelogenous leukemia: results from the CLASSIC I Trial. J Clin Oncol 30(20):2492–2499PubMedPubMedCentralCrossRef

22.

Ravandi F, Ritchie EK, Sayar H, Lancet JE, Craig MD, Vey N, Strickland SA, Schiller GJ, Jabbour E, Erba HP, Pigneux A, Horst HA, Recher C, Klimek VM, Cortes J, Roboz GJ, Odenike O, Thomas X, Havelange V, Maertens J, Derigs HG, Heuser M, Damon L, Powell BL, Gaidano G, Carella AM, Wei A, Hogge D, Craig AR, Fox JA, Ward R, Smith JA, Acton G, Mehta C, Stuart RK, Kantarjian HM (2015) Vosaroxin plus cytarabine versus placebo plus cytarabine in patients with first relapsed or refractory acute myeloid leukaemia (VALOR): a randomised, controlled, double-blind, multinational, phase 3 study. Lancet Oncol 16(9):1025–1036PubMedPubMedCentralCrossRef

23.

Vogler WR, Preisler HD, Winton EF, Gottlieb AJ, Goldberg J, Brennan J, Grunwald H, Rai K, Browman G, Miller KB et al (1986) Randomized trial of high-dose cytarabine versus amsacrine in acute myelogenous leukemia in relapse: a Leukemia Intergroup Study. Cancer Treat Rep 70(4):455–459PubMed

24.

Spriggs DR, Robbins G, Arthur K, Mayer RJ, Kufe D (1988) Prolonged high dose ARA-C infusions in acute leukemia. Leukemia 2(5):304–306PubMed

25.

Hiddemann W, Kreutzmann H, Straif K, Ludwig WD, Mertelsmann R, Donhuijsen-Ant R, Lengfelder E, Arlin Z, Büchner T (1987) High-dose cytosine arabinoside and mitoxantrone: a highly effective regimen in refractory acute myeloid leukemia. Blood 69(3):744–749PubMed

26.

Walters RS, Kantarjian H, Keating MJ, Plunkett WK, Estey EH, Andersson B, Beran M, McCredie KB, Freireich EJ (1988) Mitoxantrone and high-dose cytosine arabinoside in refractory acute myelogenous leukemia. Cancer 62(4):677–682PubMedCrossRef

27.

Martiat P, Ghilain JM, Ferrant A, Doyen C, Delannoy A, Chatelain C, Bosly A, Michaux JL, Sokal G (1990) High-dose cytosine arabinoside and amsacrine or mitoxantrone in relapsed and refractory acute myeloid leukaemia: a prospective randomized study. Eur J Haematol 45(3):164–167PubMedCrossRef

28.

Paciucci PA, Cuttner J, Holland JF (1990) Sequential intermediate-dose cytosine arabinoside and mitoxantrone for patients with relapsed and refractory acute myelocytic leukemia. Am J Hematol 35(1):22–25PubMedCrossRef

29.

Hiddemann W, Aul C, Maschmeyer G, Schönrock-Nabulsi R, Ludwig WD, Bartholomäus A, Bettelheim P, Becker K, Balleisen L, Lathan B et al (1993) High-dose versus intermediate dose cytosine arabinoside combined with mitoxantrone for the treatment of relapsed and refractory acute myeloid leukemia: results of an age adjusted randomized comparison. Leuk Lymphoma 10(Suppl):133–137PubMedCrossRef

30.

List AF, Kopecky KJ, Willman CL, Head DR, Persons DL, Slovak ML, Dorr R, Karanes C, Hynes HE, Doroshow JH, Shurafa M, Appelbaum FR (2001) Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood 98(12):3212–3220PubMedCrossRef

31.

De La Serna J, Francisco Tomás J, Solano C, García de Paredes ML, Campbell J, Grande C, Diaz-Mediavilla J (1997) Idarubicin and intermediate dose ARA-C followed by consolidation chemotherapy or bone marrow transplantation in relapsed or refractory acute myeloid leukemia. Leuk Lymphoma 25(3–4):365–372CrossRef

32.

Fiegl M, Unterhalt M, Kern W, Braess J, Spiekermann K, Staib P, Grüneisen A, Wörmann B, Schöndube D, Serve H, Reichle A, Hentrich M, Schiel X, Sauerland C, Heinecke A, Rieger C, Beelen D, Berdel WE, Büchner T, Hiddemann W, German AML Cooperative Group (AMLCG) (2014) Chemomodulation of sequential high-dose cytarabine by fludarabine in relapsed or refractory acute myeloid leukemia: a randomized trial of the AMLCG. Leukemia 28(5):1001–1007PubMedCrossRef

33.

Saito K, Nakamura Y, Aoyagi M, Waga K, Yamamoto K, Aoyagi A, Inoue F, Nakamura Y, Arai Y, Tadokoro J, Handa T, Tsurumi S, Arai H, Kawagoe Y, Gunnji H, Kitsukawa Y, Takahashi W, Furusawa S (2000) Low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor (CAG regimen) for previously treated patients with relapsed or primary resistant acute myelogenous leukemia (AML) and previously untreated elderly patients with AML, secondary AML, and refractory anemia with excess blasts in transformation. Int J Hematol 71(3):238–244PubMed

34.

Zhang X, Li Y, Zhang Y, Chen X, Zhang C, Gao L, Kong P, Liu Y, Wen Q, Zeng Y, Wang Q, Su Y, Wang C, Wang S, Yuan Z, Gao L (2013) Etoposide in combination with low-dose CAG (cytarabine, aclarubicin, G-CSF) for the treatment of relapsed or refractory acute myeloid leukemia: a multicenter, randomized control trial in southwest China. Leuk Res 37(6):657–664PubMedCrossRef

35.

Cortes J, Estey E, O'Brien S, Giles F, Shen Y, Koller C, Beran M, Thomas D, Keating M, Kantarjian H (2001) High-dose liposomal daunorubicin and high-dose cytarabine combination in patients with refractory or relapsed acute myelogenous leukemia. Cancer 92(1):7–14PubMedCrossRef

36.

Litzow MR, Othus M, Cripe LD, Gore SD, Lazarus HM, Lee SJ, Bennett JM, Paietta EM, Dewald GW, Rowe JM, Tallman MS, Eastern Cooperative Oncology Group Leukemia Committee (2010) Failure of three novel regimens to improve outcome for patients with relapsed or refractory acute myeloid leukaemia: a report from the Eastern Cooperative Oncology Group. Br J Haematol 148(2):217–225PubMedCrossRef

37.

Cortes JE, Goldberg SL, Feldman EJ, Rizzeri DA, Hogge DE, Larson M, Pigneux A, Recher C, Schiller G, Warzocha K, Kantarjian H, Louie AC, Kolitz JE (2015) Phase II, multicenter, randomized trial of CPX-351 (cytarabine:daunorubicin) liposome injection versus intensive salvage therapy in adults with first relapse AML. Cancer 121(2):234–242PubMedCrossRef

38.

Hospital MA, Prebet T, Bertoli S, Thomas X, Tavernier E, Braun T, Pautas C, Perrot A, Lioure B, Rousselot P, Tamburini J, Cluzeau T, Konopacki J, Randriamalala E, Berthon C, Gourin MP, Recher C, Cahn JY, Ifrah N, Dombret H, Boissel N (2014) Core-binding factor acute myeloid leukemia in first relapse: a retrospective study from the French AML intergroup. Blood 124(8):1312–1319PubMedCrossRef

39.

Paciucci PA, Cuttner J, Holland JF (1984) Mitoxantrone as a single agent and in combination chemotherapy in patients with refractory acute leukemia. Semin Oncol 11(3 Suppl 1):36–40PubMed

40.

Lang K, Menzin J, Earle CC, Mallick R (2002) Outcomes in patients treated with gemtuzumab ozogamicin for relapsed acute myelogenous leukemia. Am J Health Syst Pharm 59(10):941–948PubMed

41.

Büchner T, Hiddemann W, Koenigsmann M, Zuehlsdorf M, Woermann B, Boeckmann A, Aguion Freire E, Innig G, Maschmeyer G, Ludwig WD et al (1990) Recombinant human GM-CSF following chemotherapy in high-risk AML. Bone Marrow Transplant 6(Suppl 1):131–134

42.

Peters WG, Willemze R, Colly LP (1986) Results of induction and consolidation treatment with intermediate and high-dose ara-C and m-AMSA containing regimens in patients with primarily failed or relapsed acute leukemia and non-Hodgkin's lymphoma. Scand J Haematol Suppl 44:7–16PubMed

43.

Brito-Babapulle F, Catovsky D, Newland AC, Goldman JM, Galton DA (1987) Treatment of acute myeloid leukemia with intermediate-dose cytosine arabinoside and mitoxantrone. Semin Oncol 14(2 Suppl 1):51–52PubMed

44.

Peters WG, Willemze R, Colly LP (1988) Results of induction and consolidation treatment with intermediate and high-dose cytosine arabinoside and m-Amsa of patients with poor-risk acute myelogenous leukaemia. Eur J Haematol 40(3):198–204PubMedCrossRef

45.

Harousseau JL, Reiffers J, Hurteloup P, Milpied N, Guy H, Rigal-Huguet F, Facon T, Dufour P, Ifrah N (1989) Treatment of relapsed acute myeloid leukemia with idarubicin and intermediate-dose cytarabine. J Clin Oncol 7(1):45–49PubMedCrossRef

46.

Amadori S, Meloni G, Petti MC, Papa G, Miniero R, Mandelli F (1989) Phase II trial of intermediate dose ARA-C (IDAC) with sequential mitoxantrone (MITOX) in acute myelogenous leukemia. Leukemia 3(2):112–114PubMed

47.

Harousseau JL, Milpied N, Briere J, Desablens B, Ghandour C (1990) Mitoxantrone and intermediate-dose cytarabine in relapsed or refractory acute myeloblastic leukemia. Nouv Rev Fr Hematol 32:227–230PubMed

48.

Dekker AW, Nieuwenhuis HK, Verdonck LF (1990) Intermediate-dose 1055 cytosine arabinoside and amsacrine. An effective regimen with low toxicity in refractory acute nonlymphocytic leukemia. Cancer 65(9):1891–1894PubMedCrossRef

49.

Jehn U, Heinemann V (1990) Intermediate-dose Ara-C/m-AMSA for remission induction and high-dose Ara-C/m-AMSA for intensive consolidation in relapsed and refractory adult acute myelogeneous leukemia. Haematol Blood Transfus 33:333–338PubMed

50.

Sierra J, Grañena A, Bosch F, Carreras E, Martí JM, Urbano-Ispizua A, Rovira M, Rozman C (1992) Mitoxantrone and intermediate-dose cytosine arabinoside for poor-risk acute leukemias: response to treatment and factors influencing outcome. Hematol Oncol 10(6):301–309PubMedCrossRef

51.

Reece DE, Elmongy MB, Barnett MJ, Klingemann HG, Shepherd JD, Phillips GL (1993) Chemotherapy with high-dose cytosine arabinoside and mitoxantrone for poor-prognosis myeloid leukemias. Cancer Investig 11(5):509–516CrossRef

52.

MacCallum PK, Davis CL, Rohatiner AZ, Lim J, Gupta RK, Whelan JS, Price CG, Evans ML, Amess JA, Leahy M et al (1993) Mitoxantrone and cytosine arabinoside as treatment for acute myelogenous leukemia (AML) at first recurrence. Leukemia 7(10):1496–1499PubMed

53.

Jehn U, Heinemann V (1993) Phase-II study of treatment of refractory acute leukemia with intermediate-dose cytosine arabinoside and amsacrine. Ann Hematol 66(3):131–134PubMedCrossRef

54.

Yamada K, Furusawa S, Saito K, Waga K, Koike T, Arimura H, Aoyagi A, Yamato H, Sakuma H, Tsunogake S et al (1995) Concurrent use of granulocyte colony-stimulating factor with low-dose cytosine arabinoside and aclarubicin for previously treated acute myelogenous leukemia: a pilot study. Leukemia 9(1):10–14PubMed

55.

De Witte T, Suciu S, Selleslag D, Labar B, Roozendaal K, Zittoun R, Ribeiro M, Kurstjens R, Hayat M, Dardenne M, Solbu G, Muus P (1996) Salvage treatment for primary resistant acute myelogenous leukemia consisting of intermediate-dose cytosine arabinoside and interspaced continuous infusions of idarubicin: a phase-II study (no. 06901) of the EORTC Leukemia Cooperative Group. Ann Hematol 72(3):119–124PubMedCrossRef

56.

Russo D, Piccaluga PP, Michieli M, Michelutti T, Visani G, Gugliotta L, Bonini A, Pierri I, Gobbi M, Tiribelli M, Fanin R, Piccolrovazzi S, Baccarani M (2002) Liposomal daunorubicin (DaunoXome) for treatment of poor-risk acute leukemia. Ann Hematol 81(8):462–466PubMedCrossRef

57.

Wang Y, Li W, Chen S, Qiu H, Sun A, Wu D (2011) Salvage chemotherapy with low-dose cytarabine and aclarubicin in combination with granulocyte colony-stimulating factor priming in patients with refractory or relapsed acute myeloid leukemia with translocation (8;21). Leuk Res 35(5):604–607PubMedCrossRef

58.

Spadea A, Petti MC, Fazi P, Vegna ML, Arcese W, Avvisati G, Aloe Spiriti MA, Latagliata R, Meloni G, Testi AM et al (1993) Mitoxantrone, etoposide and intermediate-dose Ara-C (MEC): an effective regimen for poor risk acute myeloid leukemia. Leukemia 7(4):549–552PubMed

59.

Archimbaud E, Fenaux P, Reiffers J, Cordonnier C, Leblond V, Travade P, Troussard X, Tilly H, Auzanneau G, Marie JP et al (1993) Granulocyte-macrophage colony-stimulating factor in association to timed-sequential chemotherapy with mitoxantrone, etoposide, and cytarabine for refractory acute myelogenous leukemia. Leukemia 7(3):372–377PubMed

60.

Ohno R, Naoe T, Kanamaru A, Yoshida M, Hiraoka A, Kobayashi T, Ueda T, Minami S, Morishima Y, Saito Y et al (1994) A double-blind controlled study of granulocyte colony-stimulating factor started two days before induction chemotherapy in refractory acute myeloid leukemia. Kohseisho Leukemia Study Group. Blood 83(8):2086–2092PubMed

61.

Archimbaud E, Thomas X, Leblond V, Michallet M, Fenaux P, Cordonnier C, Dreyfus F, Troussard X, Jaubert J, Travade P et al (1995) Timed sequential chemotherapy for previously treated patients with acute myeloid leukemia: long-term follow-up of the etoposide, mitoxantrone, and cytarabine-86 trial. J Clin Oncol 13(1):11–18PubMedCrossRef

62.

Vignetti M, Orsini E, Petti MC, Moleti ML, Andrizzi C, Pinto RM, Amadori S, Meloni G (1996) Probability of long-term disease-free survival for acute myeloid leukemia patients after first relapse: a single-centre experience. Ann Oncol 7(9):933–938PubMedCrossRef

63.

Thomas X, Fenaux P, Dombret H, Delair S, Dreyfus F, Tilly H, Vekhoff A, Cony-Makhoul P, Leblond V, Troussard X, Cordonnier C, de Revel T, Simon M, Nicolini F, Stoppa AM, Janvier M, Bordessoule D, Rousselot P, Ffrench M, Marie JP, Archimbaud E (1999) Granulocyte-macrophage colony-stimulating factor (GM-CSF) to increase efficacy of intensive sequential chemotherapy with etoposide, mitoxantrone and cytarabine (EMA) in previously treated acute myeloid leukemia: a multicenter randomized placebo-controlled trial (EMA91 Trial). Leukemia 13(8):1214–1220PubMedCrossRef

64.

Revesz D, Chelghoum Y, Le QH, Elhamri M, Michallet M, Thomas X (2003) Salvage by timed sequential chemotherapy in primary resistant acute myeloid leukemia: analysis of prognostic factors. Ann Hematol 82(11):684–690PubMedCrossRef

65.

Lee SS, Lee JH, Lee JH, Kim DY, Kim SH, Lim SN, Lee YS, Seol M, Ryu SG, Kang YA, Jang S, Park CJ, Chi HS, Yun SC, Lee KH (2009) Single-dose mitoxantrone in combination with continuous infusion intermediate-dose cytarabine plus etoposide for treatment of refractory or early relapsed acute myeloid leukemia. Leuk Res 33(4):511–517PubMedCrossRef

66.

Lee JH, Choi SJ, Lee JH, Lee YS, Seol M, Ryu SG, Jang S, Park CJ, Chi HS, Lee JS, Kim WK, Lee KH (2006) Continuous infusion intermediate-dose cytarabine, mitoxantrone, plus etoposide for refractory or early relapsed acute myelogenous leukemia. Leuk Res 30(2):204–210PubMedCrossRef

67.

Price SL, Lancet JE, George TJ, Wetzstein GA, List AF, Ho VQ, Fernandez HF, Pinilla-Ibarz J, Kharfan-Dabaja MA, Komrokji RS (2011) Salvage chemotherapy regimens for acute myeloid leukemia: is one better? Efficacy comparison between CLAG and MEC regimens. Leuk Res 35(3):301–304PubMedCrossRef

68.

Carella AM, Carlier P, Pungolino E, Resegotti L, Liso V, Stasi R, Montillo M, Iacopino P, Mirto S, Pagano L et al (1993) Idarubicin in combination with intermediate-dose cytarabine and VP-16 in the treatment of refractory or rapidly relapsed patients with acute myeloid leukemia. The GIMEMA Cooperative Group. Leukemia 7(2):196–199PubMed

69.

Liu Yin JA, Wheatley K, Rees JK, Burnett AK, UK MRC Adult Leukemia Working Party (2001) Comparison of ‘sequential’ versus ‘standard’ chemotherapy as re-induction treatment, with or without cyclosporine, in refractory/relapsed acute myeloid leukaemia (AML): results of the UK Medical Research Council AML-R trial. Br J Haematol 113(3):713–726PubMedCrossRef

70.

Milligan DW, Wheatley K, Littlewood T, Craig JI, Burnett AK, NCRI Haematological Oncology Clinical Studies Group (2006) Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial. Blood 107(12):4614–4622PubMedCrossRef

71.

Sung WJ, Kim DH, Sohn SK, Kim JG, Baek JH, Jeon SB, Moon JH, Ahn BM, Lee KB (2005) Phase II trial of amsacrine plus intermediate-dose Ara-C (IDAC) with or without etoposide as salvage therapy for refractory or relapsed acute leukemia. Jpn J Clin Oncol 35(10):612–616PubMedCrossRef

72.

Song LX, Xu L, Li X, Chang CK, Zhang Y, Wu LY, He Q, Zhang QX, Li X (2012) Clinical outcome of treatment with a combined regimen of decitabine and aclacinomycin/cytarabine for patients with refractory acute myeloid leukemia. Ann Hematol 91(12):1879–1886PubMedCrossRef

73.

van Prooijen HC, Dekker AW, Punt K (1984) The use of intermediate dose cytosine arabinoside (ID Ara-C) in the treatment of acute non-lymphocytic leukaemia in relapse. Br J Haematol 57(2):291–299PubMedCrossRef

74.

Franchi A, Papa G, D'Atri S, Piccioni D, Masi M, Bonmassar E (1992) Cytotoxic effects of dacarbazine in patients with acute myelogenous leukemia: a pilot study. Haematologica 77(2):146–150PubMed

75.

Chevallier P, Delaunay J, Turlure P, Pigneux A, Hunault M, Garand R, Guillaume T, Avet-Loiseau H, Dmytruk N, Girault S, Milpied N, Ifrah N, Mohty M, Harousseau JL (2008) Long-term disease-free survival after gemtuzumab, intermediate-dose cytarabine, and mitoxantrone in patients with CD33(+) primary resistant or relapsed acute myeloid leukemia. J Clin Oncol 26(32):5192–5197PubMedCrossRef

76.

Chevallier P, Labopin M, Turlure P, Prebet T, Pigneux A, Hunault M, Filanovsky K, Cornillet-Lefebvre P, Luquet I, Lode L, Richebourg S, Blanchet O, Gachard N, Vey N, Ifrah N, Milpied N, Harousseau JL, Bene MC, Mohty M, Delaunay J (2011) A new leukemia prognostic scoring system for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study. Leukemia 25(6):939–944PubMedCrossRef

77.

Peterlin P, Guillaume T, Delaunay J, Mohty M, Garnier A, Mahe B, Dubruille V, Blin N, Voldoire M, Touzeau C, Chauvin C, Gastinne T, Béné MC, Le Gouill S, Moreau P, Chevallier P (2016) Similarity of fractionated versus single dose(s) of gemtuzumab ozogamicin as part of the MIDAM salvage regimen in relapsed/refractory acute myeloid leukemia patients. Semin Hematol 53(3):216–217PubMedCrossRef

78.

Hütter-Krönke ML, Benner A, Döhner K, Krauter J, Weber D, Moessner M, Köhne CH, Horst HA, Schmidt-Wolf IG, Rummel M, Götze K, Koller E, Petzer AL, Salwender H, Fiedler W, Kirchen H, Haase D, Kremers S, Theobald M, Matzdorff AC, Ganser A, Döhner H, Schlenk RF (2016) Salvage therapy with high-dose cytarabine and mitoxantrone in combination with all-trans retinoic acid and gemtuzumab ozogamicin in acute myeloid leukemia refractory to first induction therapy. Haematologica 101(7):839–845PubMedPubMedCentralCrossRef

79.

Link H, Freund M, Diedrich H, Wilke H, Austein J, Henke M, Wandt H, Fackler-Schwalbe E, Schlimok G, Hoffmann R et al (1990) Mitoxantrone, cytosine arabinoside, and VP-16 in 36 patients with relapsed and refractory acute myeloid leukemia. Haematol Blood Transfus 33:322–325PubMed

80.

Amadori S, Arcese W, Isacchi G, Meloni G, Petti MC, Monarca B, Testi AM, Mandelli F (1991) Mitoxantrone, etoposide, and intermediate-dose cytarabine: an effective and tolerable regimen for the treatment of refractory acute myeloid leukemia. J Clin Oncol 9(7):1210–1214PubMedCrossRef

81.

Tribalto M, Cantonetti M, Catalano G, Del Poeta G, Masi M, Pastore S, Pisani F, Stasi R, Papa G (1991) Mitoxantrone in combination with etoposide and cytarabine for treatment of poor prognosis acute non lymphoid leukemia patients. Haematologica 76(5):402–405PubMed

82.

Thomas X, Cambier N, Taksin AL, Reman O, Vekhoff A, Pautas C, Leblond V, Soler-Michel P, Ecstein-Fraïssé E, Archimbaud E (2000) Dose-escalation study of single dose mitoxantrone in combination with timed sequential chemotherapy in patients with refractory or relapsing acute myelogenous leukemia. Leuk Res 24(11):957–963PubMedCrossRef

83.

Jackson G, Taylor P, Smith GM, Marcus R, Smith A, Chu P, Littlewood TJ, Duncombe A, Hutchinson M, Mehta AB, Johnson SA, Carey P, MacKie MJ, Ganly PS, Turner GE, Deane M, Schey S, Brookes J, Tollerfield SM, Wilson MP (2001) A multicentre, open, non-comparative phase II study of a combination of fludarabine phosphate, cytarabine and granulocyte colony-stimulating factor in relapsed and refractory acute myeloid leukaemia and de novo refractory anaemia with excess of blasts in transformation. Br J Haematol 112(1):127–137PubMedCrossRef

84.

Lee SR, Yang DH, Ahn JS, Kim YK, Lee JJ, Choi YJ, Shin HJ, Chung JS, Cho YY, Chae YS, Kim JG, Sohn SK, Kim HJ (2009) The clinical outcome of FLAG chemotherapy without idarubicin in patients with relapsed or refractory acute myeloid leukemia. J Korean Med Sci 24(3):498–503PubMedPubMedCentralCrossRef

85.

Jabbour E, Garcia-Manero G, Cortes J, Ravandi F, Plunkett W, Gandhi V, Faderl S, O'Brien S, Borthakur G, Kadia T, Burger J, Konopleva M, Brandt M, Huang X, Kantarjian H (2012) Twice-daily fludarabine and cytarabine combination with or without gentuzumab ozogamicin is effective in patients with relapsed/refractory acute myeloid leukemia, high-risk myelodysplastic syndrome, and blast-phase chronic myeloid leukemia. Clin Lymphoma Myeloma Leuk 12(4):244–251PubMedCrossRef

86.

Becker PS, Kantarjian HM, Appelbaum FR, Storer B, Pierce S, Shan J, Faderl S, Estey EH (2013) Retrospective comparison of clofarabine versus fludarabine in combination with high-dose cytarabine with or without granulocyte colony-stimulating factor as salvage therapies for acute myeloid leukemia. Haematologica 98(1):114–118PubMedPubMedCentralCrossRef

87.

Becker PS, Kantarjian HM, Appelbaum FR, Petersdorf SH, Storer B, Pierce S, Shan J, Hendrie PC, Pagel JM, Shustov AR, Stirewalt DL, Faderl S, Harrington E, Estey EH (2011) Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia. Br J Haematol 155(2):182–189PubMedPubMedCentralCrossRef

88.

Kim H, Lee JH, Joo YD, Bae SH, Lee JH, Kim DY, Lee WS, Ryoo HM, Jo JC, Choi Y, Lee KH, CoOperative Study Group A for Hematology (COSAH) (2016) A prospective, multicenter phase II study of continuous infusion of FLAG for patients older than 60 yr with resistant acute myeloid leukemia: a comparison with intensive younger patients' trial. Eur J Haematol 96(2):188–197PubMedCrossRef

89.

Wrzesień-Kuś A, Robak T, Lech-Marańda E, Wierzbowska A, Dmoszyńska A, Kowal M, Hołowiecki J, Kyrcz-Krzemień S, Grosicki S, Maj S, Hellmann A, Skotnicki A, Jedrzejczak W, Kuliczkowski K, Polish Adult Leukemia Group (2003) A multicenter, open, non-comparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, and G-CSF as induction therapy in refractory acute myeloid leukemia—a report of the Polish Adult Leukemia Group (PALG). Eur J Haematol 71(3):155–162PubMedCrossRef

90.

Halpern AB, Othus M, Huebner EM, Buckley SA, Pogosova-Agadjanyan EL, Orlowski KF, Scott BL, Becker PS, Hendrie PC, Chen TL, Percival MM, Estey EH, Stirewalt DL, Walter RB (2017) Mitoxantrone, etoposide and cytarabine following epigenetic priming with decitabine in adults with relapsed/refractory acute myeloid leukemia or other high-grade myeloid neoplasms: a phase 1/2 study. Leukemia 31(12):2560–2567PubMedPubMedCentralCrossRef

91.

Pastore D, Specchia G, Carluccio P, Liso A, Mestice A, Rizzi R, Greco G, Buquicchio C, Liso V (2003) FLAG-IDA in the treatment of refractory/relapsed acute myeloid leukemia: single-center experience. Ann Hematol 82(4):231–235PubMed

92.

Martin MG, Augustin KM, Uy GL, Welch JS, Hladnik L, Goyal S, Tiwari D, Monahan RS, Reichley RM, Cashen AF, Stockerl-Goldstein K, Westervelt P, Abboud CN, Dipersio JF, Vij R (2009) Salvage therapy for acute myeloid leukemia with fludarabine, cytarabine, and idarubicin with or without gemtuzumab ozogamicin and with concurrent or sequential G-CSF. Am J Hematol 84(11):733–737PubMedCrossRef

93.

Montillo M, Ricci F, Tedeschi A, Cafro AM, Nosari AM, Nichelatti M, Marbello L, Morra E (2009) Twice daily fludarabine/Ara-C associated to idarubicin, G-CSF and ATRA is an effective salvage regimen in non-promyelocytic acute myeloid leukemia. Leuk Res 33(8):1072–1078PubMedCrossRef

94.

Kim H, Lee JH, Joo YD, Bae SH, Lee JH, Kim DY, Lee WS, Ryoo HM, Jo JC, Park JH, Lee KH (2014) Prospective, multicenter, phase II study on reducing the dosage of idarubicin and FLAG for patients younger than 65 years with resistant acute myeloid leukemia: a comparison with a higher dosage trial. Acta Haematol1 32(1):87–96CrossRef

95.

Bergua JM, Montesinos P, Martinez-Cuadrón D, Fernández-Abellán P, Serrano J, Sayas MJ, Prieto-Fernandez J, García R, García-Huerta AJ, Barrios M, Benavente C, Pérez-Encinas M, Simiele A, Rodríguez-Macias G, Herrera-Puente P, Rodríguez-Veiga R, Martínez-Sánchez MP, Amador-Barciela ML, Riaza-Grau R, Sanz MA, PETHEMA group (2016) A prognostic model for survival after salvage treatment with FLAG-Ida +/− gemtuzumab-ozogamicine in adult patients with refractory/relapsed acute myeloid leukaemia. Br J Haematol 174(5):700–710PubMedCrossRef

96.

Luo S, Cai F, Jiang L, Zhang S, Shen Z, Sun L, Gao S (2013) Clinical study of Mito-FLAG regimen in treatment of relapsed acute myeloid leukemia. Exp Ther Med 5(3):982–986PubMedPubMedCentralCrossRef

97.

Thiel A, Schetelig J, Pönisch W, Schäfer-Eckart K, Aulitzky W, Peter N, Schulze A, Maschmeyer G, Neugebauer S, Herbst R, Hänel A, Morgner A, Kroschinsky F, Bornhäuser M, Lange T, Wilhelm M, Niederwieser D, Ehninger G, Fiedler F, Hänel M, East German Study Group Hematology/Oncology (OSHO); Study Alliance Leukemia (SAL) (2015) Mito-FLAG with Ara-C as bolus versus continuous infusion in recurrent or refractory AML—long-term results of a prospective randomized intergroup study of the East German Study Group Hematology/Oncology (OSHO) and the Study Alliance Leukemia (SAL). Ann Oncol 26(7):1434–1440PubMedCrossRef

98.

Camera A, Rinaldi CR, Palmieri S, Cantore N, Mele G, Mettivier V, Miraglia E, Mastrullo L, Grimaldi F, Luciano L, Guerriero A, Rotoli B, Ferrara F (2009) Sequential continuous infusion of fludarabine and cytarabine associated with liposomal daunorubicin (DaunoXome) (FLAD) in primary refractory or relapsed adult acute myeloid leukemia patients. Ann Hematol 88(2):151–158PubMedCrossRef

99.

De Astis E, Clavio M, Raiola AM, Ghiso A, Guolo F, Minetto P, Galaverna F, Miglino M, Di Grazia C, Ballerini F, Marani C, Pastori G, Mitscheunig L, Cruciani F, Lovera D, Varaldo R, Ghiggi C, Lemoli RM, Bacigalupo A, Gobbi M (2014) Liposomal daunorubicin, fludarabine, and cytarabine (FLAD) as bridge therapy to stem cell transplant in relapsed and refractory acute leukemia. Ann Hematol 93(12):2011–2018PubMedCrossRef

100.

Wrzesień-Kuś A, Robak T, Wierzbowska A, Lech-Marańda E, Pluta A, Wawrzyniak E, Krawczyńska A, Kuliczkowski K, Mazur G, Kiebiński M, Dmoszyńska A, Wach M, Hellmann A, Baran W, Hołowiecki J, Kyrcz-Krzemień S, Grosicki S, Polish Adult Leukemia Group (2005) A multicenter, open, noncomparative, phase II study of the combination of cladribine (2-chlorodeoxyadenosine), cytarabine, granulocyte colony-stimulating factor and mitoxantrone as induction therapy in refractory acute myeloid leukemia: a report of the Polish Adult Leukemia Group. Ann Hematol 84(9):557–564PubMedCrossRef

101.

Wierzbowska A, Robak T, Pluta A, Wawrzyniak E, Cebula B, Hołowiecki J, Kyrcz-Krzemień S, Grosicki S, Giebel S, Skotnicki AB, Piatkowska-Jakubas B, Kuliczkowski K, Kiełbiński M, Zawilska K, Kłoczko J, Wrzesień-Kuś A, Polish Adult Leukemia Group (2008) Cladribine combined with high doses of arabinoside cytosine, mitoxantrone, and G-CSF (CLAG-M) is a highly effective salvage regimen in patients with refractory and relapsed acute myeloid leukemia of the poor risk: a final report of the Polish Adult Leukemia Group. Eur J Haematol 80(2):115–126PubMedCrossRef

102.

Scappini B, Gianfaldoni G, Caracciolo F, Mannelli F, Biagiotti C, Romani C, Pogliani EM, Simonetti F, Borin L, Fanci R, Cutini I, Longo G, Susini MC, Angelucci E, Bosi A (2012) Cytarabine and clofarabine after high-dose cytarabine in relapsed or refractory AML patients. Am J Hematol 87(12):1047–1051PubMedCrossRef

103.

Roberts DA, Wadleigh M, McDonnell AM, DeAngelo DJ, Stone RM, Steensma DP (2015) Low efficacy and high mortality associated with clofarabine treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndromes. Leuk Res 39(2):204–210PubMedCrossRef

104.

Kornblau SM, Gandhi V, Andreeff HM, Beran M, Kantarjian HM, Koller CA, O'Brien S, Plunkett W, Estey E (1996) Clinical and laboratory studies of 2-chlorodeoxyadenosine +/− cytosine arabinoside for relapsed or refractory acute myelogenous leukemia in adults. Leukemia 10(10):1563–1569PubMed

105.

Faderl S, Ferrajoli A, Wierda W, Huang X, Verstovsek S, Ravandi F, Estrov Z, Borthakur G, Kwari M, Kantarjian HM (2008) Clofarabine combinations as acute myeloid leukemia salvage therapy. Cancer 113(8):2090–2096PubMedPubMedCentralCrossRef

106.

Visani G, Tosi P, Zinzani PL, Manfroi S, Ottaviani E, Testoni N, Clavio M, Cenacchi A, Gamberi B, Carrara P, Gobbi M, Tura S (1994) FLAG (fludarabine + high-dose cytarabine + G-CSF): an effective and tolerable protocol for the treatment of ‘poor risk’ acute myeloid leukemia. Leukemia 8(11):1842–1846PubMed

107.

Huhmann IM, Watzke HH, Geissler K, Gisslinger H, Jäger U, Knöbl P, Pabinger I, Korninger L, Mannhalter C, Mitterbauer G, Schwarzinger I, Kalhs P, Haas OA, Lechner K (1996) FLAG (fludarabine, cytosine arabinoside, G-CSF) for refractory and relapsed acute myeloid leukemia. Ann Hematol 73(6):265–271PubMedCrossRef

108.

Nokes TJ, Johnson S, Harvey D, Goldstone AH (1997) FLAG is a useful regimen for poor prognosis adult myeloid leukaemias and myelodysplastic syndromes. Leuk Lymphoma 27(1–2):93–101PubMedCrossRef

109.

Montillo M, Mirto S, Petti MC, Latagliata R, Magrin S, Pinto A, Zagonel V, Mele G, Tedeschi A, Ferrara F (1998) Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of poor risk acute myeloid leukemia. Am J Hematol 58(2):105–109PubMedCrossRef

110.

Ferrara F, Melillo L, Montillo M, Leoni F, Pinto A, Mele G, Mirto S (1999) Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of acute myeloid leukemia relapsing after autologous stem cell transplantation. Ann Hematol 78(8):380–384PubMedCrossRef

111.

Robak T, Wrzesień-Kuś A, Lech-Marańda E, Kowal M, Dmoszyńska A (2000) Combination regimen of cladribine (2-chlorodeoxyadenosine), cytarabine and G-CSF (CLAG) as induction therapy for patients with relapsed or refractory acute myeloid leukemia. Leuk Lymphoma 39(1–2):121–129PubMedCrossRef

112.

Hänel M, Friedrichsen K, Hänel A, Herbst R, Morgner A, Neser S, Nicklisch M, Teich M, Ehninger G, Fiedler F (2001) Mito-flag as salvage therapy for relapsed and refractory acute myeloid leukemia. Onkologie 24(4):356–360PubMed

113.

Pawson R, Potter MN, Theocharous P, Lawler M, Garg M, Yin JA, Rezvani K, Craddock C, Rassam S, Prentice HG (2001) Treatment of relapse after allogeneic bone marrow transplantation with reduced intensity conditioning (FLAG +/− Ida) and second allogeneic stem cell transplant. Br J Haematol 115(3):622–629PubMedCrossRef

114.

de la Rubia J, Regadera A, Martín G, Cervera J, Sanz G, Martínez J, Jarque I, García I, Andreu R, Moscardó F, Jiménez C, Mollá S, Benlloch L, Sanz M (2002) FLAG-IDA regimen (fludarabine, cytarabine, idarubicin and G-CSF) in the treatment of patients with high-risk myeloid malignancies. Leuk Res 26(8):725–730PubMedCrossRef

115.

Kantarjian H, Gandhi V, Cortes J, Verstovsek S, Du M, Garcia-Manero G, Giles F, Faderl S, O'Brien S, Jeha S, Davis J, Shaked Z, Craig A, Keating M, Plunkett W, Freireich EJ (2003) Phase 2 clinical and pharmacologic study of clofarabine in patients with refractory or relapsed acute leukemia. Blood 102(7):2379–2386PubMedCrossRef

116.

Giles FJ, Cortes JE, Kantarjian HM, O'Brien SM, Estey E, Beran M (2004) A fludarabine, topotecan, and cytarabine regimen is active in patients with refractory acute myelogenous leukemia. Leuk Res 28(4):353–357PubMedCrossRef

117.

Faderl S, Gandhi V, O'Brien S, Bonate P, Cortes J, Estey E, Beran M, Wierda W, Garcia-Manero G, Ferrajoli A, Estrov Z, Giles FJ, Du M, Kwari M, Keating M, Plunkett W, Kantarjian H (2005) Results of a phase 1-2 study of clofarabine in combination with cytarabine (ara-C) in relapsed and refractory acute leukemias. Blood 105(3):940–947PubMedCrossRef

118.

Yavuz S, Paydas S, Disel U, Sahin B (2006) IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience. Am J Ther 13(5):389–393PubMedCrossRef

119.

Hołowiecki J, Grosicki S, Kyrcz-Krzemien S, Skotnicki AB, Piatkowska-Jakubas B, Warzocha K, Seferynska I, Zdziarska B (2008) Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome—Polish Adult Leukemia Group (PALG) pilot study. Ann Hematol 87(5):361–367PubMedCrossRef

120.

Kim H, Park JH, Lee JH, Lee JH, Joo YD, Lee WS, Bae SH, Mo Ryoo H, Lee KH, Cooperative Study Group A for Hematology (2009) Continuous infusion of intermediate-dose cytarabine and fludarabine with idarubicin for patients younger than 60 years with resistant acute myeloid leukemia: a prospective, multicenter phase II study. Am J Hematol 84(3):161–166PubMedCrossRef

121.

Martin MG, Welch JS, Augustin K, Hladnik L, DiPersio JF, Abboud CN (2009) Cladribine in the treatment of acute myeloid leukemia: a single-institution experience. Clin Lymphoma Myeloma 9(4):298–301PubMedCrossRef

122.

Agura E, Cooper B, Holmes H, Vance E, Berryman RB, Maisel C, Li S, Saracino G, Tadic-Ovcina M, Fay J (2011) Report of a phase II study of clofarabine and cytarabine in de novo and relapsed and refractory AML patients and in selected elderly patients at high risk for anthracycline toxicity. Oncologist 16(2):197–206PubMedPubMedCentralCrossRef

123.

McLaughlin B, Im A, Raptis A, Agha M, Hou JZ, Redner R, Duggal S, Lin Y, Smith C, Boyiadzis M (2012) Fludarabine and cytarabine in patients with relapsed acute myeloid leukemia refractory to initial salvage therapy. Int J Hematol 96(6):743–747PubMedCrossRef

124.

Bennett JM, Lymann GH, Cassileth PA, Glick JH, Oken MM (1984) A phase II trial of VP 16-213 in adults with refractory acute myeloid leukemia. An Eastern Cooperative Oncology Group study. Am J Clin Oncol 7(5):471–473PubMedCrossRef

125.

Harousseau JL, Hurteloup P, Reiffers J, Rigal-Huguet F, Hayat M, Dufour P, Le Prise PY, Monconduit M, Jaubert J, Carcassonne Y (1987) Idarubicin in the treatment of relapsed or refractory acute myeloid leukemia. Cancer Treat Rep 71(10):991–992PubMed

126.

Bezwoda WR, Bernasconi C, Hutchinson RM, Winfield DA, de Bock R, Mandelli F (1990) Mitoxantrone for refractory and relapsed acute leukemia. Cancer 66(3):418–422PubMedCrossRef

127.

Goldberg J, Gryn J, Raza A, Bennett J, Browman G, Bryant J, Grunwald H, Larson R, Vogler R, Preisler H (1993) Mitoxantrone and 5-azacytidine for refractory/relapsed ANLL or CML in blast crisis: a leukemia intergroup study. Am J Hematol 43(4):286–290PubMedCrossRef

128.

Vogler WR, Harrington DP, Winton EF, Lazarus HM, Bennett JM, Cassileth PA, Oken MM (1992) Phase II clinical trial of carboplatin in relapsed and refractory leukemia. Leukemia 6(10):1072–1075PubMed

129.

Welborn JL, Kopecky KJ, Meyers FJ, Veith R, Shurafa M, Doroshow JH, Balcerzak SP, Appelbaum FR (1995) Carboplatin infusion in relapsed and refractory acute myeloid leukemia—a Southwest Oncology Group trial. Leukemia 9(7):1126–1129PubMed

130.

Gordon MS, Young ML, Tallman MS, Cripe LD, Bennett JM, Paietta E, Longo W, Gerad H, Mazza J, Rowe JM (2000) Phase II trial of 2-chlorodeoxyadenosine in patients with relapsed/refractory acute myeloid leukemia: a study of the Eastern Cooperative Oncology Group (ECOG), E5995. Leuk Res 24(10):871–875PubMedCrossRef

131.

Roboz GJ, Rosenblat T, Arellano M, Gobbi M, Altman JK, Montesinos P, O'Connell C, Solomon SR, Pigneux A, Vey N, Hills R, Jacobsen TF, Gianella-Borradori A, Foss Ø, Vetrhusand S, Giles FJ (2014) International randomized phase III study of elacytarabine versus investigator choice in patients with relapsed/refractory acute myeloid leukemia. J Clin Oncol 32(18):1919–1926PubMedCrossRef

132.

Knapper S, Chevassut T, Duarte R, Bergua JM, Salamero O, Johansen M, Jacobsen TF, Hals PA, Rasch W, Gianella-Borradori A, Smith M (2014) Elacytarabine in relapsed/refractory acute myeloid leukaemia: an evaluation of clinical efficacy, pharmacokinetics, cardiac safety and effects on lipid profile. Leuk Res 38(3):346–351PubMedCrossRef

133.

Bergmann L, Heil G, Kolbe K, Lengfelder E, Puzicha E, Martin H, Lohmeyer J, Mitrou PS, Hoelzer D (1995) Interleukin-2 bolus infusion as late consolidation therapy in 2nd remission of acute myeloblastic leukemia. Leuk Lymphoma 16(3–4):271–279PubMedCrossRef

134.

Ho AD, Lipp T, Ehninger G, Illiger HJ, Meyer P, Freund M, Hunstein W (1988) Combination of mitoxantrone and etoposide in refractory acute myelogenous leukemia—an active and well-tolerated regimen. J Clin Oncol 6(2):213–217PubMedCrossRef

135.

Rowe JM, Mazza JJ, Hines JD, Cassileth PA, Oken MM, Bennett JM, Andersen J (1990) Mitoxantrone and etoposide in patients with relapsed and refractory acute nonlymphocytic leukemia. Haematol Blood Transfus 33:326–329PubMed

136.

Hilbe W, Thaler J, Eisterer W, Ludescher C, Niederwieser D (1994) Treatment of relapsed and refractory acute myelogenous leukaemia with aclacinomycin A (ACA) and etoposide (VP-16). Leuk Res 18(9):655–658PubMedCrossRef

137.

Kern W, Braess J, Grote-Metke A, Kuse H, Fuchs R, Hossfeld DK, Reichle A, Wörmann B, Büchner T, Hiddemann W (1998) Combination of aclarubicin and etoposide for the treatment of advanced acute myeloid leukemia: results of a prospective multicenter phase II trial. German AML Cooperative Group. Leukemia 12(10):1522–1526PubMedCrossRef

138.

Boyiadzis M, Redner RL, Raptis A, Hou JZ, Agha M, Foon KA (2011) Gemtuzumab ozogamicin, mitoxantrone, and etoposide in newly diagnosed acute myeloid leukemia patients with persistent leukemia after a course of induction therapy. Ann Hematol 90(6):733–735PubMedCrossRef

139.

Van Den Neste E, Martiat P, Mineur P, Delannoy A, Doyen C, Zenebergh A, Michaux JL, Ferrant A (1998) 2-Chlorodeoxyadenosine with or without daunorubicin in relapsed or refractory acute myeloid leukemia. Ann Hematol 76(1):19–23CrossRef

140.

Apostolidou E, Estey E, Cortes J, Garcia-Manero G, Faderl S, Thomas D, Tsimberidou A, Kantarjian H, Giles FJ (2003) Mitoxantrone and prolonged infusion gemcitabine as salvage therapy in patients with acute myelogenous leukemia. Leuk Res 27(4):301–304PubMedCrossRef

141.

Willemze R, Suciu S, Archimbaud E, Muus P, Stryckmans P, Louwagie EA, Berneman Z, Tjean M, Wijermans P, Dohner H, Jehn U, Labar B, Jaksic B, Dardenne M, Zittoun R (1997) A randomized phase II study on the effects of 5-Aza-2′-deoxycytidine combined with either amsacrine or idarubicin in patients with relapsed acute leukemia: an EORTC Leukemia Cooperative Group phase II study (06893). Leukemia 11(Suppl 1):S24–S27PubMed

142.

Sanz MA, Sanz GF, Martínez JA, Senent L, López F, Palau J, Martín G, Jarque I (1992) Carboplatin alone or in combination in high-risk acute nonlymphoblastic leukemia. Ann Oncol 3(Suppl 3):39–42PubMedCrossRef

143.

Letendre L, Noel P, Tefferi A, Solberg LA Jr, Gastineau DA, Hoagland HC (1995) Continuous infusion etoposide/carboplatin for treatment of refractory acute leukemia. Am J Clin Oncol 18(5):382–384PubMedCrossRef

144.

Amadori S, Picardi A, Fazi P, Testi AM, Petti MC, Montefusco E, Mandelli F (1996) A phase II study of VP-16, intermediate-dose Ara-C and carboplatin (VAC) in advanced acute myelogenous leukemia and blastic chronic myelogenous leukemia. Leukemia 10:766–768PubMed

145.

Kornblau SM, Kantarjian H, O'Brien S, Andreeff M, Koller CA, Beran M, Keating M, Estey E (1998) CECA-cyclophosphamide, etoposide, carboplatin and cytosine arabinoside--a new salvage regimen for relapsed or refractory acute myelogenous leukemia. Leuk Lymphoma 28(3–4):371–375PubMedCrossRef

146.

Belhabri A, Thomas X, Troncy J, Assouline D, Michallet M, Wattel E, Tigaud JD, Blanc M, Fière D, Archimbaud E (1999) Continuous-infusion carboplatin in combination with idarubicin or mitoxantrone for high-risk acute myeloid leukemia: a randomised phase II study. Leuk Lymphoma 36(1–2):45–55PubMedCrossRef

147.

Ferrá C, Berlanga JJ, Gallardo D, Ancín I, Marín D, González JR, Peris J, Muñoz J, Sarrá J, Grañena A (2000) Mitoxantrone, etoposide, carboplatinum and ara-C combination therapy (MECA) in refractory and relapsed acute leukemia. Leuk Lymphoma 39(5–6):583–590PubMedCrossRef

148.

Lee EJ, Egorin MJ, Van Echo DA, Cohen AE, Tait N, Schiffer CA (1988) Phase I and pharmacokinetic trial of carboplatin in refractory adult leukemia. J Natl Cancer Inst 80(2):131–135PubMedCrossRef

149.

Meyers FJ, Welborn J, Lewis JP, Flynn N (1989) Infusion carboplatin treatment of relapsed and refractory acute leukemia: evidence of efficacy with minimal extramedullary toxicity at intermediate doses. J Clin Oncol 7(2):173–178PubMedCrossRef

150.

Martínez JA, Martín G, Sanz GF, Sempere A, Jarque I, de la Rubia J, Sanz MA (1991) A phase II clinical trial of carboplatin infusion in high-risk acute nonlymphoblastic leukemia. J Clin Oncol 9(1):39–43PubMedCrossRef

151.

Horikoshi A, Takei K, Hosokawa Y, Sawada S (2008) The value of oral cytarabine ocfosfate and etoposide in the treatment of refractory and elderly AML patients. Int J Hematol 87(2):118–125PubMedCrossRef

152.

Paciucci PA, Davis RB, Holland JF, Martelo O, Schiffer CA (1990) Mitoxantrone and constant infusion etoposide for relapsed and refractory acute myelocytic leukemia. Am J Clin Oncol 13(6):516–519PubMedCrossRef

153.

Daenen S, Löwenberg B, Sonneveld P, van Putten WL, Verhoef G, Verdonck LF, van Veldhoven M, Huijgens PC (1994) Efficacy of etoposide and mitoxantrone in patients with acute myelogenous leukemia refractory to standard induction therapy and intermediate-dose cytarabine with amsidine. Dutch Hematology-Oncology Working Group for Adults (HOVON). Leukemia 8(1):6–10PubMed

154.

Jensen MK, Johansen P, Stentoft J, Jensen MK (1994) Salvage therapy with low-dose cytosine arabinoside in refractory or relapsed acute non-lymphocytic leukaemia: a report on 25 patients. Eur J Haematol 52(4):236–239PubMedCrossRef

155.

Venditti A, Stasi R, Del Poeta G, Buccisano F, Aronica G, Bruno A, Pisani F, Caravita T, Masi M, Tribalto M et al (1995) All-trans retinoic acid and low-dose cytosine arabinoside for the treatment of ‘poor prognosis’ acute myeloid leukemia. Leukemia 9(7):1121–1125PubMed

156.

Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH, Dombret H, Theobald M, Voliotis D, Bennett JM, Richie M, Leopold LH, Berger MS, Sherman ML, Loken MR, van Dongen JJ, Bernstein ID, Appelbaum FR (2005) Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer 104(7):1442–1452PubMedCrossRef

157.

Taksin AL, Legrand O, Raffoux E, de Revel T, Thomas X, Contentin N, Bouabdallah R, Pautas C, Turlure P, Reman O, Gardin C, Varet B, de Botton S, Pousset F, Farhat H, Chevret S, Dombret H, Castaigne S (2007) High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. Leukemia 21(1):66–71PubMedCrossRef

158.

Ivanoff S, Gruson B, Chantepie SP, Lemasle E, Merlusca L, Harrivel V, Charbonnier A, Votte P, Royer B, Marolleau JP (2013) 5-Azacytidine treatment for relapsed or refractory acute myeloid leukemia after intensive chemotherapy. Am J Hematol 88(7):601–605PubMedCrossRef

159.

Itzykson R, Thépot S, Berthon C, Delaunay J, Bouscary D, Cluzeau T, Turlure P, Prébet T, Dartigeas C, Marolleau JP, Recher C, Plantier I, Stamatoullas A, Devidas A, Taksin AL, Guièze R, Caillot D, Vey N, Adès L, Ifrah N, Dombret H, Fenaux P, Gardin C (2015) Azacitidine for the treatment of relapsed and refractory AML in older patients. Leuk Res 39(2):124–130PubMedCrossRef

160.

Stalh M, Podoltsev NA, DeVeaux M, Perreault S, Itzykson R, Ritchie EK, Sekeres MA, Fathi AT, Komrokji RS, Bhatt VR, Al-Kali A, Cluzeau T, Santini V, Brunner A, Roboz GJ, Fenaux P, Litzow M, Vey N, Verma V, Germing U, Montesinos P, Zelterman D, Kim TK, Prebet T, Gore SD, Zeidan AM (2016) The use of hypomethylating agents (HMAs) in patients with relapsed and refractory acute myeloid leukemia (RR-AML): clinical outcomes and their predictors in a large international patient cohort. Blood 128(21):1063

161.

Ritchie EK, Feldman EJ, Christos PJ, Rohan SD, Lagassa CB, Ippoliti C, Scandura JM, Carlson K, Roboz GJ (2013) Decitabine in patients with newly diagnosed and relapsed acute myeloid leukemia. Leuk Lymphoma 54(9):2003–2007PubMedCrossRef

162.

Raffoux E, Cras A, Recher C, Boëlle PY, de Labarthe A, Turlure P, Marolleau JP, Reman O, Gardin C, Victor M, Maury S, Rousselot P, Malfuson JV, Maarek O, Daniel MT, Fenaux P, Degos L, Chomienne C, Chevret S, Dombret H (2010) Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome. Oncotarget 1(1):34–42PubMedPubMedCentral

163.

Daver N, Kantarjian H, Ravandi F, Estey E, Wang X, Garcia-Manero G, Jabbour E, Konopleva M, O'Brien S, Verstovsek S, Kadia T, Dinardo C, Pierce S, Huang X, Pemmaraju N, Diaz-Pines-Mateo M, Cortes J, Borthakur G (2016) A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome. Leukemia 30(2):268–273PubMedCrossRef

164.

Piccaluga PP, Martinelli G, Rondoni M, Malagola M, Gaitani S, Isidori A, Bonini A, Gugliotta L, Luppi M, Morselli M, Sparaventi G, Visani G, Baccarani M (2004) Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas. Leuk Lymphoma 45(9):1791–1795PubMedCrossRef

165.

Bolaños-Meade J, Smith BD, Gore SD, McDevitt MA, Luznik L, Fuchs EJ, Jones RJ (2011) 5-azacytidine as salvage treatment in relapsed myeloid tumors after allogeneic bone marrow transplantation. Biol Blood Marrow Transplant 17(5):754–758PubMedCrossRef

166.

Al-Ali HK, Jaekel N, Junghanss C, Maschmeyer G, Krahl R, Cross M, Hoppe G, Niederwieser D (2012) Azacitidine in patients with acute myeloid leukemia medically unfit for or resistant to chemotherapy: a multicenter phase I/II study. Leuk Lymphoma 53(1):110–117PubMedCrossRef

167.

Chowdhury S, Seropian S, Marks PW (2009) Decitabine combined with fractionated gemtuzumab ozogamicin therapy in patients with relapsed or refractory acute myeloid leukemia. Am J Hematol 84(9):599–600PubMedCrossRef

168.

Estey E, Thall P, Andreeff M, Beran M, Kantarjian H, O'Brien S, Escudier S, Robertson LE, Koller C, Kornblau S et al (1994) Use of granulocyte colony-stimulating factor before, during, and after fludarabine plus cytarabine induction therapy of newly diagnosed acute myelogenous leukemia or myelodysplastic syndromes: comparison with fludarabine plus cytarabine without granulocyte colony-stimulating factor. J Clin Oncol 12(4):671–678PubMedCrossRef

169.

Tse E, Leung AY, Sim J, Lee HK, Liu HS, Yip SF, Kwong YL (2011) Clofarabine and high-dose cytosine arabinoside in the treatment of refractory or relapsed acute myeloid leukaemia. Ann Hematol 90(11):1277–1281PubMedPubMedCentralCrossRef

170.

Yang H, Hoshino K, Sanchez-Gonzalez B, Kantarjian H, Garcia-Manero G (2005) Antileukemia activity of the combination of 5-aza-2′-deoxycytidine with valproic acid. Leuk Res 29(7):739–748PubMedCrossRef

171.

Löwenberg B, van Putten W, Theobald M, Gmür J, Verdonck L, Sonneveld P, Fey M, Schouten H, de Greef G, Ferrant A, Kovacsovics T, Gratwohl A, Daenen S, Huijgens P, Boogaerts M, Dutch-Belgian Hemato-Oncology Cooperative Group; Swiss Group for Clinical Cancer Research (2003) Effect of priming with granulocyte colony-stimulating factor on the outcome of chemotherapy for acute myeloid leukemia. N Engl J Med 349(8):743–752PubMedCrossRef

172.

Leopold LH, Willemze R (2002) The treatment of acute myeloid leukemia in first relapse: a comprehensive review of the literature. Leuk Lymphoma 43(9):1715–1727PubMedCrossRef

173.

Mangan JK, Luger SM (2011) Salvage therapy for relapsed or refractory acute myeloid leukemia. Ther Adv Hematol 2(2):73–82PubMedPubMedCentralCrossRef

174.

Bryan JC, Jabbour EJ (2015) Management of relapsed/refractory acute myeloid leukemia in the elderly: current strategies and developments. Drugs Aging 32(8):623–637PubMedCrossRef

175.

Thol F, Schlenk RF, Heuser M, Ganser A (2015) How I treat refractory and early relapsed acute myeloid leukemia. Blood 126(3):319–327PubMedCrossRef

176.

Kuo YH, Qi J, Cook GJ (2016) Regain control of p53: targeting leukemia stem cells by isoform-specific HDAC inhibition. Exp Hematol 44(5):315–321PubMedPubMedCentralCrossRef

177.

Breems DA, Van Putten WL, Huijgens PC, Ossenkoppele GJ, Verhoef GE, Verdonck LF, Vellenga E, De Greef GE, Jacky E, Van der Lelie J, Boogaerts MA, Löwenberg B (2005) Prognostic index for adult patients with acute myeloid leukemia in first relapse. J Clin Oncol 23(9):1969–1978PubMedCrossRef

178.

Hiddemann W, Martin WR, Sauerland CM, Heinecke A, Büchner T (1990) Definition of refractoriness against conventional chemotherapy in acute myeloid leukemia: a proposal based on the results of retreatment by thioguanine, cytosine arabinoside, and daunorubicin (TAD 9) in 150 patients with relapse after standardized first line therapy. Leukemia 4(3):184–188PubMed

179.

Giralt S, Estey E, Albitar M, van Besien K, Rondón G, Anderlini P, O'Brien S, Khouri I, Gajewski J, Mehra R, Claxton D, Andersson B, Beran M, Przepiorka D, Koller C, Kornblau S, Kørbling M, Keating M, Kantarjian H, Champlin R (1997) Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood 89(12):4531–4536PubMed

180.

O'Donnell MR, Tallman MS, Abboud CN, Altman JK, Appelbaum FR, Arber DA, Bhatt V, Bixby D, Blum W, Coutre SE, De Lima M, Fathi AT, Fiorella M, Foran JM, Gore SD, Hall AC, Kropf P, Lancet J, Maness LJ, Marcucci G, Martin MG, Moore JO, Olin R, Peker D, Pollyea DA, Pratz K, Ravandi F, Shami PJ, Stone RM, Strickland SA, Wang ES, Wieduwilt M, Gregory K, Ogba N (2017) Acute myeloid leukemia, version 3.2017, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw 15(7):926–957CrossRef

181.

Bertoli S, Gadaud N, Tavitian S, Sarry A, Bérard E, Huguet F, Recher C (2016) Is intermediate-dose Cytarabine a good control for patients with relapsed or refractory acute myeloid leukemia? Blood 128:3991

182.

Schlenk RF, Döhner K, Mack S, Stoppel M, Király F, Götze K, Hartmann F, Horst HA, Koller E, Petzer A, Grimminger W, Kobbe G, Glasmacher A, Salwender H, Kirchen H, Haase D, Kremers S, Matzdorff A, Benner A, Döhner H (2010) Prospective evaluation of allogeneic hematopoietic stem-cell transplantation from matched related and matched unrelated donors in younger adults with high-risk acute myeloid leukemia: German-Austrian trial AMLHD98A. J Clin Oncol 28(30):4642–4648PubMedCrossRef

183.

Duval M, Klein JP, He W, Cahn JY, Cairo M, Camitta BM, Kamble R, Copelan E, de Lima M, Gupta V, Keating A, Lazarus HM, Litzow MR, Marks DI, Maziarz RT, Rizzieri DA, Schiller G, Schultz KR, Tallman MS, Weisdorf D (2010) Hematopoietic stem-cell transplantation for acute leukemia in relapse or primary induction failure. J Clin Oncol 28(23):3730–3738PubMedPubMedCentralCrossRef

184.

Wattad M, Weber D, Döhner K, Krauter J, Gaidzik VI, Paschka P, Heuser M, Thol F, Kindler T, Lübbert M, Salih HR, Kündgen A, Horst HA, Brossart P, Götze K, Nachbaur D, Köhne CH, Ringhoffer M, Wulf G, Held G, Salwender H, Benner A, Ganser A, Döhner H, Schlenk RF (2017) Impact of salvage regimens on response and overall survival in acute myeloid leukemia with induction failure. Leukemia 31(6):1306–1313PubMedCrossRef

185.

Bennett TA, Montesinos P, Moscardo F, Martinez-Cuadron D, Martinez J, Sierra J, García R, de Oteyza JP, Fernandez P, Serrano J, Fernandez A, Herrera P, Gonzalez A, Bethancourt C, Rodriguez-Macias G, Alonso A, Vera JA, Navas B, Lavilla E, Lopez JA, Jimenez S, Simiele A, Vidriales B, Gonzalez BJ, Burgaleta C, Hernandez Rivas JA, Mascuñano RC, Bautista G, Perez Simon JA, Fuente Ade L, Rayón C, Troconiz IF, Janda A, Bosanquet AG, Hernandez-Campo P, Primo D, Lopez R, Liebana B, Rojas JL, Gorrochategui J, Sanz MA, Ballesteros J (2014) Pharmacological profiles of acute myeloid leukemia treatments in patient samples by automated flow cytometry: a bridge to individualized medicine. Clin Lymphoma Myeloma Leuk 14:305–318PubMedCrossRef

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Salvage regimens using conventional chemotherapy agents for relapsed/refractory adult AML patients: a systematic literature review

Abstract

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

Europäische Ernährungsgewohnheiten: Das sind die häufigsten Fehler

Hinter dieser Appendizitis steckte ein Erreger

Demenzkranke durch Antipsychotika vielfach gefährdet

Update Innere Medizin

Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2018

Langerhans cell histiocytosis and primary hemophagocytic lymphohistiocytosis with persistent clonal T-large granular lymphocyte proliferation

Role of minimal residual disease in the management of acute myeloid leukemia—a case-based discussion

The impact of stem cell transplantation on the natural course of peripheral T-cell lymphoma: a real-world experience

Survival analysis of patients with Hodgkin lymphoma who failed high dose chemotherapy and autologous stem cell transplant

Treatment of late-onset hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: the role of corticosteroids