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The role of cladribine in acute myeloid leukemia: an old drug up to new tricks

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Pages 536-545 | Received 25 Aug 2019, Accepted 19 Sep 2019, Published online: 22 Nov 2019

References

  • Almeida AM, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1–7.
  • Rashidi A, Weisdorf DJ, Bejanyan N. Treatment of relapsed/refractory acute myeloid leukaemia in adults. Br J Haematol. 2018;181(1):27–37.
  • Rowe JM, Tallman MS. Intensifying induction therapy in acute myeloid leukemia: has a new standard of care emerged? Blood. 1997;90(6):2121–2126.
  • Büchner T, Hiddemann W, Berdel WE, et al. 6-Thioguanine, cytarabine, and daunorubicin (TAD) and high-dose cytarabine and mitoxantrone (HAM) for induction, TAD for consolidation, and either prolonged maintenance by reduced monthly TAD or TAD-HAM-TAD and one course of intensive consolidation by sequential HAM in adult patients at all ages with de novo acute myeloid leukemia (AML): a randomized trial of the German AML Cooperative Group. J Clin Oncol. 2003;21(24):4496–4504.
  • Ahmed SO, Fahad Almohareb F, Aljurf M, et al. Real-world data indicates that the addition of etoposide to idarubicin and cytarabine (3 + 7) induction in young adults (<60 years) with AML does not improve survival or remission rates. Blood. 2016;128:4010.
  • Chaoui D, Peffault De Latour R, Legrand O, et al. Acute myeloid leukemia in the elderly: etoposide when anthracyclins are contraindicated. Leuk Lymphoma. 2005;46(3):401–404.
  • Burnett AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. JCO. 2011;29(4):369–377.
  • Gandhi V, Plunkett W. Modulation of arabinosylnucleoside metabolism by arabinosylnucleotides in human leukemia cells. Cancer Res. 1988;48(2):329–334.
  • Seymour JF, Huang P, Plunkett W, et al. Influence of fludarabine on pharmacokinetics and pharmacodynamics of cytarabine: implications for a continuous infusion schedule. Clin Cancer Res. 1996;2(4):653–658.
  • Gandhi V, Estey E, Keating MJ, et al. Biochemical modulation of arabinosylcytosine for therapy of leukemias. Leuk Lymphoma. 1993;10(sup1):109–114.
  • Nodehi RS, Gharib B, Sharifian R, et al. A study of the complete response rate with a combination of high dose cytarabine and cladribine in refractory and relapsed acute leukemia. Int J Hematol Oncol Stem Cell Res. 2010;4:5–8.
  • Price SL, Lancet JE, George TJ, et al. Salvage chemotherapy regimens for acute myeloid leukemia: is one better? Efficacy comparison between CLAG and MEC regimens. Leuk Res. 2011;35(3):301–304.
  • Wierzbowska A, Robak T, Pluta A, et al. 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. 2008;80:115–126.
  • Ramsingh G, Westervelt P, McBride A, et al. Phase I study of cladribine, cytarabine, granulocyte colony stimulating factor (CLAG regimen) and midostaurin and all‐trans retinoic acid in relapsed/refractory AML. Int J Hematol. 2014;99(3):272–278.
  • Holowiecki J, Grosicki S, Giebel S, et al. Cladribine, but not fludarabine, added to daunorubicin and cytarabine during induction prolongs survival of patients with acute myeloid leukemia: a multicenter, randomized phase III study. JCO. 2012;30(20):2441–2448.
  • Holowiecki J, Grosicki S, Robak T, et al. Addition of cladribine to daunorubicin and cytarabine increases complete remission rate after a single course of induction treatment in acute myeloid leukemia. Multicenter, phase III study. Leukemia. 2004;18(5):989–997.
  • Seligson ND, Hobbs ALV, Leonard JM, et al. Evaluating the impact of the addition of cladribine to standard acute myeloid leukemia induction therapy. Ann Pharmacother. 2018;52(5):439–445.
  • Kadia TM, Cortes J, Ravandi F, et al. 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. 2018;5(9):e411–e421.
  • National Comprehensive Cancer Network. Acute Myeloid Leukemia [Version 2.2020]. 2019 Sep.
  • Pastor-Anglada M, Molina-Arcas M, Casado FJ, et al. Nucleoside transporters in chronic lymphocytic leukaemia. Leukemia. 2004;18(3):385–393.
  • Cheson B. The purine analogs–a therapeutic beauty contest. JCO. 1992;10(5):868–871.
  • Eriksson S, Arner E, Spasokoukotskaja T, et al. Properties and levels of deoxynucleoside kinases in normal and tumor cells; implications for chemotherapy. Adv Enzyme Regul. 1994;34:13–25.
  • Nomura Y, Inanami O, Takahashi K, et al. Chloro‐2'‐deoxyadenosine induces apoptosis through the Fas/Fas ligand pathway in human leukemia cell line MOLT‐4. Leukemia. 2000;14(2):299–306.
  • Marzo I, Perez‐Galan P, Giraldo P, et al. Cladribine induces apoptosis in human leukaemia cells by caspase‐dependent and ‐independent pathways acting on mitochondria. Biochem J. 2001;359(3):537–546.
  • Genini D, Adachi S, Chao Q, et al. Deoxyadenosine analogs induce programmed cell death in chronic lymphocytic leukemia cells by damaging the DNA and by directly affecting the mitochondria. Blood. 2000;96(10):3537–3543.
  • Chow KU, Boehrer S, Napieralski S, et al. In AML cell lines Ara‐C combined with purine analogues is able to exert synergistic as well as antagonistic effects on proliferation, apoptosis and disruption of mitochondrial membrane potential. Leuk Lymphoma. 2003;44(1):165–173.
  • Jamaluddin MD, Chen I, Yang F, et al. Homocysteine inhibits endothelial cell growth via DNA hypomethylation of the cyclin A gene. Blood. 2007;110(10):3648–3655.
  • Kristensen J, Nygren P, Liliemark J, et al. Interactions between cladribine (2‐chlorodeoxyadenosine) and standard antileukemic drugs in primary cultures of human tumor cells from patients with acute myelocytic leukemia. Leukemia. 1994;8(10):1712–1717.
  • Szmigielska‐Kaplon A, Ciesielska E, Szmigiero L, et al. Anthracyclines potentiate activity against murine leukemias L1210 and P388 in vivo and in vitro. Eur J Haematol. 2002;68:370–375.
  • Robak T, Korycka A. The comparison of 2-chlorodeoxyadenosine (2-Cd A) in combination with interferon alpha (IFN alpha) or interferon gamma (IFN gamma) on granulocyte-macrophage progenitor cells (CFU-GM) and clonogenic blasts in (CFU-L) in vitro cultures. Leuk Lymphoma. 1996;21(1-2):161–168.
  • Robak T, Korycka A, Góra-Tybor J. The interaction of 2‐chlorodeoxyadenosine (2‐CDA) and interferon‐alpha on normal and myeloid leukemia hematopoiesis in vitro. Leuk Res. 1994;18(4):275–281.
  • Santana VM, Mirro J, Harwood FC, et al. A phase I clinical trial of 2‐chlorodeoxyadenosine in pediatric patients with acute leukemia. JCO. 1991;9(3):416–422.
  • Santana VM, Mirro J, Jr, Kearns C, et al. 2‐Chlorodeoxyadenosine produces a high rate of complete hematologic remission in relapsed acute myeloid leukemia. JCO. 1992;10(3):364–370.
  • Rubnitz JE, Razzouk BI, Srivastava DK, et al. Phase II trial of cladribine and cytarabine in relapsed or refractory myeloid malignancies. Leuk Res. 2004;28(4):349–352.
  • Inaba H, Stewart CF, Crews KR, et al. Combination of cladribine plus topotecan for recurrent or refractory pediatric acute myeloid leukemia. Cancer. 2010;116(1):98–105.
  • Chaleff S, Hurwitz CA, Chang M, et al. Phase II study of 2‐chlorodeoxyadenosine plus idarubicin for children with acute myeloid leukaemia in first relapse: a paediatric oncology group study. Br J Haematol. 2012;156(5):649–655.
  • Santana VM, Hurwitz CA, Blakley RL, et al. Complete hematologic remissions induced by 2‐chlorodeoxyadenosine in children with newly diagnosed acute myeloid leukemia. Blood. 1994;84(4):1237–1242.
  • Krance RA, Hurwitz DR, Head SC, et al. Experience with 2‐chlorodeoxyadenosine in previously untreated children with newly diagnosed acute myeloid leukemia and myelodysplastic syndromes. JCO. 2001;19(11):2804–2811.
  • Rubnitz JE, Crews KR, Pounds S, et al. Combination of cladribine and cytarabine is effective for childhood acute myeloid leukemia: results of the St Jude AML97 trial. Leukemia. 2009;23(8):1410–1416.
  • Kornblau SM, Gandhi V, Andreeff HM, et al. Clinical and laboratory studies of 2‐chlorodeoxyadenosine +/− cytosine arabinoside for relapsed or refractory acute myelogenous leukemia in adults. Leukemia. 1996;10(10):1563–1569.
  • Vahdat L, Wong ET, Wile MJ, et al. Therapeutic and neurotoxic effects of 2‐chlorodeoxyadenosine in adults with acute myeloid leukemia. Blood. 1994;84(10):3429–3434.
  • Gordon MS, Young ML, Tallman MS, et al. 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. 2000;24(10):871–875.
  • Van Den Neste E, Martiat P, Mineur P, et al. 2‐Chlorodeoxyadenosine with or without daunorubicin in relapsed or refractory acute myeloid leukemia. Ann Hematol. 1998;76(1):19–23.
  • Wrzesien-Kus A, Robak T, et al. 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. 2003;71:155–162.
  • Zhou A, Han Q, Song H, et al. Efficacy and toxicity of cladribine for the treatment of refractory acute myeloid leukemia: a meta-analysis. DDDT. 2019;13:1867–1878.
  • Walker AR, Komrokji RS, Ifthikharuddin J, et al. Phase I study of cladribine, cytarabine (Ara‐C), granulocyte colony stimulating factor (G‐CSF) (CLAG Regimen) and simultaneous escalating doses of imatinib mesylate (Gleevec) in relapsed/refractory AML. Leuk Res. 2008;32(12):1830–1836.
  • Holowiecki J, Robak T, Kyrcz-Krzemien S, et al. Daunorubicin, cytarabine, and 2‐CdA (DAC‐7) for remission induction in de novo adult acute myeloid leukemia patients. Evaluation of safety, tolerance, and antileukemic activity. Acta Haematol Polonica. 2002;33:236–247.
  • Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361(13):1249–1259.
  • Petersdorf SH, Kopecky KJ, Slovak M, et al. A phase 3 study of gemtuzumab ozogamicin during induction and postconsolidation therapy in younger patients with acute myeloid leukemia. Blood. 2013;121(24):4854–4860.
  • Usui N, Takeshita A, Nakaseko C, et al. Phase I trial of gemtuzumab ozogamicin in intensive combination chemotherapy for relapsed or refractory adult acute myeloid leukemia (AML): Japan Adult Leukemia Study Group (JALSG)-AML206 study. Cancer Sci. 2011;102(7):1358–1365.
  • Burnett, AK, Hills RK, Milligan D, et al. Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. J Clin Oncol. 2011;29, 369–377.
  • Libura M, Giebel S, Piatkowska-Jakubas B. Cladribine added to daunorubicin-cytarabine induction prolongs survival of FLT3-ITD + normal karyotype AML patients. Blood. 2016;127:360–362.
  • Fesler MJ, Adeimy C, Petruska PJ. Cladribine plus idarubicin/cytarabine induction for untreated acute myeloid leukemia. ASH Annu Meet Abstr. 2011;118:4275.
  • Kadia T, Cortes JE, Jabbour EJ, et al. Phase II study of cladribine, idarubicin, and cytarabine (araC) in patients with Acute Myeloid Leukemia (AML). ASH Annu Meet Abstract. 2017.
  • Shen Y, Chen J, Liu Y, et al. Addition of cladribine to idarubicin and cytarabine during induction increases the overall efficacy rate in adult patients with acute myeloid leukemia: a matched-pair retrospective comparison. Chemotherapy. 2014;60(5-6):368–374.
  • Jaglal MV, Duong VH, Bello CM, et al. Cladribine, cytarabine, filgrastim, and mitoxantrone (CLAG‐M) compared to standard induction in acute myeloid leukemia from myelodysplastic syndrome after azanucleoside failure. Leuk Res. 2014;38(4):443–436.
  • Halpern AB, Othus M, Huebner EM, et al. Phase 1/2 trial of GCLAM with dose-escalated mitoxantrone for newly diagnosed AML or other high-grade myeloid neoplasms. Leukemia. 2018;32(11):2352–2362.
  • Pluta A, Robak T, Wrzesien-Kus A, et al. Addition of cladribine to the standard induction treatment improves outcomes in a subset of elderly acute myeloid leukemia patients: results of a randomized Polish Adult Leukemia Group (PALG) phase II trial. Am J Hematol. 2017;92(4):359–366.
  • Betticher DC, Fey MF, von Rohr A, et al. High incidence of infections after 2‐chlorodeoxyadenosine (2‐CDA) therapy in patients with malignant lymphomas and chronic and acute leukaemias. Ann Oncol. 1994;5(1):57–64.
  • Cheson BD. Infectious and immunosuppressive complications of purine analog therapy. JCO. 1995;13(9):2431–2448.
  • Hickish T, Serafinowski P, Cunningham D, et al. 2'-Chlorodeoxyadenosine: evaluation of a novel predominately lymphocyte selective agent in lymphoid malignancies. Br J Cancer. 1993;67(1):139–143.
  • Lech-Maranda E, Seweryn M, Giebel S, et al. Infectious complications in patients with acute myeloid leukemia treated according to the protocol with daunorubicin and cytarabine with or without addition of cladribine. A multicenter study by the Polish Adult Leukemia Group (PALG). Int J Infect Dis. 2010;14:e132–e140.
  • Sigal DS, Miller HJ, Schram ED, et al. Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood. 2010;116(16):2884–2896.
  • Hassan R, Gupta M, Kern W, et al. Acute myeloid leukemia following treatment with cladribine for hairy cell leukemia: a case report and review of the literature. Leuk Lymphoma. 2004;45(10):2149–2152.
  • Boddu P, Kantarjian HM, Ravandi F, et al. Outcomes by treatment setting and genomic profile in patients with AML on cladribine, idarubicin, and cytarabine. Blood. 2017;130:3898.
  • Thepot S, Itzykson R, Seegers V, et al. Azacitidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol. 2014;89(4):410–416.
  • Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015;126(3):291–299.
  • Lubbert M, Ruter BH, Claus R, et al. A multicenter phase II trial of decitabine as first-line treatment for older patients with acute myeloid leukemia judged unfit for induction chemotherapy. Haematologica. 2012;97(3):393–401.
  • Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012;30(21):2670–2677.
  • Heiblig M, Elhamri M, Tigaud I, et al. Treatment with low-dose cytarabine in elderly patients (age 70 years or older) with acute myeloid leukemia: a single institution experience. Mediterr J Hematol Infect Dis. 2016;8(1)e:2016009.
  • Jacob LA, Aparna S, Lakshmaiah K, et al. Decitabine compared with low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia: a pilot study of safety, efficacy, and cost-effectiveness. Adv Hematol. 2015;2015:167029.
  • Tosi P, Visani G, Ottaviani E, et al. Fludarabine + Ara‐C + G‐CSF: cytotoxic effect and induction of apoptosis on fresh acute myeloid leukemia cells. Leukemia. 1994;8(12):2076–2082.
  • Jackson G, Taylor P, Smith GM, et al. 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. 2001;112:127–137.
  • Virchis A, Koh M, Rankin P, et al. Fludarabine, cytosine arabinoside, granulocyte‐colony stimulating factor with or without idarubicin in the treatment of high risk acute leukaemia or myelodysplastic syndromes. Br J Haematol. 2004;124(1):26–32.
  • Grosicki S, Kriegler M, Bodzenta E, et al. Comparable toxicity and outcome of acute myeloid leukemia (AML) fit patients therapy independently if daunorubicin or idarubicin were added to cytarabine/cladribine induction regimens – the single centre study. ASH Annu Meet Abstr. 2012;120:4337.

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