Treatment and prognostic assessment of acute myeloid leukemia

Authors

  • Bannur Ramanna Nandeesh Department of Pharmacology, All India Institute of Medical Sciences, New Delhi,India
  • Subramanya S. Mallikarjunappa Department of Pharmacology, Mandya Medical College Mandya, Karnataka, India

DOI:

https://doi.org/10.18203/2319-2003.ijbcp20161494

Keywords:

AML, Daunorubicin, Cytarabine, FLT3 inhibitors

Abstract

Acute myeloid leukemia (AML) is a heterogeneous group of clonal malignant myeloid neoplasms. Malignant transformation of hematopoietic progenitor cell leads to clonal expansion and replacement of normal bone marrow cells with malignant cells leading to suppression of normal haematopoiesis. Advancements in our understanding of disease biology have allowed AML to be classified based on its gene expression profile, which includes previously identified cytogenetic subgroups, and distinct novel subgroups which have prognostic significance. Identification of mutations in DNMT3A and IDH 1 genes in cytogenetically normal AML (by gene sequencing) helps to identify patients with poor prognosis. Redesigning the treatment regimen consisting of cytarabine and daunorubicin has improved the treatment outcomes without increase in the treatment-related mortality. Increasing the dose of daunorubicin to 90 mg/m2 improves complete remission rates without increasing treatment-related complications both in young and elderly patients. Cytarabine (200 mg/m2 in cycle I and 2 g/m2 in cycle 2) is shown to be as effective as high dose cytarabine (1000 mg/m2 twice daily in cycle 1and 2 g/m2 twice daily in cycle 2) and is associated with less treatment-related toxicities.

References

Genovese G, Kähler AK, Handsaker RE, Lindberg J, Rose SA, Bakhoum SF, et al. Clonal hematopoiesis and blood-cancer risk inferred from blood dna sequence. N Engl J Med. 2015;372:1071-2.

Deschler B, Lübbert M. Acute myeloid leukemia: epidemiology and etiology. Cancer. 2006;1;107(9):2099-107.

Walter MJ, Shen D, Ding L, Shao J, Koboldt DC, Chen K, et al. Clonal architecture of secondary acute myeloid leukemia. N Engl J Med. 2012;366(12):1090-8.

Vardiman JW, Thiele J, Arber DA, Brunning RD, Borowitz MJ, Porwit A, et al. The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes. Blood. 2009;114(5):937-51.

Eivazi-Ziaei J. Myeloperoxidase index and subtypes of acute myeloid leukemia. J Pak Med Assoc. 2009;59(6):406-7.

Kaleem Z, Crawford E, Pathan MH, Jasper L, Covinsky MA, Johnson LR, et al. Flow cytometric analysis of acute leukemias. Diagnostic utility and critical analysis of data. Arch Pathol Lab Med. 2003;127(1):42-8.

Valk PJ, Verhaak RG, Beijen MA, Erpelinck CA, Barjesteh van Waalwijk van Doorn-Khosrovani S, Boer JM, et al. Prognostically useful gene-expression profiles in acute myeloid leukemia. N Engl J Med. 2004;350(16):1617-28.

Cancer Genome Atlas Research Network. Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059-74.

Schlenk RF, Döohner K, Krauter J, Fröhling S, Corbacioglu A, Bullinger L, et al. Mutations and treatment outcome in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358:1909-18.

Löwenberg B, Ossenkoppele GJ, van Putten W, Schouten HC, Graux C, Ferrant A, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361(13):1235-48.

Fernandez HF, Sun Z, Yao X, Litzow MR, Luger SM, Paietta EM, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361(13):1249-59.

Löwenberg B, Pabst T, Vellenga E, van Putten W, Schouten HC, Graux C, et al. Cytarabine dose for acute myeloid leukemia. N Engl J Med. 2011;364(11):1027-36.

Holowiecki J, Grosicki S, Robak T, Kyrcz-Krzemien S, Giebel S, Hellmann A, et al. Polish adult leukemia group (PALG): addition of cladribine to daunomycin and cladribine increases remission rate after a single course of induction treatment in acute myeloid leukemia. Multi-center phase 3 study. Leukemia. 2004;18(5):989-97.

Yates J, Glidewell O, Wiernik P, Cooper MR, Steinberg D, Dosik H, et al. Cytosine arabinoside with daunorubicin or adriamycin for therapy of acute myelocytic leukemia: a CALGB study. Blood. 1982;60:454-62.

De Greef GE, van Putten WL, Boogaerts M, Huijgens PC, Verdonck LF, Vellenga E, et al. Criteria for defining a complete remission in acute myeloid leukaemia revisited. An analysis of patients treated in HOVON-SAKK co-operative group studies. Br J Haematol. 2005;128(2):184-91.

Kantarjian HM, Keating MJ, Walters RS, Smith TL, Cork A, McCredie KB, et al. Therapy related leukemia and myelodysplastic syndrome: clinical, cytogenetic and prognostic features. J Clin Oncol. 1986;4(12):1748-57.

Kantarjian H, O’Brien S, Cortes J, Giles F, Faderl S, Jabbour E, et al. Results of intensive chemotherapy in 998 patients age 65 years or older with acute myeloid leukemia or high-risk myelodysplastic syndrome: predictive prognostic models for outcome. Cancer. 2006;106:1090-8.

Buchner T, Berdel WE, Haferlach C, Haferlach T, Schnittger S, Müller-Tidow C, et al. Age-related risk profile and chemotherapy dose response in acute myeloid leukemia: a study by the German Acute Myeloid Leukemia Cooperative Group. J Clin Oncol. 2009;27(1):61-9.

Frohling S, Schlenk RF, Kayser S, Morhardt M, Benner A, Döhner K, et al. Cytogenetics and age are major determinants of outcome in intensively treated acute myeloid leukemia patients older than 60 years: results from AMLSG trial AML HD98-B. Blood 2006;108:3280-8.

Schiffer CA, Lee EJ, Tomiyasu T, Wiernik PH, Testa JR. Prognostic impact of cytogenetic abnormalities in patients with de novo acute non lymphocytic leukemia. Blood. 1989;73(1):263-70.

Kindler T, Lipka DB, Fischer T. FLT3 as a therapeutic target in AML: still challenging after all these years. Blood. 2010;116(24):5089-102.

Linch DC, Hills RK, Burnett AK, Khwaja A, Gale RE. Impact of FLT3(ITD) mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia. Blood. 2014;124(2):273-6.

Marcucci G, Radmacher MD, Maharry K, Mrózek K, Ruppert AS, Paschka P, et al. MicroRNA expression in cytogenetically normal acute myeloid leukemia. N Engl J Med. 2008;358(18):1919-28.

Ley TJ, Ding L, Walter MJ, McLellan MD, Lamprecht T, Larson DE, et al. DNMT3A mutations in acute myeloid leukemia. N Engl J Med. 2010;363(25):2424-33.

Patel JP, Gönen M, Figueroa ME, Fernandez H, Sun Z, Racevskis J, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079-89.

Plunkett W, Liliemark JO, Adams TM, Nowak B, Estey E, Kantarjian H, et al. Saturation of 1-β-D-arabinofuranosylcytosine 5¢-triphosphate accumulation in leukemia cells during high-dose 1-β-Darabinofuranosylcytosine therapy. Cancer Res. 1987;47:3005-11.

Bishop JF, Matthews JP, Young GA, Szer J, Gillett A, Joshua D, et al. A randomized study of high-dose cytarabine in induction in acute myeloid leukemia. Blood. 1996;87:1710-7.

Weick JK, Kopecky KJ, Appelbaum FR, Head DR, Kingsbury LL, Balcerzak SP, et al. A randomized investigation of highdose versus standard-dose cytosine arabinoside with daunorubicin in patients with previously untreated acute myeloid leukemia: a Southwest Oncology Group study. Blood. 1996;88:2841-51.

Mayer RJ, Davis RB, Schiffer CA, Berg DT, Powell BL, Schulman P, et al. Intensive postremission chemotherapy in adults with acute myeloid leukemia. N Engl J Med. 1994;331:896-903.

Döhner H, Estey EH, Amadori S, Appelbaum FR, Büchner T, Burnett AK, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European Leukemia Net. Blood. 2010;115:453-74.

JC Byrd, AS Ruppert, K Mrózek , Carroll AJ, Edwards CG, Arthur DC, et al. Repetitive cycles of high-dose cytarabine benefit patients with acute myeloid leukemia and inv (16) (p13q22) or t (16; 16) (p13;q22): results from CALGB 8461. J Clin Oncol. 2004;22(6):1087-94.

Bianchi Scarrà GL, Romani M, Coviello DA, Garrè C, Ravazzolo R, Vidali G, et al. Terminal erythroid differentiation in the K-562 cell line by 1-beta-D-arabinofuranosylcytosine: accompaniment by c-myc messenger RNA decrease. Cancer Res. 1986;46:6327-32.

Forghieri F, Luppi M, Morselli M, Potenza L. Cytarabine-related lung infiltrates on high resolution computerized tomography: a possible complication with benign outcome in leukemic patients. Haematologica: 2007;92:e85-e90.

Langer SW, Sehested M, Jensen PB. Treatment of anthracycline extravasation with dexrazoxane. Clin Cancer Res. 2000;6:3680-6.

List AF, Kopecky KJ, Willman CL, Head DR, Persons DL, Slovak ML. Benefit of cyclosporine modulation of drug resistance in patients with poor-risk acute myeloid leukemia: a Southwest Oncology Group study. Blood. 2001;98:3212-20.

Baer MR, George SL, Dodge RK, O'Loughlin KL, Minderman H, Caligiuri MA, et al. Phase 3 study of the multidrug resistance modulator PSC-833 in previously untreated patients 60 years of age and older with acute myeloid leukemia: Cancer and Leukemia Group B Study 9720. Blood. 2002;100(4):1224-32.

Lo-Coco F, Avvisati G, Vignetti M, Thiede C, Orlando SM, Iacobelli S, et al. Retinoic acid and arsenic trioxide for acute promyelocytic leukemia. N Engl J Med. 2013;369(2):111-21.

Iland HJ, Bradstock K, Supple SG, Catalano A, Collins M, Hertzberg M, et al. All-trans-retinoic acid, idarubicin, and IV arsenic trioxide as initial therapy in acute promyelocytic leukemia (APML4). Blood. 2012;120(8):1570-80.

Grunwald MR, Levis MJ. FLT3 inhibitors for acute myeloid leukemia: a review of their efficacy and mechanisms of resistance. Int J Hematol. 2013;97(6):683-94.

Takahashi K, Kantarjian H, Pemmaraju N, Andreeff M, Borthakur G, Faderl S, et al. Salvage therapy using FLT3 inhibitors may improve long-term outcome of relapsed or refractory AML in patients with FLT3-ITD. Br J Haematol. 2013;161(5):659-66.

Stasi R, Evangelista ML, Buccisano F, Venditti A, Amadori S. Gemtuzumab ozogamicin in the treatment of acute myeloid leukemia. Cancer Treat Rev. 2008;34(1):49-60.

Larson RA, Sievers EL, Stadtmauer EA, Löwenberg B, Estey EH. Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence. Cancer. 2005;104(7):1442-52.

Chevallier P, Robillard N, Ayari S, Guillaume T, Delaunay J, Mechinaud F, et al. Persistence of CD33 expression at relapse in CD33(+) acute myeloid leukaemia patients after receiving Gemtuzumab in the course of the disease. Br J Haematol. 2008;143(5):744-6.

Petersdorf SH, Kopecky KJ, Slovak M, Willman C, Nevill T, Brandwein J, 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):4854-60.

Amadori S, Suciu S, Stasi R, Salih HR, Selleslag D, Muus P, et al. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol. 2013;31(35):4424-30.

Faderl S, Ferrajoli A, Wierda W, Huang X, Verstovsek S, Ravandi F, et al. Clofarabine combinations as acute myeloid leukemia salvage therapy. Cancer. 2008;113(8):2090-6.

Kantarjian HM, Jeha S, Gandhi V, Wess M, Faderl S. Clofarabine: past, present, and future. Leuk Lymphoma. 2007;48(10):1922-30.

Johnston DL, Mandel KM. Fatal skin and liver toxicity in a patient treated with clofarabine. Pediatr Blood Cancer. 2008;50(5):1082.

Larson ML, Venugopal P. Clofarabine: a new treatment option for patients with acute myeloid leukemia. Expert Opin Pharmacother. 2009;10(8):1353-7.

Giles F, Verstovsek S, Faderl S, Vey N, Karp J, Roboz G, et al. A phase II study of cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients with very high risk relapsed acute myeloid leukemia. Leuk Res. 2006;30:1591-5.

Pratz KW, Cortes J, Roboz GJ, Rao N, Arowojolu O, Stine A, et al. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood. 2009:23:3938-46.

Stubbs MC, Armstrong SA. FLT3 as a therapeutic target in childhood acute leukemia. Curr Drug Targets. 2007;8(6):703-14.

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Published

2016-12-30

How to Cite

Nandeesh, B. R., & Mallikarjunappa, S. S. (2016). Treatment and prognostic assessment of acute myeloid leukemia. International Journal of Basic & Clinical Pharmacology, 5(3), 579–586. https://doi.org/10.18203/2319-2003.ijbcp20161494

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Review Articles