Top

Cancer Chemotherapy and Pharmacology

Published in:

01-03-2020 | Acute Myeloid Leukemia | Original Article

A retrospective study of the correlation of in vitro chemosensitivity using ATP-TCA with patient clinical outcomes in acute myeloid leukemia

Authors: Fan Xia, Sheng Ma, Yicong Bian, Di Yu, WenXia Ma, Miao Miao, Chenrong Huang, Liyan Miao

Published in: Cancer Chemotherapy and Pharmacology | Issue 3/2020

Abstract

Purpose

To evaluate the predictive value of the in vitro chemosensitivity using ATP-TCA method to compare the clinical efficacy of patients with AML.

Methods

Bone marrow or peripheral blood samples were collected from 65 patients with AML, and the in vitro chemosensitivity of four drugs (cytarabine/idarubicin/decitabine/aclacinomycin) was measured by an ATP-tumor chemosensitivity assay.

Results

Aclacinomycin and cytarabine had the highest chemosensitivity rates (66.7%, 8/12 and 58.5%, 38/65, respectively), while idarubicin and decitabine had rates of 6.5% (3/46) and 0% (0/35), respectively. Complete remission (CR) was achieved in 66.2% (43/65) of patients, and there was a statistically significant correlation between CR and in vitro chemosensitivity for cytarabine (47.7% vs 18.5%, p = 0.002), but not for the anthracyclines (p = 0.950). In addition, three other factors significantly correlated with CR: disease status (p = 0.005), FLT3-ITD/TKD mutation (p = 0.003) and chemotherapy regimens (p = 0.004). Furthermore, multiple logistic regression analysis revealed that the sensitivity of cytarabine was one of the significant risk factors for CR [hazard ratio (HR) = 5.52; 95% confidence interval (CI) = 1.47–20.70; p = 0.011].

Conclusions

The in vitro chemosensitivity as tested by ATP-TCA demonstrated a significant correlation with CR for chemotherapy and can be a useful tool to optimize personalized treatments for patients with AML.

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):926–957. https://doi.org/10.6004/jnccn.2017.0116 CrossRef

Sargent JM, Taylor CG (1989) Appraisal of the MTT assay as a rapid test of chemosensitivity in acute myeloid leukaemia. Br J Cancer 60(2):206–210CrossRefPubMedPubMedCentral

Bosserman L, Prendergast F, Herbst R, Fleisher M, Salom E, Strickland S, Raptis A, Hallquist A, Perree M, Rajurkar S, Karimi M, Rogers K, Davidson D, Willis C, Penalver M, Homesley H, Burrell M, Garrett A, Rutledge J, Chernick M, Presant CA (2012) The microculture-kinetic (MiCK) assay: the role of a drug-induced apoptosis assay in drug development and clinical care. Cancer Res 72(16):3901–3905. https://doi.org/10.1158/0008-5472.CAN-12-0681 CrossRefPubMed

Chen Z, Zhang S, Ma S, Li C, Xu C, Shen Y, Zhao J, Miao L (2018) Evaluation of the in vitro chemosensitivity and correlation with clinical outcomes in lung cancer using the ATP-TCA. Anticancer Agents Med Chem 18(1):139–145. https://doi.org/10.2174/1871520617666170419123713 CrossRefPubMed

Zhang J, Li H (2015) Heterogeneity of tumor chemosensitivity in ovarian epithelial cancer revealed using the adenosine triphosphate-tumor chemosensitivity assay. Oncol Lett 9(5):2374–2380. https://doi.org/10.3892/ol.2015.3056 CrossRefPubMedPubMedCentral

Zhang Y, Zhao Q, Jiang Y, Yuan Z, Yang L (2013) ATP-tumor chemosensitivity assay directed chemotherapy in patients with cervical cancer. Zhong Nan Da Xue Xue Bao Yi Xue Ban 38(12):1223–1227. https://doi.org/10.3969/j.issn.1672-7347.2013.12.004 CrossRefPubMed

Ling ZQ, Qi CJ, Lu XX, Qian LJ, Gu LH, Zheng ZG, Zhao Q, Wang S, Fang XH, Yang ZX, Yin J, Mao WM (2012) Heterogeneity of chemosensitivity in esophageal cancer using ATP-tumor chemosensitivity assay. Acta Pharmacol Sin 33(3):401–406. https://doi.org/10.1038/aps.2011.195 CrossRefPubMedPubMedCentral

Fehm T, Zwirner M, Wallwiener D, Seeger H, Neubauer H (2012) Antitumor activity of zoledronic acid in primary breast cancer cells determined by the ATP tumor chemosensitivity assay. BMC Cancer 12:308. https://doi.org/10.1186/1471-2407-12-308 CrossRefPubMedPubMedCentral

Jun KR, Jang S, Chi HS, Lee KH, Lee JH, Choi SJ, Seo JJ, Moon HN, Im HJ, Park CJ (2007) Relationship between in vitro chemosensitivity assessed with MTT assay and clinical outcomes in 103 patients with acute leukemia. Korean J Lab Med 27(2):89–95CrossRefPubMed

10.

Klumper E, Pieters R, Kaspers GJ, Huismans DR, Loonen AH, Rottier MM, van Wering ER, van der Does-van den Berg A, Hahlen K, Creutzig U et al (1995) In vitro chemosensitivity assessed with the MTT assay in childhood acute non-lymphoblastic leukemia. Leukemia 9(11):1864–1869PubMed

11.

Strickland SA, Raptis A, Hallquist A, Rutledge J, Chernick M, Perree M, Talbott MS, Presant CA (2013) Correlation of the microculture-kinetic drug-induced apoptosis assay with patient outcomes in initial treatment of adult acute myelocytic leukemia. Leuk Lymphoma 54(3):528–534. https://doi.org/10.3109/10428194.2012.722217 CrossRefPubMed

12.

Kurbacher CM, Cree IA, Bruckner HW, Brenne U, Kurbacher JA, Muller K, Ackermann T, Gilster TJ, Wilhelm LM, Engel H, Mallmann PK, Andreotti PE (1998) Use of an ex vivo ATP luminescence assay to direct chemotherapy for recurrent ovarian cancer. Anticancer Drugs 9(1):51–57CrossRefPubMed

13.

Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, Schiffer CA, Doehner H, Tallman MS, Lister TA, Lo-Coco F, Willemze R, Biondi A, Hiddemann W, Larson RA, Lowenberg B, Sanz MA, Head DR, Ohno R, Bloomfield CD, International Working Group for Diagnosis SoRCTO, Reporting Standards for Therapeutic Trials in Acute Myeloid L (2003) Revised recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, Treatment Outcomes, and Reporting Standards for Therapeutic Trials in Acute Myeloid Leukemia. J Clin Oncol 21(24):4642–4649. https://doi.org/10.1200/jco.2003.04.036 CrossRefPubMed

14.

Burnett A, Wetzler M, Lowenberg B (2011) Therapeutic advances in acute myeloid leukemia. J Clin Oncol 29(5):487–494. https://doi.org/10.1200/JCO.2010.30.1820 CrossRefPubMed

15.

Kadia TM, Ravandi F, Cortes J, Kantarjian H (2015) Toward individualized therapy in acute myeloid leukemia: a contemporary review. JAMA Oncol 1(6):820–828. https://doi.org/10.1001/jamaoncol.2015.0617 CrossRefPubMed

16.

Kadia TM, Ravandi F, O’Brien S, Cortes J, Kantarjian HM (2015) Progress in acute myeloid leukemia. Clin Lymphoma Myeloma Leuk 15(3):139–151. https://doi.org/10.1016/j.clml.2014.08.006 CrossRefPubMed

17.

Luskin MR, Lee JW, Fernandez HF, Abdel-Wahab O, Bennett JM, Ketterling RP, Lazarus HM, Levine RL, Litzow MR, Paietta EM, Patel JP, Racevskis J, Rowe JM, Tallman MS, Sun Z, Luger SM (2016) Benefit of high-dose daunorubicin in AML induction extends across cytogenetic and molecular groups. Blood 127(12):1551–1558. https://doi.org/10.1182/blood-2015-07-657403 CrossRefPubMedPubMedCentral

18.

Daneshbod Y, Kohan L, Taghadosi V, Weinberg OK, Arber DA (2019) Prognostic significance of complex karyotypes in acute myeloid leukemia. Curr Treat Options Oncol 20(2):15. https://doi.org/10.1007/s11864-019-0612-y CrossRefPubMed

19.

Zwaan CM, Kaspers GJ, Pieters R, Hahlen K, Janka-Schaub GE, van Zantwijk CH, Huismans DR, de Vries E, Rots MG, Peters GJ, Jansen G, Creutzig U, Veerman AJ (2002) Different drug sensitivity profiles of acute myeloid and lymphoblastic leukemia and normal peripheral blood mononuclear cells in children with and without Down syndrome. Blood 99(1):245–251CrossRefPubMed

20.

Smith CC, Lin K, Stecula A, Sali A, Shah NP (2015) FLT3 D835 mutations confer differential resistance to type II FLT3 inhibitors. Leukemia 29(12):2390–2392. https://doi.org/10.1038/leu.2015.165 CrossRefPubMedPubMedCentral

21.

Smith RA, Pontiggia L, Waterman C, Lichtenwalner M, Wasserman J (2009) Comparison of motility, recovery, and methyl-thiazolyl-tetrazolium reduction assays for use in screening plant products for anthelmintic activity. Parasitol Res 105(5):1339–1343. https://doi.org/10.1007/s00436-009-1560-4 CrossRefPubMed

22.

Hsiao IL, Huang YJ (2011) Improving the interferences of methyl thiazolyl tetrazolium and IL-8 assays in assessing the cytotoxicity of nanoparticles. J Nanosci Nanotechnol 11(6):5228–5233CrossRefPubMed

23.

Scholz CC, Berger DP, Winterhalter BR, Henss H, Fiebig HH (1990) Correlation of drug response in patients and in the clonogenic assay with solid human tumour xenografts. Eur J Cancer 26(8):901–905CrossRefPubMed

24.

Hinkley HJ, Bosanquet AG (1992) The in vitro radiosensitivity of lymphocytes from chronic lymphocytic leukaemia using the differential staining cytotoxicity (DiSC) assay. I-Investigation of the method. Int J Radiat Biol 61(1):103–110CrossRefPubMed

25.

Irisawa C, Aikawa K, Ogihara M, Hashimoto T, Yamaguchi O, Shiraiwa Y, Koseki K (1992) Clinical results of prophylactic intravesical chemotherapy on superficial bladder cancer using the dye exclusion assay. Nihon Hinyokika Gakkai Zasshi 83(11):1828–1834PubMed

26.

Glaysher S, Cree IA (2011) Cell sensitivity assays: the ATP-based tumor chemosensitivity assay. Methods Mol Biol 731:247–257. https://doi.org/10.1007/978-1-61779-080-5_21 CrossRefPubMed

27.

Oki Y, Aoki E, Issa JP (2007) Decitabine–bedside to bench. Crit Rev Oncol Hematol 61(2):140–152. https://doi.org/10.1016/j.critrevonc.2006.07.010 CrossRefPubMed

28.

Estey E, Dohner H (2006) Acute myeloid leukaemia. Lancet 368(9550):1894–1907. https://doi.org/10.1016/S0140-6736(06)69780-8 CrossRefPubMed

29.

Kantarjian H (2016) Acute myeloid leukemia–major progress over four decades and glimpses into the future. Am J Hematol 91(1):131–145. https://doi.org/10.1002/ajh.24246 CrossRefPubMed

30.

Mims AS, Blum W (2019) Progress in the problem of relapsed or refractory acute myeloid leukemia. Curr Opin Hematol 26(2):88–95. https://doi.org/10.1097/MOH.0000000000000490 CrossRefPubMed

31.

Whitman SP, Maharry K, Radmacher MD, Becker H, Mrozek K, Margeson D, Holland KB, Wu YZ, Schwind S, Metzeler KH, Wen J, Baer MR, Powell BL, Carter TH, Kolitz JE, Wetzler M, Moore JO, Stone RM, Carroll AJ, Larson RA, Caligiuri MA, Marcucci G, Bloomfield CD (2010) FLT3 internal tandem duplication associates with adverse outcome and gene- and microRNA-expression signatures in patients 60 years of age or older with primary cytogenetically normal acute myeloid leukemia: a Cancer and Leukemia Group B study. Blood 116(18):3622–3626. https://doi.org/10.1182/blood-2010-05-283648 CrossRefPubMedPubMedCentral

32.

Whitman SP, Ruppert AS, Radmacher MD, Mrozek K, Paschka P, Langer C, Baldus CD, Wen J, Racke F, Powell BL, Kolitz JE, Larson RA, Caligiuri MA, Marcucci G, Bloomfield CD (2008) FLT3 D835/I836 mutations are associated with poor disease-free survival and a distinct gene-expression signature among younger adults with de novo cytogenetically normal acute myeloid leukemia lacking FLT3 internal tandem duplications. Blood 111(3):1552–1559. https://doi.org/10.1182/blood-2007-08-107946 CrossRefPubMedPubMedCentral

Title: A retrospective study of the correlation of in vitro chemosensitivity using ATP-TCA with patient clinical outcomes in acute myeloid leukemia
Authors: Fan Xia
Sheng Ma
Yicong Bian
Di Yu
WenXia Ma
Miao Miao
Chenrong Huang
Liyan Miao
Publication date: 01-03-2020
Publisher: Springer Berlin Heidelberg
Keywords: Acute Myeloid Leukemia
Anthracycline
Cytostatic Therapy
Published in: Cancer Chemotherapy and Pharmacology / Issue 3/2020
Print ISSN: 0344-5704
Electronic ISSN: 1432-0843
DOI: https://doi.org/10.1007/s00280-019-03973-5

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 3/2020

Population pharmacokinetic modeling of PF-06439535 (a bevacizumab biosimilar) and reference bevacizumab (Avastin®) in patients with advanced non-squamous non-small cell lung cancer

A Phase I dose-escalation, pharmacokinetics and food-effect study of oral donafenib in patients with advanced solid tumours

Evaluation of gefitinib systemic exposure in EGFR-mutated non-small cell lung cancer patients with gefitinib-induced severe hepatotoxicity

Cardioprotective effects of dapsone against doxorubicin-induced cardiotoxicity in rats

Formulae recently proposed to estimate renal glomerular filtration rate improve the prediction of carboplatin clearance

Relationship between vemurafenib plasma concentrations and survival outcomes in patients with advanced melanoma

Keynote webinar | Spotlight on antibody–drug conjugates in cancer