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Difference in causes and prognostic factors of early death between cohorts with de novo and relapsed acute promyelocytic leukemia

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Abstract

Early death (ED) remains the most critical issue in the current care of patients with acute promyelocytic leukemia (APL). Very limited data are available regarding ED in patients with relapsed APL. In this retrospective study, 285 de novo and 79 relapsed patients were included. All patients received single-agent arsenic trioxide as induction therapy. The differences in baseline clinical features, incidence, causes, and prognostic factors of ED were compared between the two patient cohorts. The relapse cohort exhibited a better overall condition than the de novo cohort upon hospital admission. The ED rate in the relapsed patients (24.1%) was somewhat higher than that in the de novo patients (17.9%), although the difference was not significant (P = 0.219). For both cohorts, hemorrhage was the main cause of ED, followed by differentiation syndrome, infection, and other causes. Increased serum creatinine level, older age, male sex, white blood cell (WBC) count > 10 × 109/L, and fibrinogen < 1 g/L were independently risk factors for ED in the de novo patients, whereas WBC count > 10 × 109/L, elevated serum uric acid level, and D-dimer > 4 mg/L were independent risk factors for ED in the relapsed patients. These data furnish clinically relevant information that might be useful for designing more appropriate risk-adapted treatment protocols aimed at reducing ED rate in patients with relapsed APL.

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References

  1. Lehmann S, Ravn A, Carlsson L, Antunovic P, Deneberg S, Möllgård L, Rangert Derolf Å, Stockelberg D, Tidefelt U, Wahlin A, Wennström L, Höglund M, Juliusson G (2011) Continuing high early death rate in acute promyelocytic leukemia: a population-based report from the Swedish Adult Acute Leukemia Registry. Leukemia 25(7):1128–1134. https://doi.org/10.1038/leu.2011.78

    Article  CAS  PubMed  Google Scholar 

  2. McClellan JS, Kohrt HE, Coutre S, Gotlib JR, Majeti R, Alizadeh AA, Medeiros BC (2012) Treatment advances have not improved the early death rate in acute promyelocytic leukemia. Haematologica 97(1):133–136. https://doi.org/10.3324/haematol.2011.046490

    Article  PubMed  PubMed Central  Google Scholar 

  3. Tallman M, Lo-Coco F, Kwaan H, Sanz M, Gore S (2011) Clinical roundtable monograph. Early death in patients with acute promyelocytic leukemia. Clin Adv Hematol Oncol 9(2):1–16

    Google Scholar 

  4. Falchi L, Verstovsek S, Ravandi-Kashani F, Kantarjian HM (2016) The evolution of arsenic in the treatment of acute promyelocytic leukemia and other myeloid neoplasms: moving toward an effective oral, outpatient therapy. Cancer 122(8):1160–1168. https://doi.org/10.1002/cncr.29852

    Article  PubMed  Google Scholar 

  5. Shen ZX, Chen GQ, Ni JH, Li XS, Xiong SM, Qiu QY, Zhu J, Tang W, Sun GL, Yang KQ, Chen Y, Zhou L, Fang ZW, Wang YT, Ma J, Zhang P, Zhang TD, Chen SJ, Chen Z, Wang ZY (1997) Use of arsenic trioxide (As2O3) in the treatment of acute promyelocytic leukemia (APL): II. Clinical efficacy and pharmacokinetics in relapsed patients. Blood 89(9):3354–3360

    CAS  PubMed  Google Scholar 

  6. Niu C, Yan H, Yu T, Sun HP, Liu JX, Li XS, Wu W, Zhang FQ, Chen Y, Zhou L, Li JM, Zeng XY, Yang RR, Yuan MM, Ren MY, Gu FY, Cao Q, Gu BW, Su XY, Chen GQ, Xiong SM, Zhang TD, Waxman S, Wang ZY, Chen Z, Hu J, Shen ZX, Chen SJ (1999) Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients. Blood 94(10):3315–3324

    CAS  PubMed  Google Scholar 

  7. Huan SY, Yang CH, Chen YC (2000) Arsenic trioxide therapy for relapsed acute promyelocytic leukemia: an useful salvage therapy. Leuk Lymphoma 38(3-4):283–293. https://doi.org/10.3109/10428190009087019

    Article  CAS  PubMed  Google Scholar 

  8. Li J, Zhu H, Hu J, Mi J, Chen S, Chen Z, Wang Z (2014) Progress in the treatment of acute promyelocytic leukemia: optimization and obstruction. Int J Hematol 100(1):38–50. https://doi.org/10.1007/s12185-014-1603-1

    Article  CAS  PubMed  Google Scholar 

  9. de la Serna J, Montesinos P, Vellenga E, Rayon C, Parody R, Leon A, Esteve J, Bergua JM, Milone G, Deben G, Rivas C, Gonzalez M, Tormo M, Diaz-Mediavilla J, Gonzalez JD, Negri S, Amutio E, Brunet S, Lowenberg B, Sanz MA (2008) Causes and prognostic factors of remission induction failure in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and idarubicin. Blood 111(7):3395–3402. https://doi.org/10.1182/blood-2007-07-100669

    Article  PubMed  Google Scholar 

  10. Ghavamzadeh A, Alimoghaddam K, Rostami S, Ghaffari SH, Jahani M, Iravani M, Mousavi SA, Bahar B, Jalili M (2011) Phase II study of single-agent arsenic trioxide for the front-line therapy of acute promyelocytic leukemia. J Clin Oncol 29(20):2753–2757. https://doi.org/10.1200/JCO.2010.32.2107

    Article  CAS  PubMed  Google Scholar 

  11. Mitrovic M, Suvajdzic N, Bogdanovic A, Kurtovic NK, Sretenovic A, Elezovic I, Tomin D (2013) International Society of Thrombosis and Hemostasis Scoring System for disseminated intravascular coagulation ≥ 6: a new predictor of hemorrhagic early death in acute promyelocytic leukemia. Med Oncol 30(1):478. https://doi.org/10.1007/s12032-013-0478-y

    Article  PubMed  Google Scholar 

  12. Hassan IB, Zaabi MR, Alam A, Hashim MJ, Tallman MS, Kristensen J (2017) Characteristics features and factors influencing early death in acute promyelocytic leukemia; experience from United Arab Emirates (UAE). Int J Hematol 106(1):90–98. https://doi.org/10.1007/s12185-017-2211-7

    Article  PubMed  Google Scholar 

  13. Mathews V, George B, Chendamarai E, Lakshmi KM, Desire S, Balasubramanian P, Viswabandya A, Thirugnanam R, Abraham A, Shaji RV, Srivastava A, Chandy M (2010) Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data. J Clin Oncol 28(24):3866–3871. https://doi.org/10.1200/JCO.2010.28.5031

    Article  CAS  PubMed  Google Scholar 

  14. Di Bona E, Avvisati G, Castaman G, Luce Vegna M, de Sanctis V, Rodeghiero F, Mandelli F, for the Gruppo Italiano per le Malattie Ematologiche dell’Adulto (2000) Early haemorrhagic morbidity and mortality during remission induction with or without all-trans retinoic acid in acute promyelocytic leukaemia. Br J Haematol 108(4):689–695. https://doi.org/10.1046/j.1365-2141.2000.01936.x

    Article  PubMed  Google Scholar 

  15. Yanada M, Matsushita T, Asou N, Kishimoto Y, Tsuzuki M, Maeda Y, Horikawa K, Okada M, Ohtake S, Yagasaki F, Matsumoto T, Kimura Y, Shinagawa K, Iwanaga M, Miyazaki Y, Ohno R, Naoe T (2007) Severe hemorrhagic complications during remission induction therapy for acute promyelocytic leukemia: incidence, risk factors, and influence on outcome. Eur J Haematol 78(3):213–219. https://doi.org/10.1111/j.1600-0609.2006.00803.x

    Article  PubMed  Google Scholar 

  16. Lou Y, Ma Y, Suo S, Ni W, Wang Y, Pan H, Tong H, Qian W, Meng H, Mai W, Huang J, Yu W, Wei J, Mao L, Jin J (2015) Prognostic factors of patients with newly diagnosed acute promyelocytic leukemia treated with arsenic trioxide-based frontline therapy. Leuk Res 39(9):938–944. https://doi.org/10.1016/j.leukres.2015.05.016

    Article  CAS  PubMed  Google Scholar 

  17. Tsimberidou AM, Kantarjian HM, Wen S, O'Brien S, Cortes J, Wierda WG, Koller C, Pierce S, Brandt M, Freireich EJ, Keating MJ, Estey EH (2008) The prognostic significance of serum beta2 microglobulin levels in acute myeloid leukemia and prognostic scores predicting survival: analysis of 1,180 patients. Clin Cancer Res 14(3):721–730. https://doi.org/10.1158/1078-0432.CCR-07-2063

    Article  CAS  PubMed  Google Scholar 

  18. Yamauchi T, Negoro E, Lee S, Takai M, Matsuda Y, Takagi K, Kishi S, Tai K, Hosono N, Tasaki T, Ikegaya S, Inai K, Yoshida A, Urasaki Y, Iwasaki H, Ueda T (2013) A high serum uric acid level is associated with poor prognosis in patients with acute myeloid leukemia. Anticancer Res 33(9):3947–3951

    PubMed  Google Scholar 

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Funding

This work was supported by the National Natural Science Foundation of China (No. 81270589), the Natural Science Foundation of Heilongjiang Province of China (No. H2017032), and the Medical Scientific Research Items (MSRI) in Hainan Province of China (No. 1321320.24A1005).

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Author notes

  1. Hongli Zhao and Yanqiu Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Hematology, The First Affiliated Hospital, Harbin Medical University, No.23, Youzheng Street, Nangang District, Harbin, 150001, China

    Hongli Zhao, Yanqiu Zhao, Jinxiao Hou, Huiyuan Yang, Wenyi Hou, Jiayue Sun, Bo Jin, Jinyue Fu, Haitao Li, Ping Wang, Fei Ge & Jin Zhou

  2. Department of Hematology, The Fourth Affiliated Hospital, Harbin Medical University, Harbin, China

    Hongli Zhao

  3. Department of Central Laboratory, The First Affiliated Hospital, Harbin Medical University, Harbin, China

    Yingmei Zhang, Fenglin Cao & Jin Zhou

  4. Department of Gastroenterology, The Hainan Province Nongken Sanya Hospital, Sanya, Hainan, China

    Yiju Yang

  5. Department of Neonatology, The First Affiliated Hospital, Harbin Medical University, Harbin, China

    Ping Wang

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  1. Hongli Zhao
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  15. Jin Zhou
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Correspondence to Jin Zhou.

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Zhao, H., Zhao, Y., Zhang, Y. et al. Difference in causes and prognostic factors of early death between cohorts with de novo and relapsed acute promyelocytic leukemia. Ann Hematol 97, 409–416 (2018). https://doi.org/10.1007/s00277-017-3216-2

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  • DOI: https://doi.org/10.1007/s00277-017-3216-2

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