Skip to main content
SpringerLink
Log in

Treatment patterns and comparative analysis of non-intensive regimens in elderly acute myeloid leukemia patients—a real-world experience from India

  • Original Article
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Elderly patients with acute myeloid leukemia have a poor prognosis. Data from developing countries is sparse in the literature. In this retrospective study, 402 patients aged ≥ 60 years, diagnosed between Jan 2013 and Dec 2017, were analyzed for treatment patterns and survival. Median age of the whole cohort was 68 years (range 61–84). A total of 213 patients (53.3%) refused care; 188 patients (46.7%) received either BSC, LDAC, or HMA. Survival (in months) was 3.9, 6.4, and 1.2 with LDAC, HMA, and BSC, respectively. One-year survival was 17.2% and 6% with HMA and LDAC, respectively (P = 0.02). Overall response rate (ORR) did not differ between HMA and LDAC group (p = 0.12). HMA cohort had higher complete responses (20.6% vs 7.4%, p = 0.02), stable disease (32.7% vs 13.5%, p = 0.02), and transfusion independence (TI) (46.5% vs 22.2%, p = 0.01). Survival did not differ between the groups if the patients achieved ORR (12.3 vs 9.8 p = 0.2) or TI (11.6 vs 6.4 p = 0.2). Stable disease with HMA led to longer survival (8.1 vs 5.3 p = 0.01). HMAs were more effective than LDAC irrespective of cytogenetic risk category and blasts, of note HMAs improved survival of poor risk patients (5.6 vs 2.9 p = 0.004). HMA treatment (HR = 0.48; 95% 0.29–0.79, p = 0.004) and transfusion independence (HR = 0.2; 95% 0.1–0.3, p = 0.0001) predicted survival in multivariate analysis. Neutropenia and febrile neutropenia were frequent in HMA. Thrombocytopenia was the common adverse event with LDAC. Novel and cost-effective drugs are essential to improve the prognosis of these patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Siegel RL, Miller KD, Jemal A (2016) Cancer statistics, 2016. CA Cancer J Clin 66(1):7–30

    Article  PubMed  Google Scholar 

  2. Klepin HD, Balducci L (2009) Acute myelogenous leukemia in older adults. Oncologist 14(3):222–232

    Article  CAS  PubMed  Google Scholar 

  3. Alibhai SMH, Leach M, Minden MD, Brandwein J (2009) Outcomes and quality of care in acute myeloid leukemia over 40 years. Cancer 115(13):2903–2911

    Article  PubMed  Google Scholar 

  4. Leith CP, Kopecky KJ, Chen IM, McConnell T, Slovak ML, Head DR, et al AML in the Elderly: a Biologically Distinct Disease in which MDR1 Expression and Unfavorable Cytogenetics Contribute to Poor Clinical Response. Studies of the Southwest Oncology Group. In: Acute Leukemias VII. Berlin, Heidelberg: Springer Berlin Heidelberg; 1998. pp. 413–21. (Haematology and Blood Transfusion / Hämatologie und Bluttransfusion; vol. 39)

  5. Burnett AK, Milligan D, Prentice AG, Goldstone AH, McMullin MF, Hills RK et al (2007) A comparison of low-dose cytarabine and hydroxyurea with or without all-trans retinoic acid for acute myeloid leukemia and high-risk myelodysplastic syndrome in patients not considered fit for intensive treatment. Cancer 109(6):1114–1124

    Article  CAS  PubMed  Google Scholar 

  6. Fathi AT, Abdel-Wahab O (2012) Mutations in epigenetic modifiers in myeloid malignancies and the prospect of novel epigenetic-targeted therapy. Adv Hematol 2012(12):469592–469512

  7. Fenaux P, Mufti GJ, Hellström-Lindberg E, Santini V, Finelli C, Giagounidis A et al (2009) Efficacy of azacitidine compared with that of conventional care regimens in the treatment of higher-risk myelodysplastic syndromes: a randomised, open-label, phase III study. Lancet Oncol 10(3):223–232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Kantarjian HM, Thomas XG, Dmoszynska A, Wierzbowska A, Mazur G, Mayer J et al (2012) 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 30(21):2670–2677

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Smith BD, Beach CL, Mahmoud D, Weber L, Henk HJ (2014) Survival and hospitalization among patients with acute myeloid leukemia treated with azacitidine or decitabine in a large managed care population: a real-world, retrospective, claims-based, comparative analysis. Exp Hematol Oncol 3(1):10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ozbalak M, Cetiner M, Bekoz H, Atesoglu EB, Ar C, Salihoglu A et al (2012) Azacitidine has limited activity in “real life” patients with MDS and AML: a single centre experience. Hematol Oncol 30(2):76–81

    Article  CAS  PubMed  Google Scholar 

  11. Radujkovic A, Dietrich S, Bochtler T, Krämer A, Schöning T, Ho AD et al (2014) Azacitidine and low-dose cytarabine in palliative patients with acute myeloid leukemia and high bone marrow blast counts – a retrospective single-center experience. Eur J Haematol 93(2):112–117

    Article  CAS  PubMed  Google Scholar 

  12. Jacob LA, Aparna S, Lakshmaiah KC, Lokanatha D, Babu G, Babu S et al (2015) 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(12):1–6

    Article  CAS  Google Scholar 

  13. Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA et al (2015) Acute myeloid leukaemia: challenges and real world data from India. Br J Haematol 170(1):110–117

    Article  PubMed  PubMed Central  Google Scholar 

  14. Mukhopadhyay S, Chitalkar P, Gupta P, Roy U, Mukhopadhyay A (2016) Oral chemotherapeutic agents in elderly acute myeloid leukemia (AML) patients, a study from a developing country. Journal of Clinical Oncology. American Society of Clinical Oncology

  15. Kapoor A, Beniwal SK, Kalwar A, Singhal MK, Nirban RK, Kumar HS (2016) Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: a prospective pilot study. South Asian J Cancer 5(2):70–72

    Article  PubMed  PubMed Central  Google Scholar 

  16. Tandon N, Banavali S, Menon H, Gujral S, Kadam PA, Bakshi A (2013) Is there a role for metronomic induction (and maintenance) therapy in elderly patients with acute myeloid leukemia? A literature review. Indian J Cancer 50(2):154–158

    Article  CAS  PubMed  Google Scholar 

  17. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al (2010) Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities amongst 5,876 younger adult patients treated in the UK Medical Research Council trials. Blood. American Society of Hematology 116(3):blood–2009–11–254441–365

  18. Gavillet M, Noetzli J, Blum S, Duchosal MA, Spertini O, Lambert J-F (2012) Transfusion independence and survival in patients with acute myeloid leukemia treated with 5azacytidine. Haematologica 97(12):1929–1931

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Al-Ali HK, Jaekel N, Junghanss C, Maschmeyer G, Krahl R, Cross M et al (2011) Azacitidine in patients with acute myeloid leukemia medically unfit for or resistant to chemotherapy: a multicenter phase I/II study. Leuk Lymphoma 53(1):110–117

    Article  CAS  PubMed  Google Scholar 

  20. Medeiros BC, Satram-Hoang S, Hurst D, Hoang KQ, Momin F, Reyes C (2015) Big data analysis of treatment patterns and outcomes among elderly acute myeloid leukemia patients in the United States. Ann Hematol 94(7):1127–1138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ma E, Bonthapally V, Chawla A, Lefebvre P, Swords R, Lafeuille M-H et al (2016) An evaluation of treatment patterns and outcomes in elderly patients newly diagnosed with acute myeloid leukemia: a retrospective analysis of electronic medical records from US community oncology practices. Clin Lymphoma Myeloma Leuk 16(11):625–636.e3

    Article  PubMed  Google Scholar 

  22. Oran B, Weisdorf DJ (2012) Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica 97(12):1916–1924

    Article  PubMed  PubMed Central  Google Scholar 

  23. Juliusson G, Lazarevic V, Hörstedt A-S, Hagberg O, Höglund M, Swedish Acute Leukemia Registry Group (2012) Acute myeloid leukemia in the real world: why populationbased registries are needed. Blood 119(17):3890–3899

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T et al (2017) Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood 129(4):424–447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Dombret H, Seymour JF, Butrym A, Wierzbowska A, Selleslag D, Jang JH et al (2015) International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood 126(3):291–299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Serrano J, de la Fuente A, Bergua J, Falantes J, Eusebio M-C, Antonio LJ et al (2011) 5Azacytidine versus intensive chemotherapy or BSC in elderly (>60 years) acute myeloid leukemia patients. A retrospective analysis. Blood 118(21):2612–2612

    Google Scholar 

  27. Thépot S, Itzykson R, Seegers V, Récher C, Raffoux E, Quesnel B et al (2014) Azacitidine in untreated acute myeloid leukemia: a report on 149 patients. Am J Hematol 89(4):410–416

    Article  CAS  PubMed  Google Scholar 

  28. Ramos F, Thépot S, Pleyer L, Maurillo L, Itzykson R, Bargay J et al (2015) Azacitidine frontline therapy for unfit acute myeloid leukemia patients: clinical use and outcome prediction. Leuk Res 39(3):296–306

    Article  CAS  PubMed  Google Scholar 

  29. Schuh AC, Döhner H, Seymour JF, Turlure P, Junghanss C, MacWhannell A et al (2017) Stable disease with hematologic improvement is clinically meaningful for older patients with Acute Myeloid Leukemia (AML) treated with azacitidine. Leuk Res 55:S68–S69

    Article  Google Scholar 

  30. Seymour JF, Fenaux P, Silverman LR, Mufti GJ, Hellström-Lindberg E, Santini V et al (2010) Effects of azacitidine compared with conventional care regimens in elderly (≥ 75 years) patients with higher-risk myelodysplastic syndromes. Crit Rev Oncol Hematol 76(3):218–227

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Kidwai Memorial Institute of Oncology, Bangalore, Karnataka, 560029, India

    Govind B. Kanakasetty, Chethan R, Lakshmaiah K C, Lokanatha Dasappa, Linu Abraham Jacob, Suresh Babu M C, Lokesh K N, Rudresha Antapura Haleshappa, Rajeev L K, Smitha Carol Saldanha, Koppaka Deepak, Patidar Rajesh & Vikas Asati

Authors
  1. Govind B. Kanakasetty
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Chethan R
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lakshmaiah K C
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lokanatha Dasappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Linu Abraham Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Suresh Babu M C
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Lokesh K N
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rudresha Antapura Haleshappa
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Rajeev L K
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Smitha Carol Saldanha
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Koppaka Deepak
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Patidar Rajesh
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Vikas Asati
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chethan R.

Ethics declarations

The study was approved by the local ethics committee. Consent was obtained from all the patients before the treatment.

Conflict of interest

The authors declare that they have no conflict of interest.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kanakasetty, G.B., R, C., K C, L. et al. Treatment patterns and comparative analysis of non-intensive regimens in elderly acute myeloid leukemia patients—a real-world experience from India. Ann Hematol 98, 881–888 (2019). https://doi.org/10.1007/s00277-019-03600-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00277-019-03600-6

Keywords

Search

Navigation