SpringerLink
Log in

Treatment challenges and outcomes of older patients with acute myeloid leukemia from India

  • Research
  • Published:
Annals of Hematology Aims and scope Submit manuscript

Abstract

Globally, overall survival (OS) of older patients with AML continues to be suboptimal with very little data from India. In a multicenter registry analysis, we evaluated 712 patients with AML older than 55 years. Only 323 (45.3%) underwent further treatment, of which 239 (74%) received HMAs, and 60 (18%) received intensive chemotherapy (IC). CR was documented in 39% of those receiving IC and 42% after HMAs. Overall, 100 (31%) patients died within 60 days of diagnosis, most commonly due to progressive disease (47%) or infections (30%). After a median follow-up of 176 days, 228 (76%) of patients had discontinued treatment. At one year from diagnosis, 211 (65%) patients had died, and the median OS was 186 days (IQR, 137–234). Only 12 (3.7%) patients underwent stem cell transplantation. Survival was significantly lower for those older than 60 years (p < 0.001). Patients who died had a higher median age (p = .027) and baseline WBC counts (p = .006). Our data highlights suboptimal outcomes in older AML patients, which are evident from 55 years of age onwards, making it necessary to evaluate HMA and targeted agent combinations along with novel consolidation strategies to improve survival in this high-risk population.

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

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Brazil)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Data availability

Data is stored centrally with Clinical Data Management Centre (CDMC), Department of Biostatistics, Christian Medical College, Vellore and is available on request.

References

  1. Bertoli S, Tavitian S, Huynh A, Borel C, Guenounou S, Luquet I et al (2017) Improved outcome for AML patients over the years 2000–2014. Blood Cancer J 7(12):635

    Article  PubMed  PubMed Central  Google Scholar 

  2. Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM (2019) Epidemiology of acute myeloid leukemia: Recent progress and enduring challenges. Blood Rev 36:70–87

    Article  PubMed  Google Scholar 

  3. Abdallah M, **e Z, Ready A, Manogna D, Mendler JH, Loh KP (2020) Management of Acute Myeloid Leukemia (AML) in older patients. Curr Oncol Rep 22(10):103

    Article  PubMed  PubMed Central  Google Scholar 

  4. Rozental A, Shimony S, Raanani P, Wolach O (2019) Analysis of Elderly Patients (≥70 years old) with Acute Leukemia in the Era of Targeted Therapy. Blood. 134:5100

    Article  Google Scholar 

  5. Talati C, Dhulipala VC, Extermann MT, Ali NA, Kim J, Komrokji R et al (2020) Comparisons of commonly used front-line regimens on survival outcomes in patients aged 70 years and older with acute myeloid leukemia. Haematologica 105(2):398–406

    Article  PubMed  PubMed Central  Google Scholar 

  6. Taenaka R, Obara T, Kohno K, Aoki K, Ogawa R (2023) Predictors of the Overall Survival with Azacitidine Monotherapy in Untreated Acute Myeloid Leukemia Patients Ineligible for Intensive Therapy. Internal medicine (Tokyo, Japan) 62(5):689–695

    Article  CAS  PubMed  Google Scholar 

  7. Döhner H, Dolnik A, Tang L, Seymour JF, Minden MD, Stone RM et al (2018) Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care. Leukemia 32(12):2546–2557

    Article  PubMed  PubMed Central  Google Scholar 

  8. 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 

  9. Kalaiyarasi JP, Ganesan P, Kannan K, Ganesan TS, Radhakrishnan V, Dhanushkodi M et al (2019) Outcomes of intensive treatment of adult acute Myeloid Leukemia Patients: a retrospective study from a single centre. Indian J Hematol Blood Transfus 35(2):248–254

    Article  PubMed  Google Scholar 

  10. Miguel BerguaBurgues J, Rodriguez-Veiga R, Cano Ferri I, Vall-LloveraCalmet F, Garcia-Guiñon A, Gomez Espuch J et al (2023) S132: updated results of Ven-a-Qui Study: a phase 1-2 trial to assess the safety and efficacy of triplets for newly diagnosed unfit aml patients: azacitidine or low-dose cytarabine with venetoclax and quizartinib. Hemasphere. 7:e8385270. https://doi.org/10.1097/01.HS9.0000967440.83852.70

    Article  Google Scholar 

  11. Tallman MS, Wang ES, Altman JK, Appelbaum FR, Bhatt VR, Bixby D et al (2019) Acute Myeloid Leukemia, Version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw 17(6):721–49

    Article  CAS  PubMed  Google Scholar 

  12. Kayal S, Sengar M, Jain H, Bonda A, George B, Kulkarni UP et al (2019) Induction related mortality in acute myeloid leukemia: multivariate model of predictive score from the Indian Acute Leukemia Research Database (INwARD) of the Hematology Cancer Consortium (HCC). Blood. 134:2615

    Article  Google Scholar 

  13. Arber DA (2019) The 2016 WHO classification of acute myeloid leukemia: What the practicing clinician needs to know. Semin Hematol 56(2):90–95

    Article  PubMed  Google Scholar 

  14. Kapoor R, Jain H, Korula A, Bhurani D, Radhakrishnan V, Philip CC et al (2018) Hematological Cancer Consortium: Multi-Center Acute Myeloid Leukemia Registry Data from India. Blood 132:4006

    Article  Google Scholar 

  15. Lazarevic VL, Bredberg A, Lorenz F, Öhlander E, Antunovic P, Cammenga J et al (2018) Acute myeloid leukemia in very old patients. Haematologica 103(12):e578–e580

    Article  PubMed  PubMed Central  Google Scholar 

  16. Zeidan AM, Podoltsev NA, Wang X, Bewersdorf JP, Shallis RM, Huntington SF et al (2019) Temporal patterns and predictors of receiving no active treatment among older patients with acute myeloid leukemia in the United States: A population-level analysis. Cancer 125(23):4241–4251

    Article  PubMed  Google Scholar 

  17. Sorror ML, Storer BE, Elsawy M, Fathi AT, Brunner AM, Gerds AT et al (2016) Intensive versus non-intensive induction therapy for patients (Pts) with newly diagnosed acute myeloid leukemia (AML) using two different novel prognostic models. Blood 128(22):216

    Article  Google Scholar 

  18. Récher C, Röllig C, Bérard E, Bertoli S, Dumas P-Y, Tavitian S et al (2022) Long-term survival after intensive chemotherapy or hypomethylating agents in AML patients aged 70 years and older: a large patient data set study from European registries. Leukemia 36(4):913–922

    Article  PubMed  Google Scholar 

  19. Juliusson G, Antunovic P, Derolf Å, Lehmann S, Möllgård L, Stockelberg D et al (2009) Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish Acute Leukemia Registry. Blood 113(18):4179–4187

    Article  CAS  PubMed  Google Scholar 

  20. Liu C-J, Hong Y-C, Kuan AS, Yeh C-M, Tsai C-K, Liu Y-C et al (2020) The risk of early mortality in elderly patients with newly diagnosed acute myeloid leukemia. Cancer Med 9(4):1572–1580

    Article  PubMed  PubMed Central  Google Scholar 

  21. Quintás-Cardama A, Ravandi F, Liu-Dumlao T, Brandt M, Faderl S, Pierce S et al (2012) Epigenetic therapy is associated with similar survival compared with intensive chemotherapy in older patients with newly diagnosed acute myeloid leukemia. Blood 120(24):4840–4845

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tober R, Schnetzke U, Fleischmann M, Yomade O, Schrenk K, Hammersen J et al (2023) Impact of treatment intensity on infectious complications in patients with acute myeloid leukemia. J Cancer Res Clin Oncol 149(4):1569–1583

    Article  CAS  PubMed  Google Scholar 

  23. Jain H, Rengaraj K, Sharma V, Bonda A, Chanana R, Thorat J et al (2020) Infection Prevalence in Adolescents and Adults With Acute Myeloid Leukemia Treated in an Indian Tertiary Care Center. JCO Global Oncology 6:1684–1695

    Article  PubMed  Google Scholar 

  24. Kumar H, Mehra N, Ganesan P, Radhakrishnan V, Dhanushkodi M et al (2018) Patterns of Infection and Mortality Associated with Intensive AML Induction Therapy: 10 Year Experience from a Tertiary Cancer Centre in India. Blood. 132:4008

    Article  Google Scholar 

  25. On S, Rath CG, Lan M, Wu B, Lau KM, Cheung E et al (2022) Characterisation of infections in patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent. Br J Haematol 197(1):63–70

    Article  PubMed  Google Scholar 

  26. Zhang A, Johnson T, Abbott D, Phupitakphol T, Gutman JA, Pollyea DA et al (2022) Incidence of invasive fungal infections in patients with previously untreated Acute Myeloid Leukemisa Receiving Venetoclax and Azacitidine. Open Forum Infectious Diseases. 9:ofac486

    Article  PubMed  PubMed Central  Google Scholar 

  27. George B, Menon H, Bhurani D, Damodar S, Apte S, Seth T et al (2020) A Prospective Observational Multi-institutional Study on Invasive Fungal Infections Following Chemotheraspy for Acute Myeloid Leukemia (MISFIC Study): A Real World Scenario from India. Indian J Hematol Blood Transfus 36(1):97–103

    Article  PubMed  Google Scholar 

  28. Prinja S, Dixit J, Gupta N, Dhankhar A, Kataki AC, Roy PS et al (2023) Financial toxicity of cancer treatment in India: towards closing the cancer care gap. Front Public Health 11:1065737

    Article  PubMed  PubMed Central  Google Scholar 

  29. Hernlund E, Redig J, Paulsson B, RangertDerolf Å, Höglund M, Vertuani S et al (2021) Socioeconomic cost of AML in Sweden—A population-based study using multiple nation-wide registers. EJHaem 2(3):385–393

    Article  PubMed  PubMed Central  Google Scholar 

  30. Niederwieser D, Hasenclever D, Berdel WE, Biemond BJ, Al-Ali HK, Chalandon Y et al (2022) Increased LFS Following Hematopoietic Cell Transplantation As Compared to Conventional Consolidation Therapy in Patients> 60 Years with AML in First Complete Remission and a Matched Donor: Results of a Randomized Phase III Study. Blood 140(Supplement 1):2126–2129

    Article  Google Scholar 

  31. Weisdorf D (2021) How old is too old for a transplant? Best Pract Res Clin Haematol 34(1):101243

    Article  PubMed  PubMed Central  Google Scholar 

  32. Sharma SK, Choudhary D, Doval D, Khandelwal V, Patel A, Setia R et al (2021) Myeloablative Versus Reduced Intensity Conditioning Regimens for Allogeneic Hematopoietic Stem Cell Transplant for Acute Myeloid Leukemia and Myelodysplastic Syndrome: A Retrospective Analysis. Indian journal of hematology & blood transfusion : an official journal of Indian Society of Hematology and Blood Transfusion 37(3):472–478

    Article  Google Scholar 

  33. Ganapule A, Nemani S, Korula A, Lakshmi KM, Abraham A, Srivastava A et al (2017) Allogeneic Stem Cell Transplant for Acute Myeloid Leukemia: Evolution of an Effective Strategy in India. J Glob Oncol 3(6):773–781

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ganser A (2023) Role of allotransplantation in older patients with AML. Blood 141(3):217–218

    Article  CAS  PubMed  Google Scholar 

  35. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH et al (2020) Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med 383(7):617–629

    Article  CAS  PubMed  Google Scholar 

  36. Appelbaum FR, Gundacker H, Head DR, Slovak ML, Willman CL, Godwin JE et al (2006) Age and acute myeloid leukemia. Blood 107(9):3481–3485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. 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 

  38. Abuelgasim KA, Albuhayri B, Munshi R, Mugairi AA, Alahmari B, Gmati G et al (2020) Impact of age and induction therapy on outcome of 180 adult patients with acute myeloid leukemia; retrospective analysis and literature review. Leukemia research reports 14:100206

    Article  PubMed  PubMed Central  Google Scholar 

  39. Zeidan AM, Wang R, Wang X, Shallis RM, Podoltsev NA, Bewersdorf JP et al (2020) Clinical outcomes of older patients with AML receiving hypomethylasssting agents: a large population-based study in the United States. Blood Adv 4(10):2192–2201

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ross K, Gillespie-Twardy AL, Agha M, Raptis A, Hou JZ, Farah R et al (2015) Intensive chemotherapy in patients aged 70 years or older newly diagnosed with acute myeloid leukemia. Oncol Res 22(2):85–92

    Article  PubMed  PubMed Central  Google Scholar 

  41. Kim DS, Kang KW, Yu ES, Kim HJ, Kim JS, Lee SR et al (2015) Selection of elderly acute myeloid leukemia patients for intensive chemotherapy: effectiveness of intensive chemotherapy and subgroup analysis. Acta Haematol 133(3):300–309

    Article  CAS  PubMed  Google Scholar 

  42. Klepin HD, Estey E, Kadia T (2019) More Versus Less Therapy for Older Adults With Acute Myeloid Leukemia: New Perspectives on an Old Debate. Am Soc Clin Oncol Educ Book 39:421–432

    Article  PubMed  Google Scholar 

  43. Rao AV (2016) Fitness in the elderly: how to make decisions regarding acute myeloid leukemia induction. Hematology Am Soc Hematol Educ Program 2016(1):339–347

    Article  PubMed  PubMed Central  Google Scholar 

  44. Min GJ, Cho BS, Park SS, Park S, Jeon YW, Shin SH et al (2022) Geriatric assessment predicts nonfatal toxicities and survival for intensively treated older adults with AML. Blood 139(11):1646–1658

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This study is supported by Hematology Cancer Consortium, India. We acknowledge the help from Clinical Data Management Centre (CDMC), Department of Biostatistics, Christian Medical College, Vellore for ensuring data quality and performing statistical analysis and source data verification. The authors gratefully acknowledge the National Cancer Grid (NCG) for their invaluable support in data collection, analysis, and resource provision.

Funding

Nil Received.

Author information

Authors and Affiliations

  1. Department of Clinical Haematology, Dayanand Medical College, Ludhiana, 141001, India

    Suvir Singh

  2. Christian Medical College, Vellore, India

    Sharon Lionel, Sushil Selvarajan, Aby Abraham & Vikram Mathews

  3. Tata Memorial Hospital, Mumbai, India

    Hasmukh Jain, Lingaraj Nayak, Bhausaheb Bagal & Manju Sengar

  4. Cancer Institute Adyar, Chennai, India

    Akhil Rajendra & Jayachandran PK

  5. Department of Biostatistics, CMC, Vellore, India

    Prasanna Samuel, Om Prakash & U Barath

  6. Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India

    Rayaz Ahmed, Narendra Aggarwal & Dinesh Bhurani

  7. Christian Medical College, Ludhiana, India

    Pavitra DS, Poojitha Byreddy & MJoseph John

  8. Army Hospital Research and Referral, New Delhi, India

    Kundan Mishra, Suman Kumar & Rajan Kapoor

  9. Rajagiri Hospital, Kochi, India

    Mobin Paul & Latha K. Abraham

  10. Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India

    Smita Kayal & Prasanth Ganesan

  11. Believers Church Medical College Hospital, Thiruvalla, India

    Chepsy C. Philip

  12. Guwahati Medical College, Guwahati, India

    Damodar Das

  13. Amala Cancer Hospital and Research Centre, Thrissur, India

    V Sreeraj

  14. Asian Institute of Medical Sciences (AIMS), Faridabad, Faridabad, India

    Prashant Mehta

  15. Malabar Cancer Centre, Kerala, India

    Vineetha Raghavan

  16. Nizam’s Institute of Medical Sciences (NIMS), Hyderabad, India

    Stalin Chowdary Bala

  17. Narayana Health Hospital, Bengaluru, India

    Ram S Bharath

  18. Ramaiah Medical College and Hospitals (RMCH), Bengaluru, India

    Swaratika Majumdar

Authors
  1. Suvir Singh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sharon Lionel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hasmukh Jain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Akhil Rajendra
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lingaraj Nayak
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Sushil Selvarajan
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Prasanna Samuel
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rayaz Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Narendra Aggarwal
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Pavitra DS
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Poojitha Byreddy
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. MJoseph John
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Kundan Mishra
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Suman Kumar
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Mobin Paul
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Latha K. Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Smita Kayal
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Prasanth Ganesan
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Chepsy C. Philip
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Damodar Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. V Sreeraj
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Prashant Mehta
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Jayachandran PK
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Vineetha Raghavan
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Stalin Chowdary Bala
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Ram S Bharath
    View author publications

    You can also search for this author in PubMed Google Scholar

  27. Swaratika Majumdar
    View author publications

    You can also search for this author in PubMed Google Scholar

  28. Om Prakash
    View author publications

    You can also search for this author in PubMed Google Scholar

  29. U Barath
    View author publications

    You can also search for this author in PubMed Google Scholar

  30. Bhausaheb Bagal
    View author publications

    You can also search for this author in PubMed Google Scholar

  31. Aby Abraham
    View author publications

    You can also search for this author in PubMed Google Scholar

  32. Rajan Kapoor
    View author publications

    You can also search for this author in PubMed Google Scholar

  33. Dinesh Bhurani
    View author publications

    You can also search for this author in PubMed Google Scholar

  34. Manju Sengar
    View author publications

    You can also search for this author in PubMed Google Scholar

  35. Vikram Mathews
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

SS and SL wrote the initial proposal and concept outline. HJ, SK, MS and VM developed and reviewed the CRF. PS, OP and BU performed data verification and statistical analysis. SS and SL wrote the paper. MS and VM oversaw overall direction and planning. HJ, AR, LN, RA, NA, PDS, PB, MJJ, KM, MP, LKA, PG, CCP, DD, VS, PM, JPK, VR, SCB, BR, SM, UB, BB, AA, RK, DB contributed to data entry and reviewed the final manuscript. 

Corresponding author

Correspondence to Suvir Singh.

Ethics declarations

Ethical approval

Ethical Committee and Institutional Research Board clearance was obtained by each institution before participation in the study in compliance with established guidelines. Documents for the same from each institution are available with the registry.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

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

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Singh, S., Lionel, S., Jain, H. et al. Treatment challenges and outcomes of older patients with acute myeloid leukemia from India. Ann Hematol (2024). https://doi.org/10.1007/s00277-024-05873-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s00277-024-05873-y

Keywords

Search

Navigation