Frequency of Induction-Related Mortality in Patients of Acute Myeloid Leukemia - Experience from a Resource Limited Country
Asian Hematology Research Journal,
Page 21-30
Abstract
Aim: Treatment-related mortality during remission induction (also known as induction-related mortality) is a significant contributing factor to poor outcome of acute myeloid leukemia (AML) patients. This is true especially for resource limited countries where there is dearth of adequate supportive care. This study is carried to analyze the frequency of induction mortality in AML patients in Pakistan and the factors that contribute to it.
Methodology: This descriptive case series was conducted in AML patients admitted in INMOL Hospital, Lahore from November 2017 to April 2018. 80 Patients aged 5-50 years of age with de-novo AML were included in the study. Their progress over 28 days following start of induction chemotherapy, including complications experienced and the outcome at end of 28 days was observed. All patients received prophylactic anti-fungal therapy as part of supportive care.
Results: The progress and outcomes of 80 patients were analyzed including 8 patients less than 15 years of age and 4 patients of acute promyelocytic leukemia. The induction-related mortality was 27.5% (n=22). Of the patients alive at the end of 28 days of start of induction, 38 achieved complete morphological remission (65.5%). Poor performance status was associated with higher induction mortality (P = .01). The cause of death in 90% of the patients was sepsis and fulminant infections.
Conclusion: The frequency of induction mortality in our population was 27.5%. This is a significantly high number when compared with data from the developed resource abundant countries. Thus it highlights the importance of allocation of increased resources to provide adequate supportive measures and infection control for this population.
Keywords:
- Acute myeloid leukemia
- induction-related mortality
- performance status
- supportive care
- resource-limited countries
How to Cite
Tariq, R., Sajid, N., Masood, M., & Shahid, A. (2021). Frequency of Induction-Related Mortality in Patients of Acute Myeloid Leukemia - Experience from a Resource Limited Country. Asian Hematology Research Journal, 5(2), 21-30. Retrieved from https://journalahrj.com/index.php/AHRJ/article/view/30173
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DOI: 10.1177/2040620713481796.
Leventakos K, Lewis R, Kontoyiannis D. Fungal infections in leukemia patients: How do we prevent and treat them? Clin Infect Dis. 2010;50(3):405-415.
Available:https://doi.org/10.1086/649879.
Pandian J, Raghavan V, Manuprasad A, Shenoy P, Nair C. Infection at diagnosis—a unique challenge in acute myeloid leukemia treatment in developing world. Support Care Cancer. 2020;28(11):5449-5454.
DOI:10.1007/s00520-020-05379-z.
Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA et al. Acute myeloid leukemia: challenges and real world data from India. Br J Haematol. 2015;170(1): 110-7.
DOI:10.1111/bjh.13406.
Fadoo Z, Mushtaq N, Alvi S, Ali M. Acute myeloid leukemia in children: experience at a tertiary care facility of Pakistan. J Pak Med Assoc. 2012;62(2):125-8.
Gamis A, Alonzo T, Meshinchi S, Sung L, Gerbing R, Raimondi S et al. Gemtuzumab Ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children's Oncology Group trial AAML0531. J Clin Oncol. 2014;32(27): 3021-3032.
DOI:10.1200/JCO.2014.55.3628.
Ullah K, Ahmed P, Raza S, Mahmood T, Khan B. Comparison of different chemotherapy regimens in the management of acute myeloid leukemia - 5 years’ experience from Pakistan. Blood. 2007;110(11):4349. Available:https://doi.org/10.1182/blood.V110.11.4349.4349.
DOI:10.1038/bcj.2016.50.
Dohner H, Estey EH, Amadori S, Appelbaum FR, Buchner 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 LeukemiaNet. Blood 2010; 115(3):453–474.
DOI:10.1182/blood-2009-07-235358.
Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20): 2391-2405.
DOI:10.1182/blood-2016-03-643544.
Yi M, Li A, Zhou L, Chu Q, Song Y, Wu K. The global burden and attributable risk factor analysis of acute myeloid leukemia in 195 countries and territories from 1990 to 2017: estimates based on the global burden of disease study 2017. J Hematol Oncol. 2020;13(1):72.
DOI:10.1186/s13045-020-00908-z.
Kayal S, Dubashi B, L Cyriac S, Basu D, Kar R, Jacob S et al. Outcome of induction therapy for newly diagnosed acute leukemia in a calendar year: real world data from a tertiary care cancer centre in South India. Archives of Oncology and Cancer Therapy. 2018;1(1):37-47.
Döhner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Büchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129:424–447.
Available:https://doi.org/10.1182/blood-2016-08-733196
Buckley SA, Othus M, Estey E, Walter RB. The treatment-related mortality score is associated with non-fatal adverse events following intensive AML induction chemotherapy. Blood Cancer J. 2015;5(1):e276.
DOI:10.1038/bcj.2014.97.
Goparaju K, O'Brien T. Treatment related mortality (TRM) for AML patients managed at a non-transplant, safety net hospital. J Clin Oncol. 2017;35(15_suppl):e18092.
DOI:10.1200/JCO.2017.35.15_suppl.e18092.
Zwaan CM, Kolb EA, Reinhardt D, Abrahamsson J, Adachi S, Aplenc R et al. Collaborative efforts driving progress in pediatric acute myeloid leukemia. J Clin Oncol. 2015;33(27):2949-2962.
DOI: 10.1200/JCO.2015.62.8289.
Walter RB, Othus M, Borthakur G, Ravandi F, Cortes JE, Pierce SA et al. Prediction of early death after induction therapy for newly diagnosed acute myeloid leukemia with pretreatment risk scores: a novel paradigm for treatment assignment. J Clin Oncol. 2011;29(33):4417-4423.
DOI:10.1200/JCO.2011.35.7525.
Kayal S, Sengar M, Jain H, Bonda A, George B, Kulkarni U et al. 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. 2019;134(Supplement_1):2615.
Available:https://doi.org/10.1182/blood-2019-127623.
Handa S, Gupta K, Sidhu J, Petrone G, Rajeeve S, Jatwani K. Etiologies and predictors of 30-day readmission in patients undergoing induction chemotherapy for acute myeloid leukemia. Blood. 2019; 134(Supplement_1):4759.
Available:https://doi.org/10.1182/blood-2019-132180.
Kumar H, Mehra N, Ganesan P, Radhakrishnan V, Dhanushkodi M, P K J et al. Patterns of infection and mortality associated with intensive AML induction therapy: 10 Year experience from a tertiary cancer centre in India. Blood. 2018;132(Supplement 1):4008.
Available:https://doi.org/10.1182/blood-2018-99-119919
Bahl A, Sharma A, Raina V, Kumar L, Bakhshi S, Gupta R, Kumar R. Long-term outcomes for patients with acute myeloid leukemia: a single-center experience from AIIMS, India. Asia Pac J Clin Oncol. 2015;11(3):242-252.
DOI:10.1111/ajco.12333.
Kakepoto G N, Burney I A, Zaki S, Adil S N. Khurshid M. Long-term outcomes of acute myeloid leukemia in adults in Pakistan; J Pak Med Assoc. 2012;52(10):482-486.
Ullah K, Ahmad P, Raza S, Satti T, Chaudhry Q, Akhtar F et al. Management of acute myeloid leukemia - 5 years’ experience at Armed Forces Bone Marrow Transplant Centre, Rawalpindi. J Pak Med Assoc. 2007;57(9):434-439.
Ghafoor T, Khalil S, Farah T, Ahmed S, Sharif I. Prognostic factors in childhood acute myeloid leukemia; Experience from a developing country. Cancer Rep (Hoboken). 2020;3(5):e1259.
DOI:10.1002/cnr2.1259.
Comis R. ECOG Performance Status - ECOG-ACRIN [Internet]. ECOG-ACRIN. 2021. Available from: https://ecog-acrin.org/resources/ecog-performance-status [Accessed 22nd March 2021].
Taplitz R, Kennedy E, Bow E, Crews J, Gleason C, Hawley D et al. Antimicrobial prophylaxis for adult patients with cancer-related immunosuppression: ASCO and IDSA clinical practice guideline update. J Clin Oncol. 2018;36(30):3043-3054.
DOI:10.1200/JCO.18.00374.
Othus M, Kantarjian H, Petersdorf S, Ravandi F, Godwin J, Cortes J et al. Declining rates of treatment-related mortality in patients with newly diagnosed AML given ‘intense’ induction regimens: a report from SWOG and MD Anderson. Leukemia. 2013;28(2):289-292.
DOI:10.1038/leu.2013.176.
Arya D, Parikh B, Shah P, Patel K, Shukla S, Anand A et al. Cost of treatment of acute myeloid leukemia – experiences from a developing country. Ann Oncol. 2012;23(Supplement 9):ix356.
Available:https://doi.org/10.1016/S0923-7534(20)33649-8.
Campos C, Caldas L, Silva L, Botura M, Almeida A, Schriefer A et al. 10-year real-world data on acute myeloid leukemia: The paradigm of a public health center in Brazil. Blood. 2020;136(Supplement 1): 33-34.
Available:https://doi.org/10.1182/blood-2020-140858.
Nganthavee V, Phutthasakda W, Atipas K, Tanpong S, Pungprasert T, Dhirachaikulpanich D et al. High incidence of invasive fungal infection during acute myeloid leukemia treatment in a resource-limited country: clinical risk factors and treatment outcomes. Support Care Cancer. 2019;27(9):3613-3622.
DOI:10.1007/s00520-019-04720-5.
Lien M, Chou C, Lin C, Bai L, Chiu C, Yeh S et al. Epidemiology and risk factors for invasive fungal infections during induction chemotherapy for newly diagnosed acute myeloid leukemia: A retrospective cohort study. PLoS One. 2018;13(6): e0197851.
DOI:10.1371/journal.pone.0197851
Zabalza A, Gorosquieta A, Equiza EP, Olavarria E. Voriconazole and its clinical potential in the prophylaxis of systemic fungal infection in patients with hematologic malignancies: a perspective review. Ther Adv Hematol. 2013;4(3): 217-30.
DOI: 10.1177/2040620713481796.
Leventakos K, Lewis R, Kontoyiannis D. Fungal infections in leukemia patients: How do we prevent and treat them? Clin Infect Dis. 2010;50(3):405-415.
Available:https://doi.org/10.1086/649879.
Pandian J, Raghavan V, Manuprasad A, Shenoy P, Nair C. Infection at diagnosis—a unique challenge in acute myeloid leukemia treatment in developing world. Support Care Cancer. 2020;28(11):5449-5454.
DOI:10.1007/s00520-020-05379-z.
Philip C, George B, Ganapule A, Korula A, Jain P, Alex AA et al. Acute myeloid leukemia: challenges and real world data from India. Br J Haematol. 2015;170(1): 110-7.
DOI:10.1111/bjh.13406.
Fadoo Z, Mushtaq N, Alvi S, Ali M. Acute myeloid leukemia in children: experience at a tertiary care facility of Pakistan. J Pak Med Assoc. 2012;62(2):125-8.
Gamis A, Alonzo T, Meshinchi S, Sung L, Gerbing R, Raimondi S et al. Gemtuzumab Ozogamicin in children and adolescents with de novo acute myeloid leukemia improves event-free survival by reducing relapse risk: results from the randomized phase III Children's Oncology Group trial AAML0531. J Clin Oncol. 2014;32(27): 3021-3032.
DOI:10.1200/JCO.2014.55.3628.
Ullah K, Ahmed P, Raza S, Mahmood T, Khan B. Comparison of different chemotherapy regimens in the management of acute myeloid leukemia - 5 years’ experience from Pakistan. Blood. 2007;110(11):4349. Available:https://doi.org/10.1182/blood.V110.11.4349.4349.
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