Longterm Outcome of Adults With Acute Myeloid Leukemia on the Basis of Their Risk Stratification in a Tertiary Care Hospital

Longterm Outcome of Adults With Acute Myeloid Leukemia on the Basis of Their Risk Stratification in a Tertiary Care Hospital | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Longterm Outcome of Adults With Acute Myeloid Leukemia on the Basis of Their Risk Stratification in a Tertiary Care Hospital Dr. Urooj Haider Hashmi, Dr. Mohammad Khurshid, Nida e zehra, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5848383/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract This study aims to assess the long-term outcomes of AML patients in LMICs, focusing on survival rates, relapse, and post-treatment morbidity, as well as factors influencing these outcomes in resource-limited settings. We analyzed the outcome of newly diagnosed AML patients who underwent chemotherapy at Aga Khan University Hospital Karachi. A total of 178 eligible patients were available for assessment. Cytogenetic and molecular workup of 152 patients was available according to which 11.8% were favorable risk, 54.6% were intermediate risk and remaining 33.5% were poor risk. Among these 178 patients who underwent chemotherapy 58.42% achieved remission, 12.92% experienced induction failure and 28.56% died during induction. A total of 13.48% patients were long term survivors who remained disease free at 5 years of follow-up. 20.79% relapsed within 1 year of therapy and 10.11% relapsed after 1 year but within 5 years. 15 patients who were disease free at 2 years did not follow up beyond that period. On the basis of risk assessment 72.22% patients in favorable risk, 51.8 % in intermediate risk and 45.09% in poor risk category achieved remission. And 27.78% favorable risk, 9.64% intermediate risk and 11.76% poor risk category were long term survivors. These results suggest long-term outcomes for AML patients in LMICs are significantly influenced by healthcare system limitations, socioeconomic challenges, and lack of access to novel therapies. To improve survival and quality of life, interventions should focus on early diagnosis, access to standard chemotherapy regimens, and post-treatment care. Oncology Acute Myeloid Leukemia (AML) Cytogenetic long-term care Novel therapies Post-treatment morbidity Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 INRODUCTION Acute myeloid leukemia is primarily a diagnosis of elderly population; the median age at diagnosis is 67 years (1). It is the most prevalent acute leukemia in adults and accounts for 80% of the cases in this age group. However, in our region the median age at presentation is much lower at 37 years (8,9,10). More is known of AML heterogeneity and prognostic molecular and cytogenetic groups have been identified.(1,3) Over the past 35 years, the course of treatment for achieving and sustaining first complete remission (CR1) in AML has generally not changed, despite advances in the identification of prognostic categories.(1) The patients with acute myeloid leukemia (AML) have extremely poor prognosis. This disease frequently requires intensive therapies, such as combination chemotherapy, to recover. Sadly, despite these rigorous treatments, many AML patients relapse or are refractory, and survival is frequently expressed in months. (3) A 2013 review from western world of 3415 patients who reached CR1 and were between the ages of 16 and 49 years revealed that the relapse rate was 60% among the 2596 patients in CR1 who were not receiving allo-HCT, with a median duration to relapse of 28.5 months.(2) In another large retrospective study the overall survival rate was reported to be 44%, however, when broken down to the risk categories, the overall survival rates were 64%, 41%, and 11% for favourable, intermediate, and adverse risk, respectively. (7) In low and middle-income countries, the prognosis of AML is generally poor owing to late presentation and infection related complications. (12) The western data may not accurately represent the outcome of disease in developing countries. It is well recognized that patients vary significantly in certain ways as a result of environmental, social, and ethnic factors. This data from The Aga Khan Hospital looks at the prognostic features, rates of remission, and long-term outcomes of adult AML patients in Pakistan. METHODS PATIENT SELECTION A total of 212 treatment-naïve AML patients in the aged 15–75 years who were enrolled in the clinical hematology department between December 2011 and March 2019 for examination. Patients with a prior history of solid malignancies, myeloproliferative neoplasms, chemotherapy, myelodysplastic syndrome or acute promyelocytic leukemia were excluded. We looked at the patient's outcome as well as the clinical and biochemical features upon presentation. Patients were followed up for five years. Patients were diagnosed AML if the percentage of myeloblasts in the bone marrow or blood was equal to or greater than 20%. The cytogenetic analysis was carried out via conventional techniques. They were categorized as favourable, intermediate or poor risk in accordance to (ELN) 2017 guidelines. TREATEMENT: All the patients received standard induction therapy 3 + 7, i.e., Daunorubicin 45–60 mg/m.sq or mitoxantrone 12 mg/m.sq intravenous bolus for 3 days in selected patients and cytosine arabinoside 100 mg/m.sq continuous intravenous infusion for 7 days. A bone marrow biopsy was perfomed on the 14th day to determine the clearance of the blast cells, and a repeated bone marrow biopsy was performed on the 30th day to assess remission status. Those who achieved remission were offered 3–4 further courses of consolidation chemotherapy that included high dose cytosine arabinoside at 3 gm/m.sq divided into 2 doses per day for 3 days at the intervals of 3–4 weeks. SUPPORTIVE CARE: All the patients received antifungal prophylaxis with fluconazole or voriconazole and antiviral prophylaxis with acyclovir. All febrile patients were investigated for blood culture, urine analysis, chest X-ray, fungal marker detection and culture from body fluids, as appropriate. The broad-spectrum antibiotics piperacillin/tazobacam along with amikacin, or carbepenem were started for any patient who developed fever and were subsequently modified on the basis of culture and sensitivity. Those who were hemodynamically unstable and had a central line were also given vancomycin, and the central line was also removed. Patients with persistent fever beyond 72 hours were given amphotericin- B. OUTCOME VARIABLES: The criteria for CR was based on no leukemic blasts in the peripheral blood, fewer than 5% blasts in the bone marrow, an absolute neutrophil count of at least 1500/µL, 100,000/µL platelets, and no extramedullary infiltration(13). Those who failed to achieve CR after induction chemotherapy were considered to have induction failure (13). Induction mortality was defined as death from treatment related complications that occur within one month of induction chemotherapy. (13). Relapse was defined by the presence of at least one of the following, a recurrence of more than 5% of myeloblasts in the bone marrow, or any myeloblast in peripheral blood or extramedullary sites.(13) Longterm survivors were considered those who remained leukemia free at 5 years of follow up. RESULTS A total of 212 adult patients who fulfilled the criteria were enrolled. The study period spanned from December 2011 to March 2019. The majority of these patients were male 135 (63.7%), and the remaining 77 (36.3%) were female, with a male to female ratio of 1.75:1. The majority of the patients were under 45 years of age. The patients' clinical and biochemical traits are shown in Table 1. Overall (N = 212) Age ≤ 45 139 (65.6%) > 45 73 (34.4%) Gender F 77 (36.3%) M 135 (63.7%) Duration of symptoms (in days) Median [Q1, Q3] 21.0 [7.00, 30.0] Hb g/dl Mean (SD) 8.33 (2.19) WBC (x 10 9 /L) Median [Q1, Q3] 18.8 [5.93, 71.9] Platelets (x 10 9 /L) Median [Q1, Q3] 38.5 [19.0, 80.3] Karyotyping was performed on 182 patients and 30 patients had inadequate samples. Among these majority n = 113 were found to have a normal karyotype, n = 17 had t(8;21) whereas inv 16, t(9;22), del 5, combined del 7 and del 5 each were present in n = 1 patient, n = 19 patients had a complex karyotype, n = 4 had del 7, and the rest had other cytogenetic abnormalities not classified in the risk stratification group. Graph 2 FLT 3 and NPM 1 were also not conducted in a number of patients due to unavailability or technical issues. The remaining n = 126 were negative for FLT 3 ITD and n = 27 were positive. Similarly, n = 125 were negative for NPM1 and n = 27 were positive. After cytogenetic and molecular analysis n = 152 patients were categorized as intermediate risk (n = 83; 54.6%), poor risk (n = 51; 33.5%) and favourable risk (n = 18; 11.8%). Risk Stratification N = 152 Favourable Risk 18 (11.8%) Intermediate Risk 83 (54.6%) Poor Risk 51 (33.5%) One of these patients was not eligible for intensive chemotherapy. N = 33 patients either refused to be treated and left against medical advice during initial phases of treatment hence were excluded from the study. A total of 178 patients were ultimately included in the assessment, of whom 23(12.92%) patients experienced induction failure. A total of 51 (28.65%) patients died during induction chemotherapy and during the recovery period due to chemotoxicity and severe infections. N = 104 (58.42%) patients achieved remission. Among these 104 patients who achieved remission 10 (5.62%) died within 5 years of follow-up for unrelated reasons. A total of 37(20.79%) patients relapsed within 1 year, and 18 (10.11%) patients relapsed after 1 year but within 5 years of follow-up. N = 24(13.48%) patients remained disease free at 5 years of follow-up. However, 15 patients did not follow beyond two years after completion of their treatment. When assessed based on their risk categories, n = 13 (72.22%) patients with favorable risk, n = 43(51.8%) with intermediate risk and n = 23(45.09%) with poor risk disease achieved CR1 whereas n = 5(27.78%) with favorable risk, n = 8(9.64%) with intermediate risk and n = 6(11.76%) with poor risk were long-term survivors. DISCUSSION Current data on the effectiveness of therapy for acute myeloid leukemia (AML) indicate a substantial gap between high-income countries (HICs) and low- and middle-income countries (LMICs)(6) This disparity is due to a variety of variables, and treatment failure in AML patients in LMICs is frequently not ascribed to the illness itself but rather to socioeconomic factors and issues with public health systems. (6) The risk stratification based on the ELN recommendation in our population compared with that reported by Mariana et al. (2017) was 11.8% vs 36.22% favorable risk, 54.6% vs 51.0% intermediate risk and 33.5%vs 12.75% poor risk(6). However, as reported by Ankur et al. (2015), their population presented favorable risk (21.6%), intermediate risk (69.3%) and poor risk (9.1%) (5). All 3 studies showed comparable distributions in intermediate risk, however, compared with the remaining two categories our population included more patients in poor risk category and fewer patients in favorable-risk category. The remission rate of 58.33% is much lower than the 76.6% reported in the Western world. (1), which is lower than the 70% reported by Ankur et al. (10) from India who reported a CR1 of 84.8% in favorable risk, 67.9% for intermediate risk and 54.2% for poor risk. Our data revealed that 72.22% of favorable risk patients, 51.8% of intermediate risk patients and 45.09% of poor risk patients achieved CR1. A previous study from Pakistan reported CR1 65.4%, which was better than what we reported in our current study (11). We further observed an induction death rate of 25.77%, which was greater than the 18.4% reported by Ankur et al. (5). The five-year survival rate in our group was 14.7%, but their anticipated five-year survival rate was 35.5%, with a relapse rate of 26.88%, which was 33.74% in our population. However, the 10 year disease free survival reported by Sumithira et al was 16.6% according to western data. Another study from northern India reported that the rates of induction death and induction failure were 18.2% and 5.8% respectively (12). Compared with our previous report from our own region,their induction mortality rate was of 29.1% and that of long-term survivors beyond 4 years was 16.6%, which is comparable to our current data (11). This observation might hold true because of the greater number of poor-risk individuals in our study. We did not find any significant difference in the dosage or delay of chemotherapy. Additionally, as reported in previous studies from our own region and from our neighboring country other than disease related factors, late presentation, advanced stage of disease, delays in treatment, poor functional status and active multidrug-resistant bacterial and invasive fungal infections at the time of induction chemotherapy are significant contributors to poor overall outcomes (11,12). This holds true in our data as well. We observed the onset of symptoms and initiation of treatment were significantly delayed. Additionally the more numbers of male patients may not be an actual reflection of the disease distribution among genders, as we often observe due to cultural biases and religious beliefs and women oppression, this particular group often faces a lack of medical care. Similarly, the decision maker mostly their male members take a favor of language barrier and deprive them off the actual information which lands up to a biased uninformed decision which may include depriving them of treatment after knowing the diagnosis. Another factor that may play a major role in delays or refusal in treatment is many patients seek spiritual treatment before deciding to proceed with the medical care and eventually lands up in a bad shape with fulminant infection or very advanced disease. Despite significant improvements in supportive care in AML patients over the past few decades, our data do not suggest any significant improvement in the overall outcome of AML patients. This finding might suggest that traditional chemotherapy alone is not sufficient to improve the outcomes in AML patients and that to improve outcome, novel targeted therapies, bone marrow transplants and immunotherapies are needed. (1) Declarations This study is approved by the Aga khan University Ethics committee and the ERC #2019-1812-5646. References Vasu S, Kohlschmidt J, Mrózek K, Eisfeld AK, Nicolet D, Sterling LJ, Becker H, Metzeler KH, Papaioannou D, Powell BL, Kolitz JE. Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission. Blood advances. 2018 Jul 10;2(13):1645-50. Burnett AK, Goldstone A, Hills RK, et al. Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission. J Clin Oncol. 2013;31(10):1293-1301. Buckley SA, Kirtane K, Walter RB, Lee SJ, Lyman GH. Patient-reported outcomes in acute myeloid leukemia: Where are we now?. Blood Reviews. 2018 Jan 1;32(1):81-7. Mrozek K, Marcucci G, Nicolet D, et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and ´ molecular alterations in adults with acute myeloid leukemia. J Clin Oncol. 2012;30(36):4515-4523. 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, I ndia. Asia‐Pacific Journal of Clinical Oncology. 2015 Sep;11(3):242-52. de Lira Benicio MT, Ribeiro AF, Américo AD, Furtado FM, Glória AB, Lima AS, Santos SM, Xavier SG, Lucena-Araujo AR, Fagundes EM, Rego EM. Evaluation of the European LeukemiaNet recommendations for predicting outcomes of patients with acute myeloid leukemia treated in low-and middle-income countries (LMIC): A Brazilian experience. Leukemia Research. 2017 Sep 1;60:109-14. Pelcovits A, Niroula R. Acute myeloid leukemia: a review. Rhode Island medical journal. 2020 Apr 1;103(3):38-40. Sultan S, Zaheer HA, Irfan SM, Ashar S. Demographic and clinical characteristics of adult acute Myeloid Leukemia-tertiary care experience. Asian Pacific Journal of Cancer Prevention. 2016;17(1):357-60. Chauhan PS, Ihsan R, Singh LC, Gupta DK, Mittal V, Kapur S. Mutation of NPM1 and FLT3 genes in acute myeloid leukemia and their association with clinical and immunophenotypic features. Disease markers. 2013 Oct 29;35:581-8. Meng CY, Noor PJ, Ismail A, Ahid MF, Zakaria Z. Cytogenetic profile of de novo acute myeloid leukemia patients in Malaysia. International journal of biomedical science: IJBS. 2013 Mar;9(1):26. Kakepoto GN, Adil SN, Khurshid M, Bumey IA, Zaki S. Long-term outcomes of acute myeloid leukemia in adults in Pakistan. Journal of Pakistan Medical Association. 2002;52:482. Chauhan P, Gupta A, Gopinathan M, Sanjeev, Garg A, Khanna S, Gupta R, Rahman K, Chandra D, Singh MK, Nityanand S. Real-world challenges in the management of acute myeloid leukemia: a single-center experience from North India. Annals of Hematology. 2022 Jun;101(6):1261-73. Shimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management. American Journal of Hematology. 2023 Mar;98(3):502-26. Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5848383","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":403462231,"identity":"e4a04e11-f90f-4316-be13-126efc558088","order_by":0,"name":"Dr. Urooj Haider Hashmi","email":"data:image/png;base64,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","orcid":"","institution":"Dow University of Health Science, Karachi","correspondingAuthor":true,"prefix":"Dr.","firstName":"Urooj","middleName":"Haider","lastName":"Hashmi","suffix":""},{"id":403463401,"identity":"d3add088-3e1f-4834-8e0b-a9b349f41b15","order_by":1,"name":"Dr. Mohammad Khurshid","email":"","orcid":"","institution":"Department of Oncology, Aga Khan University Hospital, Karachi","correspondingAuthor":false,"prefix":"Dr.","firstName":"Mohammad","middleName":"","lastName":"Khurshid","suffix":""},{"id":403463402,"identity":"31f62f41-1285-4517-b709-3f5f965338dd","order_by":2,"name":"Nida e zehra","email":"","orcid":"","institution":"Department of Oncology","correspondingAuthor":false,"prefix":"","firstName":"Nida","middleName":"e","lastName":"zehra","suffix":""},{"id":403463403,"identity":"d04c611a-ba21-43bc-a08d-ca9f0326cb23","order_by":3,"name":"Dr. Farrukh Zia Tareen","email":"","orcid":"","institution":"Department of Clinical Hematology, Buch International Hospital, Multan","correspondingAuthor":false,"prefix":"Dr.","firstName":"Farrukh","middleName":"Zia","lastName":"Tareen","suffix":""},{"id":403463404,"identity":"20432956-37e7-46f6-959c-fb332b7444a6","order_by":4,"name":"Qurat ul Ain","email":"","orcid":"","institution":"Cancer Directory- PSPO","correspondingAuthor":false,"prefix":"","firstName":"Qurat","middleName":"ul","lastName":"Ain","suffix":""}],"badges":[],"createdAt":"2025-01-17 10:36:40","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-5848383/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5848383/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":74641764,"identity":"6c9d7a03-5758-4526-a5e4-fdd2bc6ebbfd","added_by":"auto","created_at":"2025-01-24 09:22:12","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":34992,"visible":true,"origin":"","legend":"\u003cp\u003eKaryotyping was performed on 182 patients and 30 patients had inadequate samples. Among these majority n=113 were found to have a normal karyotype, n=17 had t(8;21) whereas inv 16, t(9;22), del 5, combined del 7 and del 5 each were present in n=1 patient, n=19 patients had a complex karyotype, n=4 had del 7, and the rest had other cytogenetic abnormalities not classified in the risk stratification group.\u0026nbsp;\u003c/p\u003e","description":"","filename":"Kar1.png","url":"https://assets-eu.researchsquare.com/files/rs-5848383/v1/43c5b03ea6edbd1201e4b5ae.png"},{"id":74641315,"identity":"cc529cd3-481d-44e9-9fcb-c985694b17fb","added_by":"auto","created_at":"2025-01-24 09:14:12","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":17387,"visible":true,"origin":"","legend":"\u003cp\u003eFLT 3 and NPM 1 were also not conducted in a number of patients due to unavailability or technical issues. The remaining n=126 were negative for FLT 3 ITD and n=27 were positive. Similarly, n=125 were negative for NPM1 and n=27 were positive\u003c/p\u003e","description":"","filename":"NPM2.png","url":"https://assets-eu.researchsquare.com/files/rs-5848383/v1/3c4b7f933f4648616186a856.png"},{"id":74641766,"identity":"1ef2dcbd-1335-4e9b-a28c-517918f94cdc","added_by":"auto","created_at":"2025-01-24 09:22:12","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":13383,"visible":true,"origin":"","legend":"\u003cp\u003eFLT 3 and NPM 1 were also not conducted in a number of patients due to unavailability or technical issues. The remaining n=126 were negative for FLT 3 ITD and n=27 were positive.\u003c/p\u003e","description":"","filename":"GrphFLT3.png","url":"https://assets-eu.researchsquare.com/files/rs-5848383/v1/b179e2d01aa7987423a987a2.png"},{"id":74641320,"identity":"fcef2877-9781-4cb4-8847-9810e3a62d13","added_by":"auto","created_at":"2025-01-24 09:14:12","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":20186,"visible":true,"origin":"","legend":"\u003cp\u003eAfter cytogenetic and molecular analysis n=152 patients were categorized as intermediate risk (n=83; 54.6%), poor risk (n=51; 33.5%) and favourable risk (n=18; 11.8%).\u003c/p\u003e","description":"","filename":"RS4.png","url":"https://assets-eu.researchsquare.com/files/rs-5848383/v1/d75da86d417c9c6a7f1f6b6b.png"},{"id":74641770,"identity":"ed91415b-aa0c-4f8b-bcd4-d2d9f7ffaa9e","added_by":"auto","created_at":"2025-01-24 09:22:13","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":20724,"visible":true,"origin":"","legend":"\u003cp\u003eCR1 is n=5(27.78%) with favorable risk, n=8(9.64%) with intermediate risk and n=6(11.76%) with poor risk were long-term survivors.\u003c/p\u003e","description":"","filename":"CR15.png","url":"https://assets-eu.researchsquare.com/files/rs-5848383/v1/199d75ba21e754bac63b773d.png"},{"id":74642923,"identity":"8092c914-6ede-4150-9523-de9830295a00","added_by":"auto","created_at":"2025-01-24 09:30:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":468500,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5848383/v1/53fee166-cba1-4a2b-a54c-d162d32b79a9.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eLongterm Outcome of Adults With Acute Myeloid Leukemia on the Basis of Their Risk Stratification in a Tertiary Care Hospital\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"INRODUCTION","content":"\u003cp\u003eAcute myeloid leukemia is primarily a diagnosis of elderly population; the median age at diagnosis is 67 years (1). It is the most prevalent acute leukemia in adults and accounts for 80% of the cases in this age group. However, in our region the median age at presentation is much lower at 37 years (8,9,10).\u003c/p\u003e \u003cp\u003eMore is known of AML heterogeneity and prognostic molecular and cytogenetic groups have been identified.(1,3)\u003c/p\u003e \u003cp\u003eOver the past 35 years, the course of treatment for achieving and sustaining first complete remission (CR1) in AML has generally not changed, despite advances in the identification of prognostic categories.(1)\u003c/p\u003e \u003cp\u003eThe patients with acute myeloid leukemia (AML) have extremely poor prognosis. This disease frequently requires intensive therapies, such as combination chemotherapy, to recover. Sadly, despite these rigorous treatments, many AML patients relapse or are refractory, and survival is frequently expressed in months. (3)\u003c/p\u003e \u003cp\u003eA 2013 review from western world of 3415 patients who reached CR1 and were between the ages of 16 and 49 years revealed that the relapse rate was 60% among the 2596 patients in CR1 who were not receiving allo-HCT, with a median duration to relapse of 28.5 months.(2)\u003c/p\u003e \u003cp\u003eIn another large retrospective study the overall survival rate was reported to be 44%, however, when broken down to the risk categories, the overall survival rates were 64%, 41%, and 11% for favourable, intermediate, and adverse risk, respectively. (7)\u003c/p\u003e \u003cp\u003eIn low and middle-income countries, the prognosis of AML is generally poor owing to late presentation and infection related complications. (12)\u003c/p\u003e \u003cp\u003eThe western data may not accurately represent the outcome of disease in developing countries. It is well recognized that patients vary significantly in certain ways as a result of environmental, social, and ethnic factors.\u003c/p\u003e \u003cp\u003eThis data from The Aga Khan Hospital looks at the prognostic features, rates of remission, and long-term outcomes of adult AML patients in Pakistan.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003ePATIENT SELECTION\u003c/h2\u003e \u003cp\u003eA total of 212 treatment-na\u0026iuml;ve AML patients in the aged 15\u0026ndash;75 years who were enrolled in the clinical hematology department between December 2011 and March 2019 for examination. Patients with a prior history of solid malignancies, myeloproliferative neoplasms, chemotherapy, myelodysplastic syndrome or acute promyelocytic leukemia were excluded. We looked at the patient's outcome as well as the clinical and biochemical features upon presentation. Patients were followed up for five years.\u003c/p\u003e \u003cp\u003ePatients were diagnosed AML if the percentage of myeloblasts in the bone marrow or blood was equal to or greater than 20%. The cytogenetic analysis was carried out via conventional techniques. They were categorized as favourable, intermediate or poor risk in accordance to (ELN) 2017 guidelines.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eTREATEMENT:\u003c/h3\u003e\n\u003cp\u003eAll the patients received standard induction therapy 3\u0026thinsp;+\u0026thinsp;7, i.e., Daunorubicin 45\u0026ndash;60 mg/m.sq or mitoxantrone 12 mg/m.sq intravenous bolus for 3 days in selected patients and cytosine arabinoside 100 mg/m.sq continuous intravenous infusion for 7 days.\u003c/p\u003e \u003cp\u003eA bone marrow biopsy was perfomed on the 14th day to determine the clearance of the blast cells, and a repeated bone marrow biopsy was performed on the 30th day to assess remission status. Those who achieved remission were offered 3\u0026ndash;4 further courses of consolidation chemotherapy that included high dose cytosine arabinoside at 3 gm/m.sq divided into 2 doses per day for 3 days at the intervals of 3\u0026ndash;4 weeks.\u003c/p\u003e\n\u003ch3\u003eSUPPORTIVE CARE:\u003c/h3\u003e\n\u003cp\u003eAll the patients received antifungal prophylaxis with fluconazole or voriconazole and antiviral prophylaxis with acyclovir. All febrile patients were investigated for blood culture, urine analysis, chest X-ray, fungal marker detection and culture from body fluids, as appropriate. The broad-spectrum antibiotics piperacillin/tazobacam along with amikacin, or carbepenem were started for any patient who developed fever and were subsequently modified on the basis of culture and sensitivity. Those who were hemodynamically unstable and had a central line were also given vancomycin, and the central line was also removed. Patients with persistent fever beyond 72 hours were given amphotericin- B.\u003c/p\u003e\n\u003ch3\u003eOUTCOME VARIABLES:\u003c/h3\u003e\n\u003cp\u003eThe criteria for CR was based on no leukemic blasts in the peripheral blood, fewer than 5% blasts in the bone marrow, an absolute neutrophil count of at least 1500/\u0026micro;L, 100,000/\u0026micro;L platelets, and no extramedullary infiltration(13).\u003c/p\u003e \u003cp\u003eThose who failed to achieve CR after induction chemotherapy were considered to have induction failure (13).\u003c/p\u003e \u003cp\u003eInduction mortality was defined as death from treatment related complications that occur within one month of induction chemotherapy. (13).\u003c/p\u003e \u003cp\u003eRelapse was defined by the presence of at least one of the following, a recurrence of more than 5% of myeloblasts in the bone marrow, or any myeloblast in peripheral blood or extramedullary sites.(13)\u003c/p\u003e \u003cp\u003eLongterm survivors were considered those who remained leukemia free at 5 years of follow up.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 212 adult patients who fulfilled the criteria were enrolled. The study period spanned from December 2011 to March 2019. The majority of these patients were male 135 (63.7%), and the remaining 77 (36.3%) were female, with a male to female ratio of 1.75:1. The majority of the patients were under 45 years of age.\u003c/p\u003e\n\u003cp\u003eThe patients\u0026apos; clinical and biochemical traits are shown in Table 1.\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Taba\" border=\"1\"\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOverall\u003c/p\u003e\n \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;212)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026le;\u0026thinsp;45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e139 (65.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026gt;\u0026thinsp;45\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e73 (34.4%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eGender\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e77 (36.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e135 (63.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of symptoms (in days)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian [Q1, Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21.0 [7.00, 30.0]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHb g/dl\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMean (SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e8.33 (2.19)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWBC (x 10\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian [Q1, Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18.8 [5.93, 71.9]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePlatelets (x 10\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e9\u003c/strong\u003e\u003c/sup\u003e\u003cstrong\u003e/L)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedian [Q1, Q3]\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e38.5 [19.0, 80.3]\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eKaryotyping was performed on 182 patients and 30 patients had inadequate samples. Among these majority n\u0026thinsp;=\u0026thinsp;113 were found to have a normal karyotype, n\u0026thinsp;=\u0026thinsp;17 had t(8;21) whereas inv 16, t(9;22), del 5, combined del 7 and del 5 each were present in n\u0026thinsp;=\u0026thinsp;1 patient, n\u0026thinsp;=\u0026thinsp;19 patients had a complex karyotype, n\u0026thinsp;=\u0026thinsp;4 had del 7, and the rest had other cytogenetic abnormalities not classified in the risk stratification group. Graph 2\u003c/p\u003e\n\u003cp\u003eFLT 3 and NPM 1 were also not conducted in a number of patients due to unavailability or technical issues. The remaining n\u0026thinsp;=\u0026thinsp;126 were negative for FLT 3 ITD and n\u0026thinsp;=\u0026thinsp;27 were positive. Similarly, n\u0026thinsp;=\u0026thinsp;125 were negative for NPM1 and n\u0026thinsp;=\u0026thinsp;27 were positive.\u003c/p\u003e\n\u003cp\u003eAfter cytogenetic and molecular analysis n\u0026thinsp;=\u0026thinsp;152 patients were categorized as intermediate risk (n\u0026thinsp;=\u0026thinsp;83; 54.6%), poor risk (n\u0026thinsp;=\u0026thinsp;51; 33.5%) and favourable risk (n\u0026thinsp;=\u0026thinsp;18; 11.8%).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tabb\" border=\"1\"\u003e\n \u003ccolgroup cols=\"2\"\u003e\u003c/colgroup\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRisk Stratification\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;152\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFavourable Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (11.8%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntermediate Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e83 (54.6%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoor Risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e51 (33.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eOne of these patients was not eligible for intensive chemotherapy. N\u0026thinsp;=\u0026thinsp;33 patients either refused to be treated and left against medical advice during initial phases of treatment hence were excluded from the study. A total of 178 patients were ultimately included in the assessment, of whom 23(12.92%) patients experienced induction failure. A total of 51 (28.65%) patients died during induction chemotherapy and during the recovery period due to chemotoxicity and severe infections. N\u0026thinsp;=\u0026thinsp;104 (58.42%) patients achieved remission. Among these 104 patients who achieved remission 10 (5.62%) died within 5 years of follow-up for unrelated reasons. A total of 37(20.79%) patients relapsed within 1 year, and 18 (10.11%) patients relapsed after 1 year but within 5 years of follow-up. N\u0026thinsp;=\u0026thinsp;24(13.48%) patients remained disease free at 5 years of follow-up. However, 15 patients did not follow beyond two years after completion of their treatment.\u003c/p\u003e\n\u003cp\u003eWhen assessed based on their risk categories, n\u0026thinsp;=\u0026thinsp;13 (72.22%) patients with favorable risk, n\u0026thinsp;=\u0026thinsp;43(51.8%) with intermediate risk and n\u0026thinsp;=\u0026thinsp;23(45.09%) with poor risk disease achieved CR1 whereas n\u0026thinsp;=\u0026thinsp;5(27.78%) with favorable risk, n\u0026thinsp;=\u0026thinsp;8(9.64%) with intermediate risk and n\u0026thinsp;=\u0026thinsp;6(11.76%) with poor risk were long-term survivors.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eCurrent data on the effectiveness of therapy for acute myeloid leukemia (AML) indicate a substantial gap between high-income countries (HICs) and low- and middle-income countries (LMICs)(6)\u003c/p\u003e \u003cp\u003eThis disparity is due to a variety of variables, and treatment failure in AML patients in LMICs is frequently not ascribed to the illness itself but rather to socioeconomic factors and issues with public health systems. (6)\u003c/p\u003e \u003cp\u003eThe risk stratification based on the ELN recommendation in our population compared with that reported by Mariana et al. (2017) was 11.8% vs 36.22% favorable risk, 54.6% vs 51.0% intermediate risk and 33.5%vs 12.75% poor risk(6). However, as reported by Ankur et al. (2015), their population presented favorable risk (21.6%), intermediate risk (69.3%) and poor risk (9.1%) (5). All 3 studies showed comparable distributions in intermediate risk, however, compared with the remaining two categories our population included more patients in poor risk category and fewer patients in favorable-risk category.\u003c/p\u003e \u003cp\u003eThe remission rate of 58.33% is much lower than the 76.6% reported in the Western world. (1), which is lower than the 70% reported by Ankur et al. (10) from India who reported a CR1 of 84.8% in favorable risk, 67.9% for intermediate risk and 54.2% for poor risk. Our data revealed that 72.22% of favorable risk patients, 51.8% of intermediate risk patients and 45.09% of poor risk patients achieved CR1. A previous study from Pakistan reported CR1 65.4%, which was better than what we reported in our current study (11).\u003c/p\u003e \u003cp\u003eWe further observed an induction death rate of 25.77%, which was greater than the 18.4% reported by Ankur et al. (5). The five-year survival rate in our group was 14.7%, but their anticipated five-year survival rate was 35.5%, with a relapse rate of 26.88%, which was 33.74% in our population. However, the 10 year disease free survival reported by Sumithira et al was 16.6% according to western data. Another study from northern India reported that the rates of induction death and induction failure were 18.2% and 5.8% respectively (12). Compared with our previous report from our own region,their induction mortality rate was of 29.1% and that of long-term survivors beyond 4 years was 16.6%, which is comparable to our current data (11).\u003c/p\u003e \u003cp\u003eThis observation might hold true because of the greater number of poor-risk individuals in our study. We did not find any significant difference in the dosage or delay of chemotherapy. Additionally, as reported in previous studies from our own region and from our neighboring country other than disease related factors, late presentation, advanced stage of disease, delays in treatment, poor functional status and active multidrug-resistant bacterial and invasive fungal infections at the time of induction chemotherapy are significant contributors to poor overall outcomes (11,12). This holds true in our data as well. We observed the onset of symptoms and initiation of treatment were significantly delayed. Additionally the more numbers of male patients may not be an actual reflection of the disease distribution among genders, as we often observe due to cultural biases and religious beliefs and women oppression, this particular group often faces a lack of medical care. Similarly, the decision maker mostly their male members take a favor of language barrier and deprive them off the actual information which lands up to a biased uninformed decision which may include depriving them of treatment after knowing the diagnosis. Another factor that may play a major role in delays or refusal in treatment is many patients seek spiritual treatment before deciding to proceed with the medical care and eventually lands up in a bad shape with fulminant infection or very advanced disease.\u003c/p\u003e \u003cp\u003eDespite significant improvements in supportive care in AML patients over the past few decades, our data do not suggest any significant improvement in the overall outcome of AML patients. This finding might suggest that traditional chemotherapy alone is not sufficient to improve the outcomes in AML patients and that to improve outcome, novel targeted therapies, bone marrow transplants and immunotherapies are needed. (1)\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eThis study is approved by the Aga khan University Ethics committee and the ERC #2019-1812-5646.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eVasu S, Kohlschmidt J, Mr\u0026oacute;zek K, Eisfeld AK, Nicolet D, Sterling LJ, Becker H, Metzeler KH, Papaioannou D, Powell BL, Kolitz JE. Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission. Blood advances. 2018 Jul 10;2(13):1645-50.\u003c/li\u003e\n\u003cli\u003eBurnett AK, Goldstone A, Hills RK, et al. Curability of patients with acute myeloid leukemia who did not undergo transplantation in first remission. J Clin Oncol. 2013;31(10):1293-1301.\u003c/li\u003e\n\u003cli\u003eBuckley SA, Kirtane K, Walter RB, Lee SJ, Lyman GH. Patient-reported outcomes in acute myeloid leukemia: Where are we now?. Blood Reviews. 2018 Jan 1;32(1):81-7.\u003c/li\u003e\n\u003cli\u003eMrozek K, Marcucci G, Nicolet D, et al. Prognostic significance of the European LeukemiaNet standardized system for reporting cytogenetic and \u0026acute; molecular alterations in adults with acute myeloid leukemia. J Clin Oncol. 2012;30(36):4515-4523.\u003c/li\u003e\n\u003cli\u003eBahl 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, I ndia. Asia‐Pacific Journal of Clinical Oncology. 2015 Sep;11(3):242-52.\u003c/li\u003e\n\u003cli\u003ede Lira Benicio MT, Ribeiro AF, Am\u0026eacute;rico AD, Furtado FM, Gl\u0026oacute;ria AB, Lima AS, Santos SM, Xavier SG, Lucena-Araujo AR, Fagundes EM, Rego EM. Evaluation of the European LeukemiaNet recommendations for predicting outcomes of patients with acute myeloid leukemia treated in low-and middle-income countries (LMIC): A Brazilian experience. Leukemia Research. 2017 Sep 1;60:109-14.\u003c/li\u003e\n\u003cli\u003ePelcovits A, Niroula R. Acute myeloid leukemia: a review. Rhode Island medical journal. 2020 Apr 1;103(3):38-40.\u003c/li\u003e\n\u003cli\u003eSultan S, Zaheer HA, Irfan SM, Ashar S. Demographic and clinical characteristics of adult acute Myeloid Leukemia-tertiary care experience. Asian Pacific Journal of Cancer Prevention. 2016;17(1):357-60.\u003c/li\u003e\n\u003cli\u003eChauhan PS, Ihsan R, Singh LC, Gupta DK, Mittal V, Kapur S. Mutation of NPM1 and FLT3 genes in acute myeloid leukemia and their association with clinical and immunophenotypic features. Disease markers. 2013 Oct 29;35:581-8.\u003c/li\u003e\n\u003cli\u003eMeng CY, Noor PJ, Ismail A, Ahid MF, Zakaria Z. Cytogenetic profile of de novo acute myeloid leukemia patients in Malaysia. International journal of biomedical science: IJBS. 2013 Mar;9(1):26.\u003c/li\u003e\n\u003cli\u003eKakepoto GN, Adil SN, Khurshid M, Bumey IA, Zaki S. Long-term outcomes of acute myeloid leukemia in adults in Pakistan. Journal of Pakistan Medical Association. 2002;52:482.\u003c/li\u003e\n\u003cli\u003eChauhan P, Gupta A, Gopinathan M, Sanjeev, Garg A, Khanna S, Gupta R, Rahman K, Chandra D, Singh MK, Nityanand S. Real-world challenges in the management of acute myeloid leukemia: a single-center experience from North India. Annals of Hematology. 2022 Jun;101(6):1261-73.\u003c/li\u003e\n\u003cli\u003eShimony S, Stahl M, Stone RM. Acute myeloid leukemia: 2023 update on diagnosis, risk‐stratification, and management. American Journal of Hematology. 2023 Mar;98(3):502-26.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"The Aga Khan University Hospital","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Acute Myeloid Leukemia (AML),Cytogenetic, long-term care, Novel therapies, Post-treatment morbidity","lastPublishedDoi":"10.21203/rs.3.rs-5848383/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5848383/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThis study aims to assess the long-term outcomes of AML patients in LMICs, focusing on survival rates, relapse, and post-treatment morbidity, as well as factors influencing these outcomes in resource-limited settings.\u003c/p\u003e\n\u003cp\u003eWe analyzed the outcome of newly diagnosed AML patients who underwent chemotherapy at Aga Khan University Hospital Karachi. A total of 178 eligible patients were available for assessment. Cytogenetic and molecular workup of 152 patients was available according to which 11.8% were favorable risk, 54.6% were intermediate risk and remaining 33.5% were poor risk. Among these 178 patients who underwent chemotherapy 58.42% achieved remission, 12.92% experienced induction failure and 28.56% died during induction. A total of 13.48% patients were long term survivors who remained disease free at 5 years of follow-up. 20.79% relapsed within 1 year of therapy and 10.11% relapsed after 1 year but within 5 years. 15 patients who were disease free at 2 years did not follow up beyond that period.\u003c/p\u003e\n\u003cp\u003eOn the basis of risk assessment 72.22% patients in favorable risk, 51.8 % in intermediate risk and 45.09% in poor risk category achieved remission. And 27.78% favorable risk, 9.64% intermediate risk and 11.76% poor risk category were long term survivors.\u003c/p\u003e\n\u003cp\u003eThese results suggest long-term outcomes for AML patients in LMICs are significantly influenced by healthcare system limitations, socioeconomic challenges, and lack of access to novel therapies. To improve survival and quality of life, interventions should focus on early diagnosis, access to standard chemotherapy regimens, and post-treatment care.\u003c/p\u003e","manuscriptTitle":"Longterm Outcome of Adults With Acute Myeloid Leukemia on the Basis of Their Risk Stratification in a Tertiary Care Hospital","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-24 09:14:07","doi":"10.21203/rs.3.rs-5848383/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"fd46104f-c209-4497-99f1-47feba28c709","owner":[],"postedDate":"January 24th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":43351278,"name":"Oncology"}],"tags":[],"updatedAt":"2025-01-24T09:14:08+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-24 09:14:07","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5848383","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5848383","identity":"rs-5848383","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}