Infection at diagnosis—a unique challenge in acute myeloid leukemia treatment in developing world

Pandian, Jesu; Raghavan, Vineetha; Manuprasad, Avaronnan; Shenoy, Pareen J.; Nair, Chandran K.

doi:10.1007/s00520-020-05379-z

Cited by 12 publications

(13 citation statements)

References 19 publications

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“…This is in concordance with Western literature. 2,3,22 Similar studies from the Indian subcontinent have reported relatively higher induction mortality rates, with Pandian et al 20 The strengths of this study are that the patterns of infection and infection-related outcomes are from a homogenous cohort. These data will be useful for other centers in our region.…”

Section: Discussionsupporting

confidence: 59%

“…18 Gramnegative organisms were more frequent and distributed along the treatment phases similar to other studies in the country. 6,20,21 Gram-positive organisms were seen in 25 patients during induction, but only in three patients in Infection-Related Mortality in Acute Myeloid Leukemia subsequent HIDAC cycles. This is different from the clinical trial data from the AML-BFM2004, PALG, and Children's Oncology Group trials reported in the Western literature, which showed predominantly gram-positive infections.…”

Section: Discussionmentioning

confidence: 98%

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Infection Prevalence in Adolescents and Adults With Acute Myeloid Leukemia Treated in an Indian Tertiary Care Center

Jain

Rengaraj

Sharma

et al. 2020

JCO Global Oncology

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PURPOSE Infections remain a major challenge in the treatment of acute myeloid leukemia (AML). Induction-related mortality reported in the literature is approximately < 5% in clinical trials. However, the real-world scenario is different, especially in developing countries, given the high incidence of multidrug-resistant (MDR) organisms, high incidence of fungal pneumonia at baseline, and significant delay before initiation of chemotherapy. We aimed to look at contemporary infections and infection-related mortality and analyze the patterns of infections. MATERIALS AND METHODS This retrospective study was conducted at a large tertiary care oncology center in India. Patients with newly diagnosed AML who were older than age 15 years, considered fit for intensive therapy, and treated in the general wards of the adult hematolymphoid unit from March 1, 2014, until December 31, 2015, were included. RESULTS One hundred twenty-one patients were treated during the study period. The most common presenting complaint was fever (85%). The focus of infection at presentation was found in 63% of patients, with respiratory infection being the most common (47%). MDR organisms were isolated in 55% of patients during induction from various foci. Klebsiella pneumoniae was the most common blood culture isolate (42.9%). Fungal pneumonia was diagnosed in 55% of patients during induction despite antifungal prophylaxis. Treatment-related mortality was 10.7% in all phases, with an induction mortality rate of 7.4%. Complete remission was attained in 69% of patients. Of all patients who received induction chemotherapy, 74% completed all three consolidation cycles. The 121 patients were followed up for a median period of 53 months. Four-year event-free survival was 35.8%, and 4-year overall survival was 41.5%. CONCLUSION Infections and infection-related mortality are major challenges during AML induction. Gram-negative MDR and fungal infections are particularly common in our region.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 98%

Infection Prevalence in Adolescents and Adults With Acute Myeloid Leukemia Treated in an Indian Tertiary Care Center

Jain

Rengaraj

Sharma

et al. 2020

JCO Global Oncology

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“…24 However, it is in congruence with the published data from India, which ranges between 30% and 60%. 5,6,10,22 All our patients developed infections during the study period. On univariate analysis, factors such as age, sex, symptom duration, ECOG performance status, and comorbidity, were not statistically significant for the development of fever or acquiring infection during induction therapy.…”

Section: Discussionmentioning

confidence: 84%

“…This is lower than the published data ranging from 4 to 7 weeks. 21,22 Twenty patients (36.36%) had one or more comorbidities in our study. Essential hypertension was the most common (16/55 patients; 29%), followed by diabetes mellitus (5/55 patients; 9%).…”

Section: Discussionmentioning

confidence: 90%

The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings

Mishra

Kumar

Ninawe

et al. 2021

Therapeutic Advances in Infection

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Introduction: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30–66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML. Method: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included. Result: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12–71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days ( p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 ( p = 0.063). Thirteen patients (23.63%) died during the study period. Discussion: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections. Conclusion: Infections continues to be a major cause of morbidity and mortality among AML patients.

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“…Despite the advances in supportive care, induction chemotherapy remains one of the most high-risk phases of AML therapy, with mortality at the level of 5% in developed countries, but up to 15-25% in developing countries. This is caused by the high incidence of infections by multi-drug resistant bacteria due to the unregulated use of antibiotics [5][6][7][8][9] .…”

Section: Introductionmentioning

confidence: 99%

Infectious complications of induction treatment for acute myeloid leukaemia using the "7 + 3" protocol without antibiotic prophylaxis - 15 years of experience of one clinical site

Čerňan

Szotkowski

Hubácek

et al. 2023

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Background. Infectious complications during induction chemotherapy of acute myeloid leukaemia are very common. Prophylactic use of antibiotics however is an ongoing challenge in this situation due to bacterial multi-drug resistance. The aim of this study was to provide a comprehensive overview of the incidence of infectious complications in patients with AML undergoing induction therapy using the "7+3" protocol without routine antibiotic prophylaxis at one clinical site providing specialised haematological care in the Czech Republic, over a period of 15 years. The study also evaluates the aetiological spectrum of causative agents and the development of antibiotic resistance in the context of the use of the various classes of antibiotics. The analysis includes evaluation of the importance of risk factors for infectious complications and their impact on treatment of the underlying disease. The data are compared with published figures for similar cohorts of patients. Patients and Methods. This study presents a retrospective analysis of infectious complications in 242 patients with acute myeloid leukaemia undergoing the first cycle of induction therapy without routine antibiotic prophylaxis in one clinical site in Czech Republic during years 2006-2020. Results. A total of 363 febrile episodes (FE) were recorded. At least 1 FE during the induction was detected in 229 (94.6%) patients. Clinically defined infection was the cause in 96 (26.4%) FEs and blood stream infection in 69 (19.0%) FEs. Both complications occurred simultaneously in 29 (8.0%) FEs. 169 (46.6%) FEs were evaluated as fever of unknown origin (FUO). The achievement of complete remission had a significant effect on the duration of the FE (6 vs. 9 days, P=0.0005) and on the overall survival duration (79.3 vs. 6.5 months, P<0.0001). Patients diagnosed with infection or FUO at diagnosis were significantly more likely to suffer from colonisation by multi-drug resistant bacterial strains at discharge (29.2% vs. 16.3%, P=0.022). This group of patients used antibiotic therapy for a significantly longer time (35 vs. 23 days, P<0.0001). Infection was a contributing cause of death in 18 (7.4%) patients. Mortality was significantly related to the failure to achieve complete remission (P<0.0001). Conclusion.Infectious mortality during induction treatment without routine antibiotic prophylaxis was comparable to the published cohorts with prophylaxis. Regular microbiology surveillance with adequate initial antibiotic treatment can compensate routine antibiotic prophylaxis with slower development of antibiotic resistance.

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Infection at diagnosis—a unique challenge in acute myeloid leukemia treatment in developing world

Cited by 12 publications

References 19 publications

Infection Prevalence in Adolescents and Adults With Acute Myeloid Leukemia Treated in an Indian Tertiary Care Center

Infection Prevalence in Adolescents and Adults With Acute Myeloid Leukemia Treated in an Indian Tertiary Care Center

The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings

Infectious complications of induction treatment for acute myeloid leukaemia using the "7 + 3" protocol without antibiotic prophylaxis - 15 years of experience of one clinical site

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