Epidemiology & Prognostication of Acute Myeloid Leukemia (AML) in India – A Brief Review

AML is represented by aggregation of ≥20% myeloid immature cells in the spongy marrow and most generally raise in the peripheral blood. A cytogenetic finding plays a vital role in the risk management and stratification of AML patients. AML is genetically and functionally a heterogenous malignant disease. In the western world leukemia is one of the most common among all cancers. India ranked 3rd in cancer disease after US and China. Management of AML is challenging specially for medium and low-income countries as it causes a huge economic burden to the patient and family. Molecular prognostic biomarkers will help in redefining the risk stratification more efficiently. Targeted drugs in pre-clinical and clinical trial recorded to have promising outcomes in AML. In this review we summarize the prevalence, incidence, and prognostication of AML.

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Survival Improvement Of Secondary Acute Myeloid Leukemia Over Time: Experience From 962 Patients Included In 13 EORTC-Gimema-HOVON Leukemia Group Trials

Blood ◽

10.1182/blood.v122.21.829.829 ◽

2013 ◽

Vol 122 (21) ◽

pp. 829-829 ◽

Cited By ~ 3

Author(s):

Safaa M. Ramadan ◽

Stefan Suciu ◽

Marian J.P.L. Stevens-Kroef ◽

Roelof Willemze ◽

Sergio Amadori ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Research Funding ◽

Malignant Disease ◽

Risk Group ◽

Toxic Exposure ◽

Secondary Acute Myeloid Leukemia ◽

History Of ◽

Over Time ◽

Acute Myeloid

Abstract Background Secondary acute myeloid leukemia (sAML) describes patients (pts) with a history of malignant or non-malignant disease or AML secondary to environmental, occupational or therapeutic exposures. They are generally associated with poor outcome despite the use of intensive treatments. The impact of clinical features and type of treatment on pts' outcome is still not well established. In the current analysis we evaluated sAML pts who were treated in 13 EORTC collaborative trials conducted between May 1986 and January 2008. sAML pts in the database were pooled to characterize clinical features of the disease and evaluate changes in survival over these years (yrs). Method Main selection criteria were AML with bone marrows blasts ≥20% and documented history of prior malignancy, non-malignant disease and/or toxic exposure. AML-M3 and MDS without confirmed diagnosis ≥2 months before AML were excluded. All pts were eligible for standard treatment. Induction regimens were anthracycline and AraC based: 7+3, including etoposide, intensified with high dose (HD)-AraC randomized to standard doses (SD) in younger (AML12) or gemtuzumab ozogamicin in elderly pts. Consolidation regimens were age adapted. In mid-1980s, autologous transplant was tested vs a 2nd consolidation cycle (AML8A) in pts ≤45 yrs and thereafter used systematically in pts ≤60 yrs without available donor. Allogeneic transplant (Allo-SCT) was offered to pts ≤46 yrs with HLA-compatible sibling since mid-1980s and expanded in the last decade to pts up to 59 yrs. Selected pts were divided into 3 sAML cohorts, cohort A after MDS, cohort B after other malignant diseases and cohort C after non-malignant conditions and/or toxic exposure. Results Of 8858 pts enrolled in the 13 evaluated studies, 962 were sAML. Median age was 63 yrs (range 16-85), 413 were young (≤60 yrs) and 549 were elderly (≥61 yrs); 54% were males. Cohort A consisted of 509 pts (median age 64 yrs), cohort B of 362 pts (median age 59 yrs) and cohort C of 91 pts (median age 61 yrs). In cohort B, breast cancer (24%) and lymphoma (14%) were the most frequent primary tumors. Autoimmune diseases represented 22% of non-malignant conditions. In young pts, complete remissions (CR/CRi) rate was 59%; 55% in SD-AraC vs 89% in HD-AraC treated pts. Allo-SCT in CR1 was performed in 21% of all pts. The Allo-SCT rate increased from 5% before 1990, 20% in 1990-1999 to 25% from 2000 (20% in SD-AraC vs 31% of HD-AraC treated pts). CR/CRi was achieved in 45% of elderly pts. Median follow-up was 6 yrs. Median overall-survival (OS) was 14.5 months in young and 9 months in elderly pts. The 5-yr OS was 28% and 7% respectively. Five-yr OS was 11% in cohort A and 22% in both cohort B and C. Treatment outcome of younger pts according to disease features and treatment type over time in cohort A and B are detailed in table 1 & 2. Using Cox model stratified by cohort age, gender, WBC, risk group, year of treatment and HD-AraC were independent prognostic factors for OS. In the AML12 study, compared to denovo pts, sAML pts ≤45 yrs had worse outcome if treated with SD-AraC whereas a better OS was seen if treated with HD-AraC. In elderly pts only the good/intermediate risk group of cohort B had a relatively better 5-yr OS (15%). Conclusions The outcome of sAML in younger pts has improved over the yrs in parallel with HD-AraC introduction in induction of remission. HD-AraC should be considered for younger pts with sAML. Disclosures: Ramadan: Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. Suciu:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. Meert:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other. de Schaetzen:Alwaleed Bin Talal Foundation : A research funding is under advanced negotiation with the foundation Other Other.

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Low Platelet Counts at Diagnosis Predict Better Survival for Patients with Intermediate-Risk Acute Myeloid Leukemia

Acta Haematologica ◽

10.1159/000500230 ◽

2019 ◽

Vol 143 (1) ◽

pp. 9-18 ◽

Cited By ~ 1

Author(s):

Yimin Zhang ◽

Haihui Gu ◽

Qi Chen ◽

Ying Zhang ◽

Hui Cheng ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Negative Impact ◽

Disease Free Survival ◽

Intermediate Risk ◽

Hematopoietic Stem ◽

Free Survival ◽

Risk Patients ◽

Immature Cells ◽

Acute Myeloid

Background: Aggressive growth of primitive and immature cells in the bone marrow results in reductions in megakaryocyte and platelet (PLT) counts, leading to thrombocytopenia in acute myeloid leukemia (AML). However, not all AML patients show thrombocytopenia at the time of diagnosis, and the association of PLT count with patient survival is largely unknown. Methods: A retrospective study was performed to determine PLT counts at diagnosis in the peripheral blood in 291 newly diagnosed AML patients and assess the association of PLT counts with the overall survival (OS) and disease-free survival (DFS) of these patients. Results: Low PLT counts (≤40 × 109/L) were associated with better outcomes for the whole cohort (5-year OS, 55.1 ± 3.8 vs. 35.3 ± 3.5%, p < 0.001; 5-year DFS, 49.1 ± 3.8 vs. 25.7 ± 4.0%, p < 0.001) and intermediate-risk patients (5-year OS, 64.5 ± 5.4 vs. 41.0 ± 4.8%, p < 0.001; 5-year DFS, 60.8 ± 5.6 vs. 28.6 ± 5.6%, p < 0.001). Moreover, low PLT counts were related to deeper molecular remission. Low PLT counts correlated with better survival of intermediate-risk AML patients treated with chemotherapy only. Allogeneic hematopoietic stem cell transplantation attenuated the negative impact of high PLT counts on the survival of intermediate-risk patients. Furthermore, univariate and multivariate analyses demonstrated that PLT count at diagnosis was an independent prognostic factor for intermediate-risk AML. Conclusion: PLT count at diagnosis predicts survival for patients with intermediate-risk AML.

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Azacitidine Use in a Low Income Country, Effectiveness of a 100mg Fixed Dose

Blood ◽

10.1182/blood.v128.22.5555.5555 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5555-5555

Author(s):

Jorge Carlos Torres ◽

Nidia Zapata ◽

Eduardo Cervera ◽

Sergio Sanchez ◽

Manuel Aguilar

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Low Income ◽

Survival Data ◽

Myeloid Leukemia ◽

Conflicts Of Interest ◽

Public Institution ◽

Fixed Dose ◽

Median Income ◽

Acute Myeloid

Abstract Azacitidine, a pyrimidine nucleoside analog of cytidine, causes hypomethilation of DNA. Currently FDA approved for treatment of low and intermediate MDS with complete responses around 50%. And Acute myeloid leukemia (AML) in the eldery In the CALGB studies, the usual dose is 75mg/m2 in 28 day cycles, with dose modifications according to toxicity. In low income countries such as Mexico, one course of Azacitidine is around 500 dollars, median income in Mexico is 4,910 PPP (purchasing power parity); vs 30,616 in the USA. So, azacitidine treatment is far from reach for most of the common population, particularly those who do not have insurance. This is a retrospective observational study, of a compassionate use program of a fixed dose of Aza at 100mg. We analyzed data from patients that were treated with Aza between 2012 and 2016, and collected data in 2016. The aim of the study was to assess the effectivity of the fixed dose. For that purpose, we collected information from the physical and electronic file. We analyzed: Hemoglobin level before and after treatment, independence of transfusion, ANC recovery, number of courses, and overall survival. We conducted our research in a public institution in Mexico (Instituto Nacional de Cancerología) and a private institution (Medica Sur). We included acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) patients, regardless of age, previous treatment and comorbidities (we included patients with renal failure, hypertension etc.) We included 8 patients in our study, 6 males and 2 females, with a mean age of 69.9 years (49-87). We had 2 AML and 6 MDS. We had 2 high risk AML and according to IPSS-R: 1 very low, 2 low, 1 intermediate, 1 high and 1 very high risk MDS. As for the Karyotype we had 1 complex KT, 4 normal KT and 1 Del 7q Del 5q +8. All patients received at least one dose of Aza, with mean number of cycles of 4. We have a mean survival of 439 days (110-1385). 6/8 patients achieved transfusion independency within 3 doses of Aza. 6/8 patients achieved ANC but lost eventually lost response. 5/8 patients are alive in follow up. 3 patients died of infectious complications. 2 patients never achieved transfusion independence or ANC. The information recovered suggests that a fixed dose of 100mg is as feasible as a higher dose, at least when no other treatment or higher dose can be administered. We still are analyzing the survival data in order to find other bad prognosis factor within this population. Disclosures No relevant conflicts of interest to declare.

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GATA2 mutations in patients with non-tuberculous mycobacterial or fungal infections with unknown immunodeficiency in Brazil

10.21203/rs.3.rs-19675/v1 ◽

2020 ◽

Author(s):

Daniela Palheiro Mendes de Almeida ◽

Francianne G. Andrade ◽

Filipe V. dos Santos-Bueno ◽

Dayvison F. Saraiva Freitas ◽

Rosely M. Zancopé-Oliveira ◽

...

Keyword(s):

Myeloid Leukemia ◽

Infection Prevention ◽

Malignant Disease ◽

Opportunistic Infections ◽

Fungal Infections ◽

Hematologic Malignancies ◽

Prevention Measures ◽

Subsequent Infection ◽

Infection Susceptibility ◽

Acute Myeloid

Abstract Background Non-tuberculous mycobacteria (NTM) and invasive fungal infections (IFI) may be considered opportunistic infections in immunocompromised patients with GATA2 haplodeficiency. Sporadic or familial GATA2 mutations are associated with infection susceptibility, autoimmunity, and myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). This work aimed to investigate GATA2 status in patients with NTM and/or IFI with unknown causes for immunodeficiency . Methods A series of incident patients with NTM and/or IFI from the Division of Hematology of the Institute of Infectious Diseases-FIOCRUZ at Rio de Janeiro, Brazil, from 2015 to 2018 were subject to GATA2 genotyping. Patients with HIV positivity or other immunodeficiencies were excluded. Results. Twenty-two patients and 9 of their relatives were enrolled. Seventeen patients had IFI, 4 NTM, and one patient present both infections. In 6 patients, the occurrence of malignant disease was found along with this infection, with MDS/AML (n =3) being the most frequent. The pathogenic T354M mutation was found in 4.5% (1/22) of patients and asymptomatic offspring (2/9). We also found the GATA2 polymorphisms rs2335052 and rs369850507 in 18.2% and 4.5%, respectively, and the rs11708606 intronic polymorphisms in 27.3% of cases. Conclusions GATA2 mutations are substantial findings in patients with NTM and/or IFI without known immunosuppression. As it can indicate a primary immunodeficiency and lead to cancers - particularly MDS and AML- the presentation with NTM or IFI should trigger GATA2 mutation testing. The carriers should receive genetic counseling, subsequent infection prevention measures , and surveillance for hematologic malignancies.

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MANIFESTAÇÃO ORAL DA LEUCEMIA MIELÓIDE AGUDA COMO PRIMEIRO SINAL PARA O DIAGNÓSTICO: RELATO DE CASO

Journal of Dentistry & Public Health ◽

10.17267/2596-3368dentistry.v5i2.428 ◽

2014 ◽

Vol 5 (2) ◽

Author(s):

Dhiancarlo Rocha Macedo ◽

Carlos Henrique Alves De Rezende ◽

Rogério Moreira Arcieri ◽

Renata Silva Barbosa

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Case Report ◽

Myeloid Leukemia ◽

Cervical Lymph Node ◽

Malignant Disease ◽

Medical Service ◽

Oral Manifestation ◽

The Right ◽

Acute Myeloid

Acute myeloid leukemia (AML) is a malignant disease of the bone marrow that can present systemic and oral manifestation. In this case report we describe a patient, 16 years of age, who presented the oral manifestation ulcerated lesions on the dorsum of the tongue and cervical lymph node in the right region. After clinical examination and complementary tests, it was taken as a hypothesis the diagnosis of acute leukemia, and the patient was referred to a specialized medical service. Showing the importance of the dentist in the initial diagnosis of leukemia.

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Designing A Model of Medical Equipment Purchase Management in Hospitals of Tehran University of Medical Sciences

Asia Pacific Journal of Health Management ◽

10.24083/apjhm.v16i2.745 ◽

2021 ◽

Vol 16 (2) ◽

pp. 137-147

Author(s):

Azam Lari ◽

Ali Komeili ◽

Kamran Hajinabi ◽

Leila Riahi

Keyword(s):

Low Income ◽

Content Validity ◽

Medical Equipment ◽

Health Resources ◽

Vital Role ◽

Low Income Countries ◽

Path Coefficient ◽

Medical Sciences ◽

Statistical Population ◽

Purchase Management

Objective: Medical equipment plays an effective and vital role in the diagnosis and treatment of diseases. Each society dedicates a plethora of health resources to these facilities. Since prioritizing and resource allocation are crucial in low-income countries with limited health resources, understanding and improving the purchase management of medical equipment in hospitals is a primary key for preparing high-quality health services. The aim of this study was to design a model for medical equipment purchase management at hospitals affiliated with the Tehran University of Medical Sciences. Methods: The statistical population for the present applied study, consisted of 623 people and the research sample was comprised of 420 people, which was selected using the stratified random sampling method. Data was collected using a researcher-made questionnaire whose variables were extracted from comparative studies and whose validity was measured by the relative content validity coefficient, content validity index and Cronbach's alpha coefficient. The SPSS 18 and AMOS were employed for analyses. Results: The most and the least effective aspects of medical equipment purchase management in the studied hospitals were found to be decision-making (path coefficient of 1.244) and organization respectively (path coefficient of 0. 845). Conclusion: It is crucial to take factors into consideration when using the facilities and capacities available in health and treatment centres. The proposed model can best guide buyer institutions to move towards efficient purchase mentioned in upstream policy documents.

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Role of Intraoperative Endoscopy in the Management of Small Bowel Diseases

Endoscopy in Small Bowel Diseases ◽

10.5772/intechopen.95851 ◽

2021 ◽

Author(s):

Rahul Gupta ◽

Arvind K. Singh ◽

Jyoti Gupta ◽

Houssem Ammar

Keyword(s):

Small Bowel ◽

Capsule Endoscopy ◽

Low Income ◽

Vital Role ◽

Low Income Countries ◽

Intraoperative Endoscopy ◽

Medical Centers ◽

Bowel Diseases ◽

Foreign Body Impaction ◽

Small Bowel Diseases

With the advances in the endoscopic technology, most of the small bowel diseases are being diagnosed by capsule endoscopy and device assisted enteroscopy. However, there are many clinical situations such as small bowel obstruction, foreign body impaction were these advanced endoscopic procedures cannot be performed. In such cases, intraoperative endoscopy plays a vital role in the management of these small bowel diseases. Intraoperative endoscopy is also very useful in identification of the site of obscure gastrointestinal bleeding in difficult cases. Moreover, capsule endoscopy and device assisted enteroscopy are expensive procedures and not readily available at all medical centers especially in low income countries. On the other hand, intraoperative endoscopy can be easily performed by conventional gastroscope and colonoscope. In this chapter, we have discussed the indications, techniques, outcomes and complications of intraoperative endoscopy in the current era of deep enteroscopy.

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Infectious diseases in low-income countries: where are we now?

10.1093/oso/9780198789833.003.0001 ◽

2018 ◽

Author(s):

Benjamin Roche ◽

Thierry Baldet ◽

Simard Frédéric

Keyword(s):

Infectious Diseases ◽

Low Income ◽

Control Strategies ◽

Low Income Countries ◽

Western World ◽

Human Populations ◽

Health Campaigns ◽

Human Pathogens ◽

Public Health Campaigns ◽

Made In

It is widely documented that infectious diseases have a very deep impact on numerous human populations. While public health campaigns have achieved spectacular successes, they do not appear to be evenly distributed throughout the world. Indeed, although many infectious diseases have been eliminated in the Western world, deadly pathogens are still spreading in many low-income countries. This chapter aims to describe the current epidemiological situations, reviewing control strategies and the progress that has been made in the fight against major human pathogens with the strongest impact in low-income countries. This chapter, therefore, introduces most of the pathogens that will be discussed in the book, and it describes why some epidemiological situations improved for some diseases more than for others.

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Antitumor Activity of Bortezomib Alone and in Combination with TRAIL in Human Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v110.11.4307.4307 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4307-4307

Author(s):

Concetta Conticello ◽

Luana Adamo ◽

Luisa Vicari ◽

Raffaella Giuffrida ◽

Gioacchin Iannolo ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Antitumor Activity ◽

Myeloid Leukemia ◽

Malignant Disease ◽

Bone Marrow Cells ◽

Proteasome Inhibitors ◽

Lymphoid Malignancies ◽

Human Acute Myeloid Leukemia ◽

Executioner Caspases ◽

Acute Myeloid

Abstract Acute myeloid leukemia (AML) is a malignant disease characterized by abnormal proliferation of clonal precursor cells. Although different strategies have been adopted to obtain complete remission, the disease actually progresses in about 60–70% of patients. Bortezomib has documented antitumor activity in multiple myeloma and other lymphoid malignancies. TRAIL is a member of the TNF family that induces apoptosis in tumor cells while sparing normal cells. Here we examined the sensitivity to Bortezomib alone or in combination with TRAIL of bone marrow cells from AML patients (34 patients: 25 newly-diagnosed, 4 relapsed, 5 refractory). Immunofluorescence analysis showed that NF-κB was located in the nuclei of the AML blasts and it did not translocate after exposure to Bortezomib. Bortezomib induced cell death in blasts from each patient sample. The cytotoxic effect was dose- and time-dependent (concentration from 0.001 to 10 μM for 24 and 48 hours) and was associated with down-regulation of Bcl-xL and Mcl-1, up-regulation of TRAIL-R1, TRAIL-R2, p21 and activation of executioner caspases. Moreover, low doses of Bortezomib primed TRAIL-resistant AML cells for enhanced TRAIL-mediated killing. Thus, the combination of proteasome inhibitors and TRAIL is effective for treating AML patients, even patients who are refractory to conventional chemotherapy.

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Retinoid Differentiation Therapy for Common Types of Acute Myeloid Leukemia

Leukemia Research and Treatment ◽

10.1155/2012/939021 ◽

2012 ◽

Vol 2012 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Geoffrey Brown ◽

Philip Hughes

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Promyelocytic Leukemia ◽

Leukemia Cells ◽

Differentiation Therapy ◽

Normal Cells ◽

New Approach ◽

Immature Cells ◽

Acute Myeloid ◽

Limited Lifespan

Many cancers arise in a tissue stem cell, and cell differentiation is impaired resulting in an accumulation of immature cells. The introduction of all-trans retinoic acid (ATRA) in 1987 to treat acute promyelocytic leukemia (APL), a rare subtype of acute myeloid leukemia (AML), pioneered a new approach to obtain remission in malignancies by restoring the terminal maturation of leukemia cells resulting in these cells having a limited lifespan. Differentiation therapy also offers the prospect of a less aggressive treatment by virtue of attenuated growth of leukemia cells coupled to limited damage to normal cells. The success of ATRA in differentiation therapy of APL is well known. However, ATRA does not work in non-APL AML. Here we examine some of the molecular pathways towards new retinoid-based differentiation therapy of non-APL AML. Prospects include modulation of the epigenetic status of ATRA-insensitive AML cells, agents that influence intracellular signalling events that are provoked by ATRA, and the use of novel synthetic retinoids.

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