A Case of Acute Myeloid Leukemia with Bone Marrow Basophilia and Dysmegakaryocytic Hyperplasia with Isochromosome 17q as a Sole Cytogenetic Abnormality: A Clinical Study with Literature Review

2012 ◽  
Vol 2 (4) ◽  
pp. 215
Author(s):  
Hyun-Ji Lee ◽  
In-Suk Kim ◽  
Sun Min Lee ◽  
Chulhun L. Chang ◽  
Eun Yup Lee ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Clinical Study ◽  
Literature Review ◽  
Myeloid Leukemia ◽  
Cytogenetic Abnormality ◽  
Acute Myeloid

Acute myeloid leukemia associated with t(1;3)(p36;q21) and extreme thrombocytosis: a clinical study with literature review

2010 ◽  
Vol 203 (2) ◽  
pp. 187-192 ◽  
Author(s):  
Gayoung Lim ◽  
Min Jin Kim ◽  
Seung Hwan Oh ◽  
Sun Young Cho ◽  
Hee Joo Lee ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Clinical Study ◽  
Literature Review ◽  
Myeloid Leukemia ◽  
Acute Myeloid

scholarly journals Extramedular lesions of a small intestinum in acute myeloid leukemia: case report and literature review

2019 ◽  
Vol 14 (2) ◽  
pp. 41-47
Author(s):  
I. A. Dokshina ◽  
A. V. Lyanguzov ◽  
S. V. Ignatyev ◽  
O. Yu. Sergunina ◽  
S. L. Kalinina ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Small Intestine ◽  
Case Report ◽  
Literature Review ◽  
Tumor Cells ◽  
Myeloid Leukemia ◽  
Acute Myeloid Leukemia Case ◽  
Morphological Studies ◽  
Acute Myeloid

Currently, the diagnosis of acute myeloid lekemia is based on the standards of morphological studies and immunophenotyping of the bone marrow. The manifestation of the disease can be accompanied by extramedullary lesions, which are difficult to verify. The article presents a case of diagnosis of acute myeloid lekemia in an elderly w oman, occurring with a leukemic lesion of the small in - testine. Morphological studies and immunophenotyping of small intestine biopsy revealed acute myeloid lekemia blast tumor cells. Difficulties of examination in such cases lead to late revealing of leukemic infiltrates of rare localization and significantly worsen the prognosis. 

scholarly journals Discordance Between Morphologic and Cytogenetic Findings Following Induction Chemotherapy for Acute Myeloid Leukemia Is Prevalent in Patients with Bone Marrow Blasts >2% and Is Associated with Poor Clinical Outcomes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4978-4978
Author(s):  
Lalit Saini ◽  
Joseph Brandwein ◽  
Irwindeep Sandhu
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Complete Remission ◽  
Induction Chemotherapy ◽  
Myeloid Leukemia ◽  
Cytogenetic Abnormality ◽  
White Blood Count ◽  
Post Induction ◽  
Acute Myeloid

Abstract BACKGROUND: Following induction chemotherapy for Acute Myeloid Leukemia (AML), patients in morphologic complete remission (mCR) with persistent cytogenetic abnormalities (PCA) have poor outcomes relative to those achieving a mCR without a PCA. Whether these patients have similar outcomes to those failing to achieve a mCR remains unknown. Furthermore, the reasons for the discordance between morphologic and cytogenetic findings have not been well described. To address these questions we conducted a retrospective review of AML patients treated at our centre. METHODS: All non-Acute Promyelocytic Leukemia AML patients from 2004 - 2014 were eligible for inclusion however patients with normal cytogenetics at diagnosis, those not evaluated for remission and those lacking post-induction cytogenetics were excluded. mCR was determined by the attending hematopathologists after review of the bone marrow aspirate (BMA), the bone marrow trephine biopsy (BMTB) with or without immunohistochemistry and/or flow cytometry for the detection of residual disease particularly in equivocal cases. RESULTS: Study criteria were met in 111 patients. Median age was 50 years (17.6 - 77) and 63% were males. Median white blood count at diagnosis was 5.5 x 109/L (0.4 - 307) and median BMB% was 56% (11 - 96%). Most (84%) had primary AML. Cytogenetics were favorable in 28%, intermediate in 41%, and unfavorable in 31% of the patients. Chemotherapy was anthracycline based in 88% and fludarabine based in 12% of patients. Post-induction, 94 patients (85%) had mCR (78 CR + 16 CR with incomplete count recovery, CRi) following induction, 18 (19%) of whom had a PCA and thus discordance between morphologic and cytogenetic findings. There was no difference in the rate of discordance in those age ≤60 vs. age >60 (18.8 vs. 20%, p=1.0), in those with secondary AML vs. primary AML (36 vs. 16%, p=0.13) or in those treated with an anthracycline vs. fludarabine regimen (21 vs. 9%, p=0.68). Discordance was 0%, 28% and 27% in those with favorable, intermediate and unfavorable risk cytogenetics, respectively (p=0.002). A CRi was associated with higher rates of discordance relative to those in CR (50 vs. 12.8%, p=0.002). When the effects of the quality of the BMA and BMTB on the rates of discordance was evaluated, higher rates of discordance were seen in patients with dilute BMA vs. those with non-dilute aspirates (75 vs. 16.7%, p=0.02) and in those with hypocellular BMTB vs. those with cellular/hypercellular/packed BMTB (43.8 vs. 14.7%, p=0.016). Patients with BMB% of >2% had higher rates of discordance vs. those with BMB% ≤2% (46 vs. 9%, p=0.0001) No difference in discordance rates was observed between patients whose BMA were aparticulate/pauciparticulate vs. those with particulate samples (33.3 vs. 16.5%, p=0.15), in those whose BMA samples were hypocellular vs. those that were cellular/hypercellular (20 vs. 16.4%, p=0.67) and in those who had suboptimal BMTB vs. those who had adequate vs. good/excellent samples (25 vs. 18 vs. 20%, p=0.89). In multivariate analysis only the BMB% >2% was associated with high rates of discordance (p=0.0002, odds ratio = 26) between morphologic and cytogenetic findings. The outcomes of patients in mCR with a PCA (n=18) were compared with those failing to achieve a mCR (n=17). The two groups had similar characteristics although patients in mCR with a PCA had a lower median BMB% post-induction vs. those not in a mCR (3 vs. 6%, p=0.004). Of the 18 patients in mCR with a PCA, 10 (56%) underwent an allogeneic stem cell transplant (SCT) while 8 of the 17 (47%) patients not in mCR, after additional chemotherapy, went onto a SCT. Rate of relapse following SCT was similar for those with mCR with PCA vs. those not in mCR (62.5 vs. 33.3%, p=0.35) as was time to relapse (651 vs. 1973 days, p=0.56, Fig 1A). The median overall survival was also similar for patients with mCR and PCA relative to those not in mCR (542 vs. 670 days, p=0.88, Fig 1B). Conclusions: Our results strongly reinforce the need to evaluate for persistent karyotype abnormalities post induction particularly amongst patients with BMB% >2%. Further prospective studies with larger cohorts are necessary to confirm our findings. Figure 1. Overall survival. mCR, morphological complete remission; PCA, persistent cytogenetic abnormality. Figure 1. Overall survival. mCR, morphological complete remission; PCA, persistent cytogenetic abnormality. Disclosures Sandhu: Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.

Enasidenib: First Mutant IDH2 Inhibitor for the Treatment of Refractory and Relapsed Acute Myeloid Leukemia

2019 ◽  
Vol 18 (14) ◽  
pp. 1936-1951 ◽  
Author(s):  
Raghav Dogra ◽  
Rohit Bhatia ◽  
Ravi Shankar ◽  
Parveen Bansal ◽  
Ravindra K. Rawal
Keyword(s):  
Clinical Trial ◽  
Bone Marrow ◽  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Adverse Effects ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
White Blood Cells ◽  
Phase Iii ◽  
Acute Myeloid

Background: Acute myeloid leukemia is the collective name for different types of leukemias of myeloid origin affecting blood and bone marrow. The overproduction of immature myeloblasts (white blood cells) is the characteristic feature of AML, thus flooding the bone marrow and reducing its capacity to produce normal blood cells. USFDA on August 1, 2017, approved a drug named Enasidenib formerly known as AG-221 which is being marketed under the name Idhifa to treat R/R AML with IDH2 mutation. The present review depicts the broad profile of enasidenib including various aspects of chemistry, preclinical, clinical studies, pharmacokinetics, mode of action and toxicity studies. Methods: Various reports and research articles have been referred to summarize different aspects related to chemistry and pharmacokinetics of enasidenib. Clinical data was collected from various recently published clinical reports including clinical trial outcomes. Result: The various findings of enasidenib revealed that it has been designed to allosterically inhibit mutated IDH2 to treat R/R AML patients. It has also presented good safety and efficacy profile along with 9.3 months overall survival rates of patients in which disease has relapsed. The drug is still under study either in combination or solely to treat hematological malignancies. Molecular modeling studies revealed that enasidenib binds to its target through hydrophobic interaction and hydrogen bonding inside the binding pocket. Enasidenib is found to be associated with certain adverse effects like elevated bilirubin level, diarrhea, differentiation syndrome, decreased potassium and calcium levels, etc. Conclusion: Enasidenib or AG-221was introduced by FDA as an anticancer agent which was developed as a first in class, a selective allosteric inhibitor of the tumor target i.e. IDH2 for Relapsed or Refractory AML. Phase 1/2 clinical trial of Enasidenib resulted in the overall survival rate of 40.3% with CR of 19.3%. Phase III trial on the Enasidenib is still under process along with another trial to test its potency against other cell lines. Edasidenib is associated with certain adverse effects, which can be reduced by investigators by designing its newer derivatives on the basis of SAR studies. Hence, it may come in the light as a potent lead entity for anticancer treatment in the coming years.

scholarly journals The Role of Hypoxic Bone Marrow Microenvironment in Acute Myeloid Leukemia and Future Therapeutic Opportunities

2021 ◽  
Vol 22 (13) ◽  
pp. 6857
Author(s):  
Samantha Bruno ◽  
Manuela Mancini ◽  
Sara De Santis ◽  
Cecilia Monaldi ◽  
Michele Cavo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Cell Fate ◽  
Myeloid Leukemia ◽  
Hematologic Malignancy ◽  
Bone Marrow Microenvironment ◽  
Metabolic Adaptation ◽  
Cell Fate Decisions ◽  
Wide Range ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a hematologic malignancy caused by a wide range of alterations responsible for a high grade of heterogeneity among patients. Several studies have demonstrated that the hypoxic bone marrow microenvironment (BMM) plays a crucial role in AML pathogenesis and therapy response. This review article summarizes the current literature regarding the effects of the dynamic crosstalk between leukemic stem cells (LSCs) and hypoxic BMM. The interaction between LSCs and hypoxic BMM regulates fundamental cell fate decisions, including survival, self-renewal, and proliferation capacity as a consequence of genetic, transcriptional, and metabolic adaptation of LSCs mediated by hypoxia-inducible factors (HIFs). HIF-1α and some of their targets have been associated with poor prognosis in AML. It has been demonstrated that the hypoxic BMM creates a protective niche that mediates resistance to therapy. Therefore, we also highlight how hypoxia hallmarks might be targeted in the future to hit the leukemic population to improve AML patient outcomes.

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