Cases Of Myeloid Leukemia Research Articles

Impact of aging on acute myeloid leukemia epidemiology and survival outcomes: A real-world, population-based longitudinal cohort study.

Acute myeloid leukemia (AML) is a severe and fatal form of leukemia that is prevalent in the older population. In this longitudinal retrospective study, we investigated the epidemiology and survival rates of patients diagnosed with de novo acute myeloid leukemia in South Korea from Jan 1, 2011, to Aug 31, 2020. We used real-world data from the Health Insurance Review and Assessment Service database. We observed an increase in the number of acute myeloid leukemia cases, with age-specific incidence rates escalating in older patients. In contrast a long-term decrease from 1.94 to 1.77 per 100,000 individuals was found in the age-standardized incidence rates. Meanwhile, age-standardized prevalence rates ascended from 8.93 to 9.67 per 100,000 individuals, with a remarkable increase in the age-specific prevalence rate for those aged 80 years and above. Survival rates were notably better in younger or treated patients, and in those who underwent Hematopoietic stem cell transplantation. The time of diagnosis did not affect the survival of patients younger than 65 years. However, the most recent survival rates were significantly lower for patients 65 or older, as shown in the unadjusted Cox survival analysis. After adjustments in the analysis, it was found that the overall survival rates of the most recently diagnosed group improved significantly compared with those diagnosed earlier, with a hazard ratio of 0.90 (95% confidence interval, 0.84-0.97). This improvement may potentially be influenced by the enhanced treatment alternatives available for newly diagnosed older patients aged 65 years or older. In conclusion, aging appears to fuel an increase in the number of acute myeloid leukemia cases and mortality. Further studies are warranted to understand the impact of aging on acute myeloid leukemia treatment outcomes and devise efficacious care strategies for older patients.

Integrated Clinical Genotype-Phenotype Characteristics of STAT3-Mutated Myeloid Neoplasms.

STAT3 is a key transcription factor that mediates cancer progression through phosphorylation or gain-of-function mutations. STAT3 activation in myeloid neoplasms (MN) is primarily mediated through phosphorylation. STAT3 mutation has only rarely been reported in MNs. We assessed the clinicopathologic and molecular genetic features of 32 STAT3-mutated MNs. The frequency of STAT3 mutation in MNs was <0.5%. Twenty (62.5%) cases were classified as acute myeloid leukemia, 7 (21.9%) as myelodysplastic syndrome, and 5 (15.6%) as chronic myelomonocytic leukemia, but none as myeloproliferative neoplasms. STAT3 mutations occurred at initial diagnosis in 22 (88%) cases or at relapse or upon leukemic transformation. Clonal hierarchy analysis revealed that STAT3 mutations represented the dominant clone in 30% of acute myeloid leukemia cases but were subclonal in myelodysplastic syndrome and chronic myelomonocytic leukemia. Most were missense mutations located at the SH2 domain, Y640F being the most common. STAT3 mutation was accompanied by coexisting mutations in all cases, most frequently SRSF2, TET2, ASXL1, and SETBP1. STAT3 mutations were usually associated with morphologic dysplasia, increased blasts, and monosomy 7/del7q. With a median follow-up of 24.5 months, 21 patients died, 6 had persistent disease, and 5 achieved complete remission after stem cell transplantation. STAT3 mutation is present in various MNs but not in myeloproliferative neoplasms. It is often an early event or occurs upon leukemic transformation, which suggests an important role in the pathogenesis and progression of MNs by activating the JAK-STAT pathway. It may help determine a subset of patients with MNs who may benefit from targeted therapy. See related commentary by Hochman and Frank, p. 4554.

Peripheral blood quantitation of CD26 positive leukemic stem cells as a predictor of tyrosine kinase inhibitor response in chronic myeloid leukemia.

Leukemic stem cells (LSCs) are the transcriptionally low/silent cells which are resistant to the tyrosine kinase inhibitor. These have been found to play a pivotal role in disease relapse in chronic myeloid leukemia (CML) cases. The present study evaluated the correlation of absolute CML-LSC count in the peripheral blood (PB) at diagnosis and achievement of major molecular response (MMR) at 12 months in patients of CML-CP. This was a prospective, observational, non-interventional single center study including newly diagnosed adult (>18 yrs) CML-CP patients. Absolute CD26 + CML-LSC quantification was done by multiparametric flow cytometry. Patients were treated with Imatinib treatment and subsequently monitored at 3-month intervals for BCR::ABL transcript levels. MMR was defined as a BCR::ABL1 transcript level of less than 0.1% on international scale. A total of 89 patients were enrolled in the study out of which 40.5% achieved MMR at 12 months. There was a significant difference in the median absolute CML-LSC count of the patients who achieved MMR at 12 months as compared to those who did not (58.5 vs 368.1 cells/μL; p value <0.001). Using a ROC analysis, a count of <165.69 CML LSC/μL was identified to have a sensitivity of 83.8% and specificity of 72.4%, in predicting the MMR at 12 months. Absolute CML-LSC count at diagnosis in the PB predicts the MMR achievement at 12 months. An absolute count of less than 165 cells/μL is highly predictive of achieving MMR at 12 months.

Chronic myeloid leukemia presenting with disc edema: A case report

The aim is to report a case of chronic myeloid leukemia (CML) in a 20-year-old female who initially presented with bilateral optic disc edema and headaches, and to raise awareness of uncommon causes of disc edema that could potentially be life-threatening. The patient first presented in June 2022 with blurry vision in the left eye, headache, and neck pain of 6 months duration. Initial examination revealed a young woman in no acute distress, with a blood pressure of 100/60 mm Hg and a body mass index of 26.98. Her pinhole visual acuity was 6/9 in both eyes, extraocular motility was full bilaterally, and both pupils were briskly reactive. However, she had bilateral optic disc edema. Both brain and orbital magnetic resonance imaging (MRI) revealed normal findings. Serological tests for syphilis and human immunodeficiency virus were negative. Based on these and the clinical features, an initial diagnosis of idiopathic intracranial hypertension was made, and the patient was started on acetazolamide tablets. She was followed up for approximately 1 year without resolution of symptoms. At a follow-up visit in December 2023, she was found to have developed dilated tortuous vessels with discrete retinal lesions. A peripheral blood film result showed that the patient had CML. In conclusion, a high index of suspicion should be entertained when managing a patient with unexplained bilateral disc swelling with normal brain MRI study. A complete blood workup, including a peripheral blood film, should be included as a part of the routine investigation of these patients so that diagnosis and treatment could be instituted early.

Association between direct acting agents used for chronic hepatitis C virus infection and the occurrence of acute leukaemia – A disproportionality analysis

BACKGROUND AND AIMSA recent single-center study reported a significant increase in acute myeloid leukaemia (AML) cases, including mixed-phenotype acute leukaemia (MPAL), after exposure to direct acting agents (DAA). We investigated whether DAA use increased the risk of AML in patients with chronic hepatitis C virus (HCV) infection. METHODSWe conducted a disproportionality analysis of the WHO Pharmacovigilance database Vigibase up to 2020. Queries focused on all DAAs, subclasses, combinations or each DAA separately as well as interferon and ribavirin as negative controls. The primary outcome was AML. Secondary outcomes were AML without MPAL, MPAL, acute lymphoid leukemia (ALL) and acute leukemia (AL, high-level term encompassing AML, ALL, MPAL and unspecified acute leukemia [UAL]). The information component (IC0.25) and proportional reporting ratio (PRR0.25) were computed to assess a potential pharmacovigilance signal. RESULTSWe identified 49 notifications reporting any AL occurrence after anti-HCV treatments from June 1997 to December 2020: 23 (47%) involved a DAA, 24 (49%) interferon and 12 (24%) ribavirin. The DAAs sofosbuvir and ledipasvir were suspected in 74% (n = 17) and 39% (n = 9) of cases. The events reported were AML (n = 22), ALL (n = 11), AML and ALL (n = 1) and UAL (n = 15) and no MPAL. DAA, interferon or ribavirin were not significantly associated with AML, ALL or AL. CONCLUSIONThis study did not find any association between DAA exposure and the occurrence of AML. Nevertheless, vigilance should remain, particularly for MPAL, which may not have been well captured in our study because of its rareness and high risk of misclassification.

Breast granulocytic sarcoma: a rare presentation of acute myeloid leukemia - a case report

Background: Breast extramedullary myeloid sarcoma is a rare tumor that represents 0.12% of all acute myeloid leukemia cases. Diagnosis can be a real challenge due to the non-specific clinical and radiological features. Reported case: We report a case of a 25-year-old woman who had a painful breast lump. Breast ultrasound revealed an irregular bilateral suspicious mass, and the biopsy confirmed the diagnosis of breast granulocytic sarcoma (GS). The evolution was marked by a dorsal spinal cord compression. A chemotherapy was indicated but refused by the patient. The patient was finally treated with palliative radiotherapy, and chemotherapy. Conclusion: Breast myeloid sarcoma is a rare entity with symptoms reminiscent of those of primary breast cancer making its diagnosis so difficult. Treatment typically involves surgery, chemotherapy, and radiotherapy. Although the poor prognosis of breast GS, detecting the signaling pathways associated with myeloid cell migration to extra-medullary tissues may improve outcomes in the future.

Study of Patterns of Leukaemia in a Tertiary Care Hospital

Introduction: Leukaemia arises from abnormal proliferation of hematopoietic or lymphoid cells, categorized as acute or chronic and originating from lymphoid, myeloid, or mixed lineages. Clinical manifestations result from leukemic cell proliferation and tissue infiltration. Objectives: This study aimed to determine the frequency and clinicopathological profile of leukaemia cases. Material and Methods: A three-year cross-sectional observational study was carried out in the Department of Pathology, Indira Gandhi Medical College, Shimla. Diagnosis of Leukaemia was based on complete blood count, peripheral smear examination, bone marrow analysis and cytochemistry wherever required. Data comprising of patient details, clinical examination and haematological parameters were analysed. Results: A total of 163 leukaemia cases were identified, including 102 (63%) acute and 61(37%) cases of chronic leukaemia. Acute leukaemia consisted of 58 cases of Acute Myeloid Leukaemia (AML), 25 Acute Lymphoblastic Leukaemia (ALL), and 19 undifferentiated leukaemia (UL), while chronic cases comprised 47 Chronic Myeloid Leukaemia (CML) and 14 Chronic Lymphocytic Leukaemia (CLL). Most patients were in the age group of 31-60 years, with a male predominance (M:F 1.7:1). Conclusions: Early diagnosis and typing are vital for prompt leukaemia treatment. Despite advanced technologies, cytomorphological examination with cytochemistry remains crucial, especially in resource-limited settings like India. Keywords: Leukaemia, acute, chronic, cytomorphology, observational study

Paediatric onset lymphomatoid papulosis: results of a multicentre retrospective cohort study, on behalf of the EORTC Cutaneous Lymphoma Tumours Group (CLTG).

Lymphomatoid Papulosis (LyP) is a rare cutaneous T-cell lymphoproliferative disorder. Comprehensive data on LyP in the paediatric population is scarce. To characterize epidemiological, clinical, histopathological, and prognostic features of paediatric LyP. This was a retrospective, multicentre international cohort study including 87 cases of children and adolescents with LyP diagnosed between 1998 and 2022. Patients aged ≤ 18 years old at disease onset were included. Diagnosis was made in each centre based on clinical-pathological correlation. Eighty-seven patients from 12 centres were included. The mean age at onset was 7.0 years (range 3 months-18 years) with a male to female ratio of 2:1. The mean time between onset of first cutaneous lesions and diagnosis was 1.3 years (range 0-14 years). Initial misdiagnosis concerned 26.4% of patients. Initially, LyP was most often misdiagnosed as Pityriasis lichenoides et varioliformis acuta (PLEVA), insect bites, or mollusca contagiosa. Erythematous papules or papulonodules were the most frequent clinical presentation. Pruritus was specifically mentioned for 20.7% of patients. The main histological subtype was type A in 55.1% of the cases. If analysed, monoclonal TCR rearrangement was found in 76.5% of the skin biopsies. The overall survival rate was 100% with follow up at 5 years available for 33 patients and at 15 years for 8 patients. A development of associated haematological malignancy (HM) occurred in 9.6% of the cases (7/73), including four mycosis fungoides (MF) cases, one primary cutaneous anaplastic large cell lymphoma (pc-ALCL), one systemic ALCL and one case of acute myeloid leukaemia. If we compare incidence rates of cancer with the world 0-19 years old population from 2001-2010, we estimate a significantly higher risk of associated malignancy in general, occurring before the age of 19 years old with incidence rate ratio of 87.49 (CI 86.01-88.99). We report epidemiological data from a large international cohort of children and adolescents with LyP. Overall the prognosis of the disease is good, with excellent survival rates for all patients. Due to increased risk of associated HM, a long-term follow-up should be recommended for LyP patients.

Successful Treatment of a Recalcitrant Extensive Giant Molluscum Contagiosum with Intralesional 10% Potassium Hydroxide in an Immunosuppressed Case of Acute Myeloid Leukemia: A Case Report

Successful Treatment of a Recalcitrant Extensive Giant Molluscum Contagiosum with Intralesional 10% Potassium Hydroxide in an Immunosuppressed Case of Acute Myeloid Leukemia: A Case Report

Allogeneic hematopoietic cell transplantation for acute myeloid leukemia with BCR::ABL1 fusion.

BCR::ABL1 fusion is found in<1% of de novo acute myeloid leukemia (AML) cases and confers a poor prognosis. This Japanese nationwide survey analyzed patients with AML (n=22) and mixed phenotype acute leukemia (MPAL) (n=10) with t(9;22) or BCR::ABL1 who underwent allogeneic hematopoietic cell transplantation (allo-HCT) between 2002 and 2018. The 3-year overall survival (OS) rates were 81.3% and 56.0%, respectively (p=0.15), and leukemia-free survival (LFS) rates were 76.2% and 42.0%, respectively (p=0.10) in patients with AML and MPAL. The relapse rates were 9.5% and 14.0% (p=0.93), and the non-relapse mortality (NRM) rates were 14.3% and 44.0%, respectively (p=0.10) in patients with AML and MPAL. One in 17 patients with AML, with pre-transplant tyrosine kinase inhibitors (TKI), and three in five patients with AML, without pre-transplant TKI, did not achieve complete remission (CR) before allo-HCT (p=0.024). Among the 20 patients with known disease status after allo-HCT, 95.0% were in hematological or molecular CR. None of the four patients who received post-transplant TKI for prophylaxis or measurable residual disease relapse experienced hematological relapse. In conclusion, our results suggest that pre-transplant TKI could improve disease status before allo-HCT. Moreover, allo-HCT resulted in high OS, high LFS, low relapse, and low NRM rates in patients with AML with BCR::ABL1.

Is There any Relationship Between the Repeated Complications of Sickle Cell Disease and the Potential Development of Acute Leukemia?

Sickle cell disease (SCD) is a severe monogenic hereditary hemoglobinopathy that is characterized by repeated clinical and biological manifestations able to generate stress erythopoiesis. A clonal hematopoiesis involving mainly variants of TP53, DNMT3A, ASXL1, and/or TET2 may be more prevalent in patients with SCD, suggesting that mutations in these genes may lead to an increased risk of leukemia. An increased prevalence of leukemia in patients with SCD has been confirmed by an increasing number of acute myeloid leukemia cases with myelodysplastic features reported in this patient population even in the absence of disease-modifying treatments. This leads to the hypothesis of a mechanism involving multifactorial causes through the pathophysiologic manifestations of SCD, in which cells are undergoing constant hematopoietic hyperplasia, inducing genomic damage and somatic mutations.

Abstract 1760: Mutational landscape of the canine acute myeloid leukemia exome

Abstract Over 21,000 newly diagnosed cases of human acute myeloid leukemia (hAML) and 10,000 hAML-related deaths are reported in the United States every year. hAML is considered a highly diverse aggressive hematopoietic malignancy, with over 16 recurrent gene rearrangements, 60 recurrent point mutations, and hundreds of rarely mutated genes. There are large ongoing multi-institutional studies devoted to advancing medical management for hAML by providing targeted therapeutics to patients based on their molecular characteristics. A preclinical spontaneous large animal model for testing novel therapies could accelerate the development of better treatments in people. Dogs spontaneously develop AML with similar clinical features and outcomes. As such, the dog may be a useful pre-clinical model, but little is known about the molecular landscape and/or drivers of canine AML (cAML). The goal of this work was to identify somatic mutation candidates in cAML and determine the overlapping features with hAML. We utilized whole exome sequencing at 300x coverage to identify candidate mutations in 51 cAML samples. Somatic variant calling was performed per the GATK best practice recommendations using Mutect2 and a reference panel of normals (n=77) and a variant call file of canine germline variants. We focused our analysis on novel variants predicted to have a moderate to high impact and that occurred in genes implicated in cancer. At least one variant was identified in genes involved in the RTK/RAS pathway (e.g. NRAS, KRAS, PTPN11, FLT3, KIT) in over 75% of cAML samples, a trend that is also found in people. Additionally, recurrent point mutations were predicted in NRAS and KRAS, and some of which, such as the codon changes G13R and Q61R/H in NRAS, were noted to be shared between hAML and cAML. Mutations in DNMT3A were uncommon (n=3/44) and NPM1 mutations were not identified in our cohort, both of which are common hAML-associated genes. However, mutations in other epigenetic modifiers, such as KDM5C and KDM6A, occurred at a high frequency. This data provides insight into the candidate mutations potentially driving cAML pathogenesis and highlights the overlapping molecular features with hAML. Citation Format: Robert Harris, Evan Conaway, Anne Avery. Mutational landscape of the canine acute myeloid leukemia exome [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1760.

Abstract 1763: Long-read sequencing of pediatric leukemia identifies clinically relevant genomic rearrangements

Abstract Clinical detection of genomic rearrangements currently depends on a range of complementary and overlapping methods including fluorescence in situ hybridization (FISH), karyotyping, and DNA and/or RNA sequencing. This requirement for multiple tests results in higher total costs, extended analysis time, and increased usage of sometimes limited tumor material. In our laboratory, we apply long high-fidelity reads to human samples using PacBio circular consensus sequencing (HiFi-GS) of 12-18kb DNA fragments, which offers better structural variant detection relative to short-read sequencing. Here, we assess the ability of HiFi-GS to detect clinically relevant genomic rearrangements (CRGRs) in pediatric leukemia. We selected 11 pediatric leukemia cases with corresponding normal (remission) samples, including 7 cases of B-cell acute lymphoblastic leukemia (B-ALL) and 4 cases of acute myeloid leukemia (AML); 5 of these 11 leukemia cases had known CRGRs as below. The remaining 6 leukemia cases had also undergone clinical genetic profiling via karyotyping, FISH, microarray, and sequencing yet a clinical grade genomic driver was not identified. DNA from each sample was sequenced on a Revio instrument (PacBio, Menlo Park, CA) to a target depth of 30x. The PacBio Human Whole Genome Sequencing (WGS) workflow was used to process HiFi reads for haplotagged alignment and phasing, followed by somatic structural variant calling using Severus. Subsequent analysis focused on the presence of break ends in known cancer-relevant genes. We found that HiFi-GS detected the known CRGRs in all 5 cases with prior findings, providing precise break ends and clarifying sometimes unclear cytogenetic observations (such as exact partner genes), in these cases. These included detection of an ETV6-RUNX1 fusion, NUP98-NSD1 fusion, KMT2A-AFF1 fusion, KMT2A-AFDN fusion, and RUNX1-RUNX1T1 fusion. HiFi sequencing also detected CRGRs in 2 of the 6 “undiagnosed cases”; namely, one case of ZNF384-TCF3 fusion and one case of KMT2A-MLLT10 fusion. The former can be cytogenetically cryptic, while the latter can often be missed due to its potentially complex nature. Our results demonstrate that HiFi-GS can reliably detect CRGRs, bringing us closer to the promise of a single comprehensive genetic test for cancer characterization. Additional work examining other somatic structural and copy number variants (i.e., inversions, deletions, and duplications) in these cases, as well as oncogenic sequence variants, is ongoing. Citation Format: Byunggil Yoo, Ayse Keskus, Chengpeng Bi, Lisa Lansdon, Tanveer Ahmad, Irina Pushel, Adam Walter, Margaret Gibson, Erin Guest, Tomi Pastinen, Mikhail Kolmogorov, Midhat S. Farooqi. Long-read sequencing of pediatric leukemia identifies clinically relevant genomic rearrangements [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1763.

Acute panmylelosis with myelofibrosis - A rare case report with review of literature.

Acute panmyelosis with myelofibrosis (APMF) corresponds to <1% cases of acute myeloid leukemia, which could be an underestimation due to missed diagnosis. Due to its rapidly fatal course, it warrants a timely and correct diagnosis. We present a case of a 44-year male who came with a short history of fever, generalised weakness, revealed pancytopenia with occasional circulating blast in the peripheral blood smear. Bone marrow aspirate was dry tap,biopsy revealed panmyelosis with myelofibrosis with increased (22%) blasts. Flowcytometric immunophenotyping, cytogenetics and molecular tests were undertaken. Together with clinical details, immunophenotypic profile, cytogenetics and molecular studies, the diagnosis of Acute panmyelosis with myelofibrosis was made and managed accordingly. 32 The WHO 2017 describes APMF as an acute panmyeloid proliferation with increased blasts (≥20% in the bone marrow or peripheral blood) and accompanying marrow fibrosis. APMF is rare with poor prognosis thus, must be differentiated especially from Acute megakaryoblastic leukemia to arrive at the correct diagnosis which will help reduce/prevent the early mortality by providing timely chemotherapy followed by upfront hemopoietic stem cell transplantation.

Lineage Switching from Acute Myeloid Leukemia associated with Systemic Mastocytosis to B-Acute Lymphoblastic Leukemia: A Diagnostic Dilemma

Relapse acute leukemia is defined as the reappearance of more than 5% blast in the bone marrow. In most instances, blast expresses the specific lineage (myeloid or lymphoid), similar to a diagnosis. However, it rarely converts to a different lineage, either myeloid shifting to lymphoid or vice versa, during relapse. Thus, it is labelled as switching lineage acute leukemia, after excluding the criteria for mixed phenotypic acute leukemia, which can be a challenge to diagnose. We describe a 24-year-old gentleman with a known case of acute myeloid leukemia associated with systemic mastocytosis (SM); eight months later and after two complete cycles of chemotherapy, relapse occurred with a switched lineage to B-acute lymphoblastic leukemia. The laboratory investigation approaches and the challenges in the diagnosis are also discussed in this case report

Clinical study of the efficacies of ruxolitinib plus low-dose PTCY for acute GVHD prevention after haploidentical transplantation in malignant hematological diseases

Objective: To investigate and verify a novel acute graft versus host disease (aGVHD) prevention protocol in the context of haploidentical hematopoietic stem cell transplantation (haplo-HSCT) . Methods: Patients who underwent haplo-HSCT in our center between January 2022 and December 2022 were included. All patients received reduced doses of cyclophosphamide, Rabbit anti-human tymoglobulin, ruxolitinib, methotrexate, cyclosporine, and MMF to prevent aGVHD. The transplantation outcomes, complications, and survival rate of all patients were investigated. Results: A total of 52 patients with haplo-HSCT were enrolled, 29 (55.8%) male and 23 (44.2%) female, with a median age of 28 (5-59) years. There were 25 cases of acute myeloid leukemia, 17 cases of acute lymphocyte leukemia, 6 cases of myelodysplastic syndrome, 2 cases of chronic myeloid leukemia and 2 cases of myeloproliferative neoplasms. 98.1% of patients had successful engraftment. The incidence of Ⅱ-Ⅳ aGVHD and Ⅲ-Ⅳ aGVHD was 19.2% (95% CI 8.2% -30.3% ) and 7.7% (95% CI 0.2% -15.2% ), respectively. No patients experienced severe gastrointestinal mucositis. The Epstein-Barr virus and CMV reactivation rates were 40.4% and 21.3%, respectively. 9.6% of patients relapsed during followup, with 1-year overall survival, progression-free survival, and non-relapse mortality rates of 86.5% (95% CI 76.9% -96.1% ), 78.8% (95% CI 67.4% -90.3% ) and 11.5% (95% CI 2.6% -20.5% ), respectively. Conclusion: Ruxolitinib combined with a low dose of PTCY is a safe and effective first-line aGVHD prevention strategy.

An audit of molecular measurable residual disease testing for cases of acute myeloid leukaemia diagnosed in the Western Australian public health system between 2019 to 2022

An audit of molecular measurable residual disease testing for cases of acute myeloid leukaemia diagnosed in the Western Australian public health system between 2019 to 2022

Leukemic gingival enlargement- A case report and review

Oral signs are an early indicator for a variety of systemic diseases. Gingival enlargement can be due to local factors, certain medications, hormonal changes, and malignant diseases. Leukemia is a malignancy characterized by the proliferation of abnormal white blood cells within the bone marrow; oral changes may be the first and only presenting feature in these patients, making it imperative for dental surgeons to make accurate diagnosis and timely referral to prevent a fatal situation. This article aims to discuss a case of acute myeloid leukemia (AML) that came with the chief complaint of swollen gums for 2-month duration. The case was provisionally diagnosed as a leukemic gingival enlargement on the basis of oral manifestation and lymph node examination. Accurate diagnosis and early initiation of chemotherapy for leukemic gingival enlargement can improve the prognosis of the patient and also helps in avoiding complications. Around 50–80% of patients with AML achieve complete remission, more often in children and patients under the age of 60. This paper aims at emphasizing the importance of thorough oral examination and careful investigations to identify the underlying life-threatening condition.

IDH1 and IDH2 Gene Mutations in Omani Patients with Acute Myeloid Leukemia: Prognostic Significance and Clinic-pathologic Features.

We sought to define the prevalence of isocitrate dehydrogenase (IDH) mutations, evaluate the clinicopathologic impact of IDH mutations, assess the effect of IDH mutations on the response to the currently offered treatment for acute myeloid leukemia (AML) cases, and determine the impact of other common concurrent mutations with IDH. A single-center retrospective cohort study was conducted at Sultan Qaboos University Hospital (SQUH) from October 2009 to October 2019. We included all Omani patients (pediatric and adult) treated at SQUH with the standard therapy, for whom DNA extraction was performed at diagnosis. The target mutations in both IDH1 and IDH2 genes were screened using the direct polymerase chain reaction product sequencing method. Statistical analysis was conducted using SPSS software. Survival differences were estimated using the log-rank test. Continuous variables were presented as median (IQRs), while categorical variables were presented as frequency. A total of 61 patients treated, for whom DNA extraction was performed at diagnosis were evaluated. The median age was 40 (range = 25.5-65.5). The prevalence of IDH1 R132, IDH2 R140, and IDH2 R172 mutations among the study group was 6.6%, 3.3%, and 1.6%, respectively. Clinicopathologic characteristics associated with IDH mutations at diagnosis included older age, lower white blood cell count, higher median platelet counts, normal karyotype AML, and cytogenetics intermediate-risk group. The overall survival (OS) in patients harboring IDH mutations was poor, with a median OS of nine months. This analysis confirms that the response rate and OS for both IDH-mutated and IDH wild-type AML patients were comparable. This will provide contemporary data to be used for comparison with the results of novel investigational (e.g., selective IDH inhibitor) strategies. The current study results were consistent with the other international studies of IDH mutations in AML and demonstrate the poor prognosis associated with IDH mutations. Clinicopathologic features associated with IDH mutations included older age, lower white blood cell count, higher median platelet counts, normal karyotype AML, and cytogenetics intermediate-risk group.

Molecular biology techniques for assessing the loss of HLA heterozygosity after allogeneic hematopoietic stem cell transplantation in children with acute leukemia

According to several observations, up to a third of post-transplant relapses in childhood acute leukemia are associated with the loss of heterozygosity of the major histocompatibility complex (HLA). Furthermore, the inefficacy of the graft-versus-leukemia reaction, as evidenced by the lack of therapeutic effect from the infusion of donor lymphocytes, indicates the need for timely detection of this marker to change the treatment strategy in the post-transplant period. To detect the loss of HLA heterozygosity, the method using the commercial KMR-HLA system and analysis using next-generation sequencing (NGS), as well as the method based on the analysis of highly polymorphic STR and VNTR markers located in the HLA loci region on the short arm of chromosome 6, are widely used. The primary objective of our study was to compare the informativeness of these approaches in diagnosing HLA heterozygosity loss in children during the post-transplant period. The obtained data on the frequency of detecting HLA heterozygosity loss were comparable to the literature data and constituted 23 % of cases of post-transplant relapse of B-cell acute lymphoblastic leukemia, 33 % of cases of T-cell acute lymphoblastic leukemia, and 23% of cases of acute myeloid leukemia. We also demonstrated that the method based on STR marker analysis has sensitivity comparable to allele-specific PCR and NGS sequencing methods. Meanwhile, preliminary sorting of the blast population increases the sensitivity of STR analysis and can be recommended in routine practice.