Acute Myeloid Leukemia Cases Research Articles

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.

Global, national, and regional burden of acute myeloid leukemia among 60-89 years-old individuals: insights from a study covering the period 1990 to 2019.

Our study examined the global, national, and regional trends in the incidence, mortality, and disability-adjusted life years (DALYs) associated with older people's acute myeloid leukemia (AML) over a 30 years period. AML, which predominantly affects individuals aged 60-89, is known for its severity and unfavorable prognosis. By providing insights into the growing burden of AML, our research highlights the urgent need for effective interventions and support at various levels. In this study, we analyzed older people with AML aged 60-89 using the Global Burden of Disease (GBD) database for 2019. Our goal was to assess trends and characteristics by examining the incidence rate, mortality rate, DALYs, and estimated annual percentage change (EAPC). We aimed to provide a comprehensive understanding of the disease's trajectory and development. In 2019, the older age group of 60 to 89 years reported 61,559 new cases of AML, with the corresponding number of deaths being 53,620, and the estimated DALYs standing at 990,656. Over the last 30 years, the incidence rate of AML in this age bracket increased by 1.67 per 100,000 people, the mortality rate rose by 1.57 per 100,000 people, and the rate of DALYs, indicative of disease burden, climbed by 1.42 per 100,000 people. High Socio-demographic Index (SDI) regions, particularly high-income North America and Australia, had the highest incidence rates. Germany had the highest incidence rate among the 204 countries analyzed, while Monaco reported the highest mortality and DALY rates. Smoking, high body mass index, occupational exposure to benzene, and formaldehyde were identified as significant risk factors associated with mortality from older people with AML in 2019. Our study showed that the incidence, mortality, and DALY rates of AML in the older population were strongly correlated with the SDI, and these rates have been steadily increasing. This had become an increasingly serious global health issue, particularly in areas with a high SDI. We highlighted the urgency to focus more on this disease and called for the prompt implementation of appropriate preventive and control measures.

Feasibility, accuracy, and usability analysis of MapAML, a first-in-class app for integrated diagnosis in acute myeloid leukemia.

Performing a comprehensive diagnosis of acute myeloid leukemia (AML) is complex and involves the integration of clinical information, bone marrow morphology, immunophenotyping, cytogenetic, and molecular analysis, which can be challenging to the general hematologist. The aim of this study was to evaluate the usability and accuracy of MapAML, a smartphone app for integrated diagnosis in AML, created to aid the hematologist in its clinical practice. App performance was evaluated in dedicated sessions, in which 21 hematologists or fellows in hematology performed an integrated diagnosis of deidentified real-world clinical AML cases, first without and posteriorly with MapAML use. Diagnosis accuracy increased after MapAML utilization, with the average score going from 7.08 without app to 8.88 with app use (on a scale from 0 to 10), representing a significant accuracy improvement (p = .002). Usability evaluation was very favorable, with 81% of users considering the app very or extremely simple to use. There was also a significant increase in confidence to perform a complete and accurate diagnosis in AML after app use, with 61.9% of the participants willing to use the app in their clinical practice. In this study, MapAML increased accuracy with excellent usability for integrated diagnosis in AML.

Autopsy case of acute myeloid leukemia with human herpesvirus-6B (HHV-6B) encephalitis following cord blood transplantation and persistent HHV-6B DNA detection in the blood

Autopsy case of acute myeloid leukemia with human herpesvirus-6B (HHV-6B) encephalitis following cord blood transplantation and persistent HHV-6B DNA detection in the blood

M5 C regulator-mediated methylation modification patterns and tumor microenvironment infiltration characteristics in acute myeloid leukemia.

Recently, many studies have been conducted to examine immune response modification at epigenetic level, but the candidate effect of RNA 5-methylcytosine (m5 C) modification on tumor microenvironment (TME) of acute myeloid leukemia (AML) is still unknown at present. We assessed the patterns of m5 C modification among 417 AML cases by using nine m5 C regulators. Thereafter, we associated those identified modification patterns with TME cell infiltration features. Additionally, stepwise regression and LASSO Cox regression analyses were conducted for quantifying patterns of m5 C modification among AML cases to establish the m5 C-score. Meanwhile, we validated the expression of genes in the m5C-score model by qRT-PCR. Finally, the present work analyzed the association between m5 C-score and AML clinical characteristics and prognostic outcomes. In total, three different patterns of m5 C modification (m5 C-clusters) were identified, and highly differentiated TME cell infiltration features were also identified. On this basis, evaluating patterns of m5 C modification in single cancer samples was important for evaluating the immune/stromal activities in TME and for predicting prognosis. In addition, the m5 C-score was established, which showed a close relation with the overall survival (OS) of test and training set samples. Moreover, multivariate Cox analysis suggested that our constructed m5 C-score served as the independent predicting factor for the prognosis of AML (hazard ratio = 1.57, 95% confidence interval = 1.38-1.79, p < 1e-5 ). This study shows that m5 C modification may be one of the key roles in the formation of diversity and complexity of TME. Meanwhile, assessing the patterns of m5 C modification among individual cancer samples is of great importance, which provides insights into cell infiltration features within TME, thereby helping to develop relevant immunotherapy and predict patient prognostic outcomes.

HOXA9 Regulome and Pharmacological Interventions in Leukemia.

HOXA9, an important transcription factor (TF) in hematopoiesis, is aberrantly expressed in numerous cases of both acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) and is a strong indicator of poor prognosis in patients. HOXA9 is a proto-oncogene which is both sufficient and necessary for leukemia transformation. HOXA9 expression in leukemia correlates with patient survival outcomes and response to therapy. Chromosomal transformations (such as NUP98-HOXA9), mutations, epigenetic dysregulation (e.g., MLL- MENIN -LEDGF complex or DOT1L/KMT4), transcription factors (such as USF1/USF2), and noncoding RNA (such as HOTTIP and HOTAIR) regulate HOXA9 mRNA and protein during leukemia. HOXA9 regulates survival, self-renewal, and progenitor cell cycle through several of its downstream target TFs including LMO2, antiapoptotic BCL2, SOX4, and receptor tyrosine kinase FLT3 and STAT5. This dynamic and multilayered HOXA9 regulome provides new therapeutic opportunities, including inhibitors targeting DOT1L/KMT4, MENIN, NPM1, and ENL proteins. Recent findings also suggest that HOXA9 maintains leukemia by actively repressing myeloid differentiation genes. This chapter summarizes the recent advances understanding biochemical mechanisms underlying HOXA9-mediated leukemogenesis, the clinical significance of its abnormal expression, and pharmacological approaches to treat HOXA9-driven leukemia.

Measuring response to therapy in AML: Difference from normal flow cytometry vs RQ-PCR.

Multiple technologies have been used to monitor response to therapy in acute myeloid leukemia (AML) to improve detection of leukemia over the standard of practice, morphologic counting of blasts. The two techniques most frequently used in a routine clinical setting, flow cytometry and RQ-PCR, differ in their targets, sensitivity, and ability to detect residual disease. Both flow cytometry and RQ-PCR detect the expression of abnormal gene products, at the protein level or RNA level, respectively. Flow cytometry can be applied to a broad range of AML cases while RQ-PCR is limited to specific genetic abnormalities identified in subsets of AML. This article compares the results when both techniques were used in a reference laboratory to monitor AML over the course of treatment, comparing quantitative and qualitative results.

Association of genetic predisposition studies in CYP1A1 polymorphism studies in acute myeloid leukemia

Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) gene is one of the sub-members of CYP450 family member and it encodes with the families of drug metabolizing enzyme families along with the cancers and leukemias. Among leukemias, AML is considered to be one of the important leukemia which attack the older adults. The aim of this study is to explore the role of A4889G polymorphism in CYP1A1 gene in acute myeloid leukemia (AML) in the Saudi population. This study was designed as an experimental case-control study in which 100 AML cases and 100 controls were selected. This in vivo study was carried out using genomic DNA extraction, polymerase chain reaction and agarose gel electrophoresis and then BsrDI restriction enzyme to digest the A4889G polymorphism of the PCR products. In this study, 200 subjects were digested and based on the appearance of the bands, genotypes were categorized. The attained data was used to calculate the clinical details as well as genotype analysis. The study results confirmed AG genotype (OR = 3.23, CI = 1.60–6.55, p = 0.0008), AG + GG (OR = 3.47, CI = 1.76–6.86, p = 0.0002) and GG + AA (OR = 12.47, CI = 6.18–15.17, p < 0.0001) and G vs A (OR = 3.15, CI = 1.71–5.81, p = 0.0001) were associated in AML cases. In conclusion, we confirm that A4889G polymorphism is associated with AML in the Saudi population.

Clinico-Hematological Profile of Acute Myeloid Leukemia: Experience From a Tertiary Care Cancer Center in North India.

Complete diagnosis of acute myeloid leukemia (AML) requires knowledge of clinical information combined with morphologic evaluation, immunophenotyping, karyotyping, and molecular genetic testing. The study intends to evaluate the demographic profile, clinical workup, and investigation, including flow cytometric immunophenotyping, in adult and pediatric age groups of AML. This is a retrospective study of AML patients treated between January 2017 and December 2021. Clinical and demographic characteristicsand investigation findings were recorded from case files and the hematology database. A total of 896 cases of AML were registered during the given period, of which 819 cases were de-novo AML. Among those 819 cases, more than two-thirds of cases, i.e., 78.9% (N = 646), received induction chemotherapy. A significantly higher male-to-female ratio was observed (1.5:1). The median age was 22 years. The median time for diagnosis was three days and the median time for treatment intervention was four days. There were significant differences in the Eastern Cooperative Oncology Group (ECOG) performance status scores between pediatric and adult AML patients. Pediatric AML patients presented with better ECOG performance scores (ECOG performance scores 0 and 1) than adult patients (74.76% vs. 43.14%, p < 0.001). Further comparing adult vs. pediatric AML patients, normal karyotype (60.56% vs. 31.93%, p < 0.001) and NPM1 (22.25% vs. 6.72%, p < 0.001)and FLT3-ITD mutations (20.28% vs. 7.98%, p<0.001) were more common in the adult group, whereas AML-ETO (40.76% vs. 16.34%, p < 0.001) was more common in the pediatric group. The study highlights the presenting age is lower than global figures. The median time for initial diagnosis and the start of treatment is within the acceptable norms. Normal karyotype andNPM1and FLT3 mutations were common in adult AML patients, whereas AML-ETO was more common in the pediatric cohort. These findings will help plan prospective studies and see the correlation with treatment outcomes. The laboratory workup practice currently complies with the standard guidelines at our center.

Exposure to persistent organic pollutants in newborn dried blood spots and childhood acute myeloid leukemia

Acute myeloid leukemia (AML) is a rare malignancy representing 15–20% of all leukemia diagnoses among children. Maternal exposure to persistent organic pollutants is suggestive of increased risk for childhood AML based on existing evidence. We aimed to evaluate the relationship between persistent organic pollutants and childhood AML using newborn dried bloodspots (DBS) from the Michigan BioTrust for Health. We obtained data on AML cases diagnosed prior to 15 years of age (n = 130) and controls (n = 130) matched to cases on week of birth from the Michigan Department of Health and Human Services. We quantified levels of dichlorodiphenyldichloroethylene (p,p’-DDE), hexachlorobenzene (HCB), and polybrominated diphenyl ether congener 47 (BDE-47) in newborn DBS. We also evaluated other organochlorine pesticides, polychlorinated biphenyls, polybrominated biphenyl congener 153, and polybrominated diphenyl ethers, though these were not further evaluated as >60% of observations were above the limit of detection for these chemicals. To evaluate the association between each chemical and AML, we used multivariable conditional logistic regression. In our multivariable model of HCB adjusted for month of birth, maternal age at delivery, and area poverty, we observed no association with AML (Odds Ratio [OR] per interquartile range increase: 1.17, 95% CI: 0.80, 1.69). For p,p’-DDE, ORs were significantly lower for those exposed to the highest tertile of p,’p-DDE (≥0.29 pg/mL, OR: 0.32, 95% CI: 0.11, 0.95) compared to the first tertile (<0.09 pg/mL). We observed no statistically significant associations between HCB and BDE-47 and AML. We observed a reduced odds of exposure to p,’p-DDE and an increased, though imprecise, odds of exposure to HCB among AML cases compared to controls. Future studies would benefit from a larger sample of AML patients and pooling newborn DBS across multiple states to allow for additional variability in exposures and evaluation of AML subtypes, which may have differing etiology.

C-Kit and Flt3 mutation status in acute myeloid leukaemia with cytogenetic correlation and prognosis: A series of 75 cases

Recent WHO classification (5 edition) has included Acute Myeloid Leukaemia (AML) with mutations in NPM1, CEBPA as separate entities along with AML with cytogenetic abnormalities in AML with recurrent genetic abnormalities. Even though C-kit and FLT3 mutations in AML have no diagnostic importance, prognostic significance in different subtypes of AML for the presence of these mutations are not the same.To assess the correlation between French American British (FAB) AML classification, specific cytogenetic abnormalities with C-kit, and FLT3 mutation in AML and to evaluate the prognosis and survival of AML patients with respect to cytogenetic abnormalities and C-kit and FLT3 mutation status. Retrospectively all AML cases in which C-kit and FLT3 mutation status was assessed were retrieved; C-kit D816V mutation status had been assessed by Real time PCR; For FLT3 mutation, both Internal tandem duplication (ITD) and D835V mutation status had been assessed using PCR and gel electrophoresis; The data regarding morphological with immunophenotypic diagnosis, conventional karyotyping, FISH for translocation 8;21 (t (8;21)) and inversion16 / translocation16;16 (t (16;16) were also retrieved in all these cases along with follow-up from hospital records. Total 75 cases were included; Male/ Female ratio was 1.21:1 (41/34); Median age was 31 (Range: 2 - 64); 18 cases had translocation 8;21 (t (8;21)); 3 cases showed inversion16 / translocation16;16 (t (16;16); Out of the 18 cases which showed t (8;21), 10 cases had associated loss of sex chromosome. Eight cases had C-kit D816V mutation; three of which had t (8;21) while two had inversion 16. 12 cases had FLT3 mutations among which nine were ITD while three had D835V mutation. On karyotyping, one of these cases showed hyperdiploidy while the majority had normal karyotype. A single case had both C-kit D816V mutation and FLT3 D835V mutation with inversion 16 on karyotyping; Most common type of AML in both cases with FLT3 mutation and C-kit mutation was AML-M2 (FAB); Commonest karyotyping abnormality for cases with C-kit mutation was t(8;21); while for FLT3 mutation, the majority had normal karyotype; The single case which had both C-kit D816V mutation and FLT3 D835V mutation was alive event-free at three-year follow-up. Both FLT3 ITD and TKD mutations had a worse prognosis in our study. However, AML cases with C-kit mutation had a similar prognosis comparable to C kit negative cases. A large-scale study is required to elucidate the significance of this.

Clinical analysis of allogeneic hematopoietic stem cell transplantation for seven cases of acute myeloid leukemia with BCR::ABL1 fusion

Objective: To explore the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloid leukemia (AML) patients with BCR::ABL1 fusion. Methods: The clinical data of seven AML patients with BCR::ABL1 fusion from November 2012 to January 2022 were retrospectively analyzed, and their survival status was followed up. Results: The median age of patients at the time of diagnosis was 35 years. Four cases (57.1%) were diagnosed with high leukocyte counts. All cases were assayed as BCR::ABL1 positive and accompanied by four types of gene mutations (NPM1, RUNX1, ASXL1, PHF6) . Seven patients received tyrosine kinase inhibitor (TKI) combined with induction chemotherapy and bridged to allo-HSCT, and six patients received maintenance therapy with TKI. Before allo-HSCT, six patients achieved complete remission, and four patients achieved complete molecular remission (CMR) . After allo-HSCT, the three remaining cases also achieved CMR. All patients were in remission post-allo-HSCT. One case died of infection, and the remaining cases survived without relapse. The 3-year cumulative overall survival rate was (80.0±17.9) %. Conclusions: TKI combined with traditional chemotherapy could achieve a high response rate in AML patients with BCR::ABL1 fusion. In addition, allo-HSCT could enhance the molecular response rate. Maintenance therapy post-HSCT with TKI could improve prognosis.

Clinical observation on 16 cases of DEK-NUP214 fusion gene positive acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation

Clinical observation on 16 cases of DEK-NUP214 fusion gene positive acute myeloid leukemia treated with allogeneic hematopoietic stem cell transplantation

Distinct roles of hematopoietic cytokines in the regulation of leukemia stem cells in murine MLL-AF9 leukemia

Lymphoid-primed multipotent progenitor (LMPP)-like and granulocyte-monocyte progenitor (GMP)-like leukemia stem cells (LSCs) co-exist in the blood of most patients with acute myeloid leukemia (AML). Complete elimination of both types of LSCs is required to cure AML. Using an MLL-AF9-induced murine AML model, we studied the role of hematopoietic cytokines in the survival of LMPP- and GMP-like LSCs. We found that SCF or FLT3L promotes the survival of LMPP-like LSCs by stimulating Stat5-mediated Mcl1 expression, whereas interleukin-3 (IL-3) or IL-6 induces the survival of GMP-like LSCs by stimulating Stat3/nuclear factor κB (NF-κB)-mediated Bcl2 expression. Functional study demonstrated that, compared to AML cells cultured in IL-3 and IL-6 medium, AML cells in SCF- or Flt3L-only culture are highly clonogenic in invitro culture and are highly leukemogenic invivo. Our study suggests that co-inhibition of both STAT5-MCL1 and STAT3/NF-κB-BCL2 signaling might represent an improved treatment strategy against AML, specifically AML cases with a monocytic phenotype and/or FLT3 mutations.

Analysis of acute leukemia complications in children at the disease onset and during induction

Background. Despite the progress achieved in the treatment of acute leukemia (AL) in children, complications, both at the disease onset and those resulting from antitumor therapy, remain the main cause of early mortality, which varies from 3 to 20 %.Aim. To assess the frequency, severity, etiology, risk factors, and outcomes of AL complications in children at the disease onset and during induction chemotherapy (ICT).Results. The study analyzed 92 cases of AL in children aged from 5 months to 17 years. 75 patients had acute lymphoblastic leukemia (ALL), 17 had acute myeloid leukemia (AML). In 1 (1.3 %) patient with ALL and in 5 (29.4 %) with AML, a concomitant diagnosis was Down syndrome. At the AL onset, 34 (36.9 %) patients were diagnosed with infection, of which 27 (36 %) and 7 (41.2 %) patients had ALL and AML, respectively. In both cohorts, febrile neutropenia (55.5 %; n = 15 vs. 14.3 %; n = 1), pneumonia (25.9 %; n = 7 vs. 71.4 %; n = 5), enterocolitis (7.4 %; n = 2 vs. 14.3 %; n = 1) predominated in both cohorts for AML and ALL, respectively. Due to uncontrolled infection in 5 (29.4 %) patients with AML and 13 (17.3 %) with ALL, ICT was delayed until the condition stabilized and the infection was controlled. During ICT, the incidence of infectious complications was 81.3 % (n = 61) and 100 % (n = 17) in patients with ALL and AML, respectively. The most common types were enterocolitis (41.2 %; n = 7 vs. 34.4 %; n = 21), febrile neutropenia (29.4 %; n = 5 vs. 37.7 %; n = 23), pneumonia (47.1 %; n = 8 vs. 29.5 %; n = 18), catheter-associated bloodstream infection (11.8 %; n = 2 vs. 8.2 %; n = 4) in AML and ALL, respectively. By etiology, bacterial infections predominated, accounting for 32 % (n = 8) and 36.8 % (n = 35) in the AML and ALL groups, respectively. More cases of invasive mycoses were reported in AML patients – 23.5 % (n = 4) versus 14.8 % (n = 11). Non-infectious complications were diagnosed in 32.6 % (n = 30) of patients with a predominance in ALL group (34.6 %; n = 26 vs. 23.5 %; n = 4). Hyperleukocytosis at the leukemia onset caused such complications as leukostasis (11.8 %; n = 2) and acute tumor lysis syndrome (11.8 %; n = 2). The most common post-cytostatic complications in ALL were vincristine polyneuropathy (61.5 %; n = 16), hemorrhagic syndrome (15.4 %; n = 4), methotrexate-induced encephalopathy (15.4 %; n = 4), acute tumor lysis syndrome (11.5 %; n = 3). In AML cases, the most common type of non-infectious complications were hemorrhagic (75 %; n = 3). Induction mortality in the ALL group was 2.6 % (n = 2), in the AML group it was higher – 11.8 % (n = 2), however, it should be noted that all deaths were registered in children with Down syndrome. The main cause of mortality in both groups was severe infections secondary to chemotherapy-induced hematopoietic aplasia. There were no deaths associated with non-infectious complications or chemotherapy-induced toxicity.Conclusion. The main type of toxicity in children at the AL onset and during ICT remains infectious complications of various etiologies, while in AML patients a higher frequency of invasive mycoses is registered (23.5 % vs. 14.8 %). Despite the high incidence of chemo-induced toxicity, the mortality rate in ALL remains low, amounting to 2.6 % in our cohort. In the AML group, mortality was higher – 11.8 %, but it should be noted that all cases occurred in patients with Down syndrome. There were no deaths due to non-infectious complications in any of the study cohorts.

A profile of hematological malignancies diagnosed in a tertiary care center of Assam: Highlighting the experience from a resource constraint perspective

Background: Hematological disorders require a systematic approach, from clinical examination to a complete blood count, followed by a bone marrow study for diagnosis. To effectively plan, treat, and prognosticate, immunophenotyping and molecular studies are essential to incorporate. Aims and Objectives: The aim of our study is to understand the pattern of neoplastic hematological conditions encountered in Assam and share our experience during the diagnosis. Materials and Methods: This was a single-centered, observational study carried out for 18 months (January 2022–June 2023). A thorough hematological workout was done, including cytochemical staining and conventional polymerase chain reaction for the BCR-ABL transcript, after satisfying inclusion and exclusion criteria. The data were analyzed and correlated before arriving at the final diagnosis. Results: The total of 38 neoplastic cases confirmed by bone marrow study. Out of 38 cases, 14 were chronic myeloid leukemia, 10 were chronic, 4 were in the blastic phase, and BCR-ABL was positive in 13 cases. Two cases were pediatric, of which 1 was in the blastic phase. All 8 cases of plasma cell dyscrasia presented with anemia, bone lesions, and hypercalcemia. The acute leukemia category consisted of 4 acute myeloid leukemia cases, of which 1 was acute promyelocytic leukemia. A total of 10 acute lymphoblastic leukemia (ALL) cases, where 1 case was T-ALL and the rest was B-ALL. Two cases showed a subleukemic presentation in peripheral blood. Conclusion: The experience of pathologists and their meticulous approach can greatly aid in accurate diagnosis, but the immunophenotyping facility and molecular hematology setup can provide most of the relevant information for the best decision-making.

A nomogram based on clinical features and molecular abnormalities for predicting the prognosis of patients with acute myeloid leukemia.

The high clinical and molecular heterogeneity of acute myeloid leukemia (AML) has led to an unsatisfactory clinical prognosis, thus we sought to incorporate both clinical features and molecular abnormalities to construct a new prognostic model. A database search of the Gene Expression Omnibus (GEO) revealed 238 cases of adult AML. The independent risk factors were assessed using both univariate and multivariate Cox regression, as well as least absolute shrinkage and selection operator (LASSO) regression. The predictive accuracy, discriminatory power and clinical applicability of the nomogram were determined by the consistency index (C-index), calibration curves and decision curve analysis (DCA). In addition, a single-centre cohort of 135 cases was used for external validation. Multivariate Cox regression analysis showed that the independent influences on overall survival (OS) were age, type of disease, DNMT3A, IDH2 and TP53 mutations. The area under the curve (AUC) values for the training set were 0.755, 0.745 and 0.757 at 1, 2 and 3 years respectively; the AUC for the validation set were 0.648, 0.648 and 0.654 at 1, 2 and 3 years; and the AUC for the northwest China set were 0.692, 0.724 and 0.689 at 1, 2 and 3 years. The calibration and DCA indicated good consistency and clinical utility of the nomogram. Finally, younger (age <60 years) and elderly (age ≥60 years) patients were each divided into two risk groups with significantly different survival rates. A nomogram consisting of five risk factors was developed for forecasting the prognosis of AML with guaranteed reliability.