Priapismo y leucemia mieloide crónica en adolescente. Debut poco frecuente. Reporte de caso / Priapism and chronic myeloid leukemia in an adolescent. Rare debut presentation. A case report

El priapismo es una erección dolorosa y persistente acompañada o no de estímulo sexual. Una causa poco frecuente de esta anormalidad es la leucemia mieloide crónica. Se han reportado pocos casos de priapismo como manifestación inicial de una leucemia de este tipo en pacientes adolescentes. A continuación, se informa el caso de un paciente de 16 años de edad que presentó priapismo como manifestación inicial de una leucemia mieloide crónica. Durante su evolución, no se realizó aspiración de los cuerpos cavernosos. Se inició tratamiento hematológico específico y, ante la persistencia del priapismo, fue necesario realizar un shunt de cuerpos cavernosos en dos ocasiones, tratamiento a pesar del cual existen altas probabilidades de secuelas.

Priapism is a painful and persistent erection, with or without sexual stimulation. A rare cause of such abnormality is chronic myeloid leukemia. Few cases of priapism as an initial manifestation of this type of leukemia have been reported in adolescent patients. Here we describe the case of a 16-year-old patient who presented with priapism as the initial manifestation of chronic myeloid leukemia. No cavernosal aspiration was performed. A specific hematological treatment was started and, given the persistence of priapism, the patient required 2 corpora cavernosa shunt procedures; despite this treatment, there is a high probability of sequelae.

Discovery of A New Prognostic Molecular Marker NKX2-3 for Acute Myeloid Leukemia / 中山大学学报(医学科学版)

ObjectiveTo analyze the expression of molecular marker affecting the prognosis of acute myeloid leukemia （AML） patients from bioinformatics database， thus providing an experimental basis for further exploration of a novel molecular marker for the prognosis of AML. MethodsThe prognostic data of 179 AML patients from The Cancer Genome Atlas （TCGA） database were examined for differential gene analysis and survival analysis. The bone marrow samples of 74 healthy individuals （HI） and 542 de novo AML patients in the dataset GSE13159 downloaded from the Gene Expression Omnibus （GEO） database were analyzed to detect the difference in the expression levels of differential target genes. Peripheral blood and bone marrow samples were collected from 18 de novo AML patients and 20 age- and gender-matched healthy controls， and real-time fluorescent quantitative PCR was used to validate the expression levels of the differential genes in the AML patients. ResultsBioinformatics data analysis showed that the optimal cut-off value of Homo sapiens NK2 homeobox 3 （NKX2-3） calculated by R language was 0.051. Survival analysis revealed a statistically poorer overall survival in de novo AML patients with high NKX2-3 expression than in those with low NKX2-3 expression （P = 0.0036）. NKX2-3 was highly expressed in patients with de novo AML than in HI and the difference was statistically significant （P < 0.001）. Real-time fluorescence quantitative PCR verified the expression levels of the NKX2-3 gene in AML patients and confirmed that compared with those in HI， in the de novo AML patients， NKX2-3-1 and NKX2-3-2 were highly expressed and were significantly correlated （P = 0.000， P = 0.000）. ConclusionNKX2-3 is highly expressed in de novo AML patients， and the AML patients with high NKX2-3 expression have poor overal survival. NKX2-3 may be closely related to the clinical outcome and prognosis of AML.

Research progress of FLT3 inhibitors and drug resistance mechanisms in acute myeloid leukemia / 中国临床药理学与治疗学

The FMS-like tyrosine kinase 3 (FLT3) gene mutation is the most common genetic mutation in acute myeloid leukemia (AML) and is associated with poor prognosis. Various targeted inhibitors have been developed for FLT3 mutations and have shown promising clinical efficacy. However, the emergence of resistance poses new challenges for targeted therapy in AML. This article provides an overview of the pathological and prognostic role of FLT3 mutations in AML, the current research progress on commonly used FLT3 inhibitors (type I and type II), the mechanisms of FLT3 inhibitor resistance, and strategies for overcoming resistance.

Effect of miR-141-5p/ZNF705A on adhesion of bone marrow mesenchymal stem cells in chronic myeloid leukemia cell-derived exosomes / 中国药理学通报

Aim To investigate the effect of miR-141-5p/ZNF705A in chronic myeloid leukemia(CML)cell-derived exosome(Exo)on the adhesion of bone marrow mesenchymal stem cells(BMSCs). Methods The morphology and size of Exo in peripheral blood from CML patients and K562 cells were examined by electron microscopy and NTA particle size analysis. The expressions of Exo and BMSCs marker molecules and adhesion proteins in K562 cells were detected by qRT-PCR and Western blot before and after transfection. The adhesion ability of BMSCs was detected by cell adhesion assay, and the cellular activity of BMSCs was examined using CCK-8. miR-141-5p binding to ZNF705A was detected by luciferase assay. Results qRT-PCR results showed that miR-141-5p expression was significantly reduced in both CML patients and K562 cell-derived Exo. qRT-PCR, Western blot and other results showed that BMSCs in CML patients had significantly reduced the expression of adhesion proteins CD44 and CXCL12, and were able to phagocytose K562 cell-derived Exo. Further, K562-derived Exo was found to reduce CD44 and CXCL12 expression and adhesion in Exo-promoted BMSCs compared with CD34+ cells. Meanwhile, the results of dual luciferase reporter assay verified that miR-141-5p targeted binding to ZNF705A. Finally, we found ZNF705A could be targeted by up-regulating miR-141-5p expression in Exo of K562 cells, which in turn inhibited the adhesion of BMSCs. Conclusions K562 cells down-regulate miR-141-5p expression in Exo and inhibit the adhesion function of BMSCs by targeting ZNF705A, thus regulating the bone marrow hematopoietic function in CML patients.

Analysis of effective components of Agaricus blazei Murill extract by LC-MS and network pharmacology analysis in treatment of chronic myeloid leukemia / 中国药理学通报

Aim To explore the potential targets and related signaling pathways of Agaricus blazei Murill (AbM ) extract in the treatment of chronic myeloid leukemia (CML) based on liquid chromatography mass spectrometry ( LC-MS ), network pharmacology, molecular docking, and were further verified by experiments in vitro. Methods The active components of AbM extract were retrieved from LC-MS, Swiss Target Prediction database was used to predict related targets, and CML disease target genes were obtained from Gen- eCards and DisGeNET databases. After screening the common targets of drug and CML, the protein-protein interaction network of the common targets was performed by STRING, and GO and KEGG enrichment a- nalysis were done by DAVID database. Cytoscape software was used to construct the network of target protein. Molecular docking was carried out by DockThor, and the Pymol software was used to make a visual picture. The inhibitory effect of AbM extract on leukemia cells K562 was determined by CCK-8 experiment, and the effect of AbM extract on the expression and phosphorylation level of related proteins was verified by Western blot. Results The prediction results showed that 126 active components of AbM extract, and 172 common targets were collected. KEGG pathway analysis results showed that PI3K/Akt/mTOR signaling pathway might play an important role in the treatment of CML disease. The IC

Effects of polydatin on the cell proliferation，migration，invasion and tumor growth of AML / 中国药房

OBJECTIVE To investigate the effects of polydatin （PD） on cell proliferation， migration， invasion and tumor growth of acute myeloid leukemia （AML）. METHODS Human AML cell KG-1 were divided into normal group， PD low-， medium- and high-concentration groups （10， 30， 60 μmol/L PD）， SQ22536 group [cyclic adenosine monophosphate （cAMP） inhibitor， 100 μmol/L]， high concentration of PD+SQ22536 group （60 μmol/L PD+100 μmol/L SQ22536）. The effects of PD on cell activity， apoptotic rate， invasion and migration ability， cAMP level， the expression of epithelial-mesenchymal transition （EMT） related proteins and protein kinase A （PKA） were investigated. Using BALB/c nude mice as subjects， a transplanted tumor model of AML nude mice was induced by subcutaneous inoculation of KG-1 cell suspension and then divided into control group， PD group， SQ22536 group and PD+SQ22536 group （with 6 mice in each group）. The effects of PD on tumor volume and mass were measured. RESULTS Compared with the normal group or control group， the cell viabilities， the number of migrating cells， the number of invasive cells， the relative expressions of vimentin and Snail as well as the tumor volume and mass were decreased significantly in PD groups， while the apoptotic rates， cAMP levels， the relative expressions of E-cadherin and PKA were significantly increased， with a dose-dependent manner （P＜0.05）. SQ22536 had opposite effects on cells and nude mice compared to PD， and could significantly reverse the anti-tumor activity of PD （P＜0.05）. CONCLUSIONS PD may inhibit the proliferation， migration， invasion and EMT process of KG-1 cells， induce apoptosis， and inhibit tumor growth， by activating the cAMP/PKA signaling pathway， thereby exerting anti-AML effects.

Pediatric and adolescent chronic myeloid leukemia: A follow-up study in Western India

Background: Chronic myeloid leukemia (CML) is relatively rare in pediatric and adolescent age groups. The purpose of this study was to evaluate the clinical, hematopathological, and biochemical parameters of CML in pediatric and adolescent age groups, along with an assessment of the treatment response with first-line tyrosine kinase inhibitors (TKI) and its correlation with the prognostic scoring systems of adults. Materials and Methods: A retrospective study of 44 Breakpoint Cluster Region-Abelson leukemia virus (BCR-ABL1)-positive pediatric and adolescent CML cases registered at our hospital was done. The clinical and laboratory parameters were evaluated using hospital software. The treatment response was monitored and scoring was performed using mathematical calculations. Results: The mean age was 11.6 (±4.7) years. The median hemoglobin was 8.4 g/dL and 63.6% of the cases showed white blood cell (WBC) counts >250,000/?L. The average follow-up was 21 months. A total of 97.7 and 78.1% cases achieved complete hematological response (CHR) and molecular response, respectively, during the treatment course. The maximum number of patients had low Sokal and European treatment and Outcomes Study (EUTOS) scores. Seventy-five per cent of the cases achieved CHR at 3 months, while 73.6 and 78.6% CML-Chronic phase (CP) cases with low Sokal and EUTOS scores achieved CHR at 3 months, respectively. Conclusion: This study revealed that the CML cases in pediatric and adolescent age groups are normally present with higher WBC counts at the time of diagnosis. The association of the prognostic scoring system with treatment response was statistically insignificant. However, a larger cohort study is needed to determine the treatment response of TKI in children and adolescent CML and its correlation with the prognostic scoring systems.

Prognostic factors and impact of CMV reactivation on acute myeloid leukemia patients after HLA-matched myeloablative allogeneic stem cell transplantation in a high CMV prevalence country

ABSTRACT Introduction: Relapse of acute myeloid leukemia (AML) after allogeneic stem cell transplantation (allo-SCT) leads to dismal outcomes. This study aimed to identify high-risk patients and explore the effects of cytomegalovirus (CMV) reactivation in a high CMV-seropositive population. Methods: The study involved a single-center retrospective cohort in Thailand, analyzing clinical risk factors and CMV-mediated immune responses, correlated with transplant outcomes in AML patients. Results: Eighty-five patients with AML in complete remission (CR) undergoing HLA-matched myeloablative allo-SCT between 2011 and February 2021 were enrolled. The relapse rate was 27.1% with the median time of 7 months after transplantation. The 3-year relapse-free-survival (RFS) and overall-survival (OS) were 72.2% and 80.8%, respectively. The disease status (>CR1) and absence of chronic graft-versus-host disease (cGVHD) were independently significant adverse prognostic factors of RFS and OS. Ninety-two percent of recipient-donor pairs were both CMV seropositive. The CMV reactivation occurred in 54.1% of the patients. The clinically significant CMV infection rate was 49.4%. No CMV syndrome/disease or CMV-related mortality occurred. One-year cumulative incidence of relapse among CMV-reactivation and non-reactivation groups were 14.3% and 25.6%, respectively, without a statistically significant difference. Transplantation-related mortality was 11.1%. Conclusions: The transplantation beyond CR1 and absence of cGVHD are powerful prognostic factors associated with inferior RFS and OS. In a high CMV prevalence country, there appears to be no impact of CMV reactivation on relapse in AML patients undergoing an allo-SCT.

Economic burden of acute myeloid leukemia on patients in a resource-limited tertiary hospital in the Philippines

ABSTRACT Introduction: The remission induction treatment for acute myeloid leukemia (AML) has remained unchanged in the resource-limited setting in the Philippines. AML treatment consists of induction chemotherapy followed by high dose consolidation chemotherapy or allogeneic hematopoietic stem cell transplantation. In the Philippines, the Filipino household bears the burden of health care cost of hospitalization expenditure. Insights into the treatment costs becomes an essential requirement as these guides the allocation of resources to scheme health programs. Method: This study involved a retrospective cohort analysis of AML patients who underwent treatment for AML. Review of the statements of account per admission per patient during treatment for remission induction, consolidation, relapsed and refractory disease and best supportive care from 2017 to 2019. Of the 251 eligible patients, 190 patients were included. Result: The mean healthcare expenditure for remission induction chemotherapy (Phase 1) was US $2, 504.78 (Php 125,239.29). While 3 to 4 cycles of consolidation chemotherapy cost an average of US $3,222.72 (Php 162,103.20). For patients who had relapsed and refractory disease, an additional mean cost of US $3,163.32 (Php 159,115.28) and US $2, 914.72 (Php 146,610.55) were incurred, respectively. The average cost of palliative care was US $1,687.00 (Php 84,856.59). Conclusion: The cost of chemotherapy and other therapeutics bear most of the weight of the direct healthcare cost. The cost of AML treatment represents a significant economic burden for patients and the institution. The cost increases as patients proceed through subsequent lines of treatment for induction failure. Existing subsidy for health insurance benefits could still be improved for appropriate source allocation of resources.

Outcomes and survival predictors of Latin American older adults with acute myeloid leukemia: Data from a single center

ABSTRACT Introduction: Acute myeloid leukemia (AML) is most commonly presented in older adults; however, it appears 10 years earlier in Latin American countries. Clinical evolution in older adults from this populations has not been characterized. We analyzed outcomes and survival predictors. Methods: Patients ≥ 55 years old diagnosed with AML at a hematology referral center from 2005 to 2020 receiving intensive chemotherapy (IC), low-dose cytarabine (LDAC) and best supportive care (BSC) were included. Survival analysis included the Kaplan-Meier and Cox models and the cumulative incidence of relapse (CIR). Results: Seventy-five adults were included and the overall survival (OS) was 4.87, 1.67 and 1.16 months, using IC, LDAC and BSC, respectively. The IC led to a higher OS (p < 0.001) and was a protective factor for early death, at a cost of more days spent hospitalized and more non-fatal treatment complications; non-significant differences were found between the LDAC and BSC. Eight (10.7%) patients underwent hematopoietic cell transplantation, with a higher OS (p = 0.013). Twenty (26.7%) patients achieved complete remission; 12 (60%) relapsed with a 6-month CIR of 57.9% in those < 70 years old vs. 86.5% in those ≥ 70 years old, p = 0.034. Multivariate analysis showed the white blood cell count (WBC) and IC had a significant impact on the patient survival, whereas chronological age and the Charlson comorbidity index (CCI) did not. Conclusion: AML in low-middle income countries demands a different approach; the IC improves survival, even with a high incidence of relapse, and should be offered as first-line treatment. Eligibility criteria should include WBC and a multidimensional evaluation. The age per se and the CCI should not be exclusion criteria to consider IC.

Enfermedad mínima residual en leucemia mieloide aguda no promielocítica: Resultados preliminares de un estudio colaborativo internacional / Minimal residual disease in non-myelocytic acute myeloid leukemia: preliminary results of an international collaborative study

A pesar de los avances en los protocolos de tratamiento y en las medidas de soporte en pacientes con Leucemia Mieloide Aguda (LMA), 27% presentan recaídas de la enfermedad. Esto se debe, entre otras causas, a la persistencia de pequeñas cantidades de células malignas (blastos) resistentes a la terapia. Estas pequeñas cantidades de blastos remanentes se denominan Enfermedad Mínima Residual (EMR). La determinación de EMR requiere de técnicas no solo muy sensibles, sino también específicas, y permite evaluar la respuesta individual a la terapia. La introducción de la EMR como parámetro de respuesta y estratificación está bien definida en Leucemia Linfoblástica Aguda (LLA). Por el contrario, aunque existen publicaciones sobre el impacto pronóstico de la EMR en LMA, aún no se encuentra incluida en forma sistemática en los protocolos nacionales actuales, entre otros motivos, por lo laborioso de la determinación y por la necesidad de validación de la misma. Debe tenerse en cuenta que el inmunofenotipo de los blastos mieloides suele ser más heterogéneo que el de los blastos en LLA, presentando, en muchos casos, subpoblaciones diferentes entre sí, lo cual dificulta su detección certera y no hay consenso definido en cuanto a la metodología más eficaz. En este trabajo describimos una nueva estrategia de marcación y análisis estandarizada en un estudio multicéntrico internacional para LMA y la utilidad de la EMR como parámetro de respuesta y de estratificación. Asimismo, detallamos los resultados preliminares de nuestra cohorte de pacientes (AU)

Despite the improvement in treatment and supportive care of patients with Acute Myeloid Leukemia (AML), 27% of them relapse. This is due to the persistence of small amounts of malignant cells (blasts) resistant to therapy, among other causes. These small amounts of blasts are called Minimal Residual Disease (MRD). The determination of MRD requires not only techniques with high sensitivity but also with high specificity, and allows to evaluate the individual response to treatment. The introduction of MRD as a response parameter is well established in Acute Lymphoblastic Leukemia (ALL), and it is used in current stratification protocols. On the other hand, even though there are some reports regarding the prognostic impact of MRD in AML, it is still not included in the current national protocols due to the lack of validation of the determination, among other causes. This is due to the fact that the immunophenotype of myeloid blasts is more heterogeneous than in ALL, presenting different subpopulations, which difficults their accurate detection. Thus, there is still no consensus regarding the most effective approach. In this article, we describe a new staining and analysis strategy standardized by an international multicentric study, and the utility of EMR as a response and stratification parameter. Additionally, we show the preliminary results of our patient cohort. (AU)

Treatment of grade four hemorrhoids in a patient with acute myeloid leukemia with severe thrombocytopenia by laser hemorrhoidopexy: A case report

Here, we present the case of a 66-year-old female patient with acute myeloid leukemia and severe thrombocytopenia who came with the complaints of painful per anal mass and bleeding per rectum for 1 year. The patient is a known case of hypertension, and diabetes mellitus and has received three cycles of chemotherapy with decitabine. On examination, she was found to have fourth-degree hemorrhoids at 3, 7, and 11 oclock positions with acute edematous changes. We successfully treated this patient with laser hemorrhoidopexy, whereby laser energy was delivered to each hemorrhoidal cushion. While lasers for the successful treatment of grade 2 and 3 hemorrhoids are well documented in the literature, we successfully treated this patient with prolapsing fourth-degree hemorrhoids with just laser energy delivery. With these results, we would also like to consider laser hemorrhoidopexy as an effective treatment option for four-degree hemorrhoids for which open Milligan–Morgan hemorrhoidectomy and stapler hemorrhoidectomy are currently considered treatment options

Hematoma espontáneo de la vaina de los rectos en paciente con COVID-19 y leucemia mieloide crónica. Reporte de un caso clínico y revisión de la literatura

Introducción: El hematoma de la vaina de los rectos es poco frecuente. En este reporte se presenta un caso clínico de este cuadro en un paciente con neumonía por COVID-19 y leucemia mieloide crónica, junto con una revisión de literatura. Caso Clínico: Paciente masculino de 55 años, hospitalizado por neumonía por COVID-19 y leucemia mieloide crónica, presenta taquicardia, hipotensión y aumento de volumen abdominal asimétrico. En la tomografía computarizada se evidencia un hematoma de la vaina de los rectos. Se realiza drenaje quirúrgico y control del sangrado. No presentó complicaciones postoperatorias ni necesidad de reoperación. Discusión: Las complicaciones hemorrágicas en pacientes con COVID-19 están poco descritas. El sangrado es una posible complicación en pacientes con leucemia mieloide crónica. Es relevante tener en cuenta el hematoma de la vaina de los rectos en pacientes con COVID-19 y/o leucemia mieloide crónica que presenten aumento de volumen abdominal, para un manejo precoz por un equipo multidisciplinario. Conclusión: La vigilancia activa y el alto índice de sospecha son clave para identificar posibles complicaciones hemorrágicas en pacientes con COVID-19 y/o leucemia mieloide crónica.

Introduction: Rectus sheath hematoma is a rare entity. This report presents a clinical case of a rectus sheath hematoma in a patient with COVID-19 pneumonia and chronic myeloid leukemia, along with a review of the literature. Case Report: A 55-year-old male patient, hospitalized for COVID-19 pneumonia and chronic myeloid leukemia, presents with tachycardia and hypotension. Computed tomography shows a rectus sheath hematoma. Surgical management was performed to control bleeding and drainage of the hematoma. There were no postoperative complications or need for reoperation. Discussion: Hemorrhagic complications in patients with COVID-19 are seldomly reported. Bleeding is a possible complication in patients with chronic myeloid leukemia. It is important to take into account rectus sheath hematoma in patients with COVID-19 and/or chronic myeloid leukemia who present with abdominal pain, for early management by a multidisciplinary team. Conclusion: Active surveillance and a high index of suspicion are key to identifying potential bleeding complications in patients with COVID-19 and/or chronic myeloid leukemia.

Prognostic value of serum progranulin in de novo adult acute myeloid leukemia patients

Abstract Background Elevated serum progranulin (PGRN) levels have been associated with a wide range of different human malignancies. However, data available on the role of PGRN in hematological malignancies are limited. Methods Measurement of the PGRN level in serum of adult de novo acute myeloid leukemia (AML) patients using enzyme-linked immunosorbent assay (ELISA) was performed. Results The mean serum PGRN level in AML patients was higher than that in controls (346.08 pg/ml ± 64.46 vs 155 pg/ml ± 63 respectively; p= 0.001). After a mean duration of follow-up equaling 140 days, patients with high serum PGRN (i.e., higher than 370.5 pg/ml) had inferior overall survival (OS) in comparison to patients with low serum PGRN (i.e., lower than 370.5 pg/ml) (OS = 25% vs 60.7%, mean survival = 107 days vs 256.5 days, p= 0.007). On the other hand, remitted patients on day 28 with high serum PGRN (i.e., higher than 307.5 pg/ml) did not differ from those with low serum PGRN (i.e., lower than 307.5 pg/ml) regarding disease-free survival (DFS) (DFS = 78.6% vs. 87.5%, mean survival = 301.3 days vs. 283.5 days, p= 0.789). Moreover, the serum PGRN level was associated with inferior OS (p= 0.024) on multivariate analysis. Conclusion Adult de novo AML patients have elevated serum PGRN levels and a high PGRN level is associated with an inferior OS.

Incidence and clinical significance of FLT3 and nucleophosmin mutation in childhood acute myeloid leukemia in Chile

Abstract Introduction Acute myeloid leukemia (AML) is a heterogeneous disease and approximately one-third of its carriers do not have evident genetic abnormalities. The mutation of specific molecular markers, such as fms-like tyrosine kinase 3 (FTL3) internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD) and nucleophosmin (NPM1), are associated with an adverse and favorable prognosis, respectively. Objective The objective was to determine the prevalence of FLT3/ITD and NPM1 in Chilean patients and their association with clinical data and prognosis. Method and Results Two hundred and thirty-two children were studied between 2011 and 2017, the median being 8.6 years (ranging from 1 to 18 months). Acute promyelocytic leukemia (APL) was diagnosed in 29%. The FLT3/ITD-mutated in non-promyelocytic AML was at 10% (14/133) and the FLT3/TKD, at 3.7% (2/54). In APL, it was at 25.4% (16/63). In non-promyelocytic AML, the FLT3/ITD-mutated was associated with a high leucocyte count, the median being 28.5 x mm3 (n= 14) versus 19.4 x mm3 (n= 119), (p= 0.25), in non-mutated cases. In APL, the median was 33.6 x mm3 (n= 15) versus 2.8 x mm3 (n= 47), (p < 0.001). The five-year overall survival (OS) in non-promyelocytic AML with non-mutated and mutated FLT3/ITD were 62.7% and 21.4%, respectively, (p < 0.001); the 5-year event-free survival (EFS) were 79.5% and 50%, respectively, (p < 0.01). The five-year OS in APL with non-mutated and mutated FLT3/ITD was 84.7% and 62.5%, respectively, (p= 0.05); the 5-year EFS was 84.7% and 68.8%, respectively, (p= 0.122). The NPM1 mutation was observed in 3.2% (5/155), all non-promyelocytic AML with the normal karyotype. Conclusion The FLT3/ITD mutation was observed more frequently in APL and associated with a higher white cell count at diagnosis. However, the most important finding was that the FLT3/ITD mutation was associated with a shorter survival in non-promyelocytic AML.

Response to Tyrosine Kinase Inhibitors in Patients with BCR-ABL1 Positive Chronic Myeloid Leukemia; 13.5 Years’ Experience at Patan Hospital, Nepal

Background:Since the advent of Tyrosine Kinase Inhibitor (TKI), well controlled studies in developed world have shown that the life expectancy of patients with CML is comparable to normal people without the disease. But long-term follow up studies are lacking in resource poor setting. Methods:This is a retrospective follow up study looking at the molecular response and resistance to Tyrosine Kinase Inhibitors (TKI) in patients enrolled in the Max Access Program since February 2003 till March 2017. Patients with twoor more BCR-ABL1 levels by Karyotyping/ fluorescent in situ hybridization (FISH) / reverse transcriptase polymerase chain reaction (RT-PCR) were included. At baseline, complete blood count (CBC), renal function test (RFT), and liver function test (LFT) were evaluated. Bone marrow aspiration and biopsy for morphology, cytogenetic analysis by Karyotyping/FISH and/or molecular analysis by RT-PCR were also done if these tests were not performed earlier. FISH or RT-PCR was done on peripheral blood every 3–12 months as necessary if the patient could afford. Patients with warning response/failure underwent BCR-ABL1 Resistance Mutation Analysis (IRMA).Results:Three hundred and forty six (346) patients had two or more BCR-ABL1 monitoring tests done. Optimal response was seen in 49.42%. Similarly, suboptimal response and failure were seen in 16.5% and 34% respectively. Overall Survival is 89.6% (at 1.8 -165 months, mean 62 months) . If only CML related events is considered survival is 95.9%. Seventy seven (77) patients with a total of 80 BCR-ABL1 domain Imatinib Resistance Mutation Analyses (IRMA) showed 19 different types of mutations with the most common being T315I mutation (8 and 19.5%). About 22.25% of the total patients showed resistance to Glivec out of which 10.98% showed mutations. Nine patients underwent trial for treatment free response (TFR) and 5 of them relapsed between 2-8 months.Conclusions:Despite all the odds of having financial problem, accessibility problem due to distances, transportation, etc. and difficulty monitoring with routine BCR-ABL1 and IRMA, our findings show that the outcome of TKI therapy in our CML patients is comparable to well controlled studies done elsewhere. Overall survival, molecular and cytogenetic responses and mutations in our patients who developed resistance as well as TFR are also similar to other studies. The resistance rate of 22.25% is slightly higher compared to other studies in developed world. This is mainly because of poor monitoring due to unavailability of the test including IRMA in our country and affordability until 2012. It proves that TKI is very effective in CML even in a resource-poor, developing country

EVALUATION OF PANCYTOPENIA WITH BONE MARROW INTERPRETATION

Background: Pancytopenia is one of the most common clinico-haematological entity observed in our day to day clinical practice. It is a disorder in which all the three major elements of blood (i.e. red blood cells, white blood cells and platelets) are decreased in number. The causes of pancytopenia may be due to decrease in hematopoietic cell production in the marrow resulting from infections, toxins, malignant cell in?ltration, post- chemotherapy or post-radiation. Aims and Objectives: 1) To study the etiology and clinical presentation of pancytopenia in all age groups. 2) To correlate with bone marrow interpretation Materials & Methods: This is a prospective study which was conducted among 50 patients of pancytopenia in the Clinical Pathology, Government General Hospital,Kurnool from January 2021 to October 2022 Bone marrow aspiration was done by using Salah's bone marrow puncture needle. Smears were made from bone marrow aspirate (BMA) and stained by Leishman stain and special stains like Perl`s wherever necessary. The smears were assessed for cellularity, differentiation and maturation of erythroid, myeloid and megakaryocytic lineage, M:E ratio, Plasma cells, Lymphocytes and parasites/ abnormal cells. In the present study the commonest cause of Pancytopenia was Megaloblastic anemia (70%) followed by Results: Dimorphic anemia (20%). The less common conditions were Multiple Myeloma (6%),Chronic Myeloid Leukemia(2%),Acute Leukemia(2%). The present study concludes that complete primary hematological Interpretation and Conclusion: investigations along with bone marrow aspiration in pancytopenic patients are helpful for understanding disease process and to diagnose or to the rule out causes of pancytopenia. These are also helpful in planning for further investigations and management

Study on DRG grouping of acute myeloid leukemia based on decision tree model / 中华医院管理杂志

Objective:To explore the influencing factors of hospitalization cost of acute myeloid leukemia, to group the cases based on decision tree model and to provide reference for improving the DRG management in this regard.Methods:Homepage data were retrieved from the medical records with acute myeloid leukemia as the main diagnosis (the top four ICD codes were C92.0, C92.4, C92.5, and C93.0). These patients were discharged from the clinical hematology department of the Fujian Institute of Hematology from January 2020 to December 2021. Then the influencing factors of hospitalization expenses were identified using Wilcoxon rank sum test or Kruskal-Wallis rank sum test and multiple linear stepwise regression analysis, with such factors used as classification nodes. The decision tree model of χ2 automatic interactive testing method was used to group the cases so included. At the same time, the included cases were grouped according to the trial run C-DRG version in Fujian province, for comparison of the differences between the two grouping methods. Results:The length of stay, the type of treatment, whether associated complications and age of patients were found as the influencing factors for the hospitalization costs of patients with acute myeloid leukemia, and such factors were included in the decision tree model to form 9 case mixes. The variance reduction of this model was 75.77%, featuring a high inter-group heterogeneity, and the coefficient of variation was 0.33-0.61, featuring a low in-group difference. The patients were divided into two groups according to the C-DRG version in Fujian province. The variance reduction of this method was 27.57%, featuring a low inter-group heterogeneity, and the coefficients of variation were 0.59 and 1.25, featuring high in-group difference.Conclusions:The cases of acute myeloid leukemia were grouped based on length of stay, type of treatment, whether accompanied by complications, and age proved reasonable enough to serve as reference for DRG management and cost control of this disease.

Analysis of laboratory characteristics and evaluation of prognostic value of patients with NPM1 mutated acute myeloid leukemia / 中华检验医学杂志

Objective:To analyze the clinical and laboratory characteristics of acute myeloid leukemia (AML) patients with NPM1 mutation, and to explore the prognostic factors.Methods:A total of 77 AML patients with NPM1 gene mutation admitted to Hebei Yanda Ludaopei Hospital from May 1st 2012 to December 31st 2021 were enrolled in the study, including 34 male and 43 female patients. The median age was 40 (3, 68) years old. Patients were selected and divided into 4 groups according to the morphological FAB classification. There were 29 cases (37.7%) of M1 type, 13 cases (16.9%) of M2 type, 23 cases (29.9%) of M4 type, and 12 cases (15.5%) of M5 type. The clinical characteristics, bone marrow/peripheral blood cell morphology, immunophenotype, cytogenetics, molecular biology and overall survival of different groups were retrospectively analyzed, and the risk factors affecting the prognosis of AML were also explored. Cox multivariate regression was used to analyze the clinical influencing factors of survival and prognosis.Results:The white blood cell counts were highest in M4 and M5 patients and lowest in M2 patients, while no significant difference in the red blood cell, hemoglobin, and platelet counts( P>0.05). Morphologically, there were significant differences in the percentage of blasts and blasts with cup-like nuclei on bone marrow (BM) and peripheral blood (PB). The proportion of blasts in BM and PB was the highest in M1 and the lowest in M2 ( P<0.001). The positive rate of blasts with cup-like nuclei was the highest in M1 and the lowest in M5 of BM ( P<0.001), while the highest in M2 and the lowest in M5 of PB ( P=0.006). The scores of myeloperoxidase and chloroacetate esterase were all the highest in M1 and the lowest in M5 ( P<0.001, 0.001, respectively). In terms of molecular biology, the occurence rate of blasts combined with DNMT3A mutation was the highest in M4 and the lowest in M2 ( P=0.044), while those combined with FLT3-ITD mutation was the highest in M4 and the lowest in M5 ( P=0.002). In immunophenotype, there were significant differences in the expression positivities of seven antigens including HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO ( P<0.05). Multivariate COX regression analysis showed that no recurrence after treatment ( P<0.001), complete remission after treatment ( P=0.015) and transplantation ( P<0.001) were correlated with overall survival (OS). No recurrence after treatment ( P=0.033), transplantation ( P=0.027), no mutation of FLT3-ITD ( P=0.040), and hemoglobin concentration ( P=0.023) were associated with relapse-free survival (RFS). Survival analysis by Kaplan-Meier curve showed that there was no significant difference in survival time between the M1, M2, M4 and M5 groups in OS and RFS. Conclusion:There were significant differences in the white blood count, the percentage of blasts and blasts with cup-like nuclear morphology, cytochemical staining (MPO integration, CE integration and percentage of NAS-DCE), gene mutation (DNMT3A and FLT3-ITD) and immunophenotypes (HLA-DR, CD56, CD11c, CD15, CD14, CD96 and cMPO) between the four groups. The multivariate analysis revealed that no recurrence after treatment and transplantation were independent prognostic factors in NPM1 mut AML patients. On the other hand, FLT3-ITD mutation and hemoglobin concentration were associated with RFS and complete remission after treatment was associated with OS in the entire NPM1 mut cohort.

Application of artificial intelligence assists bone marrow cytomorphology analysis in the diagnosis and treatment of acute myeloid leukemia / 中华检验医学杂志

Objective:To investigate the value of artificial intelligence (AI) cytomorphologic analysis system in the cytomorphological diagnosis and therapeutic evaluation of acute myeloid leukemia (AML).Methods:Bone marrow smear samples were collected from 150 patients with newly diagnosed and treated acute myeloid leukemia who were inpatients and outpatients at the Department of Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from June 1, 2021 to July 31, 2022 for retrospective analysis. Among them, there were 50 patients in the newly diagnosed group, including 28 males and 22 females, with the onset age of 43.5(32.3,58.8)years. There were 100 patients in the post-treatment group, including 36 males and 64 females, with the onset age of 34.5(23.0,47.0)years. The results from cytomorphology expert were used as the gold standard and the Python 3.6.7 was used for analysis to evaluate the accuracy, sensitivity, and specificity of the AI cytomorphologic analysis system for blast cell recognition in AML diagnosis and treatment.Results:The proportion of blasts in AI analysis of 50 samples in the newly diagnosed group was≥20%, which met the diagnostic criteria of AML. AI analysis of blasts had an accuracy of 90.3%, sensitivity of 85.5%, and specificity of 98.0%. The correlation coefficient between AI and the proportion of blasts analyzed by experts was positively correlated( r=0.882, P<0.001). Meanwhile, in the post-treatment group, the sensitivity and specificity of AI analysis of blasts were 89.7% and 99.2%, respectively. The correlation coefficient between AI and the proportion of blasts analyzed by experts was positively correlated( r=0.957, P<0.001). According to AI analysis data, there are 8 samples in this group whose AI efficacy evaluation results on AML are inconsistent with expert analysis. Conclusion:AI cytomorphologic analysis system has high accuracy, sensitivity and specificity for blast cell recognition in AML morphological diagnosis and therapeutic evaluation.