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

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.

Berberine targets the electron transport chain complex I and reveals the landscape of OXPHOS dependency in acute myeloid leukemia with IDH1 mutation / 中国天然药物

Metabolic reprogramming, a newly recognized trait of tumor biology, is an intensively studied prospect for oncology medicines. For numerous tumors and cancer cell subpopulations, oxidative phosphorylation (OXPHOS) is essential for their biosynthetic and bioenergetic functions. Cancer cells with mutations in isocitrate dehydrogenase 1 (IDH1) exhibit differentiation arrest, epigenetic and transcriptional reprogramming, and sensitivity to mitochondrial OXPHOS inhibitors. In this study, we report that berberine, which is widely used in China to treat intestinal infections, acted solely at the mitochondrial electron transport chain (ETC) complex I, and that its association with IDH1 mutant inhibitor (IDH1mi) AG-120 decreased mitochondrial activity and enhanced antileukemic effect in vitro andin vivo. Our study gives a scientific rationale for the therapy of IDH1 mutant acute myeloid leukemia (AML) patients using combinatory mitochondrial targeted medicines, particularly those who are resistant to or relapsing from IDH1mi.

Effect and safety of 10-day decitabine-containing conditioning regimen for allogeneic hematopoietic stem cell transplantation in 31 patients with acute myeloid leukemia/myelodysplastic syndrome / 中华血液学杂志

Objective: To investigate the early effect and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a 10-day decitabine-containing conditioning regimen in the treatment of acute myeloid leukemia (AML) /myelodysplastic syndrome (MDS) . Methods: From April 2021 to May 2022, 31 AML/MDS patients who received allo-HSCT with a 10-day decitabine-containing conditioning regimen were analyzed. Results: AML (n=10), MDS-AML (n=6), CMML-AML (n=1), and MDS (n=14) were identified in 31 patients, 16 males, and 15 females, with a median age of 41 (20-55) yr. Neutrophils and platelets were successfully implanted in 31 patients (100%), with a median implantation duration of 12 (9-30) and 14 (9-42) days, respectively. During the preconditioning period, 16 patients (51.6%) developed oral mucositis, with 15 cases of Ⅰ/Ⅱ grade (48.4%) and one case of Ⅲ grade (3.2%). After transplantation, 13 patients (41.9%) developed CMV viremia, six patients (19.4%) developed hemorrhagic cystitis, and four patients (12.9%) developed a local infection. The median time of acute graft versus host disease (aGVHD) following transplantation was 33 (12-111) days. The cumulative incidence of aGVHD and Ⅲ/Ⅳ grade aGVHD was 41.9% (95% CI 26.9%-61.0%) and 22.9% (95% CI 13.5%-47.5%), respectively. There was no severe cGVHD, and mild and moderate chronic GVHD (cGVHD) incidence was 23.5% (95% CI 12.1%-43.6%). As of November 30, 2022, only one of the 31 patients had relapsed, with a 1-yr cumulative relapse rate (CIR) of 3.2% (95% CI 0.5%-20.7%). There was only one relapse patient death and no non-relapse deaths. The 1-yr overall survival (OS) and disease-free survival (DFS) rates were 92.9% (95% CI 80.3%-100%) and 96.8% (95% CI 90.8%-100%), respectively. Conclusions: A 10-day decitabine-containing conditioning regimen for allo-HSCT reduced relapse and was safe and feasible in treating AML/MDS.

RUNX1::RUNX1T1 Fusion in Pediatric Acute Myeloid Leukemia: A description of two cases

@#RUNX1::RUNX1T1 is a core-binding factor driving fusion gene which arises from t(8;21)(q22;q22). It is one of the most common chromosomal rearrangements in both pediatric and adult Acute Myeloid Leukemia (AML) with a reported incidence o 15% in children and young adults. There are few case reports documenting RUNX1::RUNX1T1 translocation in pediatric AML. Although this is generally associated with a favorable prognosis, we report two (2) cases of de novo pediatric AML in the Philippines harboring a RUNX1::RUNX1T1 translocation, one eventually relapsed while the other attained remission but succumbed to sepsis.

Analysis of ABO gene mRNA expression in peripheral blood of patients with acute myeloid leukemia / 中国输血杂志

【Objective】 To investigate the expression characteristics of ABO gene mRNA in peripheral blood of patients with acute myeloid leukemia. 【Methods】 The RNA-seq data of acute myeloid leukemia in TCGA database and the whole blood RNA-seq data in GTEx database were downloaded. The difference of ABO gene mRNA expression between acute myeloid leukemia and GTEx whole blood samples was analyzed by R software, and the relationship between ABO gene mRNA expression and DNA methylation, immune infiltration and prognosis was analyzed. 【Results】 The expression level of ABO gene mRNA in acute myeloid leukemia(median: 1.333, P25: 3.654, P75: 0.401)was significantly lower than that in the control group(median: 3.576, P25: 3.747, P75: 3.470)(P<0.001). The expression level of ABO gene mRNA in acute myeloid leukemia was negatively correlated with the methylation of + 82(r=-0.249, P<0.001), + 618(r=-0.268, P<0.001), + 1 080(r=-0.105, P<0.001) and + 1 409(r=-0.210, P<0.001) at downstream of transcription start site, and positively correlated with the immune infiltration of nine types of immune cells (B cells, CD8 T cells, Cytotoxic cells, pDC, T cells, T helper cells, Tcm, Tfh and Treg) (P<0.001). There was no significant difference in overall survival between patients with high (median survival time: 366 days, confidence interval: 304-731 days) and low (median survival time: 731 days, confidence interval: 335-1 402 days) expression of ABO gene mRNA in acute myeloid leukemia (P>0.05). 【Conclusion】 The mRNA expression of ABO gene in peripheral blood of patients with acute myeloid leukemia is decreased, which is associated with DNA methylation of the first intron of ABO gene and immune infiltration, but not with the prognosis.

Molecular genetics research of a Chinese family carrying triple HLA-A alleles / 中国输血杂志

【Objective】 To determine molecular basis of a rare HLA-A typing results carrying triple A alleles in potential allo-HSCT donor and her family. 【Methods】 HLA-A, -B, -C, -DRB1, -DQB1, -E, -F, -G of 5 members in the family were genotyped at a high-resolution level using next-generation sequencing (NGS). HLA-A of probosita was re-checked using polymerase chain reaction-sequence-based typing (PCR-SBT), and SNP oligonucleotide probes (SNP-array)were scanned with genomic DNA of probosita. 【Results】 There was 162.9Kb duplication in 6p22.1(29, 803, 377-29, 966, 301)of probosita who carried triple A alleles A*02∶01∶01, A*11∶01∶01, A*24∶02∶01. Other two family members were found to carry this haplotype: A*02∶01∶01, A*24∶02∶01, B*54∶01∶01, C*01∶02∶01, DRB1*04∶05∶01, DQB1*04∶01∶01, E*01∶01∶01∶03, F*01∶01∶01, G*01∶01∶01∶01, which as a Mendelian gene was segregated and stably transmitted through two generations. 【Conclusion】 Tiny gene duplication induces one haplotype carries two HLA-A alleles in a potential healthy donor for allo-transplantaion and stably transmits through two generations.Routine HLA typing laboratories should pay more attention to this situation and accurately report.

Effects of Peripheral Blood Stem Cell Transplantation from Haploidentical Versus Matched Sibling Donors on High-risk and Refractory/Relapsed Acute Myeloid Leukemia / 肿瘤防治研究

Objective To investigate the clinical efficacy of peripheral blood stem cell transplantation from haploidentical and matched sibling donors for treatment of high-risk and refractory/relapsed acute myeloid leukemia (AML). Methods Data on the efficacy of haploidentical peripheral blood stem cell transplantation (Haplo-HSCT) with myeloablative conditioning regimen were retrospectively analyzed and compared with that of matched sibling donors' peripheral blood stem cell transplantation (MSD-HSCT) for treatment of high-risk refractory/relapsed AML in our center from January 1st, 2010 to June 30th, 2020. Results A total of 98 patients were enrolled, including 62 patients in the Haplo-HSCT group and 36 patients in MSD-HSCT group. The median age, conditioning regimen, and infusion doses of MNC and CD34+ cells were significantly different between the two groups, but no significant differences in other baseline parameters were found. Transplantation-related infectious complications and the incidence of acute and chronic graft-versus-host disease (GVHD) were also not significantly different between the two groups. The 3-year cumulative relapse in the Haplo-HSCT group was significantly lower than that in the MSD-HSCT group (16.2% vs. 41.1%, P=0.036). The 3-year DFS of the Haplo-HSCT and MSD-HSCT groups were 66.98% and 41.8%, respectively (P=0.140), and their OS were 73.37% and 51.41%, respectively (P=0.105). Conclusion The clinical efficacy of Haplo-HSCT for the treatment of high-risk and refractory/relapsed AML is similar to that of MSD-HSCT, and Haplo-HSCT may have better GVL effect.

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.

Advances in conditioning regimens for allogeneic hematopoietic stem cell transplantation in elderly patients with acute myeloid leukemia / 中华器官移植杂志

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a sole viable treatment for acute myeloid leukemia (AML). As the median age of AML is approaching 68 years and the global population is aging, allo-HSCT for is becoming more vital for elderly AML patients (60 years and over). Conditioning regimen is important in determining the clinical outcomes of post-allo-HSCT patients.This review summarized the classic and latest conditioning regimens and evaluated their respective clinical outcomes.Clinicians may appreciate the advantages of each conditioning regimen and formulate optimal options for elderly AML patients.

Development and application of a highly sensitive method for detection of mutation of FMS-like tyrosine kinase-3-tyrosine kinase domain of acute myeloid leukemia / 中国生物制品学杂志

@#ObjectiveTo develop a highly sensitive method for detection of mutation of FMS-like tyrosine kinase-3-tyrosine kinase domain(FLT3-TKD)of acute myeloid leukemia(AML)and apply to the monitor of minimal residual disease(MRD).MethodsRecombinant plasmids containing wild FLT3 and mutant FLT3-D835Y were constructed respectively and mixed at certain ratios.The obtained standard plasmids with mutation rates of 50%,1%,0.1% and 0% respectively were determined by restriction fragment length polymorphism(RFLP)in combination with Sanger method.The plasmid DNA standards and blood DNA standards,at various FLT3-D835Y mutation rates,were determined by the developed method to verify the sensitivity.The genomic DNA samples of patients with AML before and after treatment were determined by the developed method to monitor the MRD.ResultsSequencing proved that both the recombinant plasmids containing wild FLT3 and mutant FLT3-D835Y were constructed correctly.The sensitivity of developed method increased to 0.1% through Sanger method combined with digestion with EcoR Ⅴ/Xho Ⅰ and recovery of mutant fragments in determination of purified plasmid DNA and collected blood DNA samples.MRD was detected in the peripheral blood sample of a patients with AML in complete remission period by the developed method but not by Sanger method.ConclusionA highly sensitive method for detection of FLT3-TKD mutation was developed,which was of an important clinical significance in guiding the treatment of AML and monitoring the MRD in complete remission period.

Prevention and treatment of high-risk acute myeloid leukemia recurrence after allogeneic hematopoietic stem cell transplantation / 器官移植

Acute myeloid leukemia (AML) is a group of highly-heterogeneous clonal diseases. Chemotherapy and hematopoietic stem cell transplantation are considered as effective treatment for AML. For high-risk AML patients, allogeneic hematopoietic stem cell transplantation is an effective therapeutic option. However, some AML patients may still face the problem of disease recurrence after hematopoietic stem cell transplantation. A majority of recurrent patients cannot be effectively treated by chemotherapy or secondary transplantation, which is the main cause of death after allogeneic hematopoietic stem cell transplantation. Therefore, it is of significance to strengthen follow-up of AML patients after allogeneic hematopoietic stem cell transplantation and implement appropriate measures to prevent postoperative recurrence. In this article, the monitoring, drug prevention and cell therapy of recurrence after allogeneic hematopoietic stem cell transplantation in high-risk AML patients were reviewed, aiming to provide reference for improving clinical prognosis of high-risk AML patients undergoing allogeneic hematopoietic stem cell transplantation.

Heliangin acts as a covalent ligand of RPS2 that disrupts pre-rRNA metabolic processes in NPM1-mutated acute myeloid leukemia

Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.