Acute Promyelocytic Leukemia Asian Consortium study of arsenic trioxide in newly diagnosed patients: impact and outcome.

The Acute Promyelocytic Leukemia (APL) Asian Consortium analyzed a contemporaneous cohort of newly diagnosed patients with APL treated with and without frontline arsenic trioxide (ATO) in 6 centers. The objectives were to define the impact of ATO on early deaths and relapses and its optimal positioning in the overall treatment strategy. In a 21.

Implications of Clonal Hematopoiesis in Hematological and Non-Hematological Disorders.

Clonal hematopoiesis (CH) is associated with an increased risk of developing myeloid neoplasms (MNs) such as myelodysplastic neoplasm (MDS) and acute myeloid leukemia (AML). In general, CH comprises clonal hematopoiesis of indeterminate potential (CHIP) and clonal cytopenia of undetermined significance (CCUS). It is an age-related phenomenon characterized by the presence of somatic mutations in hematopoietic stem cells (HSCs) and hematopoietic stem and progenitor cells (HSPCs) that acquire a fitness advantage under selection pressure.

Allogeneic haematopoietic stem cell transplantation for myelofibrosis: prognostic indicators and the role of JAK2V617F measurable-residual disease monitoring by droplet-digital polymerase chain reaction.

Relapse after allogeneic haematopoietic stem cell transplantation (HSCT) is one of the key determinants of outcome in myelofibrosis (MF) and remains an important unmet need. In this retrospective single-centre study, we evaluated 35 consecutive patients with MF receiving allogeneic HSCT. At 30 days post-HSCT, full donor chimerism was achieved in 31 patients (88.

Acute promyelocytic leukaemia: population-based study of epidemiology and outcome with ATRA and oral-ATO from 1991 to 2021.

Background: The epidemiology and treatment of acute promyelocytic leukaemia (APL) are changing. We have incorporated oral arsenic trioxide (oral-ATO) into induction/maintenance.

Methods: Newly-diagnosed APL from 1991 to 2021 divided into three 10-year periods were studied to define its epidemiology and how oral-ATO impacted on its outcome.

Pan-cancer analysis of oncogenic TNFAIP2 identifying its prognostic value and immunological function in acute myeloid leukemia.

Background: Tumor necrosis factor alpha-induced protein 2 (TNFAIP2), a TNFα-inducible gene, appears to participate in inflammation, immune response, hematopoiesis, and carcinogenesis. However, the potential role of TNFAIP2 in the development of acute myeloid leukemia (AML) remains unknow yet. Therefore, we aimed to study the biological role of TNFAIP2 in leukemogenesis.

Single-Nucleotide Variations, Insertions/Deletions and Copy Number Variations in Myelodysplastic Syndrome during Disease Progression Revealed by a Single-Cell DNA Sequencing Platform.

Myelodysplastic syndrome (MDS) is a clonal myeloid neoplasm characterized by ineffective hematopoiesis, cytopenia, dysplasia, and clonal instability, leading to leukemic transformation. Hypomethylating agents are the mainstay of treatment in higher-risk MDS. However, treatment resistance and disease transformation into acute myeloid leukemia (AML) is observed in the majority of patients and is indicative of a dismal outcome.

Molecular Targeted Therapy and Immunotherapy for Myelodysplastic Syndrome.

Myelodysplastic syndrome (MDS) is a heterogeneous, clonal hematological disorder characterized by ineffective hematopoiesis, cytopenia, morphologic dysplasia, and predisposition to acute myeloid leukemia (AML). Stem cell genomic instability, microenvironmental aberrations, and somatic mutations contribute to leukemic transformation. The hypomethylating agents (HMAs), azacitidine and decitabine are the standard of care for patients with higher-risk MDS.

Myeloproliferative neoplasms treated with hydroxyurea, pegylated interferon alpha-2A or ruxolitinib: clinicohematologic responses, quality-of-life changes and safety in the real-world setting.

Real-world data of responses, quality-of-life (QOL) changes and adverse events in patients with myeloproliferative neoplasms (MPN) on conventional therapy (hydroxyurea ± anagrelide), pegylated interferon alpha-2A (PEG-IFNα-2A) or ruxolitinib are limited. We prospectively studied MPN patients receiving conventional therapy, PEG-IFNα-2A or ruxolitinib. Next-generation sequencing of 69 myeloid-related genes was performed.

Oral arsenic trioxide, all-trans retinoic acid, and ascorbic acid maintenance after first complete remission in acute promyelocytic leukemia: Long-term results and unique prognostic indicators.

Background: The role of arsenic trioxide (As O ) in the maintenance of first complete remission (CR1) in acute promyelocytic leukemia (APL) is unclear.

Methods: A total of 129 consecutive adult patients with APL of all risk categories who achieved CR1 with conventional induction (all-trans retinoic acid [ATRA]/daunorubicin) and consolidation (daunorubicin/cytarabine [induction daunorubicin and consolidation omitted for age ≥70 years]) underwent maintenance comprising ATRA (45 mg/m /day), oral As O (10 mg/day), and ascorbic acid (1 g/day) (AAA) for 2 weeks every 2 months for 2 years.

Results: Over a 17-year period from August 1, 2002, to July 31, 2019, 63 men and 66 women (median age, 46 years [range, 18-82 years]) received AAA maintenance, which was already completed in 117 patients.

Clofarabine, cytarabine, and mitoxantrone in refractory/relapsed acute myeloid leukemia: High response rates and effective bridge to allogeneic hematopoietic stem cell transplantation.

Clofarabine is active in refractory/relapsed acute myeloid leukemia (AML). In this phase 2 study, we treated 18- to 65-year-old AML patients refractory to first-line 3 + 7 daunorubicin/cytarabine induction or relapsing after 3 + 7 induction and high-dose cytarabine consolidation, with clofarabine (30 mg/m /d, Days 1-5), cytarabine (750 mg/m /d, Days 1-5), and mitoxantrone (12 mg/m /d, Days 3-5) (CLAM). Patients achieving remission received up to two consolidation cycles of 50% CLAM, with eligible cases bridged to allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Oral arsenic trioxide incorporation into frontline treatment with all-trans retinoic acid and chemotherapy in newly diagnosed acute promyelocytic leukemia: A 5-year prospective study.

Background: Strategies using oral arsenic trioxide (As O ) are efficacious in relapsed acute promyelocytic leukemia (APL), but they have not been examined in newly diagnosed cases.

Methods: Sixty-two consecutive patients (24 men and 38 women) with a median age of 52 years (range, 22-85 years), 36% of whom had high-risk features, underwent induction with all-trans retinoic acid at 45 mg/m /d, oral As O at 10 mg/d, and ascorbic acid at 1 g/d (the all-trans retinoic acid-arsenic trioxide-ascorbic acid [AAA] regimen) for 6 weeks (with patients younger than 70 years additionally receiving daunorubicin at 50 mg/m /d × 3); they then underwent consolidation with 2 monthly cycles of daunorubicin (50 mg/m /d × 2) and cytarabine (100 mg/m /d × 5) and received AAA maintenance (2 weeks every 8 weeks) for 2 years. A contemporaneous cohort of 37 newly diagnosed patients (15 men and 22 women) with a median age of 51 years (range, 23-78 years), not consenting to oral As O induction but receiving similar induction, consolidation, and AAA maintenance, served as a comparator group; 46% of these patients had high-risk features.

Next-generation sequencing with a 54-gene panel identified unique mutational profile and prognostic markers in Chinese patients with myelofibrosis.

Current prognostication in myelofibrosis (MF) is based on clinicopathological features and mutations in a limited number of driver genes. The impact of other genetic mutations remains unclear. We evaluated for mutations in a myeloid panel of 54 genes using next-generation sequencing.

The association of high-intensity zones on MRI and low back pain: a systematic review.

Background: Magnetic resonance imaging (MRI) of the lumbar spine is commonly used to identify the source of low back pain (LBP); however, its use has been questionable. Throughout the years, numerous lumbar phenotypes (e.g.

Long-term outcome of relapsed acute promyelocytic leukemia treated with oral arsenic trioxide-based reinduction and maintenance regimens: A 15-year prospective study.

Background: For patients who have acute promyelocytic leukemia (APL) in second complete remission (CR2), optimal postremission strategies remain undefined.

Methods: The role of an oral arsenic trioxide (As O )-based regimen in the management of patients who had APL in CR2 was examined.

Results: Seventy-three patients with APL in first relapse (R1) were studied.

Methylation of miR-155-3p in mantle cell lymphoma and other non-Hodgkin's lymphomas.

Mantle cell lymphoma (MCL) is an aggressive B-cell non-Hodgkin's lymphoma (NHL). In cancers, tumor suppressive microRNAs may be silenced by DNA hypermethylation. By microRNA profiling of representative EBV-negative MCL cell lines before and after demethylation treatment, miR-155-3p was found significantly restored.

A systematic review of the safety and efficacy of mesenchymal stem cells for disc degeneration: insights and future directions for regenerative therapeutics.

Intervertebral disc degeneration is associated with low-back pain. Mesenchymal stem cells (MSCs) have been used to "regenerate" the disc. The aim of this study was to perform a systematic review of comparative controlled studies that have assessed the safety and efficacy of using MSCs for disc regeneration.

Epigenetic inactivation of the MIR129-2 in hematological malignancies.

Background: MIR129-2 has been shown to be a tumor suppressor microRNA hypermethylated in epithelial cancers.

Patients And Methods: Epigenetic inactivation of MIR129-2 was studied by methylation-specific PCR (MSP) in 13 cell lines (eight myeloma and five lymphoma), 15 normal controls and 344 primary samples including acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML), chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), multiple myeloma (MM) at diagnosis, MM at relapse/progression, and monoclonal gammopathy of undetermined significance (MGUS). Expression of MIR129 and its target, SOX4, in cell lines was measured before and after hypomethylating treatment and MIR129 overexpression.

DNA Methylation of Tumor Suppressive miRNAs in Non-Hodgkin's Lymphomas.

DNA methylation is an epigenetic alteration leading to heritable phenotypic changes of cells with functional consequences. It is important in early embryonic development, stem cell differentiation, and tissue-specific gene expression. In normal cells, promoter-associated CpG islands (CGI) are generally unmethylated except in X-chromosome inactivation or genomic imprinting.

Epigenetic inactivation of the MIR34B/C in multiple myeloma.

We postulated that MIR34B/C, a direct transcriptional target of TP53, might be inactivated by promoter hypermethylation in multiple myeloma (MM). MIR34B/C promoter methylation was studied in 8 normal marrow controls, 8 MM cell lines, 95 diagnostic, and 23 relapsed/progressed MM samples by methylation-specific PCR. MIR34B/C was methylated in 6 (75.

The impact of integrating mental and general health services on mental health's share of total health care spending in Alberta.

Objective: In April 2003 the Alberta government integrated specialized mental health services, formerly organized independently, with the health regions, which are responsible for general health services. The objective of this article is to determine whether the transfer was associated with an increase or decrease in the share of resources in the region allocated to mental health care relative to total spending for health care.

Methods: The measure of the share for mental health care is the total costs for mental health care resources as a percentage of total health care spending.

Expenditures on mental health and addictions for Canadian provinces in 2003 and 2004.

Objective: To measure total public and private expenditures on mental health in each province.

Method: Data for expenditures on mental health services were collected in the following categories: physician expenditures (general and psychiatrist fees for service and alternative funding), inpatient hospital (psychiatric and general), outpatient hospital, community mental health, pharmaceuticals, and substance abuse. Data for 2 years, 2003 and 2004, were collected from the Canadian Institute for Health Information (hospital inpatient and fees for service physicians), the individual provinces (pharmaceuticals, alternative physician payments, hospital outpatient, and community), and the Canadian Centre on Substance Abuse.