Efficacy of conventional-dose cytarabine, idarubicin and thioguanine versus intermediate-dose cytarabine and idarubicin in the induction treatment of acute myeloid leukemia: Long-term results of the prospective randomized nationwide AML-2003 study by the Finnish Leukemia Group.

Objectives: AML-2003 study sought to compare the long-term efficacy and safety of IAT and IdAraC-Ida in induction chemotherapy of acute myeloid leukemia (AML) and introduce the results of an integrated genetic and clinical risk classification guided treatment strategy.

Methods: Patients were randomized to receive either IAT or IdAraC-Ida as the first induction treatment. Intensified postremission strategies were employed based on measurable residual disease (MRD) and risk classification.

Expression of a specific extracellular matrix signature is a favorable prognostic factor in acute myeloid leukemia.

Relapse of acute myeloid leukemia (AML) is still dramatically frequent, imposing the need for early markers to quantify such risk. Recent evidence point to a prominent role for extracellular matrix (ECM) in AML, but its prognostic value has not yet been investigated. Here we have investigated whether the expression of a 15-ECM gene signature could be applied to clinical AML research evaluating a retrospective cohort of 61 AML patients and 12 healthy donors.

Bloodstream infections in acute myeloid leukemia patients treated according to the Finnish Leukemia Group AML-2003 protocol - a prospective nationwide study.

Background: Infections greatly influence the outcome of acute myeloid leukemia (AML) patients receiving intensive treatment. The aim of this study was to establish the incidence, microbial etiology, risk factors and prognosis of bloodstream infections (BSIs) in patients with AML and compare the results with the previous treatment protocol (AML-92).

Methods: Registery data were gathered prospectively from 357 patients aged 16-65 years recruited on the AML-2003 treatment protocol between November 2003 and November 2011 during different treatment cycles.

Somatic STAT3 mutations in large granular lymphocytic leukemia.

Background: T-cell large granular lymphocytic leukemia is a rare lymphoproliferative disorder characterized by the expansion of clonal CD3+CD8+ cytotoxic T lymphocytes (CTLs) and often associated with autoimmune disorders and immune-mediated cytopenias.

Methods: We used next-generation exome sequencing to identify somatic mutations in CTLs from an index patient with large granular lymphocytic leukemia. Targeted resequencing was performed in a well-characterized cohort of 76 patients with this disorder, characterized by clonal T-cell-receptor rearrangements and increased numbers of large granular lymphocytes.

The effect of bone marrow microenvironment on the functional properties of the therapeutic bone marrow-derived cells in patients with acute myocardial infarction.

Background: Treatment of acute myocardial infarction with stem cell transplantation has achieved beneficial effects in many clinical trials. The bone marrow microenvironment of ST-elevation myocardial infarction (STEMI) patients has never been studied even though myocardial infarction is known to cause an imbalance in the acid-base status of these patients. The aim of this study was to assess if the blood gas levels in the bone marrow of STEMI patients affect the characteristics of the bone marrow cells (BMCs) and, furthermore, do they influence the change in cardiac function after autologous BMC transplantation.

Cardiac Function, Perfusion, Metabolism, and Innervation following Autologous Stem Cell Therapy for Acute ST-Elevation Myocardial Infarction. A FINCELL-INSIGHT Sub-Study with PET and MRI.

Purpose: Beneficial mechanisms of bone marrow cell (BMC) therapy for acute ST-segment elevation myocardial infarct (STEMI) are largely unknown in humans. Therefore, we evaluated the feasibility of serial positron emission tomography (PET) and MRI studies to provide insight into the effects of BMCs on the healing process of ischemic myocardial damage.

Methods: Nineteen patients with successful primary reteplase thrombolysis (mean 2.

Effects of intracoronary injection of autologous bone marrow-derived stem cells on natriuretic peptides and inflammatory markers in patients with acute ST-elevation myocardial infarction.

Background: Intracoronary administration of autologous bone marrow stem cells (BMC) has been shown to result in a subtle improvement of global left ventricular ejection fraction after ST-elevation myocardial infarction (STEMI), but the overall benefits of BMC therapy are still unclear. We studied the influence of intracoronary injections of BMC on levels of natriuretic peptides and inflammatory mediators, which are well established prognostic biomarkers, in patients with STEMI.

Methods: In this randomized, double-blind study, consecutive patients with an acute STEMI treated with thrombolysis followed by PCI 2-6 days after STEMI, were randomly assigned to receive either intracoronary BMC or placebo medium into the infarct-related artery.

Prognostic classification of patients with acute lymphoblastic leukemia by using gene copy number profiles identified from array-based comparative genomic hybridization data.

The development of risk-adapted therapy has improved the treatment results of acute lymphoblastic leukemia (ALL) especially in children. However, more accurate risk classifiers are warranted. In this study we aimed at defining a prognostic classifier based on DNA copy number alterations of adolescent and young adult (AYA) (10-25 yrs) ALL patients (n=60) determined by microarray CGH and the relapse status of the patients.

Determinants of functional recovery after myocardial infarction of patients treated with bone marrow-derived stem cells after thrombolytic therapy.

Objective: To assess the determinants of functional recovery in patients with ST-elevation myocardial infarction (STEMI) treated initially with thrombolysis, followed by percutaneous coronary intervention and intracoronary injection of bone marrow-derived stem cells (BMC).

Design: A randomised, placebo-controlled, double-blind study (substudy of FINCELL).

Setting: Two tertiary cardiac centres.

Acute lymphoblastic leukemias with normal karyotypes are not without genomic aberrations.

Current cytogenetic techniques have enabled more accurate definition of genetic aberrations in the lymphoblasts of patients with acute lymphoblastic leukemia (ALL), at least in most cases. Detecting the cryptic aberrations undetected by conventional cytogenetic methods is important for disease classification, evaluation of prognosis, and minimal residual disease follow-up. We have studied DNA copy number alterations of 27 adolescent ALL patients with normal (n=26) or failed (n=1) karyotype at diagnosis using microarray comparative genomic hybridization (CGH).

Clinical Candida krusei isolates remain susceptible during extensive exposure to antifungal drugs.

We have previously reported a Candida krusei outbreak during which a number of our patients were infected or colonized by several different closely related Candida krusei genotypes. The treatment response in many of our patients was at best modest and the patients remained positive for Candida krusei. We speculated that extended exposure to antifungals in patients with an incomplete treatment response might lead to the conditions for selection of drug resistance in the multiple Candida krusei clones.

Influence of chemotherapy courses on the rate of bloodstream infections during neutropenia in adult acute myeloid leukaemia.

To evaluate the effect of various chemotherapy courses on the rate of bloodstream infections (BSI) during therapy-related neutropenia, all infection episodes of adult patients with acute myeloid leukaemia (AML) during 7 y were retrospectively analysed in a university hospital. Of the 182 infection episodes in 76 AML patients, 37% (n = 68) were BSI. The riskratio (RR) of BSI was highest after regimens containing high-dose cytarabine (2.

Effects of intracoronary injection of mononuclear bone marrow cells on left ventricular function, arrhythmia risk profile, and restenosis after thrombolytic therapy of acute myocardial infarction.

Aims: To assess the efficacy and safety of bone marrow cell (BMC) therapy after thrombolytic therapy of an acute ST-elevation myocardial infarction (STEMI).

Methods And Results: Patients with STEMI treated with thrombolysis followed by percutaneous coronary intervention (PCI) 2-6 days after STEMI were randomly assigned to receive intracoronary BMCs (n = 40) or placebo medium (n = 40), collected and prepared 3-6 h prior PCI and injected into the infarct artery immediately after stenting. Efficacy was assessed by the measurement of global left ventricular ejection fraction (LVEF) by left ventricular angiography and 2-D echocardiography, and safety by measuring arrhythmia risk variables and restenosis of the stented vessel by intravascular ultrasound.

Acute lymphoblastic leukemia in adolescents and young adults in Finland.

Background: Interest has recently been paid to adolescents and young adults with acute lymphoblastic leukemia, particularly because all reports so far published indicate that these patients have a better outcome when treated with pediatric rather than adult therapeutic protocols. There are different biological subtypes of acute lymphoblastic leukemia with distinct features and prognoses; the distribution of these subtypes is not well known among adolescents. We, therefore, studied acute lymphoblastic leukemia in adolescents and young adults aged 10 to 25 years in Finland.

CDKN2A deletions in acute lymphoblastic leukemia of adolescents and young adults: an array CGH study.

Deletion in chromosome 9p involving the CDKN2A locus (9p21.3) is known in many malignancies. To detect this deletion in adolescent ALL patients we used oligo array CGH and studied 54 patients aged 10-25 years.

A cluster of Candida krusei infections in a haematological unit.

Background: Candida krusei infections are associated with high mortality. In order to explore ways to prevent these infections, we investigated potential routes for nosocomial spread and possible clonality of C. krusei in a haematological unit which had experienced an unusually high incidence of cases.

Valproic acid combined with 13-cis retinoic acid and 1,25-dihydroxyvitamin D3 in the treatment of patients with myelodysplastic syndromes.

Valproic acid (VPA), an inhibitor of histone deacetylases, inhibits the growth of leukemia cells and induces their differentiation in vitro. In the present study, VPA in combination with two differentiating agents, 13-cis retinoic acid and 1,25-dihydroxyvitamin D3, was given to 19 previously untreated patients with MDS or CMML. Eight patients had to discontinue treatment before week 16 due to toxicity.

Long-term outcome of intensive chemotherapy for adults with de novo acute myeloid leukaemia (AML): the nationwide AML-92 study by the Finnish Leukaemia Group.

Objective: To investigate the long-term outcome of idarubicin- and cytarabine-based intensive chemotherapy in adult acute myeloid leukaemia (AML).

Patients And Methods: A total of 327 consecutive patients with de novo AML (promyelocytic leukaemia excluded) aged 16-65 yr were recruited into the study between September 1992 and December 2001. The latest follow-up data were collected in October 2006.

An association between manganese superoxide dismutase polymorphism and outcome of chemotherapy in acute myeloid leukemia.

Manganese superoxide dismutase (MnSOD) protects cells against oxidative stress by eliminating superoxides. Hypothetically, decreased MnSOD levels in cancer might lead to increased oxidative stress and, thus, to increased sensitivity of cells to chemotherapy agents. Eighty-nine patients with acute myeloid leukemia (AML) were analyzed for a functional C to T polymorphism of MnSOD, which could potentially lead to decreased enzyme concentrations inside mitochondria.

Increase in Ara-C cytotoxicity in the presence of valproate, a histone deacetylase inhibitor, is associated with the concurrent expression of cyclin D1 and p27(Kip 1) in acute myeloblastic leukemia cells.

The effects of valproate and butyrate were investigated in an acute myeloblastic cell line (OCI/AML-2) on cytotoxicity, cell cycle profile and expression of cell cycle regulating proteins in the presence of cytarabine (Ara-C) and etoposide. As a single agent valproate and butyrate inhibited AML cell growth but did not significantly induce cell death. A dramatic increase in cytotoxicity was observed when combining valproate or butyrate with Ara-C, whereas, co-addition of them with etoposide had much smaller effect on cell death.