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. Structured questionnaire forms were used to gather data prospectively. RESULTS: A total of 356 AML patients with a median age of 53 years participated in the study. Long-term overall survival (OS) and relapse-free survival (RFS) were both 49% at 10 years. The median follow-up was 114 months. No significant difference in remission rate, OS or RFS was observed between the two induction treatments. Risk classification according to the protocol, MRD after the first and the last consolidation treatment affected the OS and RFS significantly (p < .001). CONCLUSIONS: Intensified cytarabine dose in the first induction treatment was not better than IAT in patients with AML. Intensification of postremission treatment in patients with clinical risk factors or MRD seems reasonable, but randomized controlled studies are warranted in the future.

Thromboembolism prophylaxis in patients with Philadelphia-negative myeloproliferative neoplasms-Clinical practice among Nordic specialists.

BACKGROUND: Patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) have higher risks of developing thromboembolisms compared to the general population. International guidelines on the management of MPNs therefore include recommendations concerning thromboembolism prophylaxis. In clinical practice, strict adherence to guidelines may be challenging and dependent on factors such as physician experience, outpatient clinic setting, and access to therapy; however, no data exist on physician adherence or patient compliance to thromboembolism prophylaxis in MPNs. OBJECTIVES: The Nordic Myeloproliferative Neoplasm Study Group (NMPN) performed a survey among Nordic hematology specialists with the aim of documenting the implementation of international recommendations in a region of Northern Europe with similar healthcare systems. RESULTS: The study showed that Nordic specialists managed their patients in accordance with international guidelines concerning medical intervention, but to a lesser degree regarding the management of additional cardiovascular risk factors. The survey also drew attention to the common clinical dilemma of combining antiaggregatory agents with vitamin K antagonists (VKA), or novel oral anticoagulants (NOAC), as well as phlebotomy limits in female polycythemia vera patients. CONCLUSIONS: The results of this study highlight the importance of considering all risk factors for thrombosis and an optimal collaboration with the primary healthcare sector.

Short-term side effects and attitudes towards second donation: A comparison of related and unrelated haematopoietic stem cell donors.

The Nordic Register of Haematopoietic Stem Cell Donors (NRHSD) has registered related and unrelated donors from 10 transplant centres in Sweden, Norway, Finland and Denmark since 1998. We present a prospective, observational study of 1,957 donors, focusing mainly on the differences between related and unrelated donors. Related donors are reported to have more comorbidities, but similar side effects compared with unrelated donors. Side effects after BM or PBSC donation are generally of short duration and in this study no deaths, myocardial infarctions, splenic ruptures, or thromboembolic events are reported. Interestingly, related donors express more hesitancy towards donating again when asked 1 month after donation.

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. RESULTS: Blood culture data were available on 977 treatment episodes, in which there were 503 BSIs (51%). The overall incidence rate (IR) for BSIs (per 1000 hospital days) was 16.7. Twenty patients (5.6%) died due to an infection and 16 of them (80%) had a BSI. The most commonly detected microbes (polymicrobial episodes included) in blood cultures were coagulase-negative staphylococci (CoNS, 24.7%), viridans group streptococci (VGS, 19.1%), enterococci (13.9%) and Enterobacteriacae group (25.9%). The etiology of BSIs varied greatly from treatment cycle to cycle. CONCLUSIONS: Enterococcal BSIs have increased compared to our previous treatment protocol, and they represent significant pathogens in blood cultures. Infection-related mortality has decreased despite the increase in the IR of BSIs. Enterococci seem to be an increasingly prominent pathogen underlying BSIs in the AML patients, especially during induction therapy (20%).

A minor role of asparaginase in predisposing to cerebral venous thromboses in adult acute lymphoblastic leukemia patients.

Cerebral venous thrombosis (CVT) covers up to a third of all venous thromboses (VTs) detected in patients with acute lymphoblastic leukemia (ALL). It usually hampers patients' lives and may also endanger efficient leukemia treatment. Although many factors have been suggested to account for an elevated risk of VTs in patients with ALL, there still is a lack of studies focusing on CVTs and especially in the setting of adult ALL patients. We studied in our retrospective population-based cohort the occurrence, characteristics, as well as risk factors for VTs in 186 consecutively diagnosed Finnish adult ALL patients treated with a national pediatric-inspired treatment protocol ALL2000. In the risk factor analyses for VTs we found a distinction of the characteristics of the patients acquiring CVT from those with other kinds of VTs or without thrombosis. In contrast to previous studies we were also able to compare the effects of asparaginase in relation to CVT occurrence. Notably, more than half of the CVTs were diagnosed prior the administration of asparaginase which accentuates the role of other risk factors on the pathophysiology of CVT compared to truncal or central venous line (CVL) VTs in adult ALL patients.

Treatment of adult acute myeloid leukemia.

The aim of this study was to analyze the treatment results of 180 adult AML patients treated at Turku University Hospital from 2002 to 2012. 124 patients received intensive therapy according to the protocol of the Finnish Leukemia Group. 86% of them achieved remission. 46 patients underwent allogeneic stem cell transplantation which was beneficial for high and intermediate risk disease. 60 - 70% of patients under 60 years old can be cured. The genetic profile of the disease, patient age and treatment response had a significant impact on survival. Our treatment results are comparable with data in literature.

[Adult acute lymphoblastic leukemia - 20-year treatment results at TYKS]. / Aikuisten akuutti lymfaattinen leukemia - 20 vuoden hoitotulokset TYks:ssa.

Approximately 30 cases of adult acute lymphoblastic leukemia (ALL) emerge in Finland yearly. In literature 35 to 40% of those under the age of 60 are reported to recover from their illness. Of the 67 adult ALL patients treated at the Turku University Hospital from 1990 to 2010, 96% achieved remission. The five-year survival rate was 53%. After remission, an allogeneic stem cell transplant was performed for 22 patients (37%), with 38 patients (63%) continuing on cytotoxic drugs. There was no difference in survival between modes of treatment or risk groups.

[Stem cell transplantation in myelofibrosis]. / Allogeeninen kantasolusiirto myelofibroosin hoidossa.

Allogeneic hematopoietic stem cell transplantation (ASCT) offers the only potentially curative therapy for myelofibrosis, a malignant myeloproliferative disease. The transplant-related mortality is still high, 10-48%, but use of reduced-intensity conditioning is less toxic and allows transplantation to be performed up to 65-70 years of age. Fabourable treatment response will be attained at least in a third of patients, in another third the disease will progress, and nearly one third will succumb due to transplant complications. Thirteen patients with myelofibrosis underwent ASCT at our institution between 1999 and 2009. The outcome of the patients treated with reduced-intensity conditioning corresponds well with those reported in the literature.

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. DESIGN AND METHODS: This population-based study included 225 consecutive patients aged 10-25 years diagnosed with acute lymphoblastic leukemia during 1990-2004. One hundred and twenty-eight patients (10-16 years) were treated with pediatric Nordic (NOPHO) protocols, and 97 patients (17-25 years) with Finnish Leukemia Group National protocols. We characterized the biological subtypes, clinical features and outcome of these patients. RESULTS: For the whole cohort, the remission rate was 96%, 5-year event-free survival 62% and overall survival 72%. The 5-year event-free survival was 67% for the pediatric treatment group and 60% for the adult treatment group (p=n.s.). Patients with inferior outcome were those with a white blood cell count >or= 100 x 10(9)/L, the Philadelphia chromosome and MLL. Good prognostic features were TEL-AML1, hyperdiploidy, and pediatric intermediate risk stratification. CONCLUSIONS: Unlike all previous studies, we found that the outcome of adolescents and young adults with acute lymphoblastic leukemia treated with pediatric or adult therapeutic protocols was comparable. The success of the adult acute lymphoblastic leukemia therapy emphasizes the benefit of central referral of patients to academic centers and adherence to research protocols.

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. According to international working group criteria, three patients (16%) responded to treatment. No correlation between VPA serum level, histone acetylation or clinical response was observed.

Double versus single autotransplantation in multiple myeloma; a single center experience of 100 patients.

One hundred patients with newly diagnosed multiple myeloma (MM) were treated with high-dose chemotherapy followed by single or double autologous stem cell transplantation (ASCT). Up-front treatment with a double ASCT tended to prolong progression-free and overall survival.