Marjut Kauppila

Acute lymphoblastic leukemia in adolescents and young adults in Finland

Recent reports indicate that adolescents and young adults with acute lymphoblastic leukemia have a better outcome when treated with pediatric rather than adult therapeutic protocols. This Finnish study did not show any major difference between patients treated with pediatric protocols and those treated with adult protocols, but confirmed that adolescents and young adults with acute lymphoblastic leukemia still have a poorer outcome than children below 10 years of age. See related perspective article on page 1124. 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 bood cell count ≥ 100×109/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. Key words: acute lymphoblastic leukemia, adolescents, survival, treatment outcome, young adults.

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

Abstract 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%).

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.

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

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.

Application of Sensitive AlleleSEQR Chimerism PCR from Peripheral Blood in Allografted AML/MDS Patients Treated with Pre-emptive Posttransplant Immunomodulation

PCR technique based on short tandem repeats (STR, microsatellites) is currently most widely used to monitor chimerism after allogeneic hematopoietic stem cell transplantation. Analysis of the proportion of donor and recipient derived cells enables an early detection of graft rejection or secondary graft failure. In malignant diseases increasing recipient chimerism has also been used to predict relapse, particularly in patients who lack disease-specific PCR marker to detect minimal residual disease (MRD). In these patients serial chimerism analyses may guide the use of post-transplant pre-emptive immunomodulation with the goal of avoiding clinical relapse. However, the sensitivity of the recently standardized STR-PCR, ranging between 0.8 and 1.6%, may not be sufficient to allow detection of impending relapse early enough in rapidly proliferating diseases like acute myeloid leukemia (AML) [1]. Therefore, we have tested the Abbott AlleleSEQR chimerism analysis system in AML patients who received pre-emptive post-transplant immunomodulation. The patients were routinely investigated for chimerism with STR-PCR monthly from whole blood and from blood T-cell fraction during post-transplant period and from bone marrow CD34 positive precursor cell fraction at 2-3 month intervals. In high risk patients with AML or myelodysplastic syndrome (MDS), we have applied posttransplant immunomodulation with azacytidine, lenalidomide and/ or donor lymphocyte infusions (DLI) based on findings in MRD and chimerism analyses the target being MRD negativity and full donor chimerism. In this retrospective study the routinely collected samples were additionally analyzed by Abbott AlleleSEQR chimerism assay.

High‐dose chemotherapy with autologous stem cell support for the treatment of advanced ovarian cancer — initial experience in Uppsala and Turku

Background. With current standard‐dose chemotherapy ovarian cancer is a chemosensitive but not chemocurable disease in the majority of cases. The widely used first‐line chemotherapy including a platinum analogue combined with cyclophosphamide results in response rates of 60–80%. However, only 10–20% of patients with advanced disease are alive 5 years after the diagnosis. The efficacy of high‐dose chemotherapy supported by autologous stem cell transplantation (ASCT) is currently under intensive investigation.