Efficacy of intrathecal chemotherapy in patients with central nervous system involvement of hematological malignancies: a retrospective analysis.

INTRODUCTION: Central nervous system (CNS) involvement, especially involvement of the cerebrospinal fluid (CSF), is common in several haematological malignancies. Intrathecal (IT) chemotherapy can be used to manage CSF involvement. METHODS: Here we evaluated the effectiveness of IT chemotherapy among 80 patients with haematological malignancies and CSF localization who were treated with IT chemotherapy from 2001 to 2012. RESULTS: The majority of patients was diagnosed with diffuse large B-cell lymphoma (26%) or acute lymphoblastic leukaemia/lymphoblastic lymphoma (19%). After first-line IT chemotherapy, which mainly consisted of methotrexate (MTX) and corticosteroids, CSF complete response (CSF CR) was achieved in 76% of patients. 91% reached CSF CR when including second-line IT-chemotherapy. Clinical response was documented in 75%. Although most patients were additionally treated with systemic chemotherapy, response rate did not differ between patients treated with CNS-penetrating and CNS-non-penetrating drugs. CNS progression/relapse occurred in 40% of patients with median progression-free survival of 12.2 months. The median overall survival was 18.3 months; 55% of the patients died during follow-up. CONCLUSIONS: Our analysis shows a high response rate after first-line IT chemotherapy, but also a relatively high progression/relapse percentage.

Impact of Advanced External Beam Radiotherapy on Second Haematological Cancer Risk in Prostate Cancer Survivors.

AIMS: External beam radiotherapy (EBRT) for prostate cancer (PCa) has rapidly advanced over the years. Advanced techniques with altered dose distributions may have an impact on second haematological cancer (SHC) risks. We assessed SHC risk after EBRT for PCa and explored whether this risk has changed over the years. MATERIALS AND METHODS: Patients diagnosed with a T1-T3 PCa between 1990 and 2015 were selected from the Netherlands Cancer Registry. Patients treated with EBRT were assigned to EBRT eras based on the date of diagnosis. These eras represented two-dimensional radiotherapy (2D-RT; 1991-1996), three-dimensional conformal radiotherapy (3D-CRT; 1998-2005) or advanced EBRT (2008-2015). Standardised incidence ratios (SIR) and absolute excess risks (AER) were calculated overall and by EBRT era. Sub-hazard ratios (sHRs) were calculated for the comparison of EBRT versus radical prostatectomy and active surveillance. RESULTS: PCa patients with EBRT as the primary treatment (n = 37 762) had an increased risk of developing a SHC (SIR = 1.20; 95% confidence interval 1.13-1.28) compared with the Dutch male general population. Estimated risks were highest for the 2D-RT era (SIR = 1.32; 95% confidence interval 1.14-1.67) compared with the 3D-CRT era (SIR = 1.16; 95% confidence interval 1.05-1.27) and the advanced EBRT era (SIR = 1.21; 95% confidence interval 1.07-1.36). AER were limited, with about five to six extra cases per 10 000 person-years. Relative risk analysis (EBRT versus radical prostatectomy/active surveillance) showed significant elevation with EBRT versus active surveillance (sHR = 1.17; 95% confidence interval 1.03-1.33; P = 0.017), but not for EBRT versus radical prostatectomy (sHR = 1.08; 95% confidence interval 0.94-1.23; P = 0.281). CONCLUSION: Increased SHC risks after EBRT for PCa cancer were observed for all EBRT eras compared with the general Dutch male population. Excess risks for EBRT versus other PCa treatment groups were found for only EBRT versus active surveillance.

Improved survival for children and young adolescents with acute myeloid leukemia: a Dutch study on incidence, survival and mortality.

Variation in survival of pediatric acute myeloid leukemia (pAML) over time and between Western European countries exists. The aim of the current study is to assess the progress made for the Dutch pAML population (0-17 years) during 1990-2015, based on trends in incidence, survival and mortality. Data from the population-based Netherlands Cancer Registry were merged with leukemia-related characteristics and treatment specifics from the Dutch Childhood Leukemia Study Group (Dutch Childhood Oncology Group (DCOG) from 2002 onwards). Mortality data (1980-2016) were obtained from the cause of death registry of Statistics Netherlands. Trend analyses were performed over time and by treatment protocol. Between 1990 and 2015, a total of 635 children aged 0-17 years were diagnosed with AML for an average of 25 patients (range 18-36) per year. There was a slight increase in the incidence at age 1-4 years (average annual percentage change (AAPC) of +2.2% per year (95% CI 0.8-3.5, p < 0.01)). Overall, the 5-year survival significantly improved over the past 26 years and nearly doubled from 40% in the early 1990s to 74% in 2010-2015. Multivariable analysis showed a 49% reduction in risk of death for pAML patients treated according to the latest DB-AML 01 protocol (p = 0.03). The continuing decrease of mortality (AAPC -2.8% per year (95% CI -4.1 to -1.5)) supports the conclusion of true progress against pAML in the Netherlands.

Improved survival in adult patients with acute lymphoblastic leukemia in the Netherlands: a population-based study on treatment, trial participation and survival.

This nationwide population-based study assessed trends in treatment, trial participation and survival among 1833 adult patients diagnosed with acute lymphoblastic leukemia (ALL) in the Netherlands between 1989 and 2012 reported to the Netherlands Cancer Registry. Patients were categorized into four periods and five age groups (18-24, 25-39, 40-59, 60-69 and ⩾70 years). The application of allogeneic stem cell transplantation (alloSCT), particularly reduced-intensity conditioning (RIC) alloSCT, increased over time up to age 70 years. The inclusion rate in the trials was 67, 66, 55, 58 and 0% for the five age groups. Survival improved over time for patients below 70 years. Five-year relative survival in the period 2007-2012 was 75, 57, 37, 22 and 5% for the five age groups. In that same period, 5-year overall survival among patients aged 18-39 years was 68% for the chemotherapy-alone group and 66% for the alloSCT group. For patients aged 40-69 years, the corresponding estimates were 24 and 41%. Pronounced survival improvement observed among patients aged 18-39 years might mainly be explained by implementation of pediatric-based regimens since 2005, whereas among patients aged 40-69 years, increased application of RIC-alloSCT has contributed significantly to the observed improvement. Outcome of patients aged ⩾70 remains unsatisfactory, indicating a need for specific trials for the elderly.

Treatment, trial participation and survival in adult acute myeloid leukemia: a population-based study in the Netherlands, 1989-2012.

Large, comprehensive population-based studies in acute myeloid leukemia (AML) are scarce. We conducted a nationwide population-based study on treatment, trial participation and survival among all adult patients diagnosed with AML (n=12,032) and acute promyelocytic leukemia (APL; n=585) in the Netherlands between 1989-2012. Patients were categorized into four periods and four age groups (18-40, 41-60, 61-70 and >70 years). The application of allogeneic stem cell transplantation increased over time among AML patients up to age 70 years. For APL patients, the use of chemotherapy increased across all age groups. When a clinical trial was open for accrual in the Netherlands, the inclusion rates were 68%, 57%, 30% and 12% for AML patients in the four age groups, respectively (data for APL unavailable). Relative survival improved over time among AML (up to age 70 years) and APL patients. In the period 2007-2012, 5-year relative survival rates were 54%, 38%, 14% and 2% for AML patients and 84%, 75%, 54% and 37% for APL patients in the four age groups, respectively. As survival remained poor for older AML patients over the last two decades, clinical trials and active participation in those trials, are warranted that explore innovative treatment strategies for this elderly population.

Added value of interferon-gamma release assays in screening for tuberculous infection in the Netherlands.

BACKGROUND: Interferon-gamma release assays (IGRAs) are reported to be more specific for the diagnosis of latent tuberculous infection (LTBI) than the tuberculin skin test (TST). The two-step procedure, TST followed by an IGRA, is reported to be cost-effective in high-income countries, but it requires more financial resources. OBJECTIVE: To assess the added value of IGRA compared to TST alone in the Netherlands. METHODS: Test results and background data on persons tested with an IGRA were recorded by the Public Municipal Health Services in a web-based database. The number of persons diagnosed with LTBI using different screening algorithms was calculated. RESULTS: In those tested with an IGRA, at least 60% of persons who would have been diagnosed with LTBI based on TST alone had a negative IGRA. Among those with a TST reaction below the cut-off for the diagnosis of LTBI, 13% had a positive IGRA. For 41% of persons tested with an IGRA after TST, the IGRA influenced whether or not an LTBI diagnosis would be made. CONCLUSION: With the IGRA as reference standard, a high proportion of persons in low-prevalence settings are treated unnecessarily for LTBI if tested with TST alone, while a small proportion eligible for preventive treatment are missed. Incremental costs of the two-step strategy seem to be balanced by the improved targeting of preventive treatment.