Mikko Arola

Effects of a home-based exercise program on metabolic risk factors and fitness in long-term survivors of childhood acute lymphoblastic leukemia†

Long‐term survivors of childhood acute lymphoblastic leukemia (ALL) have increased risk of cardiovascular disease (CVD). The prevalence of insulin resistance and other cardiometabolic risk factors is increased in ALL survivors, and insufficient physical activity (PA) and low cardiopulmonary fitness are common. The purpose of this study was to evaluate the effects of a simple, inexpensive home‐based exercise program on cardiometabolic risk factors and fitness in long‐term ALL survivors.

Cardiovascular morbidity in long-term survivors of early-onset cancer: A population-based study

Improvements in cancer therapy have resulted in an expanding population of early‐onset cancer survivors. In contrast to childhood and adolescent cancer survivors, there is still a lack of data concerning late morbidities among young adult (YA) cancer survivors. Thus, our aim was to investigate cardiac and vascular morbidity among early‐onset cancer survivors with a special interest in YA cancer survivors. In a population‐based setting, we explored the risk of cardiovascular disease in early‐onset cancer survivors compared to healthy siblings. Patients diagnosed with cancer below 35 years of age since 1975 were identified from the Finnish Cancer Registry, and 5‐year survivors were included in our study (N = 13,860). Information on cardiovascular morbidity was collected from the national hospital discharge registry. Compared to siblings, cancer survivors aged 0–19 and 20–34 at diagnosis had significantly elevated hazard ratios (HRs) for the studied outcomes: HR 13.5 (95% CI 8.9–20.4) and 3.6 (95% CI 2.8–4.6) for cardiomyopathy/cardiac insufficiency; HR 3.4 (95% CI 2.3–5.1) and 1.7 (95% CI 1.4–2.0) for atherosclerosis/brain vascular thrombosis; HR 3.3 (95% CI 1.7–6.5) and 1.8 (95% CI 1.5–2.1) for myocardial infarction/cardiac ischemia and HR 1.7 (95% CI 1.2–2.6) and 1.4 (95% CI 1.2–1.7) for cardiac arrhythmia. In both groups, depending on the outcome, the HR for adverse events was highest among lymphoma, brain tumor, leukemia and testicular malignancy survivors. Our results regarding late effects of childhood cancer survivors confirmed previous findings. Additionally, our study provides novel information concerning the YA cancer survivor population. Hence, our data may help in planning the risk‐based long‐term follow‐up of early‐onset cancer survivors.

Late mortality among 5-year survivors of early onset cancer: A population-based register study

To date, only few studies have been published documenting late mortality among early onset cancer survivors, especially regarding young adulthood (YA) malignancies. Our nation‐wide population‐based registry study provides information concerning cause‐specific long‐term mortality among 16,769 5‐year survivors of early onset cancer (aged 0–34 years at diagnosis), with follow‐up for death extending from 1971 through 2012. A sibling cohort and population data were used as reference. The overall standardized mortality ratio (SMR) of cancer patients was 4.6‐fold, (95% CI 4.4–4.8). Highest SMRs were found for malignancies (12.8, 95% CI 12.3–13.3), infectious (4.8, 95%CI 2.9–6.7) and cardiovascular diseases (1.9, 95% CI 1.7–2.1). Malignancies and cardiovascular diseases accounted for the largest number of deaths. Childhood and YA cancer survivors with the same primary cancer site had a similarly elevated overall SMR with the exception of markedly higher SMRs after childhood Hodgkin lymphoma. The highest cumulative non‐malignancy‐related mortality was due to cardiovascular disease with a steady rise throughout the follow‐up, but strongly dependent on the primary cancer site and age at diagnosis. In childhood cancer survivors, the cumulative cardiovascular mortality did not reduce over time. However, overall and malignancy‐related mortality showed a declining tendency towards the most recent periods after both, childhood and YA cancer. Our findings on non‐malignancy‐related mortality stress the need to set up long‐term individual follow‐up with a focus on cardiovascular late effects for early onset cancer survivors, especially for YA cancer survivors still lacking those.

Radiation therapy and concurrent topotecan followed by maintenance triple anti‐angiogenic therapy with thalidomide, etoposide, and celecoxib for pediatric diffuse intrinsic pontine glioma

Despite major treatment attempts, the prognosis for pediatric diffuse intrinsic pontine gliomas (DIPGs) remains dismal. Gliomas are highly vascularized tumors, suggesting that the prevention of vessel formation by anti‐angiogenic treatment might be effective.

Quality of life and late-effects among childhood brain tumor survivors: a mixed method analysis

Reports on the quality of life (QOL) of childhood brain tumor (BT) survivors have been inconsistent. As cognitive limitations may restrict their participation in questionnaire‐based studies, our aim was to evaluate in depth the QOL with a mixed‐method analysis.

Late morbidity in long-term survivors of childhood brain tumors: a nationwide registry-based study in Finland

BACKGROUND The population of long-term survivors of childhood brain tumors (BTs) is growing. The aim of our study was to evaluate late-appearing morbidity in BT survivors. METHODS Patients diagnosed with a BT at the age of 0-15 years between 1970 and 2004, and surviving at least 5 years, were identified from the Finnish Cancer Registry (n = 740). Their late new morbidity ≥ 5 years after cancer diagnosis was assessed using the Hospital Discharge Registry containing hospitalizations and outpatient visits in specialized health care settings. The morbidity of BT survivors was compared with that of the sibling cohort (n = 3615). RESULTS The 5-year survivors had a significantly increased hazard ratio (HR) for endocrine diseases (HR, 14.7), psychiatric disorders (HR, 1.8), cognitive and developmental disorders (HR, 16.6), neurological diseases (HR, 9.8), disorders of vision and hearing (HR, 10.5), and diseases of the circulatory system (HR, 2.7) compared with the sibling cohort. The HRs for disorders of musculoskeletal system (HR, 1.4) and diseases of the kidney (HR, 2.1) were not significantly increased. Radiation treatment did not explain all of the excess morbidity. Female survivors had a higher risk for disorders of vision and hearing (P = .046). Age at diagnosis did not show an effect on HRs. The HRs for endocrine diseases and disorders of vision or hearing loss were highest for survivors treated in the 1980s or later. CONCLUSIONS Pediatric BT survivors had significant neurocognitive consequences. This, together with the considerable risk for endocrine morbidity, will motivate us to organize systematic follow-up procedures for pediatric BT survivors.

Endothelial function in long-term survivors of childhood acute lymphoblastic leukemia: Effects of a home-based exercise program

The risk for cardiovascular disease (CVD) is increased in long‐term survivors of childhood acute lymphoblastic leukemia (ALL). Chemotherapy may have direct toxic effects on vascular endothelium, potentially increasing the significance of endothelial dysfunction in the development of CVD in ALL survivors. Endothelial structure and function can be measured with carotid intima media thickness (IMT) and brachial flow mediated dilation (FMD). IMT and FMD are intermediate markers of CVD. We studied endothelial function and the effects of an exercise program on vascular endothelium in long‐term survivors of childhood ALL.

Evaluation of the effects of different transfusion trigger levels during the treatment of childhood acute lymphoblastic leukemia.

Differences in the triggering levels for red blood cell (RBC) and platelet (PLT) transfusions were analyzed in association to the amount and total costs of transfusions and the number of febrile episodes during childhood acute lymphoblastic leukemia (ALL) treatment. Transfusions are given with hemoglobin (Hb) ≤90 to 100 g/L and PLT count ≤20 to 30×109/L in Tampere, and with Hb ≤80 g/L and PLT count ≤10×109/L in Turku. Median pretransfusion PLT count was 48×109/L in Tampere, and 16×109/L in Turku. The number and costs of PLT transfusions were 35% higher in Tampere. Median Hb before transfusion was 95 g/L in Tampere, and 77 g/L in Turku. The costs of RBC transfusions were 29% lower in Turku as child units (90 mL) were preferred. The number of RBC transfusions was associated with the treatment protocol (P=0.001), and PLT transfusions with the treatment protocol (P<0.001) and the treatment center (P=0.04). The number of febrile episodes was associated with the treatment protocol (P=0.03), and age at diagnosis (P=0.07). Lower trigger levels did not cause more delays or complications in treatment. Clinical trials are, however, necessary to determine optimal criteria for supportive blood transfusions in childhood cancer patients.

Complications associated with central venous access device in children with haemophilia: a nationwide multicentre study in Finland.

Children with haemophilia require venous access for regular infusion of coagulation factors. A central venous access device (CVAD) ensures long‐term access but associates with infectious and non‐infectious complications with proposed risk factors of young age at initial CVAD implantation and presence of an inhibitor. Our aim was to evaluate the incidence and risk factors for complications associated with CVAD usage in a retrospective nationwide multicentre study in five Finnish Paediatric Haemophilia Treatment Centers. Our study investigated 106 CVADs in 58 patients with 137 971 CVAD days. The median access survival was 1159 CVAD days, and most often a malfunction led to CVAD removal after a long survival (median of 1640 CVAD days). We detected a very low bloodstream infection rate (0.12/1000 CVAD days). The presence of neutralizing inhibitor was a significant risk factor for infection. Heparin vs. saline flushing did not influence the CVAD outcome. We detected a lower infection rate than previously reported, although 90% of the patients were very young (<2 years) at first insertion (median age = 1.02 year). Port access was frequent after initial implantation: six patients (10%) used the port daily for immune tolerance induction therapy and 74% at least twice weekly for prophylaxis. Young age did not increase the risk of infections, as 59% of the CVAD‐related infections were recorded in children over 6 years of age. Our national experience confirms the safety of prophylactic factor concentrate administration via ports even in very young children.

A high circulating copy number of HHV‐6 due to chromosomal integration in a child with acute lymphoblastic leukemia

We report a case of a 3.5‐year‐old female with a very high copy number of human herpesvirus 6 (HHV‐6) detected by PCR in blood during acute lymphoblastic leukemia induction therapy. The patient was unsuccessfully treated with antiviral drugs. HHV‐6 genome was shown to be constitutively integrated into chromosome 22q‐tel, likely to be inherited from the mother who was found to carry high HHV‐6 copy number. This case highlights the importance of excluding HHV‐6 chromosomal integration before diagnosing HHV‐6 infection or reactivation in immunocompromised patients. Pediatr Blood Cancer. 2010;55:1236–1238.