Posterior Reversible Encephalopathy Syndrome: Risk Factors and Impact on the Outcome in Children With Acute Lymphoblastic Leukemia Treated With Nordic Protocols.

Posterior reversible encephalopathy syndrome (PRES) in children with acute lymphoblastic leukemia has been increasingly recognized as a clinicoradiological entity. Our aim was to describe the incidence of PRES in pediatric patients with ALL, identify its risk factors, and examine its prognostic importance. For this research, we conducted a systematic, retrospective review of the patient records in a population-based series of children with acute lymphoblastic leukemia (n=643) treated in Finland from 1992 to 2008. Of the patients with ALL, 4.5% (n=29) developed radiologically confirmed PRES, of which 28 cases occurred during induction. Hypertension (P=0.006; odds ratio [OR], 4.10, confidence interval [CI], 1.50-11.25), constipation (P=0.001; OR, 5.60; CI, 2.02-15.52), and >14 days of alkalinization (P=0.017; OR, 3.27; CI, 1.23-8.68) were significant independent risk factors for PRES. One-third of the patients developed epilepsy. Relapses occurred significantly more often in those patients with PRES (P=0.001), which was associated with worse overall survival (P=0.040; 5-year survival=75.9% [60.3%-91.4%] vs. 88.4% [85.8%-90.9%]). Using NOPHO-ALL 92/2000 protocols, PRES is a significant early complication of therapy in ALL, and was associated with a poorer prognosis and significant neurological morbidity.

Coinfusion of mobilized hematopoietic stem cells from an HLA-mismatched third-party donor with umbilical cord blood graft to support engraftment.

We evaluated the role of mismatched third-party hematopoietic stem cells (TPC) in shortening the neutropenia after umbilical cord blood transplantation (UCBT). A TPC graft was given to 7/37 children with UCBT to support engraftment due to anticipated increased risk of nonengraftment (N=6) or active infection (N=1). TPC grafts were collected with apheresis from haploidentical family members. The median UCB and CD34 cell counts were 5.10 (range, 4.13 to 9.98)×10/kg and 5.98 (range, 4.40 to 14.00)×10/kg, respectively. The median time to neutrophil engraftment was shorter in the patients with TPC (12 d; range, 9 to 24 d) than those without (23 d; range, 12 to 44 d) (P=0.010). TPC chimerism was lost in median at 28 (range, 24 to 103) days posttransplant. TPC grafts from mothers engrafted similarly as the grafts from other family members. UCB graft cell count and the use of methotrexate posttransplant strongly contributed to engraftment. TPC may form a valuable transient bridging graft over the neutropenia after UCBT in patients with anticipated high-risk of nonengraftment or toxicity due to pretransplant infections.

Physical performance of nontransplanted childhood ALL survivors is comparable to healthy controls.

Physical fitness is an essential feature of overall health. Our objective was to compare the physical performance between nontransplanted acute lymphoblastic leukemia (ALL) patients (study patients), healthy controls, and ALL patients after stem cell transplantation (SCT). Forty-five ALL patients (median age, 13.3 y) treated without cranial irradiation were compared with 34 ALL patients (12.0 y) treated with SCT and total body irradiation and 522 age-matched and sex-matched controls. Their physical performance was assessed by 6 muscle tests measuring speed and dynamic endurance, flexibility, acceleration, maximal speed, and speed differentiation. The patients were tested at a minimum of 3 years after treatment. The muscle test results of the study patients did not differ from that of the healthy controls. The study patients had normal body mass indexes (BMI). Only 42% of them exercised at least once a week. Those who exercised >3 times a week and those with a BMI below median had better results. SCT patients had inferior results in 4 out of 6 tests. The physical performance of nontransplanted ALL patients did not differ from that of healthy controls. A higher physical exercise activity and a BMI below median positively correlated with better muscle performance, supporting the importance of encouraging ALL survivors to exercise and avoid obesity.

Multiple viral infections post-hematopoietic stem cell transplantation are linked to the appearance of chronic GVHD among pediatric recipients of allogeneic grafts.

Delayed immune reconstitution and the ensuing opportunistic infections among children following hematopoietic stem cell transplantation (HSCT) are associated with increased treatment-related morbidity and mortality (TRM). We retrospectively evaluated the impact of viral infections on the posttransplant recovery of pediatric recipients of stem cell grafts as a reflection of their posttransplant immunoreconstitution in a single institution setting. The case histories of 124 children (during 1/1999-9/2006) were reviewed for infectious episodes, and correlated with their respective clinical parameters. Patients with a high risk for CMV received prophylaxis, but failures in the prophylaxis were common (40%). 110/124 (89%) of these allogeneic patients had at least one viral reactivation/clinical infection posttransplant. In this group of pediatric patients chronic GVHD (P<0.001) and secondary graft failure were significantly (P=0.001) associated with early (during the first 100 days post HSCT), multiple (> or = 2) viral infections. Our data indicate that viruses are common pathogens among pediatric recipients of allogeneic stem cell grafts. In this group of patients multiple viral infections early on seem to reflect an even more severe degree of immunological derangement in the recipient and identify a group of patients with an increased risk of chronic GVHD and secondary graft failure.

Osteosarcoma in Finland from 1971 through 1990: a nationwide study of epidemiology and outcome.

BACKGROUND AND PURPOSE: There have only been a few nationwide studies on the epidemiology and outcome of osteosarcoma. We report the clinical features, treatment, and prognosis of osteosarcoma in Finland for the period 1971-1990. METHODS: The study material was derived from population-based data from the national Finnish Cancer Registry. 302 osteosarcomas were reported during the study period. Histological slides could be retrieved for 199 cases and from histological re-examination, 139 (83%) of these cases were confirmed as osteosarcoma and were included in the analysis. The mean length of follow-up was 8 (0.1-28) years. RESULTS: The overall 5-year survival for the whole study population was 58%, with an improvement in survival during 1981-1990 (65%) compared to the period 1971-1980 (47%) (p=0.01). More chemotherapy was administered in the later time period. For metastasis-free survival, diagnosis in the 1970s as opposed to the 1980s (p=0.01) and large tumor size worsened outcome in univariate analysis. Patients who developed metastatic relapse within 10 months of the diagnosis had worse sarcoma-specific survival than those who developed metastases later. Limb-salvage surgery increased from 12% to 23% for patients with a peripheral tumor, with no increase in local relapses. INTERPRETATION: We recommend aggressive approach to treat recurrent disease, with a view to further improving survival. In a small country such as Finland it is necessary to concentrate treatment to only a few centers, to ensure a high quality of treatment.