Johan Arvidson

Post-transplant lymphoproliferative disease and other Epstein-Barr virus diseases in allogeneic haematopoietic stem cell transplantation after introduction of monitoring of viral load by polymerase chain reaction

The clinical value of monitoring of Epstein-Barr virus (EBV) viraemia by quantitative polymerase chain reaction during 1 y was evaluated. 39 recipients of allogeneic hematopoietic stem cell transplantation (SCT) were followed. More than 100 EBV genome equivalents (gEq)/ml in blood or plasma were found in 16/39 patients (41%) at 34 d (range 1–139) post-transplant. Seven of these 16 patients developed EBV disease; 3 post-transplant lymphoproliferative disease (PTLD), 1 myelitis, 1 encephalitis and 2 reactivations with fever. EBV diseases were only found in the high-risk group among recipients of mismatched related or unrelated donor grafts or in patients who underwent reduced-intensity conditioning. In this group, 3/20 (15%) developed PTLD. Conditioning with antithymocyte globulin was significantly associated with EBV disease (p<0.01). EBV load in plasma was more strongly associated with EBV disease than viral load in blood. A cut-off level of 1000 gEq/ml plasma distinguished EBV disease from asymptomatic viraemia, but not PTLD from other EBV diseases. Weekly monitoring of EBV load in plasma in high-risk patients in the first 3 months following SCT seems to be of value for prediction of EBV disease. Therapy for PTLD including rituximab was evaluated during 2 y and showed response in 4/6 cases.

Comparison of a Duplex Quantitative Real-Time PCR Assay and the COBAS Amplicor CMV Monitor Test for Detection of Cytomegalovirus

ABSTRACT A duplex quantitative real-time PCR (qPCR) assay was designed to detect both the polymerase gene (pol) and the glycoprotein gene (gB) of cytomegalovirus (CMV). The detection limit of the qPCR was determined to be 1 to 3 copies/reaction and the linear measure interval was 103 to 108 copies/ml. The qPCR system was compared to the COBAS Amplicor CMV Monitor test (COBAS) by an analysis of 138 plasma samples. Both systems detected CMV in 71 cases and had negative results for 33 samples. In addition, 34 samples were positive by qPCR and negative by the COBAS assay, but in no case was the COBAS result positive and the qPCR result negative. Thus, qPCR detected 48% more positive cases than the COBAS method. For samples with ≥105 copies/ml by qPCR, a saturation effect was seen in the COBAS assay and quantification required dilution. Copy numbers for pol and gB by qPCR generally agreed. However, the reproducibility of qPCR assays and the need for an international standard are discussed. Discrepant copy numbers for pol and gB by qPCR were found for samples from two patients, and sequence analysis revealed that the corresponding CMV strains were mismatched at four nucleotide positions compared with the gB fragment primer sequences. In conclusion, a duplex qPCR assay in a real-time format facilitates quantitative measurements and minimizes the risk of false-negative results.

A long-term follow-up study of psychosocial functioning after autologous bone marrow transplantation in childhood

Psychosocial functioning was assessed in 26 subjects treated with autologous bone marrow transplantation (ABMT) for leukaemia or lymphoma before the age of 18 years. The median time from ABMT was 7 years (range 2–10 years), and the median age of the subjects at the evaluation was 16 years (range 7–24 years). Patients, parents and teachers were used as informants. Parents of subjects in the ABMT group reported more behaviour problems than in a normative sample of school children, in particular of the internalising problem type, a finding also supported by the teachers’ report on the childrens behaviour at school. The magnitude of the behaviour problems correlated positively to CNS treatment intensity. The parents rated their childrens school competence as lower than did parents of a normative sample. All school children (n=18) were in regular education, although five pupils were receiving individual tutorial help. Overall, the patients reported a positive view on their own functioning, in contrast to the higher levels of psychosocial problems reported by their parents and teachers. The results thus show, that the psychosocial functioning seen in children treated because of cancer is dependent on the type of informant used. Copyright

Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood

Frisk P, Arvidson J, Larsson M, Naessén T. Risk factors for cardiovascular disease are increased in young adults treated with stem cell transplantation during childhood.

Neuropsychological functioning after treatment for hematological malignancies in childhood, including autologous bone marrow transplantation

Neuropsychological functioning and academic achievement were assessed in 26 patients 2-10 years after autologous bone marrow transplantation (ABMT) for childhood hematological malignancies. Serial tests of general intelligence before and after ABMT were supplemented with a cross-sectional study of neuropsychological functioning. Test results for general intelligence were in the normal range and mainly unaffected over time, but below average performance in specific neuropsychological tests was found in a higher number of children than expected, especially for the variables Strategies, Attention, and Memory. All school children were in regular classes; 5/15 obtained extra tutorial help and two of them had major learning difficulties. Eight young adults reported normal academic achievement. Low age at diagnosis and long time since ABMT correlated significantly with lower test results on general intelligence and Attention, and high intensity of treatment directed to the central nervous system correlated with more learning difficulties as assessed by teachers. Children with identified problems in school were offered educational counseling based on their test profiles. To enable such counseling, it is suggested that both IQ tests and neuropsychological tests on memory and attention be included in follow-up programs for children who have received high-intensity cancer treatment.

Patterns of psychological responses in parents of children that underwent stem cell transplantation

Hematopoietic stem cell transplantation (HSCT) is curative in several life‐threatening pediatric diseases but may affect children and their families inducing depression, anxiety, burnout symptoms, and post‐traumatic stress symptoms, as well as post‐traumatic growth (PTG). The aim of this study was to investigate the co‐occurrence of different aspects of such responses in parents of children that had undergone HSCT.

Self‐reported quality of life in long‐term survivors of childhood lymphoblastic malignancy treated with hematopoietic stem cell transplantation versus conventional therapy

Chronic health conditions are known to be both abundant and severe after pediatric hematopoietic stem cell transplantation (SCT). The present objective was to investigate the impact of disease and treatment on individual QoL and health‐related quality of life (HRQoL) in long‐term survivors of childhood lymphoblastic malignancy treated with conventional therapy versus SCT.

Glomerular and tubular function in young adults treated with stem-cell transplantation in childhood

We evaluated renal function at a median follow-up of 18xa0(range 10.3–22.1)xa0years after total body irradiation in 18 patients treated with stem-cell transplantation (SCT) (autologous SCT in 15 and allogeneic SCT in three) for hematologic malignancies and compared them with 18 healthy controls. No patient had chronic graft-versus-host disease. We found no difference in glomerular filtration rate estimated from cystatin C (105 vs 111xa0ml/min/1.73xa0m2, pu2009=u20090.28). Patients had higher albumin excretion (0.8 vs 0.4xa0mg/mmol, pu2009=u20090.001), but no patient had overt albuminuria (>200xa0mg/L). Patients had higher diastolic blood pressure (74 vs 67xa0mmHg, pu2009=u20090.003). Two patients (11%) had hypertension. Patients had lower tubular reabsorption of phosphate (0.78 vs 0.91xa0mmol/L, pu2009=u20090.014) and higher excretion of α-1-microglobulin (AMG/urine creatinine, 0.4 vs 0.25xa0mg/mmol, pu2009=u20090.038), which correlated with time after SCT (ru2009=u20090.6, pu2009=u20090.01). We found no difference in fractional excretion (FE) of other electrolytes, amino acid excretion, or urine osmolality. We conclude that renal function was relatively well preserved at a median follow-up of 18xa0years after childhood SCT. The higher albumin excretion in our patients is of concern, as is the association between excretion of AMG and time after SCT, suggesting that both glomerular and tubular function may deteriorate further.

Does school attendance during initial cancer treatment in childhood increase the risk of infection

The present study aimed to investigate the relationship between school attendance and infection requiring antimicrobial treatment in children undergoing treatment for cancer.

Parents and children's perceptions of distress related to oral mucositis during haematopoietic stem cell transplantation

Oral mucositis is a common and debilitating side effect of haematopoietic stem cell transplantation. Our study investigated parents and childrens experiences of oral mucositis treatment and whether the parents perceptions accurately reflected the childrens views.