Eva Bergsträsser

Procarbazine-Free OEPA-COPDAC Chemotherapy in Boys and Standard OPPA-COPP in Girls Have Comparable Effectiveness in Pediatric Hodgkin's Lymphoma: The GPOH-HD-2002 Study

PURPOSE Vincristine, etoposide, prednisone, and doxorubicin (OEPA)-cyclophosphamide, vincristine, prednisone, and dacarbazine (COPDAC) is derived from standard vincristine, procarbazine, prednisone, and doxorubicin (OPPA)-cyclophosphamide, vincristine, procarbazine, and prednisone (COPP) chemotherapy by replacing procarbazine with etoposide and dacarbazine for a potentially less gonadotoxic regimen for boys with Hodgkins lymphoma (HL). PATIENTS AND METHODS Five hundred seventy-three pediatric patients with classical HL were enrolled onto the German Society of Pediatric Oncology and Hematology-Hodgkins Disease (GPOH-HD) -2002 study between November 2002 and December 2005. Boys received two courses of OEPA and girls received two courses of OPPA for induction. Treatment group (TG) -2 (intermediate stages) and TG-3 (advanced stages) patients received further two or four cycles COPP (girls) or COPDAC (boys), respectively. After chemotherapy all patients received involved-field irradiation with 19.8 Gy, except for patients with early-stage disease (TG-1) in complete remission. RESULTS Five hundred seventy-three patients (287 males and 286 females) were less than 18 years old and fulfilled all inclusion criteria; 195 patients (34.0%) were allocated to TG-1, 139 (24.3%) were allocated to TG-2, and 239 (41.7%) were allocated to TG-3. Toxicity of OEPA-COPDAC was tolerable overall. Hematotoxicity was more pronounced with OEPA than OPPA, whereas it was less pronounced with COPDAC compared with COPP. The median observation time was 58.6 months. Overall survival and event-free survival (EFS) rates (+/- SE) at 5 years were 97.4% +/- 0.7% and 89.0% +/- 1.4%, respectively. In TG-1, overall EFS was 92.0% +/- 2.0%. EFS of patients without irradiation (93.2% +/- 3.3%) was similar to that of irradiated patients (91.7% +/- 2.5%), confirming results of the previous GPOH-HD-95 study. In TG-2+3, EFS did not significantly differ between boys and girls (90.2% +/- 2.3 v 84.7% +/- 2.7, respectively; P = .12). CONCLUSION In TG-2+3, results in boys and girls are superimposable. OPPA-COPP and OEPA-COPDAC seem to be exchangeable regimens in intermediate- and advanced-stage classical HL in pediatric patients.

The International Prognostic Scoring System (IPSS) for childhood myelodysplastic syndrome (MDS) and juvenile myelomonocytic leukemia (JMML)

The International Prognostic Scoring System (IPSS) for myelodysplastic syndrome (MDS) is based upon weighted data on bone marrow (BM) blast percentage, cytopenia, and cytogenetics, separating patients into four prognostic groups. We analyzed the value of the IPSS in 142 children with de novo MDS and 166 children with juvenile myelomonocytic leukemia (JMML) enrolled in retro- and prospective studies of the European Working Group on childhood MDS (EWOG-MDS). Survivals in MDS and JMML were analyzed separately. Among the criteria considered by the IPSS score, only BM blasts <5% and platelets >100 × 109/l were significantly associated with a superior survival in MDS. In JMML, better survival was associated with platelets >40 × 109/l, but not with any other IPSS factors including cytogenetics. In conclusion, the IPSS is of limited value in both pediatric MDS and JMML. The results reflect the differences between myelodysplastic and myeloproliferative diseases in children and adults.

Normal values for aortic diameters in children and adolescents – assessment in vivo by contrast-enhanced CMR-angiography

BackgroundContrast-enhanced CMR angiography (CE-CMRA) is being increasingly used for diagnosing aortic arch anomalies, planning interventions and follow-up assessment. We sought to establish normal values for the diameters of the thoracic aorta and reference curves related to body growth in children using CE-CMRA.ResultsCE-CMRA was performed in 53 children without cardiovascular disease. The median age was 9 years (range 2 – 20 years), weight 30 kg (range 12 – 75 kg), height 131 cm (range 81 – 184 cm), body surface area (BSA) 1.05 m2 (range 0.52–1.9 m2). Aortic diameters were measured at nine standardized sites on oblique maximum-intensity projection (MIP) images. Regression analysis of diameters in relation to BSA demonstrated linear relationship between the cross-sectional aortic diameters and the square root of BSA (BSA0.5). Normative diameters were (0.57 + 19.37*BSA0.5) mm for the aortic sinus, (-3.52 + 18.66*BSA0.5) mm for the first segment of the aortic arch, (-3.37 + 16.52*BSA0.5) mm for the isthmic region and (-1.27 + 9.89*BSA0.5) mm for the descending aorta at the level of the diaphragm. Normative curves are presented.ConclusionThis study provides normative values for aortic diameters in children measured by CE-CMRA. These data may serve for making the diagnosis of pediatric arch anomalies, assessing the need for treatment and planning interventions.

qPET – a quantitative extension of the Deauville scale to assess response in interim FDG-PET scans in lymphoma

BackgroundInterim FDG-PET is used for treatment tailoring in lymphoma. Deauville response criteria consist of five ordinal categories based on visual comparison of residual tumor uptake to physiological reference uptakes. However, PET-response is a continuum and visual assessments can be distorted by optical illusions.ObjectivesWith a novel semi-automatic quantification tool we eliminate optical illusions and extend the Deauville score to a continuous scale.Patients and methodsSUVpeak of residual tumors and average uptake of the liver is measured with standardized volumes of interest. The qPET value is the quotient of these measurements. Deauville scores and qPET-values were determined in 898 pediatric Hodgkin’s lymphoma patients after two OEPA chemotherapy cycles.ResultsDeauville categories translate to thresholds on the qPET scale: Categories 3, 4, 5 correspond to qPET values of 0.95, 1.3 and 2.0, respectively. The distribution of qPET values is unimodal with a peak representing metabolically normal responses and a tail of clearly abnormal outliers. In our patients, the peak is at qPET = 0.95 coinciding with the border between Deauville 2 and 3. qPET cut values of 1.3 or 2 (determined by fitting mixture models) select abnormal metabolic responses with high sensitivity, respectively, specificity.ConclusionsqPET methodology provides semi-automatic quantification for interim FDG-PET response in lymphoma extending ordinal Deauville scoring to a continuous scale. Deauville categories correspond to certain qPET cut values. Thresholds between normal and abnormal response can be derived from the qPET-distribution without need for follow-up data. In our patients, qPET < 1.3 excludes abnormal response with high sensitivity.

Port-A-Cath–Related Thrombosis and Postthrombotic Syndrome in Pediatric Oncology Patients

OBJECTIVE To investigate Port-A-Cath (PAC)-related thrombosis and postthrombotic syndrome (PTS) in children with cancer. STUDY DESIGN The study population was a consecutive cohort of children diagnosed with cancer and a PAC implanted at diagnosis. Children were evaluated for the presence of PAC-related thrombosis by magnetic resonance venography and the presence of congenital prothrombotic risk factors and PTS. RESULTS A total of 114 children (median age, 6.04 years) were included. Of these children, 48 (42%) were treated for solid tumors and 66 (58%) were treated for hematopoietic tumors, including 38 for acute lymphoblastic leukemia. At the time of magnetic resonance venography, 42 children (37%) had the PAC still in place, and 72 (63%) had the PAC removed. Overall, PACs were in place for a total of 324.92 PAC-years. PAC-related thrombosis was detected in 45 children (39.5%) with a current or previous PAC. Of these, 21 (47%) had a solid tumor, 14 (31%) had acute lymphoblastic leukemia, and 10 (22%) had another hematopoietic tumor. Younger age at diagnosis, female sex, duration of PAC use, and left-side PAC placement were independently associated with an increased risk of thrombosis, whereas asparaginase therapy and the presence of inherited prothrombotic risk factors were not. Mild PTS (ie, presence of prominent collateral vessels in the skin) was present in 5.6% of the children. CONCLUSION PAC-related thrombosis is common in pediatric oncology patients. In some children, thrombotic complications can lead to the development of PTS.

Information needs in parents of long-term childhood cancer survivors.

Parents’ knowledge about cancer, treatment, potential late effects and necessary follow‐up is important to reassure themselves and motivate their child to participate in regular follow‐up. We aimed to describe (i) parents’ perception of information received during and after treatment; (ii) parents’ current needs for information today, and to investigate; and (iii) associations between information needs and socio‐demographic and clinical characteristics.

Paraneoplastic syndromes in ganglioneuroblastoma: contrasting symptoms of constipation and diarrhoea

A paraneoplastic syndrome is occasionally the first clinical symptom seen with tumours. We report on two children who initially presented with paraneoplastic syndromes due to ganglioneuroblastomas: the first with severe watery diarrhoea caused by a ganglioneuroma producing vasoactive intestinal peptide, the second with non-treatable constipation, caused by ganglioneuroma-produced anti-neuronal nuclear antibodies. Conclusion: Either severe diarrhoea or chronic constipation may represent rare paraneoplastic syndromes in ganglioneuroblastomas.

Self-Monitoring of Oral Anticoagulation Therapy in Children

This study aimed to investigate the accuracy of home International Normalized Ratio (INR) self-monitoring in pediatric patients on long-term oral anticoagulation therapy. Statistical and clinical agreement of INR values from capillary whole blood samples measured by 2 different portable prothrombin time monitors (CoaguChek S and XS) and venous blood samples measured by a laboratory coagulation analyzer were evaluated using the Bland-Altman analysis. Eighty-three INR comparisons (56 using the CoaguChek S and 27 using the CoaguChek XS) were obtained from 35 children aged 4 months to 18 years. Mean differences between venous and capillary INR values and their limits of agreement were –0.04 (–0.63 to 0.55) overall, 0.006 (–0.63 to 0.65) for the CoaguChek S and –0.13 (–0.57 to 0.31) for the CoaguChek XS. The Pearson correlation coefficients were 0.88 overall, 0.84 for the CoaguChek S and 0.95 for the CoaguChek XS. Expanded and narrow agreements for all patients were 97.6 and 94%, respectively. In conclusion, home INR self-monitoring is accurate for children requiring long-term oral anticoagulation therapy. Our data suggest that INR self-monitoring with the newer CoaguChek XS is more accurate than with the older CoaguChek S monitor.

Haemophagocytosis in early congenital syphilis

Abstract A previously healthy male infant developed hepatosplenomegaly, severe anaemia and thrombocytopenia 5 weeks after birth. Marked haemophagocytosis was present in the bone marrow. A typical maculopapular rash suggested early congenital syphilis. The diagnosis was confirmed by serology and by the presence of untreated syphilis in both parents. Conclusion Syphilis needs to be excluded in infants suspected of haemophagocytic lymphohistiocytosis.

Mutational analysis of SHOC2, a novel gene for Noonan-like syndrome, in JMML

To the editor: Cordeddu et al recently reported the discovery of a specific SHOC2 gene mutation underlying a variant of the neuro-cardio-facio-cutaneous (NCFC) syndrome family.[1][1] The common denominator of mutations associated with this group of disorders is their involvement in the