| 1. |
- Chargari, Cyrus, et al.
(author)
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Brachytherapy for Pediatric Patients at Gustave Roussy Cancer Campus : A Model of International Cooperation for Highly Specialized Treatments
- 2022
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In: International Journal of Radiation Oncology Biology Physics. - : Elsevier BV. - 0360-3016. ; 113:3, s. 602-613
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Journal article (peer-reviewed)abstract
- Purpose: Childhood cancer is rare, and treatment is frequently associated with long-term morbidity. Disparities in survival and long-term side effects encourage the establishment of networks to increase access to complex organ-conservative strategies, such as brachytherapy. We report our experience of an international cooperation model in childhood cancers. Methods and Materials: We examined the outcome of all children referred to our center from national or international networks to be treated according to a multimodal organ-conservative approach, including brachytherapy. Results: We identified 305 patients whose median age at diagnosis was 2.2 years (range, 1.4 months to 17.2 years). Among these patients, 99 (32.4%) were treated between 2015 and 2020; 172 (56.4%) were referred from national centers; and 133 (43.6%) were international patients from 31 countries (mainly Europe). Also, 263 patients were referred for primary treatment and 42 patients were referred for salvage treatment. Genitourinary tumors were the most frequent sites, with 56.4% bladder/prostate rhabdomyosarcoma and 28.5% gynecologic tumors. In addition to brachytherapy, local treatment consisted of partial tumor resection in 207 patients (67.9%), and 39 patients (13%) had additional external radiation therapy. Median follow-up was 58 months (range, 1 month to 48 years), 93 months for national patients, and 37 months for international patients (P < .0001). Five-year local control, disease-free survival, and overall survival rates were 90.8% (95% confidence interval [CI], 87.3%-94.4%), 84.4% (95% CI, 80.1%-89.0%), and 93.3% (95% CI, 90.1%-96.5%), respectively. Patients referred for salvage treatment had poorer disease-free survival (P < .01). Implementation of image guided pulse-dose-rate brachytherapy was associated with better local control among patients with rhabdomyosarcoma referred for primary treatment (hazard ratio, 9.72; 95% CI, 1.24-71.0). At last follow-up, 16.7% patients had long-term severe treatment-related complications, and 2 patients (0.7%) had developed second malignancy. Conclusions: This retrospective series shows the feasibility of a multinational referral network for brachytherapy allowing high patient numbers in rare pediatric cancers. High local control probability and acceptable late severe complication probability could be achieved despite very challenging situations. This cooperation model could serve as a basis for generating international reference networks for high-tech radiation such as brachytherapy to increase treatment care opportunities and cure probability.
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| 2. |
- Ljung, Rolf, et al.
(author)
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BAY 81-8973 Efficacy and Safety in Previously Untreated and Minimally Treated Children with Severe Hemophilia A : The LEOPOLD Kids Trial
- 2023
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In: Thrombosis and Haemostasis. - : Georg Thieme Verlag KG. - 0340-6245 .- 2567-689X. ; 123:1, s. 27-39
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Journal article (peer-reviewed)abstract
- INTRODUCTION: BAY 81-8973, a full-length recombinant factor VIII for hemophilia A treatment, has been extensively evaluated in previously treated patients in the LEOPOLD (Long-Term Efficacy Open-Label Program in Severe Hemophilia A Disease) clinical trials.AIM: To assess BAY 81-8973 efficacy and safety when used for bleed prophylaxis and treatment in previously untreated/minimally treated patients (PUPs/MTPs).METHODS: In this phase III, multicenter, open-label, uncontrolled study, PUPs/MTPs (<6 years old) with severe hemophilia A received BAY 81-8973 (15-50 IU/kg) at least once weekly as prophylaxis. Primary efficacy endpoint was the annualized bleeding rate (ABR) within 48 hours after prophylaxis infusion. Adverse events and immunogenicity were assessed. Patients who developed inhibitors were offered immune tolerance induction (ITI) treatment in an optional extension phase.RESULTS: Fifty-two patients were enrolled, with 43 patients (mean age: 13.6 months) treated. Median (interquartile range) ABR for all bleeds within 48 hours of prophylaxis infusion was 0.0 (0.0-1.8) among patients without inhibitors ( n = 20) and 0.0 (0.0-2.2) among all patients. As expected, inhibitors were the most frequent treatment-related adverse event (high titer: 17 [39.5%] patients; low titer: 6 [13.9%] patients). Six of 12 patients who underwent ITI treatment in the extension phase (high titer [ n = 5], low titer [ n = 1]) achieved a negative inhibitor titer. CONCLUSION: BAY 81-8973 was effective for bleed prevention and treatment in PUPs/MTPs. The observed inhibitor rate was strongly influenced by a cluster of inhibitor cases, and consequently, slightly higher than in other PUP/MTP studies. Overall, the BAY 81-8973 benefit-risk profile remains unchanged and supported by ongoing safety surveillance. Immune tolerance can be achieved with BAY 81-8973.
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| 3. |
- Molgaard-Hansen, Lene, et al.
(author)
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Early and treatment-related deaths in childhood acute myeloid leukaemia in the Nordic countries: 1984-2003.
- 2010
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In: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 151:5, s. 447-59
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Journal article (peer-reviewed)abstract
- Despite major improvements in the cure rate of childhood acute myeloid leukaemia (AML), 5-15% of patients still die from treatment-related complications. In a historical prospective cohort study, we analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment-related deaths (TRD) in 525 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-84, -88 and -93 trials. Seventy patients (13%) died before starting treatment or from treatment-related complications. The death rate rose from 11% in NOPHO-AML-84 to 29% in -88, but then fell to 8% in -93. Sixteen patients (3%) died within the first 2 weeks, mainly from bleeding or leucostasis. Hyperleucocytosis, age <2 or ≥10 years were risk factors. After day 15, 10% of patients died from treatment-related complications with infection as the main cause of death. Risk factors were age <2 or ≥10 years and treatment according to the NOPHO-AML-88 protocol. The number of EDs and TRDs in AML is high. Therefore optimal antifungal prophylaxis is essential, and studies on the benefit of antibacterial prophylaxis and individual risk factors for ED and TRD are needed.
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| 4. |
- Molgaard-Hansen, Lene, et al.
(author)
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Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only : a NOPHO-AML study
- 2011
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 57:7, s. 1222-1229
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Journal article (peer-reviewed)abstract
- BACKGROUND: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services, health experience, social outcomes, and lifestyle behavior of AML survivors with that of their sibling controls. METHODS: This population-based study included 138 children treated for AML according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO)-AML-84, -88, and -93 trials, and alive by June 30, 2007. Patients treated with hematopoietic stem cell transplantation (HSCT) or relapse were not included. Altogether, 102 (74%) survivors and 91% of their siblings completed a questionnaire. RESULTS: The median follow-up was 11 (range 4-25) years after diagnosis. AML survivors had no increased rate of hospitalization compared with sibling controls, but were more often receiving prescription drugs, especially for asthma (23% vs. 9%, P = 0.03). Self-reported health experience was excellent or very good in 77% and comparable with that of siblings. Educational achievement, employment, and marital status were comparable in the two groups. Among surviving AML patients, 23% were current smokers and 24% of their siblings were current smokers. CONCLUSIONS: The self-reported health of children treated on NOPHO-AML protocols without HSCT was good, and their use of health care services was limited. Reported health and social outcomes were comparable to those of their siblings. Many survivors were smoking which may increase the risk of late effects.
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| 5. |
- Molgaard-Hansen, Lene, et al.
(author)
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Treatment-related deaths in second complete remission in childhood acute myeloid leukaemia.
- 2011
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In: British journal of haematology. - : Wiley. - 1365-2141 .- 0007-1048. ; 152:5, s. 623-30
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Journal article (peer-reviewed)abstract
- The frequency and causes of treatment-related deaths (TRD) in second complete remission (CR2) in acute myeloid leukaemia (AML) were investigated in a historical, prospective cohort study of 429 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-88 and -93 trials. Relapse occurred in 158 children (39%). Seventeen (18%) of the 96 patients entering CR2 suffered TRD. The main causes were infection (59%) and complications from graft-versus-host disease (22%). Fourteen (82%) of 17 TRDs occurred in children undergoing haematopoietic stem cell transplantations (HSCT). Optimal supportive care after HSCT is essential, and studies on risk factors for TRD are needed.
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| 6. |
- Mårtensson, Annika, et al.
(author)
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Origin of pathogenic variant and mosaicism in families with a sporadic case of haemophilia B
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In: Haemophilia. - 1351-8216.
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Journal article (peer-reviewed)abstract
- Introduction: Of newly diagnosed cases of haemophilia B, the proportion of sporadic cases is usually 50% of severe cases and 25% of moderate/mild cases. However, cases presumed to be sporadic due to family history may not always be sporadic. Few case reports have been published on mosaicism in haemophilia B. Aim: The present study aimed to trace the origin of the pathogenic variant in a well-defined cohort of sporadic cases of haemophilia B by haplotyping markers. It also aimed to determine the frequency of mosaicism in presumed non-carrier mothers. Methods: The study group was 40 families, each with a sporadic case of haemophilia B analysed in two-to-three generations by Sanger sequencing, haplotyping and using the sensitive droplet digital polymerase chain reaction (ddPCR) technique. Results: In 31/40 (78%) of the families, the mother carried the same pathogenic variant as her son, while Sanger sequencing showed that 9/40 (22%) of the mothers did not carry this variant. Of these variants, 2/9 (22%) were shown to be mosaics by using the ddPCR technique. 16/21 carrier mothers, with samples from three generations available, had a de novo pathogenic variant of which 14 derived from the healthy maternal grandfather. Conclusion: The origin of the pathogenic variant in sporadic cases of haemophilia B is most often found in the X-chromosome derived from the maternal grandfather or, less often, from the maternal grandmother. Mosaic females seem to be found at the same frequency as in haemophilia A but at a lower percentage of the pathogenic variant.
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| 7. |
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| 8. |
- Skou, Anne-Sofie, et al.
(author)
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Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study.
- 2014
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In: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 61:9, s. 1638-1643
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Journal article (peer-reviewed)abstract
- BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society of Pediatric Hematology and Oncology (NOPHO).METHODS: A population-based cohort of children treated for AML according to the NOPHO-AML-84, -88, and -93 trials included 138 eligible survivors of whom 102 (74%) completed a questionnaire and 104 (75%) had a clinical examination and blood sampling performed. Eighty-five of 94 (90%) eligible sibling controls completed a similar questionnaire. Siblings had no clinical examination or blood sampling performed.RESULTS: At a median of 11 years (range 4-25) after diagnosis, renal, gastrointestinal, and hepatic disorders were rare both in survivors of childhood AML and in sibling controls, with no significant differences. Ferritin was elevated in 21 (21%) AML survivors but none had biochemical signs of liver damage. Viral hepatitis was present in three and cholelithiasis in two AML survivors. One adult survivor had hypertension, two had slightly elevated systolic blood pressure, and eight survivors had slightly elevated diastolic blood pressure. These persons all had normal creatinine and cystatin C levels. Marginal abnormalities in potassium, magnesium, calcium, or bicarbonate levels were found in 34 survivors.CONCLUSION: Survivors of childhood AML treated with chemotherapy only experienced few renal, gastrointestinal, and hepatic late effects.
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| 9. |
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| 10. |
- Wilhelmsson, Mari, et al.
(author)
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Long-term health outcomes in survivors of childhood AML treated with allogeneic HSCT: a NOPHO-AML Study.
- 2019
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In: Bone marrow transplantation. - : Springer Science and Business Media LLC. - 1476-5365 .- 0268-3369. ; 54:726-736
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Journal article (peer-reviewed)abstract
- Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improves event-free survival in acute myeloid leukemia (AML); however, the burden of late effects may be increased. We compared health-related outcomes in childhood AML survivors treated according to the NOPHO-AML protocols either with or without allo-HSCT at age<21 years. Out of the 147 eligible AML survivors treated with allo-HSCT, 95 (65%) and 53 (75%) of their eligible siblings completed a questionnaire. Their data were compared to corresponding data collected previously from NOPHO-AML survivors treated with chemotherapy only (CT) (n=101). The median follow-up was 12 (range 2-28) years after allo-HSCT and 47% had received total body irradiation (TBI)-based conditioning. Allo-HSCT survivors reported significantly more physical health limitations (39% vs 7%, p<0.005), medications for cardiovascular disease (10% vs 1%, p<0.05) and use of analgesics (32% vs 11%, p<0.01) than CT survivors. Health problems prevented 16% of the allo-HSCT survivors from attending school or managing a job vs. 3% among CT survivors (p<0.05). Among 73 allo-HSCT survivors (age≥15 years), seven females reported natural pregnancies and three males reported unassisted conceptions in partners. Survivors of childhood AML treated with allo-HSCT experienced more physical health limitations and used more medications than the survivors treated with chemotherapy only.
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| 11. |
- Zeller, Bernward, et al.
(author)
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Hyperleucocytosis in paediatric acute myeloid leukaemia : the challenge of white blood cell counts above 200 x 109/l. The NOPHO experience 1984-2014
- 2017
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In: British Journal of Haematology. - : Wiley. - 0007-1048 .- 1365-2141. ; 178:3, s. 448-456
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Journal article (peer-reviewed)abstract
- Hyperleucocytosis in paediatric acute myeloid leukaemia (AML) is associated with increased morbidity and mortality. We studied hyperleucocytosis in 890 patients with AML aged 0-18 years registered in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) registry, with special focus on very high white blood cell counts (WBC > 200 x 10/l). Eighty-six patients (10%) had WBC 100-199 x 109/l and 57 (6%) had WBC >= 200 x 109/l. Patients with WBC >= 200 x 109/l had a high frequency of t(9;11) and a paucity of trisomy 8. Due to the high frequency of deaths within the first 2 weeks (30% vs. 1% for all others), overall survival in this group was inferior to patients with WBC <200 x 109/l (39% vs. 61%). Main cause of early death was intracranial haemorrhage and leucostasis. Twenty-six per cent of these patients never started antileukaemic protocol therapy. Leukapheresis or exchange transfusion was used in 24% of patients with hyperleucocytosis without impact on survival. Patients with hyperleucocytosis surviving the first week had identical survival as patients with lower WBC. We conclude that death within the first days after diagnosis is the major challenge in patients with high WBC and advocate rapid initiation of intensive chemotherapy.
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