| 1. |
- Abrahamsson, Jonas, 1954, et al.
(författare)
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Associations between neutrophil recovery time, infections and relapse in pediatric acute myeloid leukemia
- 2018
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:9
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundChildren with acute myeloid leukemia (AML) treated similarly show different toxicity and leukemic responses. We investigated associations between neutrophil recovery time after the first induction course, infection and relapse in children treated according to NOPHO-AML 2004 and DB AML-01. ProcedureNewly diagnosed patients with AML with bone marrow blast<5% between day 15 after the start of the treatment and the start of second induction course, and in complete remission after the second induction course were included (n=279). Neutrophil recovery time was defined as the time from the start of the course to the last day with absolute neutrophil count<0.5x10(9)/l. Linear and Cox regressions were used to investigate associations. ResultsNeutrophil recovery time after the first induction course was positively associated with neutrophil recovery time after the remaining courses, and longer neutrophil recovery time (25 days) was associated with increased risk of grade 3-4 infections (hazard ratio 1.4, 95% confidence interval [CI], 1.1-1.8). Longer neutrophil recovery time after the first induction (>30 days) was associated with the increased risk of relapse (5-year cumulative incidence: 48% vs. 42%, hazard ratio 1.7, 95% CI, 1.1-2.6) for cases not treated with hematopoietic stem cell transplantation in first complete remission. ConclusionLonger neutrophil recovery time after the first induction course was associated with grade 3-4 infections and relapse. If confirmed, this knowledge could be incorporated into risk stratification strategies in pediatric AML.
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| 2. |
- Abrahamsson, Jonas, 1954, et al.
(författare)
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Use of granulocyte colony-stimulating factor and risk of relapse in pediatric patients treated for acute myeloid leukemia according to NOPHO-AML 2004 and DB AML-01.
- 2019
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Ingår i: Pediatric blood & cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 66:6
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Tidskriftsartikel (refereegranskat)abstract
- Supportive-care use of granulocyte colony-stimulating factor (G-CSF) in pediatric acute myeloid leukemia (AML) remains controversial due to a theoretical increased risk of relapse and limited impact on neutropenic complications. We describe the use of G-CSF in patients treated according to NOPHO-AML 2004 and DB AML-01 and investigated associations with relapse.Patients diagnosed with de novo AML completing the first week of therapy and not treated with hematopoietic stem cell transplantation in the first complete remission were included (n=367). Information on G-CSF treatment after each course (yes/no) was registered prospectively in the study database and detailed information was gathered retrospectively from each center. Descriptive statistics were used to describe G-CSF use and Cox regression to assess the association between G-CSF and risk of relapse.G-CSF as supportive care was given to 128 (35%) patients after 268 (39%) courses, with a large variation between centers (0-93%). The use decreased with time-the country-adjusted odds ratio was 0.8/diagnostic year (95% confidence interval [CI] 0.7-0.9). The median daily dose was 5 μg/kg (range 3-12 μg/kg) and the median cumulative dose was 75 μg/kg (range 7-1460 μg/kg). Filgrastim was used in 82% of G-CSF administrations and infection was the indication in 44% of G-CSF administrations. G-CSF was associated with increased risk of relapse-the adjusted hazard ratio was 1.5 (95% CI 1.1-2.2).G-CSF as supportive care was used in a third of patients, and use decreased with time. Our results indicate that the use of G-CSF may be associated with an increased risk of relapse.
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| 3. |
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| 4. |
- af Sandeberg, Margareta, et al.
(författare)
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Does school attendance during initial cancer treatment in childhood increase the risk of infection?
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:8, s. 1307-1312
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Tidskriftsartikel (refereegranskat)abstract
- Background The present study aimed to investigate the relationship between school attendance and infection requiring antimicrobial treatment in children undergoing treatment for cancer. Procedure A national cohort of children aged 7-16 years undergoing cancer treatment was assessed during two observation periods of 19 days each, 1 month (n=89) and 2.5 months (n=89) poststart of treatment. Children free from infection at start of each observation period were included. Multivariable logistic regression analyses were performed including factors potentially associated with start of antimicrobial treatment. Results Twenty-seven (30%) children started antimicrobial treatment during the first observation period. Factors associated with an increased risk of starting antimicrobial treatment were diagnosed with sarcoma (OR=24.37, P=0.002) or non-Hodgkin lymphoma (OR=17.57, P=0.025), having neutropenia (OR=5.92, P=0.020) and age less than 13 years (OR=8.54, P=0.014). During the second observation period, when 20 (22%) children started antimicrobial treatment, the probability of starting treatment was increased in children with neutropenia (OR=4.25, P=0.007). There was no statistically significant association between starting treatment for infection and school attendance. Conclusions In this study, children attending school while undergoing cancer treatment did not run a higher risk of starting antimicrobial treatment than children absent from school. However, there is a need for further studies evaluating risk of infections in children with ongoing cancer treatment.
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| 5. |
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| 6. |
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| 7. |
- Aksnes, L. H., et al.
(författare)
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Health Status at Long-Term Follow-Up in Patients Treated for Extremity Localized Ewing Sarcoma or Osteosarcoma: A Scandinavian Sarcoma Group Study
- 2009
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 53:1, s. 84-89
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Tidskriftsartikel (refereegranskat)abstract
- Background. The purpose of this study was to evaluate late effects and symptom complaints in long-term survivors (>5 years) of Extremity Bone Sarcoma (EBS Survivors). The results were compared with findings in age- and gender-matched individuals from the general Population (NORMs). Patients and Methods. Among 155 EBS Survivors approached, 133 (86%) were included, and 110 of them (83%) attended an outpatient examination. Health status was evaluated by a mailed questionnaire concerning demographic and current health issues, and physical examinations at the outpatient clinic. Age- and gender-adjusted normative controls were drawn from participants of the Health Study of Nord-Trondelag County (HUNT 2). Results. Median age at follow-up was 29 (15-57) years. Median follow-up Was 12 (6-22) years. Of EBS Survivors 42% had >= 1 somatic disease, 33% had ototoxicity and 13% had reduced renal Function. EBS Survivors were more likely to have heart disease (odds ratio [OR], 7.9; 95% confidence interval [95% CI], 2.5-25.3; P=0.001), hypertension (OR, 3.4; 95% Cl, 1.1-10.1; P=0.03) and thyroid disease (OR, 3.0; 95%, Cl, 1.1-8.3; P=0.04) compared to NORMs. EBS Survivors reported more diarrhoea (29% vs. 19%, P=0.02), palpitations (23% vs. 13%, P=0.01) and shortness of breath (11% vs. 5%, P=0.01) than NORMs. Conclusions. EBS Survivors have poorer health status compared to age- and gender-matched controls. Long-term follow-up of these patients is therefore mandatory. Pediatr Blood Cancer 2009;53:84-89. (C) 2009 Wiley-Liss, Inc.
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| 8. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Does minimal central nervous system involvement in childhood acute lymphoblastic leukemia increase the risk for central nervous system toxicity?
- 2022
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 69:7
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Tidskriftsartikel (refereegranskat)abstract
- Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) implicates enhanced intrathecal chemotherapy, which is related to CNS toxicity. Whether CNS involvement alone contributes to CNS toxicity remains unclear. We studied the occurrence of all CNS toxicities, seizures, and posterior reversible encephalopathy syndrome (PRES) in children with ALL without enhanced intrathecal chemotherapy with CNS involvement (n = 64) or without CNS involvement (n = 256) by flow cytometry. CNS involvement increased the risk for all CNS toxicities, seizures, and PRES in univariate analysis and, after adjusting for induction therapy, for seizures (hazard ratio [HR] = 3.33; 95% confidence interval [CI]: 1.26-8.82; p = 0.016) and PRES (HR = 4.85; 95% CI: 1.71-13.75; p = 0.003).
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| 9. |
- Anastasopoulou, Stavroula, et al.
(författare)
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Posterior reversible encephalopathy syndrome in children with acute lymphoblastic leukemia : Clinical characteristics, risk factors, course, and outcome of disease
- 2019
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Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 66:5
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Tidskriftsartikel (refereegranskat)abstract
- Background: Posterior reversible encephalopathy syndrome (PRES) is a distinct entity with incompletely known predisposing factors. The aim of this study is to describe the incidence, risk factors, clinical course, and outcome of PRES in childhood acute lymphoblastic leukemia (ALL).Procedure: Patients aged 1.0 to 17.9 years diagnosed with ALL from July 2008 to December 2015 and treated according to the Nordic Society of Pediatric Hematology and Oncology (NOPHO) ALL2008 protocol were included. Patients with PRES were identified in the prospective NOPHO leukemia toxicity registry, and clinical data were collected from the medical records.Results: The study group included 1378 patients, of whom 52 met the criteria for PRES. The cumulative incidence of PRES at one month was 1.7% (95% CI, 1.1-2.5) and at one year 3.7% (95% CI, 2.9-4.9). Older age (hazard ratios [HR] for each one-year increase in age 1.1; 95% CI, 1.0-1.2, P = 0.001) and T-cell immunophenotype (HR, 2.9; 95% CI, 1.6-5.3, P = 0.0005) were associated with PRES. Central nervous system (CNS) involvement (odds ratios [OR] = 2.8; 95% CI, 1.2-6.5, P = 0.015) was associated with early PRES and high-risk block treatment (HR = 2.63; 95% CI, 1.1-6.4, P = 0.033) with late PRES. At follow-up of the PRES patients, seven patients had epilepsy and seven had neurocognitive difficulties.Conclusion: PRES is a neurotoxicity in the treatment of childhood ALL with both acute and long-term morbidity. Older age, T-cell leukemia, CNS involvement and high-risk block treatment are risk factors for PRES.
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| 10. |
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| 11. |
- Anderzen-Carlsson, Agneta, 1966-, et al.
(författare)
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CHILDREN'S NARRATIVES OF SUPPORT FROM PARENTS WHEN EXPERIENCING FEAR RELATED TO ACUTE LYMPHOBLASTIC LEUKEMIA
- 2022
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 69:Suppl. 5, s. S528-S528
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and Aims: Children diagnosed with Acute Lymphoblastic Leukemia (ALL) typically undergo intense treatment with frequent hospitalizations. Medical, as well as existential fears have been identified. It has also been found that children's coping strategies develop during their illness trajectory. The literature on what children with ALL find to be valuable support from parents when experiencing fear is sparse. Thus, the aim of this presentation is to describe what young children find to be important support from their parents when experiencing fear related to ALL.Methods: The study had a longitudinal descriptive qualitative design. Thirteen children (3 girls and 10 boys), initially 5-9 years old were interviewed once to three times during their treatment period (approximately 2 months after the diagnosis, after 1 year, and at end of treatment). Data were analyzed using a matrix-based qualitative analysis method.Results: The parents’ physical and emotional closeness was the most frequently reported support. It eased the children's medical and existential fears. The children also found it supportive when the parents facilitated for them to participate in their care and when the parents acted as their advocate. Other supportive measures were offering distraction, talking to the child about their fears, assisting the professionals in alleviating pain and fear, being playful and encouraging. Five children also appreciated when their parents restricted them, during medical procedures. The experiences of support varied between children and between different time points during treatment.Conclusions: Although being quite young, the children were able to describe what they found to be supportive when experiencing fear, or for preventing fear. The parental support had an impact on the child's emotional, social and physical wellbeing. Professionals should encourage parents to stay with their child, and offer support to the parents, so that they in turn can support their child.
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| 12. |
- Anderzén Carlsson, Agneta, 1966-, et al.
(författare)
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Children’s Narratives of Support From Professionals when Experiencing Fear Related to Acute Lymphoblastic Leukemia
- 2020
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 67:S4, s. 120-120
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Tidskriftsartikel (refereegranskat)abstract
- Children diagnosed with Acute Lymphoblastic Leukemia (ALL) typically face 2.5 years treatment, which initially is intense and includes frequent hospitalizations. Previous research has identified various fears during treatment: fear of getting needles, removal of adhesive tapes, having a feeding tube, taking tablets and the physical changes related to ALL itself, as well as to treatments. The children’s coping strategies develop during the course of illness. The literature on what children with ALL find to be supportive when experiencing fear is sparse. The aim of this presentation is thus to describe what children 5-9 years old find to be important support from professionals when experiencing fear related to ALL.
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| 13. |
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| 14. |
- Anderzen-Carlsson, Agneta, 1966-, et al.
(författare)
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Fear and Coping During Treatment for Acute Lymphatic Leukemia - from the Perspective of Children 5-9 Years Old
- 2018
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Ingår i: Pediatric Blood & Cancer. - : John Wiley & Sons. - 1545-5009 .- 1545-5017. ; 65:Suppl.2, s. S598-S598
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background/Objectives: The concept of fear can be defined as ”an unpleasant often strong emotion caused by expectation of danger”. It is reasonable to believe that fear and coping of fear, can vary during the course of treatment for ALL. The aim of the present study was to describe a longitudinal perspective on fear related to having ALL, based on children's perspective, as well as to describe the strategies these children use when experiencing fear.Design/Methods: The study has a longitudinal descriptive qualitative design. Three girls and 10 boys, initially aged 5-9 were interviewed once to three times during their treatment period (approximately two months after the diagnosis, after one year and at the end of the 2.5-year long treatment). In total, 35 interviews were conducted. Data were analyzed using a matrix-based qualitative analysis method.Results: The children described fear of being subjected to needles and related to having a feeding tube, removing adhesive tape and taking tablets, as well as fear related to the bodily changes caused by the ALL. Existential fears were most frequently mentioned at the end of treatment. The children wanted to participate i n their care. They used cognitive strategies, such as ”thinking the right way” and emotional strategies, such as crying out loud and kicking. The fears changed over time, but the fear of being subjected to needles remained for half of the children, but was less intense at the end of treatment. The strategies developed, and became more sophisticated over the treatment period.Conclusions: The fear changed throughout the course of treatment, and so did the strategies used. It is reasonable to believe that the need for support also vary, which i s a topic for future research.
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| 15. |
- Arvidsson, Yvonne, 1960, et al.
(författare)
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Neuroblastoma-specific cytotoxicity mediated by the Mash1-promoter and E. coli purine nucleoside phosphorylase.
- 2005
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Ingår i: Pediatric blood & cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 44:1, s. 77-84
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Neuroblastoma is derived from cells of neural crest origin and often expresses the transcription factor human achaete-scute homolog 1 (HASH1). The aim of this study was to selectively kill neuroblastoma cells by expressing the suicide gene E. coli purine nucleoside phosphorylase (PNP) under the control of the Mash1 promoter, the murine homolog of HASH1. PROCEDURE: The E. coli PNP gene regulated by the Mash1 promoter was cloned into an expression vector and transfected into neuroblastoma and non-neuroblastoma cell lines. After addition of the prodrug M2-fluoroadenine 9-beta-D-arabinofuranoside (F-araA) the cell-specific toxicity was examined. To optimize the cell specific activity, different sizes of the Mash1 promoter were analyzed in neuroblastoma cell lines and compared with the activity in non-neuroblastoma cells. RESULTS: Estimated as the percentages of CMV enhancer-promoter, the activity was significantly higher in the neuroblastoma cells, ranging from 17 to 58% when the shortest and the most active promoter was measured. The non-neuroblastoma cells yielded only 1-6% of the CMV promoter activity. When the shortest Mash1 promoter was combined with the E. coli PNP gene the cytotoxicity was 65% in the neuroblastoma cells with low cell death in the non-neuroblastoma cell lines, relative to the cytotoxicity where the E.coli PNP gene was regulated by the strong but non-specific CMV enhancer-promoter. CONCLUSIONS: We show here that the Mash1 promoter regulating the PNP gene confers a cell-type selective toxicity in neuroblastoma cell lines. These results indicate the feasibility to use the Mash1 promoter for regulating E.coli PNP expression in gene-directed enzyme prodrug therapy (GDEPT) of neuroblastoma.
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| 16. |
- Asdahl, Peter H, et al.
(författare)
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The adult life after childhood cancer in scandinavia (ALiCCS) study: Design and characteristics.
- 2015
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 62:12, s. 2204-2210
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Tidskriftsartikel (refereegranskat)abstract
- During the last five decades, survival of childhood cancer has increased from 25% to 80%. At the same time, however, it has become evident that survivors experience a broad range of therapy-related late adverse health effects. The aim of the Adult Life after Childhood Cancer in Scandinavia (ALiCCS) study is to investigate long-term health consequences of past and current therapies in order to improve follow-up care of survivors and to reduce treatment-related morbidity of future patients.
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| 17. |
- Attarbaschi, A., et al.
(författare)
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Rare non-Hodgkin lymphoma of childhood and adolescence: A consensus diagnostic and therapeutic approach to pediatric-type follicular lymphoma, marginal zone lymphoma, and nonanaplastic peripheral T-cell lymphoma
- 2020
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 67:8
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Tidskriftsartikel (refereegranskat)abstract
- Pediatric-type follicular (PTFL), marginal zone (MZL), and peripheral T-cell lymphoma (PTCL) account each for <2% of childhood non-Hodgkin lymphoma. We present clinical and histopathological features of PTFL, MZL, and few subtypes of PTCL and provide treatment recommendations. For localized PTFL and MZL, watchful waiting after complete resection is the therapy of choice. For PTCL, therapy is subtype-dependent and ranges from a block-like anaplastic large cell lymphoma (ALCL)-derived and, alternatively, leukemia-derived therapy in PTCL not otherwise specified and subcutaneous panniculitis-like T-cell lymphoma to a block-like mature B-NHL-derived or, preferentially, ALCL-derived treatment followed by hematopoietic stem cell transplantation in first remission in hepatosplenic and angioimmunoblastic T-cell lymphoma.
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| 18. |
- Banerjee, Joanna, et al.
(författare)
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The spectrum of acute central nervous system symptoms during the treatment of childhood acute lymphoblastic leukaemia
- 2020
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Ingår i: Pediatric Blood & Cancer. - : WILEY. - 1545-5009 .- 1545-5017. ; 67:2
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Tidskriftsartikel (refereegranskat)abstract
- Background: Children with central nervous system (CNS) toxicity during therapy for acute lymphoblastic leukaemia (ALL) are at risk for treatment modifications, long-term sequelae and even higher mortality. A better understanding of CNS symptoms and their complications improves the potential to prevent and treat them.Methods: Patient files from 649 children treated with Nordic Society of Pediatric Hematology and Oncology ALL92 and ALL2000 protocols in Finland were reviewed retrospectively for any acute CNS symptom. Detailed data on symptoms, examinations and treatment of the underlying CNS complications were collected from the medical records. Disease-related and outcome data were retrieved from the Nordic leukaemia registry.Results: Altogether, 13% (86) of patients with ALL had acute CNS symptoms. Most symptoms (64%) occurred during the first 2 months of therapy. Posterior reversible encephalopathy syndrome was the most frequent complication (4.5%). Cerebrovascular events were diagnosed in 10 cases (1.6%), while methotrexate-related stroke-like syndrome (SLS) was observed in only one patient (0.2%). CNS symptoms due to systemic or unclear conditions, especially sepsis, were important for differential diagnosis. CNS leukaemia was associated with CNS symptoms (hazard ratio [HR] = 4.03; P = .003), and epilepsy was a common sequel of CNS complications (19%).Conclusions: Acute CNS symptoms are common during ALL therapy, occurring mainly during the first 2 months of treatment. Patients with CNS leukaemia at diagnosis are at a higher risk for CNS toxicity. Despite intensive CNS-directed methotrexate treatment, SLS was diagnosed extremely rarely in our series.
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| 19. |
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| 20. |
- Bergmann, Anke K., et al.
(författare)
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DNA methylation profiling of pediatric B-cell lymphoblastic leukemia with KMT2A rearrangement identifies hypomethylation at enhancer sites
- 2017
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 64:3
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Tidskriftsartikel (refereegranskat)abstract
- Deregulation of the epigenome is an important pathogenetic mechanism in acute lymphoblastic leukemia (ALL) with lysine (K)-specific methyltransferase 2A rearrangement (KMT2Ar). We performed array-based DNA methylation profiling of KMT2Ar ALL cells from 26 children in comparison to normal B-cell precursors. Significant changes in DNA methylation in KMT2Ar ALL were identified in 2,545 CpG loci, influenced by age and the translocation partners AFF1 and MLLT1. In KMT2Ar ALL, DNA methylation loss was enriched at enhancers and for certain transcription factor binding sites such as BCL11A, EBF, and MEF2A. In summary, DNA methylation changes in KMT2Ar ALL target enhancers, genes involved in leukemogenesis and normal hematopoiesis, as well as transcription factor networks.
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| 21. |
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| 22. |
- Berntorp, Erik
(författare)
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Von Willebrand disease.
- 2012
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009.
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Tidskriftsartikel (refereegranskat)abstract
- Long-term prophylaxis is not as well known in Von Willebrand disease (VWD) as in hemophilia but attempts to evaluate prophylaxis scientifically in VWD have started. A few cohort studies have been reported. In an international effort the Von Willebrand disease prophylaxis network (VWD PN) has been formed to investigate the role of prophylaxis in clinically severe VWD (e.g., patients with type 3 VWD) that is nonresponsive to other treatments. Findings from the VWD PN studies will hopefully provide more robust evidence for which patients might best benefit from prophylaxis and for appropriate dosing regimens for prophylaxis in patients with VWD. Pediatr Blood Cancer © 2012 Wiley Periodicals, Inc.
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| 23. |
- Björk, M B, et al.
(författare)
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Childhood cancer: the family experience
- 2004
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 43:4, s. 336-336
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Konferensbidrag (refereegranskat)
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| 24. |
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| 25. |
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| 26. |
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| 27. |
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| 28. |
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| 29. |
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| 30. |
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| 31. |
- Borssén, Magnus, et al.
(författare)
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DNA Methylation Adds Prognostic Value to Minimal Residual Disease Status in Pediatric T-Cell Acute Lymphoblastic Leukemia
- 2016
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 63:7, s. 1185-1192
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Tidskriftsartikel (refereegranskat)abstract
- Background. Despite increased knowledge about genetic aberrations in pediatric T-cell acute lymphoblastic leukemia (T-ALL), no clinically feasible treatment-stratifying marker exists at diagnosis. Instead patients are enrolled in intensive induction therapies with substantial side effects. In modern protocols, therapy response is monitored by minimal residual disease (MRD) analysis and used for postinduction risk group stratification. DNA methylation profiling is a candidate for subtype discrimination at diagnosis and we investigated its role as a prognostic marker in pediatric T-ALL. Procedure. Sixty-five diagnostic T-ALL samples from Nordic pediatric patients treated according to the Nordic Society of Pediatric Hematology and Oncology ALL 2008 (NOPHO ALL 2008) protocol were analyzed by HumMeth450K genome wide DNA methylation arrays. Methylation status was analyzed in relation to clinical data and early T-cell precursor (ETP) phenotype. Results. Two distinct CpG island methylator phenotype (CIMP) groups were identified. Patients with a CIMP-negative profile had an inferior response to treatment compared to CIMP-positive patients (3-year cumulative incidence of relapse (CIR3y) rate: 29% vs. 6%, P = 0.01). Most importantly, CIMP classification at diagnosis allowed subgrouping of high-risk T-ALL patients (MRD >= 0.1% at day 29) into two groups with significant differences in outcome (CIR3y rates: CIMP negative 50% vs. CIMP positive 12%; P = 0.02). These groups did not differ regarding ETP phenotype, but the CIMP-negative group was younger (P = 0.02) and had higher white blood cell count at diagnosis (P = 0.004) compared with the CIMP-positive group. Conclusions. CIMP classification at diagnosis in combination with MRD during induction therapy is a strong candidate for further risk classification and could confer important information in treatment decision making.
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| 32. |
- Boye, Kjetil, et al.
(författare)
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High-Dose Chemotherapy with Stem Cell Rescue in the Primary Treatment of Metastatic and Pelvic Osteosarcoma: Final Results of the ISG/SSG II Study
- 2014
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 61:5, s. 840-845
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPatients with metastatic osteosarcoma at diagnosis or axial primary tumors have a poor prognosis. The aim of the study was to evaluate the feasibility and efficacy of intensified treatment with high-dose chemotherapy (HDCT) and stem cell rescue in this group. MethodsFrom May 1996 to August 2004, 71 patients were included in a Scandinavian-Italian single arm phase II study. Preoperative chemotherapy included methotrexate, doxorubicin, cisplatin and ifosfamide, and postoperative treatment consisted of two cycles of doxorubicin, one cycle of cyclophosphamide and etoposide and two courses of high-dose etoposide and carboplatin with stem cell rescue. ResultsTwenty-nine patients (43%) received two courses and 10 patients (15%) received one course of HDCT. HDCT was associated with significant toxicity, but no treatment-related deaths were recorded. Fourteen patients (20%) had disease progression before completion of the study protocol, and only 29/71 patients (41%) received the full planned treatment. Median event-free survival (EFS) was 18 months, and estimated 5-year EFS was 27%. Median overall survival (OS) was 34 months, and estimated 5-year OS was 31%. When patients who did not receive HDCT due to disease progression were excluded, there was no difference in EFS (P=0.72) or OS (P=0.49) between patients who did or did not receive HDCT. ConclusionsThe administration of high-dose chemotherapy with stem cell rescue was feasible, but associated with significant toxicity. Patient outcome seemed comparable to previous studies using conventional chemotherapy. We conclude that HDCT with carboplatin and etoposide should not be further explored as a treatment strategy in high-risk osteosarcoma. Pediatr Blood Cancer 2014;61:840-845. (c) 2013 Wiley Periodicals, Inc.
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| 33. |
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| 34. |
- Brown, Morven C., et al.
(författare)
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The Views of European Clinicians on Guidelines for Long-Term Follow-Up of Childhood Cancer Survivors
- 2015
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 62:2, s. 322-328
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Tidskriftsartikel (refereegranskat)abstract
- Background. Evidence-based guidelines are needed to guide effective long-term follow-up (LTFU) of childhood cancer survivors (CCS) at risk of late adverse effects (LAEs). We aimed to ascertain the use of LTFU guidelines throughout Europe, and seek views on the need for pan-European LTFU guidelines. Procedures. One expert clinician from each of 44 European countries was invited to participate in an online survey. Information was sought regarding the use and content of LTFU guidelines in the respondent's centre and country, and their views about developing pan-European LTFU guidelines. Results. Thirty-one countries (70%) responded, including 24 of 26 full EU countries (92%). LTFU guidelines were implemented nationally in 17 countries (55%). All guidelines included recommendations about physical LAEs, specific risk groups and frequency of surveillance, and the majority about psychosocial LAEs (70%), and healthy lifestyle promotion (65%). A minority of guidelines described recommendations about transition to age-appropriate LTFU services (22%), where LTFU should be performed (22%) and by whom (30%). Most respondents (94%) agreed on the need for pan-European LTFU guidelines, specifically including recommendations about surveillance for specific physical LAEs (97%), action to be taken if a specific LAE is detected (90%), minimum requirements for LTFU (93%), transition and health promotion (both 87%). Conclusions. Guidelines are not universally used throughout Europe. However, there is strong support for developing pan-European LTFU guidelines for CCS. PanCareSurFup (www.pancare.eu) will collaborate with partners to develop such guidelines, including recommendations for hitherto relatively neglected topics, such as minimum LTFU requirements, transition and health promotion. Pediatr Blood Cancer 2015;62:322-328. (C) 2014 Wiley Periodicals, Inc.
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| 35. |
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| 36. |
- Cario, Holger, et al.
(författare)
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Erythrocytosis in Children and Adolescents : Classification, Characterization, and Consensus Recommendations for the Diagnostic Approach
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:11, s. 1734-1738
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Tidskriftsartikel (refereegranskat)abstract
- During recent years, the increasing knowledge of genetic and physiological changes in polycythemia vera (PV) and of different types of congenital erythrocytosis has led to fundamental changes in recommendations for the diagnostic approach to patients with erythrocytosis. Although widely accepted for adult patients this approach may not be appropriate with regard to children and adolescents affected by erythrocytosis. The congenital erythrocytosis working group established within the framework of the MPN&MPNr-EuroNet (COST action BM0902) addressed this question in a consensus finding process and developed a specific algorithm for the diagnosis of erythrocytosis in childhood and adolescence which is presented here. Pediatr Blood Cancer 2013;60:1734-1738. (c) 2013 Wiley Periodicals, Inc.
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| 37. |
- Carlsson, Göran, et al.
(författare)
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Compound heterozygous HAX1 mutations in a Swedish patient with severe congenital neutropenia and no neurodevelopmental abnormalities
- 2009
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 53:6, s. 1143-1146
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Tidskriftsartikel (refereegranskat)abstract
- Kostmann disease or severe congenital neutropenia (SCN) is an autosomal recessive disorder of neutrophil production. Homozygous HAX1 mutations were recently identified in SCN patients belonging to the original family in northern Sweden described by Kostmann. Moreover, recent studies have suggested an association between neurological dysfunction and HAX1 deficiency. Here we describe a patient with a compound heterozygous HAX1 mutation consisting of a nonsense mutation (c.568C > T, p.Glu190X) and a frame-shift mutation (c.91delG, p.Glu31LysfsX54) resulting in a premature stop codon. The patient has a history of neutropenia and a propensity for infections, but has shown no signs of neurodevelopmental abnormalities.
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| 38. |
- Carlsson, G, et al.
(författare)
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Hematopoietic stem cell transplantation in severe congenital neutropenia
- 2011
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 56:3, s. 444-451
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Severe congenital neutropenia (SCN) is an immunodeficiency characterized by disturbed myelopoiesis and an absolute neutrophil count (ANC) <0.5 × 10(9)/L. SCN is also a premalignant condition; a significant proportion of patients develop myelodysplastic syndrome or leukemia (MDS/L). Allogeneic hematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCN.PROCEDURE:Since 2004, eight HSCT have been performed in seven patients at our center. The indications were transformation to MDS/L (n = 2), granulocyte colony-stimulating factor receptor (CSF3R) mutation(s) (n = 2), granulocyte colony-stimulating factor (G-CSF) resistance (n = 2), and at the patient's own request (n = 1).RESULTS:The mean age at transplantation was 13 years (2.8-28 years) (mean follow-up 32 months, range 21-60). Three patients harbored ELANE mutations, three HAX1 mutations, and in one patient no causative mutation was identified. Two of the ELANE mutations were novel mutations. Three patients initially received myeloablative conditioning and four had reduced intensity conditioning (RIC). Three grafts were from HLA-identical siblings, three from matched unrelated donors and two were cord blood units. Engraftment occurred in all patients. Two of seven (29%) patients died; both had MDS/L and both were among the three that underwent myeloablative conditioning. One patient has chronic GVHD 2 years post-transplant.CONCLUSIONS:The role of HSCT should be explored further in patients with SCN. In particular, the influence of the conditioning regime needs to be evaluated in a larger cohort of patients.
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| 39. |
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| 40. |
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| 41. |
- Creutzig, Ursula, et al.
(författare)
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Characteristics and outcome in patients with central nervous system involvement treated in European pediatric acute myeloid leukemia study groups.
- 2017
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Ingår i: Pediatric blood & cancer. - : Wiley. - 1545-5017 .- 1545-5009. ; 64:12
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Tidskriftsartikel (refereegranskat)abstract
- There is no consensus on the treatment for pediatric patients with acute myeloid leukemia and initial central nervous system (CNS) involvement.To evaluate different CNS-directed treatment options (intrathecal [IT] therapy, CNS irradiation, hematopoietic stem cell transplantation [HSCT]), 261 patients (excluding acute promyelocytic leukemia) with initial CNS involvement treated in trials with similar intensive chemotherapy by four cooperative European study groups (1998-2013) were studied and compared with CNS-negative patients from the Berlin-Frankfurt-Münster group.Patient characteristics in the different study groups were comparable. Young age, high white blood cell count, extramedullary involvement other than the CNS, monoblastic morphology, and inv(16) were associated with CNS involvement (each P < 0.0001). There were no major differences in outcome between the study groups. The cumulative incidence of relapse (CIR) regarding the CNS was higher in initially CNS-positive versus initially CNS-negative patients (all: 8 ± 2% vs. 3 ± 1%, P(Gray) = 0.001; isolated: 4 ± 1% vs. 1 ± 0%, P(Gray) = 0.03). However, global outcome of the CNS-positive cohort (overall survival, 64 ± 3%; event-free survival 48 ± 3%; and CIR 33% ± 3%) did not differ significantly from CNS-negative patients. Risk groups defined by cytogenetics were of likewise prognostic significance in CNS-positive and -negative patients. CNS treatment with cranial irradiation was not superior compared to IT therapy and systemic chemotherapy (± HSCT).Although CNS relapses occurred more frequently in initially CNS-positive patients, their global outcome was similar as in CNS-negative patients. Intensified IT therapy was heterogeneous; however, at least eight applications, preferably with triple IT chemotherapy, seem to be appropriate to accompany dose-intensive systemic chemotherapy.
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| 42. |
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| 43. |
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| 44. |
- Dantonello, Tobias M, et al.
(författare)
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Embryonal rhabdomyosarcoma with metastases confined to the lungs : Report from the CWS Study Group.
- 2011
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 56:5, s. 725-732
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Embryonal rhabdomyosarcoma [RME] is the most common pediatric soft tissue sarcoma. Whereas the prognosis of localized rhabdomyosarcoma has improved, it remains poor for metastatic disease. METHODS: We analyzed RME-patients with isolated pulmonary metastases [PRME] treated in four consecutive CWS-trials. Treatment included multiagent chemotherapy and local treatment of the primary tumor. Therapy of lung metastases after induction chemotherapy depended on response and individual decisions. RESULTS: Twenty-nine patients <21 years had PRME. Their median age was six years, the median follow-up nine years. Twenty-eight children had their primary tumor located in an unfavorable site and 22 of the primaries were >5 cm. In addition to conventional chemotherapy, seven patients received high-dose treatment and eight patients oral metronomic chemotherapy. The lung metastases were in remission after induction chemotherapy in 22 individuals. 19 patients received no local treatment of metastases; 3 patients had pulmonary metastasectomy and lung radiation was administered to 9 individuals. In total, 24/29 patients achieved a complete remission [CR]. Actuarial 5-year event-free and overall survival for all patients was 37.9 ± 18% and 48.7 ± 18%, respectively; it was 45.8 ± 20% and 58.3 ± 20% for the 24 patients who achieved a CR. Local treatment of metastases had no impact on the failure pattern. Younger age, good response, achievement of CR and maintenance-treatment were favorable prognostic factors in univariate analysis. CONCLUSIONS: Children with PRME have a fair prognosis. Local treatment of metastases did not improve outcome in our sample. Metronomic treatment may be an attractive option for PREM-patients. [correction made here after initial online publication].
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| 45. |
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| 46. |
- Dantonello, Tobias M, et al.
(författare)
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Malignant ectomesenchymoma in children and adolescents : Report from the Cooperative Weichteilsarkom Studiengruppe (CWS)
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:2, s. 224-229
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Malignant ectomesenchymoma (MEM) is a soft tissue tumor with heterologous rhabdomyoblastic components believed to arise from pluripotent migratory neural crest cells. To date merely 50 cases have been published and the knowledge about the course of disease and optimal treatment is limited.METHODS: Six patients with MEM were registered 1996-2009. The diagnosis was confirmed according to current criteria. Their treatment and outcome was analyzed.RESULTS:The median age of the three females and three males was 0.6 years (range, 0.2-13.5). The mesenchymal component in all tumors was rhabdomyosarcoma (RMS), the neural component ganglioneuroblastoma/neuroblastoma (n = 5) and peripheral primitive neuroectodermal tumor in one case. Five patients presented with localized, one with metastatic disease. All but one patient received multiagent chemotherapy during their initial treatment. The tumors of 4/5 patients with localized MEM were at least grossly resected at best surgery; the patient without gross resection was additionally irradiated. Three of four evaluable tumors responded well to induction chemotherapy. All patients achieved a first complete remission (CR), but three recurrences (two local, one systemic) occurred. The individual with metastatic MEM did not survive, but all five patients with localized MEM are currently alive in CR with a median follow-up of 5 years (range: 2.1-13.7).CONCLUSIONS: Risk-factors and outcome of MEM appear to be comparable with other highly malignant pediatric soft tissue sarcoma when a multimodal treatment strategy including chemotherapy and adequate local treatment is pursued. We propose that treatment of patients with MEM be done according to pediatric protocols similar to other rhabdomyosarcoma-like soft tissue sarcoma.
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| 47. |
- Dantonello, Tobias M., et al.
(författare)
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Survival following disease recurrence of primary localized alveolar rhabdomyosarcoma
- 2013
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 60:8, s. 1267-1273
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Tidskriftsartikel (refereegranskat)abstract
- Background Recurrences in primary localized alveolar rhabdomyosarcoma (RMA) are common. Post-relapse survival is poor. We evaluated prognostic factors including relapse treatment in patients with recurrent RMA. Methods Relapses occurred in 115/235 patients with nonmetastatic RMA treated in four consecutive CWS-trials after achievement of a complete remission. Sufficient information about post-relapse treatment and outcome could be obtained in 99 patients and was retrospectively analyzed. Results Nine of 99 patients received no salvage therapy and died after a median of 2 months. The remaining 90 patients received multimodal relapse treatment including mandatory chemotherapy. Recurrences were grossly resected in 39 patients; 57 patients received radiation. At a median follow-up from relapse of 8 years, 20 patients were alive and disease-free (5-year post-relapse survival [PROS] 21.3 +/- 8). All surviving patients apart from a single individual had an isolated, circumscribed recurrence. Sixteen of 20 survivors were treated with adequate local relapse therapy (ALRT, i.e., either complete resection or gross resection+radiation). Survival in the subgroup of 27 individuals with circumscribed recurrences and ALRT was significantly better (PROS 53.7 +/- 19) compared with disseminated recurrences and/or tumors treated without ALRT. Absence of primary lymph node involvement, circumscribed relapses, ALRT, and achievement of a second CR were identified as independent favorable risk factors. Conclusion Post-relapse survival for primary localized RMA is generally poor. However, certain patient groups differed significantly in their likelihood of survival and 50% of patients with circumscribed relapses treated with ALRT survived. These findings may form the basis for an evidence-based risk-stratification for recurrent disease including relapse treatment.
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| 48. |
- Dantonello, Tobias M, et al.
(författare)
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Tumour volume reduction after neoadjuvant chemotherapy impacts outcome in localised embryonal rhabdomyosarcoma
- 2015
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Ingår i: Pediatric Blood & Cancer. - : Wiley. - 1545-5009 .- 1545-5017. ; 62:1, s. 16-23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Response (tumour volume reduction) to induction chemotherapy has been used to stratify secondary local and systemic treatment of Intergroup Rhabdomyosarcoma Study Group III (IRSG-III) embryonal rhabdomyosarcoma (RME) in consecutive CWS-trials. To evaluate its actual impact we studied response-related treatment and outcomes.PROCEDURE: Patients with IRSG-III RME <21 years and non-response (NR, <33% volume reduction) in five consecutive CWS-trials were analysed and compared with partial responders (PAR, ≥33% reduction). The NR was reviewed and sub-classified as Objective Response (OR, <0%-33% reduction) or Stable/Progressive Disease (SPD).RESULTS: Fifty-nine of 529 patients had NR (n = 34 OR, n = 25 SPD). Primary risk-factors including age, tumour size, and TN-classification did not differ between NR and PAR groups but NR had more patients with unfavourable sites comparatively (P = 0.04). There were no differences in primary risk-factors between OR and SPD. Significant factors associated with poor outcome in multivariate analysis were NR, TN-classification, age >10 years, tumour size >5 cm and therapy in older trials. After response assessment n = 24 NR continued to receive induction chemotherapy, n = 32 received other combinations and n = 3 no further chemotherapy. Forty-two non-responders were irradiated, and the tumours were completely resected in n = 20. After a median follow-up of 8 years, 34 NR are alive. Seventeen of 21 failures leading to disease-related deaths were locoregional. The five-year overall survival rate (OS) was 76 ± 4% for PAR, 79 ± 14% for OR, but only 40 ± 19% for SPD (P < 0.001).CONCLUSION: Response to induction chemotherapy appears to be an important surrogate marker of poor outcome in patients with SPD largely due to ineffective local control.
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