ABSTRACT
In contrast to transplant recipients, there is a paucity of data regarding frequency and clinical significance of viraemia in children receiving conventional chemotherapy. In a prospective observational study, we assessed the frequency of and clinical impact of viraemia with cytomegalovirus (CMV), Epstein-Barr virus (EBV), adenovirus, human herpesvirus-6 (HHV6) and herpes-simplex virus 1/2 (HSV1/2) in paediatric cancer patients at diagnosis, at a routine examination during intensive chemotherapy, and during febrile neutropenia (FN). Seventy-nine patients (median age 6 years; 66 children with haematological malignancies) were included in the study. Overall, 362 blood samples were analysed, 72 from the time at diagnosis (11.1% with positive PCR result), 118 during a regular control after chemotherapy (11.0% positive), and 159 during FN (8.8% positive). The overall positivity rate was 9.6% (CMV 3.3%, HHV6 2.7%, HSV 2.2%, EBV 0.8% and adenovirus 0.3%). There were no significant differences between FN episodes with and without viraemia in terms of duration of fever or neutropenia/lymphopenia, severity of mucositis (> II0), incidence of diarrhea and ICU admission. Our results indicate that viraemia in paediatric cancer patients generally does not have a major clinical impact, and may help in the decision regarding the indication of routine evaluation for viraemia in febrile neutropenic, but otherwise asymptomatic children.
Subject(s)
Neoplasms , Viremia , Humans , Child , Female , Male , Child, Preschool , Neoplasms/drug therapy , Neoplasms/complications , Adolescent , Prospective Studies , Infant , Febrile Neutropenia/epidemiology , Hematologic Neoplasms/therapyABSTRACT
PURPOSE: This study assesses fertility treatment outcomes in female patients who had undergone successful oocyte retrieval following cancer therapy. METHODS: Between January 2020 and December 2022, we collected fertility treatment data from six participating centres in Spain and Germany. All patients associated with this data had undergone successful oocyte retrieval following cancer treatment. RESULTS: Women had most frequently been diagnosed with a haematological (41.9%), breast (22.6%) or gynaecological malignancy (12.9%); two thirds (67.7%) had previously received a chemotherapy, half a radiotherapy (53.3%) and 45.2% had undergone surgery. On average, 7 years (range 0-28) had passed between cancer treatment and first ovarian stimulation cycle. Forty-nine ovarian stimulation cycles had been conducted on these 31 women between 2004 and 2021 (mean age at first oocyte collection following treatment: 34.8 ± 5.7 years). On average, 7 oocytes were collected per cycle (range 0-26) and 11 were collected per patient (range 0-51). Out of the 190 oocytes collected for immediate use of artificial reproductive technique, 139 were fertilised at a rate of 73%. Live birth rate per fresh transfer was 45% (9/20); no births were reported following cryotransfer (0/10). Mean values of anti-Mullerian hormone (AMH) before stimulation declined with time since treatment; however, oocytes were successfully collected from four women with an AMH of <0.5 ng/ml, although no pregnancies were reported. Ten pregnancies were documented; 3 ended in miscarriage. Two twin and 5 single pregnancies resulted in nine live births. On average, children were carried to term. CONCLUSION: In this small cohort, oocytes were successfully collected after chemotherapy and radiotherapy, despite-in individual cases-low AMH values. Further studies are needed to enrich the database and ultimately provide appropriate counselling to female cancer patients regarding expectations and ART outcome following cancer therapy.
Subject(s)
Neoplasms , Oocyte Retrieval , Humans , Female , Retrospective Studies , Adult , Oocyte Retrieval/methods , Neoplasms/therapy , Spain , Germany , Pregnancy , Fertility Preservation/methods , Ovulation Induction/methods , OocytesABSTRACT
Pneumocystis jirovecii can cause life-threatening pneumonia (PjP), and patients with haematological malignancies are at high risk of this infection. Prophylactic measures have significantly decreased morbidity and mortality, but there is a paucity of contemporary data on the incidence and clinical course of PjP in well-defined and homogenous patient populations, such as children suffering from acute lymphoblastic leukaemia (ALL). In the multi-international trial AIEOP-BFM ALL2009, PjP was diagnosed in six children (incidence 1/1000) and was associated with insufficient prophylaxis in five of them. Although none of the patients died of PjP, the long-term impact of the infection is unclear.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Pneumocystis carinii , Pneumonia, Pneumocystis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Humans , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Child , Male , Female , Child, Preschool , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Adolescent , IncidenceABSTRACT
INTRODUCTION: In German-speaking countries children with cancer are treated in about 70 hospitals. While national and European curricula for pediatric oncology and hematology (POH) have been developed, little is known, how far these curricula have been implemented into daily training and what topics are deemed urgent by instructors. METHODS AND MATERIALS: In 2022 the Didactics and Educational working party of the German Pediatric Hematology/Oncology Society conducted a survey plus interview by phone call on local educational conditions in POH and needs of educators. RESULTS: Thirty-two (45%) POH centers answered the questionary, half have appointed persons overseeing the training. A wide range educational scenarios were described in some centers. Trainees identified urgent needs in areas such as hybrid education and demanded training workshops on specific topics and intensified networking and a general curriculum implemented into daily care as mandatory. CONCLUSION: This is the first survey on educational issues in POH in German speaking centers, describing the current situation before and under pandemic conditions. Great individual efforts have already been achieved by dedicated teachers. A comprehensive training program in POH is still missing, which translates the national curriculum into daily practice, while improving networking and balancing the resources of the individual centers.
ABSTRACT
PURPOSE: Prophylactic anti-infective strategies are used in patients with cancer to decrease the risk for infection. Dietary restrictions do not allow raw vegetables and fresh fruits to limit the introduction of potentially harmful pathogens in the gastrointestinal tract, but the efficacy is unclear. PATIENTS AND METHODS: In this study analyzing the impact of the dietary restrictions on infectious complications, all children treated between April 2014 and March 2018 for ALL and AML or non-Hodgkin lymphoma (NHL) were included. Dietary restrictions were standard until March 2016, but were stopped in April 2016. Patients with dietary restrictions (treated April 2014-March 2016) and patients not advised for dietary restrictions (treated April 2016-March 2018) were compared regarding infectious complications, including bloodstream infection, pneumonia, diarrhea, and fever of unknown origin (FUO). RESULTS: Eighty-six patients (25 female; 62 ALL; nine AML, 15 NHL) experienced 223 infections. The 46 patients with dietary restrictions and the 40 patients without food restrictions did not significantly differ regarding the number of infections per patient, bloodstream infections, pneumonia, diarrhea, FUO, admission to intensive care, and death. CONCLUSION: Our data suggest that dietary restrictions do not affect the risk for infectious complications. Therefore, the indication of dietary restrictions should be reconsidered in pediatric patients with cancer.
Subject(s)
Fever of Unknown Origin , Leukemia, Myeloid, Acute , Pneumonia , Sepsis , Humans , Child , Female , Fever of Unknown Origin/etiology , Fever of Unknown Origin/prevention & control , Pneumonia/epidemiology , Pneumonia/prevention & control , Pneumonia/complications , Leukemia, Myeloid, Acute/complications , Diarrhea/epidemiology , Diarrhea/complicationsABSTRACT
Introduction: Increasing survival rates after hematopoietic stem cell transplantation (HSCT) in childhood should put focus on improving the quality of life as adults. An essential aspect is fertility and its preservation. In order to take advantage of the possibility of fertility preservation, fertility counseling should be provided to patients and their parents prior to gonadotoxic therapies. Methods: The aim of this survey was to analyze the impact of fertility counseling in pediatric stem cell transplantation in patients and their parents using questionnaires designed for the study questions. Fifty-one parents and 7 adolescent patients were interviewed between February 2019 and October 2021 about the counseling, their perceptions of fertility issues, and the nature of decision- making concerning fertility preservation. The study included patients with malignant (e.g., leukemia, lymphoma, neuroblastoma) and nonmalignant diseases (e.g., thalassemia, sickle cell disease, immunodeficiency) who received counseling on fertility preservation before HSCT based on an in-house standard and analysed the impact for both groups. Results: Two-thirds of the study participants were concerned about having children and grandchildren respectively; for half of all respondents, the topic of fertility and fertility preservation proved to be hopeful. Forty percent of the study participants were burdened by the risk of possible fertility limitations after HSCT. Concerns about fertility was particularly significant for parents whose children were advised to undergo fertility preservation. Parents of children <12 years found deciding on appropriate measures more difficult. Parents with children >7 years involved their children in the decision. All study participants agreed that fertility counseling had not negatively affected the parent-child relationship. More than 90% of all study participants were in favor of addressing fertility, its potential limitations and fertility preservation measures before HSCT. There was no significant difference between the malignant and the non-malignant cohort in all study questions. Discussion: Overall, the standardized fertility counseling provided in our center of pediatric stem cell transplantation resulted in high satisfaction among patients and their parents. Multiple counseling on infertility risk, including the younger patients in the decision-making and further options after gonadotoxic therapy may increase the satisfaction of the counseled patients and their parents.
ABSTRACT
The current standard therapy for children and adolescents with newly diagnosed Langerhans cell histiocytosis (LCH) is based on the two drugs prednisone and vinblastine. In patients with insufficient treatment response or disease relapse, the choice of second-line treatment depends on risk organ involvement (liver, spleen, and hematopoietic system). This article will give an overview of current data concerning therapeutic options in the different settings of children and adolescents with LCH. Due to limited evidence, these strategies have not been described in detail in the updated guidelines on pediatric LCH. In addition, the use of targeted therapy such as MAP-kinase inhibitors will be discussed. The reference center for LCH should be contacted if therapeutic options beyond the standard regimen are considered for treatment. All children and adolescents with LCH should be enrolled in registries or prospective studies.
Subject(s)
Histiocytosis, Langerhans-Cell , Vinblastine , Adolescent , Child , Humans , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/drug therapy , Prednisone/therapeutic use , Prospective Studies , Recurrence , Vinblastine/therapeutic useABSTRACT
Langerhans cell Histiocytosis is a rare neoplastic disease, which occurs mainly in children and adolescents. The disease may affect any organ, and therefore, the clinical symptoms vary widely. Some patients have a spontaneous remission of the disease, whereas others experience a rapid and potentially lethal clinical course. The therapeutic approach depends on the extent of the disease, and reaches from a watch-and-wait strategy to chemotherapy with the standard drugs vinblastine and prednisone. The identification of mutations in the MAPK-pathway resulted in growing interest in targeted therapy using compounds such as the BRAF inhibitors. Chronic relapses and permanent sequelae are important problems of LCH and are the focus of current research.
Subject(s)
Histiocytosis, Langerhans-Cell , Child , Humans , Adolescent , Histiocytosis, Langerhans-Cell/diagnosis , Histiocytosis, Langerhans-Cell/genetics , Histiocytosis, Langerhans-Cell/therapy , Prednisone/therapeutic use , Molecular Targeted Therapy , Mutation , Disease Progression , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins B-raf/therapeutic useABSTRACT
BACKGROUND: The outcome of children with refractory or relapsed soft tissue sarcoma (STS) is extremely poor. Whereas larger clinical trials evaluated specific treatment modalities, real-life data on individual multimodal therapeutic strategies, given alone or in combination, are scarce. PATIENTS AND METHODS: We retrospectively analyzed the clinical course of 18 pediatric patients with progression of or relapsed STS treated between 2008 and 2018 in our institution. RESULTS: A total of 18 patients (median age 12.4 years) suffered from progression or relapse of alveolar (n=7), embryonal (n=5), undifferentiated (n=2) rhabdomyosarcoma or desmoplastic small round cell tumor (n=4). 14 patents had an initial stage IV disease. All but one patient died. Median survival was 12.5 months. Shortest survival was seen in patients with systemic progression of the disease, longest in patients with local relapse. Patients with an Oberlin score<2 at the time of relapse had a significant longer time of survival than those with a score≥2. No significant advantage of a specific therapeutic modality was observed. DISCUSSION: We critically analyzed the clinical course in the real-life setting, in which various treatment options were applied to an individual patient according to the best of available data. We observed that some patients died within a short period of time despite multiple treatment modalities, which underlines the need for better prognostic parameters. CONCLUSION: In addition to well characterized clinical factors such as local or systemic relapse, the Oberlin score could be helpful in counselling patients and their families for choosing the best strategy of care.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Sarcoma , Humans , Child , Retrospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoplasm Recurrence, Local/therapy , Sarcoma/therapy , Sarcoma/pathology , Prognosis , Chronic Disease , Disease ProgressionSubject(s)
Invasive Fungal Infections , Child , Humans , Invasive Fungal Infections/diagnosis , Antigens, FungalABSTRACT
PURPOSE: The purpose of this study was to verify whether there is a prognostic benefit of electroencephalogram (EEG) performed during initial work-up of children with newly diagnosed acute lymphoblastic leukemia (ALL). METHODS: In this retrospective monocenter study, we analyzed the value of electroencephalogram (EEG) performed during initial work-up of children with newly diagnosed acute lymphoblastic leukemia (ALL). All pediatric patients were included in this study who were diagnosed with de novo ALL in our institution between January 1, 2005, and December 31, 2018, and in whom an EEG was performed for initial work-up within 30 days of diagnosis of ALL. EEG findings were associated with the occurrence and the etiology of neurologic complications occurring during intensive chemotherapy. RESULTS: Out of 242 children, EEG revealed pathological findings in 6 patients. Two of them developed a seizure at a later time point due to adverse effects of chemotherapy, whereas 4 children had an uneventful clinical course. In contrast, 18 patients with normal initial EEG findings developed seizures during therapy for different reasons. CONCLUSION: We conclude that routine EEG does not predict seizure susceptibility in children with newly diagnosed ALL and is unnecessary in the initial work-up as EEG investigation in young and often sick children requires sleep deprivation and/or sedation, and our data demonstrate no benefit in predicting neurological complications.
Subject(s)
Electroencephalography , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Child , Humans , Retrospective Studies , Seizures/etiology , Prognosis , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complicationsABSTRACT
Infection of a cerebrospinal fluid system is a serious medical complication. We performed a retrospective monocentric analysis on temporary and permanent cerebrospinal fluid devices in children with and without cancer, covering a period of over 14 years. Between 2004 and 2017, 275 children with a cerebrospinal fluid system were seen at our institution. Thirty-eight children suffered from 51 microbiologically proven infectious episodes of the cerebrospinal fluid system (12 children with cancer and 26 children without cancer). Independently of the cerebrospinal fluid system used, the incidence of infection did not significantly differ between children with and without cancer and was the highest in children younger than one year. Infection occurred earlier in external ventricular drain (EVD) than ventriculoperitoneal (VP) shunt, and in EVD significantly earlier in children with cancer compared with patients without cancer. The pathogens isolated were mainly Gram-positive bacteria, in particular Staphylococcus spp., which should be taken into account for empirical antimicrobial therapy.
ABSTRACT
Whereas the clinical approach in pediatric cancer patients with febrile neutropenia is well established, data on non-neutropenic infectious episodes are limited. We therefore prospectively collected over a period of 4 years of data on all infectious complications in children treated for acute lymphoblastic or myeloid leukemia (ALL or AML) and non-Hodgkin lymphoma (NHL) at two major pediatric cancer centers. Infections were categorized as fever of unknown origin (FUO), and microbiologically or clinically documented infections. A total of 210 patients (median age 6 years; 142 ALL, 23 AML, 38 NHL, 7 leukemia relapse) experienced a total of 776 infectious episodes (571 during neutropenia, 205 without neutropenia). The distribution of FUO, microbiologically and clinically documented infections, did not significantly differ between neutropenic and non-neutropenic episodes. In contrast to neutropenic patients, corticosteroids did not have an impact on the infectious risk in non-neutropenic children. All but one bloodstream infection in non-neutropenic patients were due to Gram-positive pathogens. Three patients died in the context of non-neutropenic infectious episodes (mortality 1.4%). Our results well help to inform clinical practice guidelines in pediatric non-neutropenic cancer patients presenting with fever, in their attempt to safely restrict broad-spectrum antibiotics and improve the quality of life by decreasing hospitalization.
ABSTRACT
Since the survival rates of pediatric patients undergoing cancer treatment or hematopoietic stem cell transplantation (HSCT) have increased rapidly in recent decades, the late effects of treatment are now an important focus of patient care. Access to fertility preservation (FP) procedures as well as their financing differs considerably across Europe. However, some countries in Europe have recently changed the legal basis for financing FP procedures; therefore, the implementation of structures is mandatory to give patients access to FP. In this prospective cohort study, we characterized the process for establishing pediatric fertility counseling, including the development of an in-house standard procedure for recommendations regarding FP with potentially gonadotoxic treatment and valuating data from all FP counseling sessions. All data concerning patient characteristics (pubertal status, disease group) and recommendation of FP measures were prospectively collected and adoption of FP measures analyzed. Prior to the establishment of a structured process for FP in our pediatric oncology and stem cell transplantation center, there was no standardized FP counseling. We demonstrate that with the establishment of an inhouse standard procedure, it is possible to give consistent yet individualized FP counseling to approximately 90% of our patients facing gonadotoxic treatment, counseling over 200 patients between 2017 and 2019. This pilot study could potentially be adapted in other pediatric hematology, oncology, and stem cell transplantation centers to allow a more standardized handling of FP counseling for all patients facing gonadotoxic treatment.
Subject(s)
Counseling/methods , Fertility Preservation/methods , Adolescent , Antineoplastic Agents/adverse effects , Child , Child, Preschool , Cryopreservation , Female , Fertility Preservation/economics , Fertility Preservation/standards , Hematopoietic Stem Cell Transplantation , Humans , Infant , Infertility, Female/chemically induced , Infertility, Female/etiology , Infertility, Female/prevention & control , Infertility, Male/chemically induced , Infertility, Male/etiology , Infertility, Male/prevention & control , Male , Neoplasms/therapy , Oocyte Retrieval , Ovary/transplantation , Prospective Studies , Puberty , Radiation Injuries/prevention & control , Radiotherapy/adverse effects , Semen Preservation , Transplantation Conditioning/adverse effects , Young AdultABSTRACT
Female patients with childhood, adolescent, and young adult cancer are at increased risk for fertility impairment when treatment adversely affects the function of reproductive organs. Patients and their families desire biological children but substantial variations in clinical practice guidelines reduce consistent and timely implementation of effective interventions for fertility preservation across institutions. As part of the PanCareLIFE Consortium, and in collaboration with the International Late Effects of Childhood Cancer Guideline Harmonization Group, we reviewed the current literature and developed a clinical practice guideline for fertility preservation in female patients who were diagnosed with childhood, adolescent, and young adult cancer at age 25 years or younger, including guidance on risk assessment and available methods for fertility preservation. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and to form the recommendations. This clinical practice guideline leverages existing evidence and international expertise to develop transparent recommendations that are easy to use to facilitate the care of female patients with childhood, adolescent, and young adult cancer who are at high risk for fertility impairment. A complete review of the existing evidence, including a quality assessment, transparent reporting of the guideline panel's decisions, and achievement of global interdisciplinary consensus, is an important result of this intensive collaboration.
Subject(s)
Cancer Survivors , Fertility Preservation/trends , Neoplasms/epidemiology , Neoplasms/therapy , Adolescent , Adult , Child , Female , Guidelines as Topic , Humans , Neoplasms/complications , Neoplasms/pathology , Risk Assessment , Young AdultABSTRACT
Allogeneic hematopoietic stem cell transplantation (alloHSCT) has become a well-established treatment option for many patients suffering from malignant and non-malignant diseases. In the past decade, high-resolution HLA-typing, remission surveillance, pre-emptive immune intervention, and standardisation in supportive care measures have substantially improved transplant outcomes. This retrospective study evaluated transplant procedures in 162 paediatric patients with acute lymphoblastic leukaemia (n = 124) or acute myeloid leukaemia (n = 38) who received their first alloHSCT in our institution over an 11-year period. We observed a significant reduction in risk of non-relapse mortality (NRM) over time (HR = 0.34, 95% CI 0.12-0.98; P = 0.05), the 4-year NRM estimate decreased from 20% in 2005-2008 to 7% in 2012-2016 (P = 0.02) and an increase in survival after relapse. There was no significant difference in patients who received a graft from a sibling, haplo, or an unrelated donor with regard to their overall survival (P = 0.45), event-free survival (P = 0.61), and non-relapse mortality (P = 0.19). Our data suggest that a specific transplant infrastructure with a highly experienced team in an accredited transplant centre likely contributes to better transplant outcomes for acute leukaemia patients in complete remission regardless of donor type.