Pediatric Hemato-oncologists Research Articles

Early removal of a permanent catheter during the acute management of the unstable pediatric hemato-oncology patient with suspected catheter-related bloodstream infection: a multi-disciplinary survey and review of the literature.

Our study findings reflect the need for uniform guidelines on permanent central catheter use and indications for its removal in the hemodynamically unstable pediatric patient. We suggest that permanent central catheter removal should be urgently considered in a deteriorating patient who failed to be stabilized with medical treatment. •There are no guidelines for the optimal choice and timing of permanent central catheter removal in the hemodynamically unstable pediatric hemato-oncology patient with suspected catheter-related bloodstream infection (CRBSI). •We found variations in practices among pediatricians from diverse subspecialties and conflicting data in the literature. •There is a need for prospective studies to provide uniform guidelines for optimal management of suspected CRBSI in the hemodynamically unstable pediatric patient.

Leukemic Optic Neuropathy

Background: Leukemic infiltration of the optic nerve is a neuro-oncologic emergency and also a sign of extramedullary central nervous system relapse. It presents a clinical dilemma in the early stages due to multiple differentials. Patients with leukemia receive radiation and chemotherapy are thus, susceptible to inflammatory, toxic, and infectious causes of optic neuropathy, besides infiltration with tumor cells. Clinical Description: A 15-year-old boy treated for acute lymphoblastic leukemia (ALL) and in remission for 7 months, presented with the unilateral decreased vision for 7 days. A structured evaluation was done, comprising visual acuity, color vision, field of vision, fundus, ophthalmoscopy, ultrasound b-scan, and magnetic resonance imaging of the orbit. The final diagnosis was leukemic infiltration of the optic nerve. Cerebrospinal fluid (CSF) analysis confirmed the presence of atypical lymphocytes. Management: The patient was diagnosed with extramedullary relapse of ALL. Since there are no standard guidelines, a literature review was performed, and the treating team decided to start the patient on stand-alone chemotherapy. Symptomatic resolution became apparent within 10 days. On follow-up, the optic nerve lesion resolved with residual gliosis in the surrounding retina. The CSF has become clear, and the patient is now considered to be in remission. Conclusion: It is important to use a structured clinical approach coupled with investigations to recognize the ocular involvement of ALL (especially in younger patients). There is a need for a regular routine ophthalmological examination in patients in remission for early detection of a relapse. There is a strong felt need for pediatric hemato-oncologists to plan research in this area to generate data so that recommendations for the management of extramedullary relapses are formulated.

How to recognize inborn errors of immunity in a child presenting with a malignancy: guidelines for the pediatric hemato-oncologist

Inborn errors of immunity (IEI) are a group of disorders caused by genetically determined defects in the immune system, leading to infections, autoimmunity, autoinflammation and an increased risk of malignancy. In some cases, a malignancy might be the first sign of an underlying IEI. As therapeutic strategies might be different in these patients, recognition of the underlying IEI by the pediatric hemato-oncologist is important. This article, written by a group of experts in pediatric immunology, hemato-oncology, pathology and genetics, aims to provide guidelines for pediatric hemato-oncologists on how to recognize a possible underlying IEI and what diagnostic tests can be performed, and gives some consideration to treatment possibilities.

Securing access to innovative anticancer therapies for children, adolescents, and young adults outside clinical trials: The SACHA study of the French Society of Pediatric Oncology (SFCE).

10006 Background: Access to innovative anticancer therapies for children, adolescents and young adults within clinical trials in France is steadily increasing in the last years. However, current clinical trials portfolios are still inadequate and thus pediatric hemato-oncologists regularly prescribe innovative medicines outside their marketing authorization, and/or experimental drugs through compassionate use. Methods: The Secured Access to innovative medicines for CHildren with cAncer (SACHA) is a French prospective observational study developed by the French Society of Pediatric Oncology (SFCE) with Gustave Roussy as the legal sponsor to prospectively collect real-world safety and activity data of innovative therapies administered to patients ≤ 25 years-old with pediatric malignancies (solid tumor or leukemia) or other related conditions, either on compassionate use of experimental drugs or off-label use of anti-cancer medicines that have been first approved in adults after 2007. Prior to SACHA inclusion, multicenter tumor board discussion defining best available therapeutic options for each patient with a relapsed malignancy is mandatory. Results: The SACHA study opened in March 2020 and by February 2022, 283 patients have been included from 29/31 SFCE recruiting centers; median age: 11.0 years (range: 0.3-24.4). Main cancer types were central nervous system (CNS) tumors (47%), followed by non-CNS tumors (40%) and leukemias (13%). Innovative therapies prescribed in > 10 patients with reported objective response rate (ORR) and related CTCAE v.5 grade ≥2 clinical and/or grade ≥3 biological adverse drug reactions (ADRs) are described in Table. Conclusions: SACHA confirms the feasibility of this type of prospective real word registry, with a high participation of French centers. Based on this French experience, the Innovative Therapies for Children with Cancer (ITCC) consortium is currently developing a “SACHA International Project” to be opened in ITCC and collaborating countries. [Table: see text]

Bone morbidity in pediatric acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL), currently the most common pediatric leukemia, has a high curability rate of up to 90%. Endocrine disorders are highly prevalent in children with ALL, and skeletal morbidity is a major issue induced by multiple factors associated with ALL. Leukemia itself is a predominant risk factor for decreased bone formation, and major bone destruction occurs secondary to chemotherapeutic agents. Glucocorticoids are cornerstone drugs used throughout the course of ALL treatment that exert significant effects on demineralization and osteoclastogenesis. After completion of treatment, ALL survivors are prone to multiple hormone deficiencies that eventually affect bone mineral accrual. Dual-energy X-ray absorptiometry, the most widely used method of measuring bone mineral density, is used to determine the presence of childhood osteoporosis and vertebral fracture. Supplementation with calcium and vitamin D, administration of pyrophosphate analogues, and promotion of mobility and exercise are effective options to prevent further bone resorption and fracture incidence. This review focuses on addressing bone morbidity after pediatric ALL treatment and provides an overview of bone pathology based on skeletal outcomes to increase awareness among pediatric hemato-oncologists and endocrinologists.

Acute Invasive Fungal Rhinosinusitis in Children With Hematologic Malignancies: Outcome of Surgical Treatment

The incidence of acute invasive fungal rhinosinusitis (AIFR) is rising due to more aggressive chemotherapy and longer survival of immunosuppressed patients. Early diagnosis and appropriate but nonmutilating surgical treatment are particularly problematic in the pediatric population. This study aimed to evaluate the outcome of surgery for pediatric AIFR. Medical records of children surgically treated for AIFR between 1998 and 2014 were reviewed. Diagnosis was based on both histopathological and microbiological confirmation. Surgery was performed with curative intent and repeated for any resectable extension. The children underwent endoscopy and magnetic resonance imaging every 2 and 6 months, respectively, during the first postoperative year. Thirteen patients (2–18 years old) met the EORTC/MSG criteria for proven invasive fungal sinusitis; fungal invasion was diagnosed by preoperative biopsy and confirmed in the surgical specimen. All patients underwent an average of two endoscopic procedures (range 1–3), and four of them also underwent an open surgery. The local control rate was at least 79%. There was no facial disfiguration during follow-up (average 41 months). Although AIFR is still associated with high mortality, aggressive medical and surgical treatment provides local control in most cases. Fair outcome should encourage a maximal joint effort of pediatric hemato-oncologists and otorhinolaryngologists in the management of AIFR.

Dissecting the heterogeneity of macrophage activation syndrome

Methods Patient data were collected retrospectively by pediatric rheumatologists (PR) or pediatric hemato-oncologists (PHO). Clinical features, treatments and outcome were compared between groups by Mann-Whitney or chisquare tests. “Severe course” was defined as ICU admission or death. Results 362 patients with MAS in sJIA were collected by 95 investigators from 33 countries. 179 patients (49.4%) were enrolled in Europe (EU), 72 (19.9%) in North America (NA) and 111 (30.7%) in other continents (OC). 79 (21.8%) patients were included by PHO. HP was detected in 44% of patients and was not detected or looked for in 56%. Severe course was reported in 92 (25%) patients. Comparison by geographic origin showed a lower frequency of CNS disease in EU patients. NA physicians used more frequently ivIg and biologics. Patients entered by PHO had greater frequency of multiorgan failure and were given more commonly biologics and etoposide, whereas PR used more frequently cyclosporine (CsA). Patients with HP had shorter duration of sJIA at MAS onset, higher prevalence of hepatosplenomegaly, lower levels of platelets and fibrinogen and received more frequently CsA, ivIg and etoposide. Patients with severe course were older, had longer duration of sJIA at MAS onset, greater frequency of haemorrhages and CNS dysfunction, lower levels of ESR, albumin and fibrinogen, higher levels of LDH and D-dimer and were treated more commonly with CsA, ivIg and etoposide. Conclusion

Biology of Childhood Acute Lymphoblastic Leukemia

Acute lymphoblastic leukemia (ALL) is the most common malignancy in childhood, accounting for almost 30% of pediatric cancers. Despite the high rate of cure, ALL is one of the leading causes of death in children with tumor. For this reason, there is a keen interest in identifying genetic and biological features that influence the pathogenesis of ALL and the risk of treatment failure. The application of standard diagnostic technologies such as a conventional karyotype and polymerase chain reaction methodologies, together with gene expression profiling and genome-wide analyses, allows us to genetically characterize almost 100% of children with ALL. This review provides basic information about well-established genetic alterations associated with specific clinical subtypes and new molecular lesions with potential prognostic impact. New insights are reported on the natural history of ALL. Genetic aberrations in childhood ALL are considered both markers of disease and potential targets of treatment. Here, each biological subtype under the genetic point of view has been dissected, including genes involved in the development of lymphocytes and considerations on ALL in infancy. It is also crucial to discuss the issue of relapse. Finally, as future treatment will be individualized on the basis of biological features, the pediatric hemato-oncologists need to be ready and prepared to tailor the "right treatment" to the "right children" with ALL.

Situación actual de los adolescentes con cáncer en las unidades de hemato-oncología pediátrica españolas

Little attention was paid to adolescents with Cancer in Spain up to 2010. In 2011 an “Adolescents with Cancer Committee” was established by the Spanish Society of Pediatric Hemato-Oncology (SEHOP) to care for the needs of these patients. The aim of this national survey was to outline the present situation of adolescents with cancer in Spanish Pediatric Hemato-Oncology units.A web based survey assessed institutional management of adolescents with cancer. The survey was personally sent to one member of the staff of each Pediatric Hemato-Oncology unit in Spain. It included questions about epidemiology, management, psycho-social coverage, specific facilities, and follow up of these patients.A total of 40 institutions out of 41 responded to the survey (overall response rate 98%). Fifty-six percent of the institutions had patients over 14, but only 36% of the institutions treated patients up to 18 years old. Only 25.6% of the units have more than 40 new pediatric cases every year. The percentage of patients between 14 and 18 years of age is below 10% in most of the units (77%).In 30.8% and 48.7% of the institutions, pediatric hemato-oncologists treat adolescents with hematological and solid tumors, respectively. The rest of the patients are seen by adult oncologists. There is only one institution that has a physician specifically dedicated to adolescent patients, and only two units have a “teenager's room”. Only 2 units have a psychologist specifically trained to treat adolescents with cancer.The survey shows that most adolescents with cancer in Spain between 14 and 18 years of age are treated by adult oncologists. Most pediatric institutions still do not have specific facilities and psychosocial support for adolescents. The SEHOP is working hard in order to improve the quality of cancer care, and the quality of survival of this population.

Pediatric oncologists' attitudes towards involving adolescents in decision‐making concerning research participation

Various regulations and guidelines stipulate the importance of involving adolescents in decision-making concerning research participation. Several studies have shown that in the context of pediatric oncology this involvement is difficult to achieve due to emotional stress, the complexity of research protocols and limited time. Still, up to 80% of adolescents with cancer enter onto a trial during their illness. The aim of this study was to determine clinicians' views and attitudes towards enrolling adolescents in research, considering the difficulties surrounding their involvement in decision-making. A qualitative multicenter study was performed, using in-depth semi-structured interviews on the informed consent process with 15 pediatric hemato-oncologists. Four central themes emerged that characterize clinicians' attitudes towards involving adolescents in the decision-making process: (1) clinicians regard most adolescents as not capable of participating meaningfully in discussions regarding research; (2) clinicians do not always provide adolescents with all information; (3) proxy consent from parents is obtained and is deemed sufficient; (4) clinician-investigator integrity: clinicians judge research protocols as not being harmful and even in the best interest of the adolescent. Clinicians justify not involving adolescents in research discussions by referring to best interest arguments (adolescents' incompetence, proxy consent, and investigator integrity), although this is not in line with legal regulations and ethical guidelines.

SYSTEMIC TYPE EPSTEIN-BARR VIRUS-RELATED LYMPHOPROLIFERATIVE DISEASES IN CHILDREN AND YOUNG ADULTS: Challenges for Pediatric Hemato-Oncologists and Infectious Disease Specialists

Involvement of Epstein-Barr virus (EBV) has long been known in the development of various tumor-forming proliferating diseases, such as nasopharyngeal carcinoma in adults. However, in children and young adults more attention should be focused on systemic, severe type EBV-related diseases, such as fatal infectious mononucleosis, hemophagocytic syndrome, or chronic active EBV infection (CAEBV). These disorders show the typical clinical features of hemophagocytic lymphohistiocytosis (HLH). Although viral infectious diseases are mostly taken care of by infectious disease specialists, pediatric hemato-oncologists need to intervene in the treatment of this kind of disease because of their clonal and neoplastic disease characteristics and of their hematologically problematic, rapid, and life-threatening clinical courses.