AlloHSCT in paediatric ALL and AML in complete remission: improvement over time impacted by accreditation?

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.

Pre-Emptive Immunotherapy for Clearance of Molecular Disease in Childhood Acute Lymphoblastic Leukemia after Transplantation.

Monitoring of minimal residual disease (MRD) or chimerism may help guide pre-emptive immunotherapy (IT) with a view to preventing relapse in childhood acute lymphoblastic leukemia (ALL) after transplantation. Patients with ALL who consecutively underwent transplantation in Frankfurt/Main, Germany between January 1, 2005 and July 1, 2014 were included in this retrospective study. Chimerism monitoring was performed in all, and MRD assessment was performed in 58 of 89 patients. IT was guided in 19 of 24 patients with mixed chimerism (MC) and MRD and by MRD only in another 4 patients with complete chimerism (CC). The 3-year probabilities of event-free survival (EFS) were .69 ± .06 for the cohort without IT and .69 ± .10 for IT patients. Incidences of relapse (CIR) and treatment-related mortality (CITRM) were equally distributed between both cohorts (without IT: 3-year CIR, .21 ± .05, 3-year CITRM, .10 ± .04; IT patients: 3-year CIR, .18 ± .09, 3-year CITRM .13 ± .07). Accordingly, 3-year EFS and 3-year CIR were similar in CC and MC patients with IT, whereas MC patients without IT experienced relapse. IT was neither associated with an enhanced immune recovery nor an increased risk for acute graft-versus-host disease. Relapse prevention by IT in patients at risk may lead to the same favorable outcome as found in CC and MRD-negative-patients. This underlines the importance of excellent MRD and chimerism monitoring after transplantation as the basis for IT to improve survival in childhood ALL.

Gastrectomy with isoperistaltic jejunal parallel pouch in a 15-year-old adolescent boy with gastric adenocarcinoma and autosomal recessive agammaglobulinemia.

A 15-year-old adolescent boy with autosomal recessive agammaglobulinemia underwent endoscopy because of unexplained growth failure and malnutrition. Esophagogastroduodenoscopy revealed antropyloric stenosis, and a biopsy showed an invasive gastric adenocarcinoma. Chronic atrophic corpus gastritis type A and Helicobacter pylori were also identified. Abdominal magnetic resonance imaging confirmed the stenosis resulting from a semicircular intramural tumor without obvious local or distant metastatic spread. Gastrectomy with an extended lymphadenectomy was performed. Esophagoduodenal continuity was restored by an interposed jejunal parallel pouch developed from the first jejunal loop. Oral feeding was supplemented by parenteral nutrition via a Broviac catheter, and the patient is well 4 months later. Several cases of gastric cancer have been reported in children with hereditary agammaglobulinemia. Thus, endoscopy is mandatory in such patients with gastrointestinal symptoms to identify and treat tumors before metastasis occurs. Total gastrectomy, extended lymphadenectomy, and reconstruction using a jejunal reservoir with maintenance of duodenal continuity should be considered.

Rapid immune recovery and low TRM in haploidentical stem cell transplantation in children and adolescence using CD3/CD19-depleted stem cells.

Allogeneic stem cell transplantation has become an important option in the curative treatment of many patients with malignant and non-malignant systemic diseases. Non-availability of HLA identical donors can limit access to this life-saving treatment, especially in ethnic minority patients, for whom identical donors are often not available [1,2]. For many years, a central aim has been the development of stem cell transplantation across the HLA barrier and the use of haploidentical parents as stem cell donors. Such an approach will allow allogeneic transplantation of all patients in need. During the past years, it has become possible to optimize in vitro graft manipulation procedures making this transplant procedure safer and more efficient. Therefore this haploidentical transplantation procedure can now serve as a basis for further cellular immunotherapy in the treatment of malignant and non-malignant diseases.

Detection of Meningeosis neoplastica by real-time quantitation of telomerase activity.

BACKGROUND: Analysis of cerebrospinal fluid (CSF) to discriminate between benign and malignant conditions is of fundamental importance for the physician and the patient because of the differential therapeutic options and resulting morbidity and mortality. Most human tumours demonstrate increased telomerase activity (TA). Recent technical advances in the detection of TA allow for sensitive and specific detection within 4 h. Thus, the detection of TA is suitable for routine clinical testing. METHODS: This study examines TA in cellular proteins in CSF from 111 patients compared to cytomorphological and laboratory examination. RESULTS: A positive result for TA in cellular proteins of CSF was correlated significantly with Meningeosis neoplastica, but not with non-malignant conditions. Telomerase was not detected in CSF supernatant, despite positive results in cellular proteins from identical patients. Furthermore, a 48-h time delay during the pre-analytic processing is not critical for detection of TA detection in native CSF when stored at room temperature. CONCLUSIONS: We conclude that TA is a promising marker for the detection of Meningeosis neoplastica and warrants further study.

Intracranial germinoma: a rare but important differential diagnosis in children with growth retardation.

AIM: Intracranial germinoma is a rare malignant tumour in childhood with an excellent prognosis under adequate therapy. Finding the right diagnosis at an early stage is difficult because of the slow-growing tumour and the resulting lack of clinical symptoms. METHODS: Our patients with histologically secured germinoma were retrospectively assessed concerning growth retardation, pituitary hormone status, magnetic resonance imaging scan results and clinical symptoms to find out whether there is a leading parameter. RESULTS: In all our patients, the leading symptom was growth retardation of at least 2 y before being diagnosed. CONCLUSION: Growth retardation seems to be a very early sign of germinoma in the suprasellar region. Therefore, early neuroradiological imaging combined with pituitary hormone status should be considered in every paediatric patient with a history of secondary growth retardation.

Propofol versus midazolam/ketamine for procedural sedation in pediatric oncology.

Different pharmacologic agents have been used for sedation in children undergoing invasive procedures. The authors prospectively compared the efficacy, the occurrence of adverse effects, cardiovascular parameters, oxygen saturation and induction, and recovery time in propofol with or without morphine versus midazolam/ketamine sedation for procedural sedation in children with malignancies and hematologic disorders. Fifty children received either propofol with or without morphine or ketamine/midazolam sedation for invasive procedures. Intravenous sedation consisted of 0.1 mg midazolam/kg and 1.0 mg ketamine/kg or 2 mg propofol/kg with or without 0.1 mg morphine/kg. Incremental dosages of ketamine or propofol were given, if necessary, to achieve or to maintain adequate sedation levels. Systolic and diastolic blood pressure, heart rate, oxygen saturation, time to induce sedation, recovery time, and adverse effects were recorded. All invasive procedures were successfully completed, with satisfactory sedation levels in all 25 patients in the propofol group and 23 of the 25 patients in the ketamine group. In 14 of the 25 procedures in the propofol group and 4 of the 25 procedures in the ketamine group, sedation was associated with side effects, the most common being oxygen desaturation. There was a significant increase in diastolic blood pressure after ketamine medication and a significant decrease in systolic and diastolic blood pressure and heart rate in the propofol group. Induction and recovery times in the propofol group were significantly shorter. Both regimens for procedural sedation are efficacious in achieving satisfactory sedation levels for invasive procedures. Propofol offers a quicker onset of sedation and a faster, smoother recovery but is associated with a higher rate of side effects. Considering the substantial rate of adverse effects, these procedural sedations should be performed only by physicians trained in advanced airway management and life support.

First report of a vincristine dose-related Raynaud's phenomenon in an adolescent with malignant brain tumor.

The authors report a case of a vincristine-induced, reproducible dose-related Raynaud's phenomenon. It occurred in a 14-year-old boy with a malignant brain tumor who received repeated vincristine injections. The authors describe how they handled this severe secondary Raynaud's phenomenon with acral cutaneous tissue necrosis. Reducing the dose of the vinca-alkaloid injections, together with an additional medication with a calcium-channel blocking agent, was a successful strategy in this patient. There are few case reports of secondary Raynaud's phenomenon in adult oncologic patients receiving certain anticancer drugs (including vincristine, bleomycin, and cisplatin), and to the authors' knowledge this kind of vincristine toxicity has not previously been described in either adults or children.

Ganglianeuroma: radiological and metabolic features in 4 children.

Ganglioneuroma constitutes a benign and surgically treatable tumor. The authors studied 4 patients with histopathologically proven ganglioneuroma focusing on radiological and metabolic features. The results confirm previous investigations that have shown metabolic activity in ganglioneuroma and characteristic patterns in imaging studies. Although for definite diagnosis tissue investigation is required, certain clinical and radiological features are suggestive of ganglioneuroma.