24 research outputs found
Distinct mutations in STXBP2 are associated with variable clinical presentations in patients with familial hemophagocytic lymphohistiocytosis type 5 (FHL5)
Integrative medicine during the intensive phase of chemotherapy in pediatric oncology in Germany: a randomized controlled trial with 5-year follow up
Background: Integrative medicine is used frequently alongside chemotherapy treatment in pediatric oncology, but little is known about the influence on toxicity. This German, multi-center, open-label, randomized controlled trial assessed the effects of complementary treatments on toxicity related to intensive-phase chemotherapy treatment in children aged 1-18 with the primary outcome of the toxicity sum score. Secondary outcomes were chemotherapy-related toxicity, overall and event-free survival after 5 years in study patients.
Methods: Intervention and control were given standard chemotherapy according to malignancy & tumor type. The intervention arm was provided with anthroposophic supportive treatment (AST); given as anthroposophic base medication (AMP), as a base medication for all patients and additional on-demand treatment tailored to the intervention malignancy groups. The control was given no AMP. The toxicity sum score (TSS) was assessed using NCI-CTC scales.
Results: Data of 288 patients could be analyzed. Analysis did not reveal any statistically significant differences between the AST and the control group for the primary endpoint or the toxicity measures (secondary endpoints). Furthermore, groups did not differ significantly in the five-year overall and event-free survival follow up.
Discussion: In this trial findings showed that AST was able to be safely administered in a clinical setting, although no beneficial effects of AST between group toxicity scores, overall or event-free survival were shown
Phase I/II intra-patient dose escalation study of vorinostat in children with relapsed solid tumor, lymphoma, or leukemia
Background: Until today, adult and pediatric clinical trials investigating single-agent or combinatorial HDAC inhibitors including vorinostat in solid tumors have largely failed to demonstrate efficacy. These results may in part be explained by data from preclinical models showing significant activity only at higher concentrations compared to those achieved with current dosing regimens. In the current pediatric trial, we applied an intra-patient dose escalation design. The purpose of this trial was to determine a safe dose recommendation (SDR) of single-agent vorinostat for intra-patient dose escalation, pharmacokinetic analyses (PK), and activity evaluation in children (3-18 years) with relapsed or therapy-refractory malignancies. Results: A phase I intra-patient dose (de)escalation was performed until individual maximum tolerated dose (MTD). The starting dose was 180 mg/m(2)/day with weekly dose escalations of 50 mg/m(2) until DLT/maximum dose. After MTD determination, patients seamlessly continued in phase II with disease assessments every 3 months. PK and plasma cytokine profiles were determined. Fifty of 52 patients received treatment. n = 27/50 (54%) completed the intra-patient (de)escalation and entered phase II. An SDR of 130 mg/m(2)/day was determined (maximum, 580 mg/m(2)/day). n = 46/50 (92%) patients experienced treatment-related AEs which were mostly reversible and included thrombocytopenia, fatigue, nausea, diarrhea, anemia, and vomiting. n = 6/50 (12%) had treatment-related SAEs. No treatment-related deaths occurred. Higher dose levels resulted in higher C-max. Five patients achieved prolonged disease control (> 12 months) and showed a higher C-max (> 270 ng/mL) and MTDs. Best overall response (combining PR and SD, no CR observed) rate in phase II was 6/27 (22%) with a median PFS and OS of 5.3 and 22.4 months. Low levels of baseline cytokine expression were significantly correlated with favorable outcome. Conclusion: An SDR of 130 mg/m(2)/day for individual dose escalation was determined. Higher drug exposure was associated with responses and long-term disease stabilization with manageable toxicity. Patients with low expression of plasma cytokine levels at baseline were able to tolerate higher doses of vorinostat and benefited from treatment. Baseline cytokine profile is a promising potential predictive biomarker
Triosephosphate-Isomerase Deficiency: Epiphenomenon or Cause of Loin Pain Haematuria Syndrome?
A 32-year-old male patient presented the clinical picture of loin pain haematuria syndrome with pain attacks accompanied by macrohaematuria. In renal biopsy, the preglomerular vessels showed segmental wall hyalinosis in the sense of low-grade nephrosclerosis, and glomerular capillaries with slightly but diffusely thickened, non-split basal membranes on electron microscopy. Notable were irregularly deformed, different dense erythrocytes in the glomerular capillaries, and several tubular lumina. The suspicion of erythrocytic enzyme deficiency could be confirmed. The enzyme activities of the erythrocytes were predominantly normal or slightly increased; only the activity of triosephosphate isomerase, a critical key enzyme of glycolysis, was reduced to 71% (resp. 57%) of the normal level, compatible with a heterozygous carrier status that could not be found. Patients with genomic triosephosphate-isomerase deficiency have degraded enzyme activities in virtually all tissues, such as leucocytes, platelets, and muscle cells. An association with neuromuscular symptoms is also known. Thus, it is possible that smooth muscle and intrarenal vascular spasms trigger clinical symptoms consisting of flank pain and phases of macrohaematuria. An aspirin-like defect (thrombocytopathy) had previously been found in connection with epistaxis (also due to TPI deficiency?). Enalapril treatment drastically reduced the frequency of macrohaematuria and pain attacks decreased to a lesser extent
Surgery for childhood “radiation-induced cavernous hemangioma” (RICH): A case report and literature review
Radiation-Induced Cavernous Hemangioma (RICH) is a possible consequence of brain irradiation that rarely causes symptoms but can result in severe hemorrhage and neurological symptoms. To date, only small numbers of RICH cases have been reported in the literature. We report on a case of a 16-year old male who underwent surgery for RICH due to intralesional hemorrhage. Follow-up imaging showed increasing hemorrhage of one of the lesions over time since irradiation. Additionally, the patient experienced headache and seizure-like events. Therefore, microsurgical resection was performed to prevent further hemorrhage and the risk of a symptomatic bleeding event. Imaging carried out after surgery showed no sign of any new hemorrhage but still multiple other RICH lesions.Patients with RICH are often asymptomatic, but still it can lead to severe hemorrhage. Thus, follow-up imaging after brain irradiation is crucial to detect early signs of RICH and assess its evolution. To prevent symptomatic hemorrhage, surgery for RICH should be carefully considered on a case-by-case basis if the patient becomes symptomatic or if imaging shows increasing hemorrhage
The long-term impact of in vitro drug sensitivity on risk stratification and treatment outcome in acute lymphoblastic leukemia of childhood (CoALL 06-97)
Background In a study of childhood acute lymphoblastic leukemia (CoALL 06-97 study), the in vitro sensitivityof the patients' cells to prednisolone, vincristine and asparaginase was introduced as anew additional risk parameter for treatment stratification. In parallel in vivo treatment responsewas assessed by determining the presence and extent of minimal residual disease in a subset ofpatients (n=224). Here we report the long-term impact of in vitro sensitivity-based risk stratificationaccording to survival and compare the results of in vitro sensitivity with in vivo response. Design and Methods Patients with a sensitive in vitro profile were treated with a reduced intensity protocol (n=167)whereas patients defined as low risk according to conventional parameters but with a resistantin vitro profile were given intensified therapy (n=47). Results At a median follow-up of 6.8 years event-free survival was 0.80±0.03 for patients with a sensitiveprofile, 0.73±0.03 for those with an intermediate profile and 0.67±0.08 for those with aresistant profile (P=0.015). Overall, the treatment results of the cases stratified according to invitro sensitivity were similar to those of the historical control group stratified based on conventionalrisk factors. Minimal residual disease at the end of induction was a strong predictor ofoutcome in B-precursor and T-cell acute lymphoblastic leukemia. There was no correlationbetween in vitro and in vivo treatment response in B-precursor leukemia (Spearman's r=0.13;P=0.15) in contrast to T-cell acute lymphoblastic leukemia (Spearman's r=0.63; P<0.001) Conclusions A moderate reduction in treatment intensity for patients with a sensitive in vitro profile waspossible without jeopardizing treatment outcome. However, in vitro drug testing was affectedby a decrease in risk predictive power over time and was not correlated with in vivo assessmentof minimal residual disease in B-precursor acute lymphoblastic leukemia. It was, therefore,abandoned in favor of the assessment of in vivo response in subsequent CoALL trials