scholarly journals Effect of low-dose macrolide antibiotics on theophylline disposition in pediatric patients

2007 ◽  
Vol 18 (1) ◽  
pp. 7-13
Author(s):  
Yoshifusa Abe ◽  
Yuko Nanri ◽  
Hideyasu Oto ◽  
Taeru Kitabayashi ◽  
Shuichiro Watanabe ◽  
...  
Keyword(s):  
Low Dose ◽  
Pediatric Patients ◽  
Macrolide Antibiotics ◽  
Theophylline Disposition

Cortisol Response to Low-Dose ACTH Stimulation Test in Non-Stressed Pediatric Patients

2011 ◽  
pp. P2-741-P2-741
Author(s):  
Joran Sequeira ◽  
Richard A Noto ◽  
Qiuhu Shi ◽  
Mamatha Sandu ◽  
Figen Altunkaya ◽  
...  
Keyword(s):  
Low Dose ◽  
Pediatric Patients ◽  
Stimulation Test ◽  
Cortisol Response ◽  
Acth Stimulation Test ◽  
Acth Stimulation

Low-dose metronomic topotecan and pazopanib in children with recurrent or refractory solid tumors: A C17 Canadian phase I trial (TOPAZ).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 10020-10020
Author(s):  
Arif Manji ◽  
Daniel A. Morgenstern ◽  
Yvan Samson ◽  
Rebecca Deyell ◽  
Donna Johnston ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Stable Disease ◽  
Low Dose ◽  
Pediatric Patients ◽  
Novel Approach ◽  
Best Response ◽  
Grade 3 ◽  
Relapsed Disease

10020 Background: Low-dose metronomic topotecan (mTP) represents a novel approach to chemotherapy delivery which, in preclinical models, may work synergistically with pazopanib (PZ) in targeting angiogenesis. This study was designed to determine the recommended phase 2 dose (RP2D) of mTP/PZ in pediatric patients with solid tumors, while describing the safety and toxicity of this regimen. Methods: A phase I dose-escalation, pharmacokinetic (PK) and pharmacodynamic (PD) study of mTP/PZ was conducted at ten sites across Canada, enrolling pediatric patients aged 2-21 years with relapsed/refractory solid tumors. Patients were treated with oral mTP and PZ suspension daily without interruption in 28-day cycles, with dose escalation in accordance with the rolling-six design. Five dose levels (0.12/125, 0.16/125, 0.22/125, 0.22/160, and 0.3/160 mg/m2/day of mTP/PZ) were evaluated. PK studies were performed on day 1 and at steady state, and PD studies included circulating angiogenic factors VEGFR1, VEGFR2, VEGF, endoglin and placental growth factor. Results: Thirty patients (pts) were enrolled, of whom 26 were evaluable for dose-limiting toxicity (DLT), with median age 12 years (3-20). The most common diagnoses included osteosarcoma (8), neuroblastoma (NB, 7), Ewing sarcoma/PNET (4), and rhabdomyosarcoma (4). The most common grade 3/4 adverse events (AEs) related to protocol therapy were neutropenia (18%), thrombocytopenia (11%), lymphocytopenia (11%), AST elevation (11%), and lipase elevation (11%). Only 2 cycle-1 DLTs were observed on study, both at the 0.3/160 mg/m2 mTP/PZ dose level (2/5 pts) comprising persistent grade 3 thrombocytopenia and grade 3 ALT elevation. No AEs experienced beyond cycle-1 required treatment discontinuation. Best response was stable disease in 10/25 pts (40%) for a median duration of 6.4 months (1.7-45.1). One patient with refractory NB achieved stable disease for 45 months and continued on mTP/PZ via compassionate access after study closure. PK and PD results are pending at this time. Conclusions: The combination of oral mTP and PZ is safe and tolerable in pediatric patients with solid tumors, with a RP2D of mTP 0.22 mg/m2/day and PZ suspension 160 mg/m2/day. Ten patients achieved stable disease for a median of 6 months. The lack of objective responses suggests that this combination is likely of limited benefit for relapsed disease, but may play a role as maintenance therapy. Clinical trial information: NCT02303028.

Analysis of the Incidence and Characteristics of Venoocclusive Disease (VOD) of the Liver in Pediatric Hematopoietic Progenitor Cell Transplant (HPCT) Patients with Heparin Alone Vs. Heparin and Ursodiol Prophylaxis at the Medical College of Wisconsin.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4306-4306
Author(s):  
Julie-An Talano ◽  
Jessica Brown ◽  
Jennifer McArthur ◽  
Mollie Mulberry ◽  
Daniel Eastwood ◽  
...  
Keyword(s):  
Medical Records ◽  
Low Dose ◽  
Pediatric Patients ◽  
Hematologic Malignancy ◽  
Post Transplant ◽  
Dose Heparin ◽  
Group I ◽  
Group 2 ◽  
Low Dose Heparin ◽  
Group 1

Abstract Abstract 4306 VOD is a serious and potentially life-threatening complication of HPCT as a result of liver injury from the effect of chemotherapy and/or radiation. The reported incidence rate in pediatric HPCT patients varies widely from 5% to 40%. Previous studies have shown the beneficial effects of post-transplant pharmacological therapies such as ursodeoxyholic acid (ursodiol), heparin, and defibrotide at preventing VOD. However, the combined effect of heparin and ursodiol prophylaxis in preventing VOD in pediatric patients has yet to be determined. This study evaluated retrospectively whether there was a benefit of such combined therapy in pediatric HPCT patients. Our center adopted as standard practice for all HPCT patients the initiation of low dose heparin at 4 units/kg/hour with the commencement of conditioning for HPCT until day +28 post transplant. In 2003, we combined ursodiol 10 mg/kg TID to start with HPCT conditioning and to continue until day + 100 post transplant with low dose heparin through day + 28 for all pediatric HPCT patients. We performed a retrospective chart review and compared the characteristics and the incidence of VOD in patients who underwent transplantation from 1996-2002 and received heparin alone compared to 2003-2008 when the patients received the combination of heparin and ursodiol prophylaxis. Patients were identified through medical records with the ICD diagnosis of VOD. The medical records were reviewed and those patients who did not meet the Baltimore criteria for the diagnosis of VOD were excluded. Only patients who developed VOD with their first transplants were included. Group I = Heparin (216) Group II = Heparin + Ursodiol (220) Allogeneic 187 (86.5%) 160 (72.7%) Autologous 29 (13.5%) 60 (27.3%) Median Age 9 yrs 8 yrs Male 123 (57%) 135 (62%) Female 93 (43%) 85 (38%) Non-malignant 34 (15.7%) 50 (22.8%) Hematologic malignancy 143 (66.2%) 109 (49.5%) Non-hematologic malignancy 39 (18.1%) 61 (27.7%) # VOD 13 5 The 100 day incidence of VOD was 0.0605 (SE 0.01618) in group 1 and 0.0227 (SE 0.01002) in group 2. The difference is 0.0377 (SE 0.0190) and based on a standard normal distribution with a p = 0.0473. The estimated risk of VOD for patients receiving Heparin + Ursodiol is 0.94 (risk or hazard ratio) that of the risk with Heparin alone, with a 95% confidence interval of (0.918, 0.960). This represents about a 6% reduction in risk for those receiving Heparin + Ursodiol. The day 100 survival in the VOD patients was 6 out of 13 in group 1 and 3 out of 5 in group 2. In conclusion, low dose heparin and ursodiol prophylaxis appears to be an effective strategy in VOD prevention in pediatric patients. The combination appeared to be more effective than heparin alone. However, this study is limited in that it is retrospective in nature. Disclosures: Off Label Use: heparin and ursodiol as VOD prophylaxis.

Ex Vivo T Cell-Depleted Haploidentical HCT for Children with Acute Leukemia after a Reduced-Intensity Preparative Regimen Containing Low-Dose TBI

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4673-4673
Author(s):  
Yeon Jung Lim ◽  
Ho Joon Im ◽  
Sung Han Kang ◽  
Hyery Kim ◽  
Kyung-Nam Koh ◽  
...  
Keyword(s):  
T Cell ◽  
Acute Leukemia ◽  
Low Dose ◽  
Pediatric Patients ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Reduced Intensity

Abstract Background: Recent advances in haploidentical hematopoietic cell transplantation (HHCT) enabled this transplant using haploidentical family donor to be a viable option for pediatric patients lacking matched related or unrelated donor. In our center, HHCT using ex vivo T cell-depleted (TCD) grafts after reduced-intensity conditioning (RIC) was conducted since 2008. The safety and efficacy of this transplantation modality for pediatric with acute leukemia were investigated. Methods: Thirty-one pediatric patients with acute leukemia received ex vivo T cell-depleted HHCT at Asan Medical Center Children's Hospital between July 2008 and June 2016. Four patients received CD3-depleted grafts and 27 received TCRαβ-depleted stem cells. Among 31 patients, 9 had ALL (3 CR1, 6 CR2-3), 22 had AML (18 CR1-3, 4 NR). Seven patients had relapsed after previous allogeneic HCT. All 31 patients underwent a uniform RIC regimen consisting of low-dose total body irradiation (LD-TBI; 600 cGy), fludarabine (FLU; 180 mg/m2), cyclophosphamide (CY; 100 mg/kg), and rabbit anti-thymocyte globulin (r-ATG; 3 mg/kg). Results: The median age at HHCT was 14 years (range, 1-19). All 31 patients achieved sustained neutrophil engraftment at a median of 10 days (range, 9-17) post-transplant. The cumulative incidence of acute GVHD grade II-III and III were 30% and 21%, respectively. None developed grade IV. Two of 26 evaluable patients developed extensive chronic GVHD. As of July 2016, 18 of the 31 patients survive free of disease with a median follow-up of 26 months (range, 2-98 months). Ten patients have died. Causes of death were relapse (n=9) and disseminated tuberculosis (n=1). Only one patient died of non-relapse cause, leading to TRM of 5.3% at 1 year. EFS and OS at 2 years for all patients were 51% and 60%, respectively. Sixteen patients with AML who received a first HHCT in any CR showed a favorable outcome (EFS of 85%), whereas, 6 patients with ALL who received a first HHCT in CR showed a poor EFS of 28%. In addition, all patients (6 with AML and 3 with ALL) who received a subsequent HCT in CR or were not in remission developed relapse. Conclusions: This study demonstrated that our ex vivo T cell-depleted HHCT using RIC is a feasible therapy with low TRM for pediatric patients with acute leukemia. The outcome of patients with AML who received their first transplant in CR was excellent in this treatment modality. However, the outcome of ALL was poor suggesting that more intensified conditioning regimen may be required for those diseases. Furthermore, an innovative treatment strategy is warranted to improve the outcome for patients with relapsed or refractory acute leukemia. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document