Individualized 6-mercaptopurine increments in consolidation treatment of childhood acute lymphoblastic leukemia: A NOPHO randomized controlled trial

2017 ◽  
Vol 100 (1) ◽  
pp. 53-60 ◽  
Author(s):  
Morten Tulstrup ◽  
Thomas L. Frandsen ◽  
Jonas Abrahamsson ◽  
Bendik Lund ◽  
Kim Vettenranta ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Controlled Trial ◽  
Childhood Acute Lymphoblastic Leukemia ◽  
Consolidation Treatment ◽  
Randomized Controlled

scholarly journals Hydrocortisone as an Intervention for Dexamethasone-Induced Adverse Effects in Pediatric Patients With Acute Lymphoblastic Leukemia: Results of a Double-Blind, Randomized Controlled Trial

2016 ◽  
Vol 34 (19) ◽  
pp. 2287-2293 ◽  
Author(s):  
Lidewij T. Warris ◽  
Marry M. van den Heuvel-Eibrink ◽  
Femke K. Aarsen ◽  
Saskia M.F. Pluijm ◽  
Marc B. Bierings ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Acute Lymphoblastic Leukemia ◽  
Adverse Effects ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Controlled Trial ◽  
Metabolic Parameters ◽  
Dexamethasone Treatment ◽  
Double Blind ◽  
Randomized Controlled

Purpose Dexamethasone is a key component in the treatment of pediatric acute lymphoblastic leukemia (ALL), but can induce serious adverse effects. Recent studies have led to the hypothesis that neuropsychological adverse effects may be a result of cortisol depletion of the cerebral mineralocorticoid receptors. We examined whether including a physiologic dose of hydrocortisone in dexamethasone treatment can reduce neuropsychologic and metabolic adverse effects in children with ALL. Patients and Methods We performed a multicenter, double-blind, randomized controlled trial with a crossover design. Of 116 potentially eligible patients (age 3 to 16 years), 50 were enrolled and were treated with two consecutive courses of dexamethasone in accordance with Dutch Childhood Oncology Group ALL protocols. Patients were randomly assigned to receive either hydrocortisone or placebo in a circadian rhythm (10 mg/m2/d) during both dexamethasone courses. Primary outcome measure was parent-reported Strength and Difficulties Questionnaire in Dutch, which assesses psychosocial problems. Other end points included questionnaires, neuropsychological tests, and metabolic parameters. Results Of 48 patients who completed both courses, hydrocortisone had no significant effect on outcome; however, a more detailed analysis revealed that in 16 patients who developed clinically relevant psychosocial adverse effects, addition of hydrocortisone substantially reduced their Strength and Difficulties Questionnaire in Dutch scores in the following domains: total difficulties, emotional symptoms, conduct problems, and impact of difficulties. Moreover, in nine patients who developed clinically relevant, sleep-related difficulties, addition of hydrocortisone reduced total sleeping problems and disorders of initiating and maintaining sleep. In contrast, hydrocortisone had no effect on metabolic parameters. Conclusion Our results suggest that adding a physiologic dose of hydrocortisone to dexamethasone treatment can reduce the occurrence of serious neuropsychological adverse effects and sleep-related difficulties in pediatric patients with ALL.

scholarly journals Vincristine Induced Peripheral Neuropathy: A Randomized Controlled Trial Comparing Bolus Injections with One Hour Infusions during Induction in a Pediatric Population of Acute Lymphoblastic Leukemia and Hodgkin's Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5200-5200
Author(s):  
Mirjam Esther Velde ◽  
Machteld Heleen van den Berg ◽  
Floor Abbink ◽  
Heidi Segers ◽  
Barbara De Moerloose ◽  
...  
Keyword(s):  
Randomized Controlled Trial ◽  
Acute Lymphoblastic Leukemia ◽  
Peripheral Neuropathy ◽  
Lymphoblastic Leukemia ◽  
Controlled Trial ◽  
Current Analysis ◽  
Randomized Controlled ◽  
Sum Score ◽  
Total Treatment ◽  
The One

Abstract Purpose Vincristine (VCR) is a commonly used drug in the treatment of several pediatric cancers. Unfortunately, children suffer from dose-limiting vincristine-induced peripheral neuropathy (VIPN). We aimed to assess whether the administration of VCR by means of one-hour infusions, resulting in lower peak levels, leads to less VIPN than bolus injections in children having completed the induction phase of their treatment for acute lymphoblastic leukemia (ALL) or Hodgkin's lymphoma (HL). Methods The study is part of the VINCA trial, an international randomized controlled trial studying the effect of administration method of VCR on the development and severity of VIPN during treatment of several types of childhood cancer. Participants were measured 3-6 times (depending on the number of VCR administrations and the total treatment period) and one final measurement 6 months after cessation of therapy. VIPN was assessed using the pediatric modified total neuropathy scale (ped-mTNS) and four items of the common toxicity criteria of adverse events (CTCAE version 4.03) items: constipation, peripheral sensory neuropathy, peripheral motor neuropathy and neuralgia. For the current analysis two measurements were taken into account. The first measurement was performed before onset of VCR therapy and the second after induction at day 33 (after 4 VCR administrations) in case of ALL or in week 7 (after 6 VCR administrations) in case of HL. VIPN was defined as a CTCAE sum score of ≥ 2 and/or a total ped-mTNS score of ≥ 5, whereas severe PNP was defined as an individual CTCAE item score of ≥ 3 or a total ped-mTNS score of ≥ 10. Analysis were done using logistic regression or cox-regression. Results were corrected for age, gender and ethnicity. Results In total, 91 children participated in the study, 58 (64%) of whom were treated for ALL and 18 (20%) for HL. 15 (20%) dropped out of the trial or could not be included in the current analysis due to insufficient data (n=6 drop-out or no measurements available after induction, n=9 time between measurement was larger than 64 days). Of the remaining 61, 35 (57%) were randomized in the bolus group and 26 (43%) in the one-hour group. Overall, there was a mean increase of 2.77 for the CTCAE sum score and 7.81 for the ped-mTNS sum score in the bolus group, compared to 2.12 and 6.38, respectively, in the one-hour group (CTCAE: β=-0.71, CI: -1.7-0.44, ped-mTNS: β=-0.84, CI=-3.65-1.97). 27 (77%) children developed neuropathy in the bolus group and 19 (73%) in the one-hour group. Children in the bolus group had a slightly increased, but not significant, risk of developing VIPN compared to children in the one-hour group (hazard ratio=1.21; 95% CI: 0.66 - 2.20). The proportion of children with severe neuropathy was equal in both groups (42%). Conclusions Children treated for ALL or HL who receive VCR by means of one-hour infusions or bolus injections seem to be at equal or diminished risk of developing VIPN during induction therapy. Results of longer follow-up that includes the total treatment period should demonstrate whether VIPN occurs less frequently and/or is less severe in case VCR is administered through one-hour infusions compared to administrations by bolus injections. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document