To investigate the HPA axis function and the glucocorticoid receptor function after high-dose glucocorticoid therapy during treatment for childhood ALL and lymphoma. With these results, a more robust approach on glucocorticoid coverage during…
ID
Source
Brief title
Condition
- Leukaemias
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
One week after the last (tapering) dose of the glucocorticoid courses, patients
will be screened for HPA axis suppression by the low-dose ACTH stimulation test
(LD ACTH test). In case of suppression, this test will be repeated until
cortisol levels are normalized. Hereby, we will detect the number of patients
with HPA axis suppression and the recovery time of the HPA axis function after
high-dose glucocorticoid therapy.
In addition, the predictive value of the low dose dexamethasone suppression
test for developing HPA axis suppression will be determined.
To determine the incidence of symptomatic (relative) hypocortisolism after
administration of glucocorticoids, serum cortisol of all included patients
presenting at our hospital with clinical symptoms of (relative) hypocortisolism
during periods of stress, will be collected.
Secondary outcome
Before starting the first glucocorticoid course, one week after the last
(tapering) dose of this glucocorticoid course and after finishing treatment,
blood will be drawn to measure the sensitivity of the glucocorticoid receptors
on immune cells after high-dose glucocorticoid therapy.
Background summary
Since treatment and survival rates of childhood acute lymphoblastic leukemia
(ALL) and lymphoma improve over time, morbidity and mortality due to
treatment-related side effects become more and more important. The main cause
of treatment-related morbidity and mortality is infection.
Glucocorticoids, like predniso(lo)ne and dexamethasone, play a major role in
the treatment of children with ALL or lymphoma. They are also important as
graft versus host disease (GVHD) prophylaxis and treatment, following
hematopoietic stem cell transplantation (HSCT). However, supraphysiologic doses
of glucocorticoids may suppress the hypothalamic-pituitary-adrenal (HPA) axis.
Suppression of the HPA axis, resulting in reduced cortisol levels, may cause
life-threatening hypoglycemia and/or hypotension, an impaired inflammatory
response and an inadequate host-response against infections.
The effectiveness of the stress response and the anti-inflammatory response by
the HPA axis does not solely depend on absolute levels of circulating cortisol,
but also on the sensitivity of glucocorticoid receptors in immune cells.
Chronically elevated levels of cortisol and administration of pharmacologic
doses of glucocorticoids may alter the sensitivity of the glucocorticoid
receptors on peripheral blood mononuclear cells (PBMC).
Suppression of the HPA axis and alteration of the sensitivity of the
glucocorticoid receptors may lead to an altered inflammatory response and an
increased infection risk.
Our hypothesis is that treatment with high-dose glucocorticoid therapy for
childhood ALL or lymphoma:
1. causes prolonged suppression of the HPA axis resulting in reduced cortisol
production so that a proportion of the patients will not be recovered at eight
weeks after finishing glucocorticoid therapy.
2. alters the sensitivity of glucocorticoid receptors on immune cells.
Study objective
To investigate the HPA axis function and the glucocorticoid receptor function
after high-dose glucocorticoid therapy during treatment for childhood ALL and
lymphoma. With these results, a more robust approach on glucocorticoid coverage
during periods of stress after cessation of glucocorticoid therapy in childhood
ALL or lymphoma can be formulated. Participants of this study with an impaired
HPA axis function demonstrated by LD ACTH tests, will receive hydrocortisone
coverage during periods of stress.
Study design
A prospective, multicenter observational cohort study.
Study burden and risks
Reliable research on HPA axis function in childhood ALL or lymphoma can only be
conducted with the participation of minors. The LD ACTH test and the low dose
dexamethasone suppression test are well-known and widely used tests and the
risks are considered negligible. All blood samples will be drawn from a central
venous line and will be synchronized with the chemotherapy schedule avoiding
extra blood sampling moments and extra hospital visits.
Participants with an impaired HPA axis function demonstrated by LD ACTH tests
will benefit from this study because they will consequently receive
glucocorticoid coverage during periods of stress to reduce the risk of life
threatening hypocortisolism (hypoglycemia, hypotension).
De Boelelaan 1117
Amsterdam 1007 MB
NL
De Boelelaan 1117
Amsterdam 1007 MB
NL
Listed location countries
Age
Inclusion criteria
* Newly diagnosed ALL, aged 1-19 years, treated according to the DCOG ALL-10 or its successor protocol.
* Newly diagnosed Hodgkin lymphoma, aged 0-18 years, treated according to the EuroNet-Paediatric Hodgkin*s Lymphoma (PHL)-C1 protocol or the BEACOPP protocol or its successors.
* Newly diagnosed non-Hodgkin lymphoma, aged 0-18 years, treated according the DCOG B-NHL/B-ALL 2008, the ALCL 99 protocol or the DCOG EURO-LB-02 protocol or its successors.
* ALL or (non-)Hodgkin lymphoma, treated with high-dose glucocorticoids following HSCT.
* Written informed consent of parents and in addition of children aged above 12 years.
Exclusion criteria
* Glucocorticoid therapy for other reasons than treatment for ALL or (non-)Hodgkin lymphoma, since one year before diagnosis.
* Personal or family history of HPA axis related diseases.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL32368.029.10 |