In this study we aim to gain more insights into immune reconstitution of various leukocyte populations after SCT. By application of heavy water labeling we investigate if and how the production- and death rate of leukocytes changes after an SCT.
ID
Source
Brief title
Condition
- White blood cell disorders
- Immunodeficiency syndromes
- Haematological and lymphoid tissue therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main parameter of this study is the amount of deuterium (label) that the
various leukocyte populations have incorporated in their DNA by cell division
at a given time. For this purpose blood withdrawals are done both in the period
during which participants drink 2H2O (uplabeling phase) and in the period after
stopping with 2H2O intake (downlabeling phase). Data obtained during uplabeling
and downlabeling phases can be interpreted by mathematical models that describe
the dynamics of leukocyte populations.
Secondary outcome
Deuterium enrichment in urine. This parameter will allow us to determine the
level of deuterium in body water that was available to be incorporated into the
various cell populations. This level can vary between individuals, dependent on
how much normal (unlabeled) water was drunk by the participant. (ii) T cell
excision circles and plasma levels of growth- survival- and inflammatory
factors. (iii). The composition of the transplant. The presence of various
leukocyte populations in the transplant can possibly influence the
reconstitution rate of these cell populations.
Background summary
When patients affected with hematological malignancies are treated with a stem
cell transplantation, they often suffer from a severe and long-lasting
deficiency of the adaptive immune system, which increases the patient*s
vulnerability to infections and tumor relapses. At present it is still unclear
why it takes so long for the adaptive immune system to recover from a stem cell
transplantation (SCT). Following an SCT, the production- and death rate of
lymphocytes may be disturbed, as the pre-SCT conditioning may severely damage
the primary lymphoid organs (bone marrow and thymus). An alternative
explanation for the slow reconstitution of leukocyte populations after SCT may
in fact be the reflection of a slow production rate in the healthy situation.
In this study we aim to gain more insight in immune reconstitution by
determining the production- and death rate of various leukocyte populations
after SCT. As we investigate the production- and death rate of these cell
populations in healthy individuals in a parallel study, we will be able to
detect possible differences in cell dynamics after SCT. More insights in
leukocyte dynamics after SCT will facilitate the development of strategies to
accelerate immune reconstitution, and thereby reduce infectious complications
and tumor relapses in the clinic.
Study objective
In this study we aim to gain more insights into immune reconstitution of
various leukocyte populations after SCT. By application of heavy water labeling
we investigate if and how the production- and death rate of leukocytes changes
after an SCT.
Study design
The study concerns longitudinal observational research with invasive acts. It
is composed of temporary consumption of deuterated (heavy) water (2H2O) and
prospective blood withdrawals and urine sampling for laboratory research. Blood
is drawn 4 times in the period during which participants drink heavy water
(uplabeling phase) and 6 times in the period that follows (donwlabeling phase).
From the blood samples various leukocyte populations will be sorted after which
in the DNA of these samples deuterium enrichment can be quantified using gas
chromatography and mass spectrometry (GC-MS). Frequent sampling of urine makes
it possible to correct, per time point, for the intake of unlabeled water by an
individual.
Study burden and risks
The frequent blood- and urine sampling and associated hospital visits make the
burden of this study substantial. In addition, the questionnaires can be
considered an incursion to one*s privacy. There is no direct advantage of
participation. The necessary amounts of heavy water are not harmful. The total
volume of withdrawn blood falls within the limits applied by Sanquin bloedbank.
Participation hence comes with burden, but is safe.
Lundlaan 6
Utrecht 3584 EA
NL
Lundlaan 6
Utrecht 3584 EA
NL
Listed location countries
Age
Inclusion criteria
(i) At least 18 years of age;
(ii) Ability to understand and voluntarily sign the informed consent form for this study and ability to follow the study protocol;
(iii) Treatment for hematological malignancy with an autologous stem cell transplantation for which
(iv) the autologous transplant consists of non-T cell depleted stem cells, that are isolated from peripheral blood, and mobilized with G-CSF (and possibly Plexirafor);
(v) sufficient kidney function, defined by serum creatinine level * 1.5 × upper limit of normal (ULN) and glomerular filtration rate > 30 mL/min (calculated by Cockcroft and Gault formula);
(vi) sufficient liver function, defined by total serum bilirubin * 1.5 × ULN;
(vii) serum aspartate transaminase (AST) and/or alanine transaminase (ALT) * 2.5 × ULN;
(viii) women of child bearing potential must agree to use an adequate and medically accepted method of contraception
(ix) patients starting the protocol 12-18 months post-transplantation should have a naive CD4+ T-cell count of at least 20/µl peripheral blood.
Exclusion criteria
(i) Infection with human immunodeficiency virus (HIV);
(ii) Active infection with hepatitis B or C or other active liver disease
(iii) Other active uncontrolled infections, like malaria, infectious mononucleosis, sexually transmitted diseases;
(iv) Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study;
(v) Uncontrolled or significant cardiovascular disease, including: A myocardial infarction within 12 months; Uncontrolled angina within 6 months; Current or history of congestive heart failure New York Heart Association (NYHA) class 3 or 4;
(vi) Body weight below 50 kg
(vii) Pregnancy or parent*s wish in the coming year;
(viii) Excessive alcohol consumption
(ix) Drug use
(x) Extreme sensitivity to sea- and/or car sickness.
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 | NL36260.041.11 |