α1-antitrypsin (AAT) Levels and Functions in Allogeneic Bone Marrow Transplantation and Throughout Progression Into GVHD (AATGVHD-MARK)

Rambam Health Care Campus

Status

Completed

Conditions

Bone Marrow Transplant Failure

GVHD

Alpha 1-Antitrypsin

Study type

Observational

Funder types

Other

Identifiers

NCT03188601

0196-17-RMB

A1373 (Other Grant/Funding Number)

Details and patient eligibility

About

Create a personalized time and context curve of patient circulating α1-antitrypsin (AAT) levels and functions before hematopoietic stem cell transplantation and throughout progression into GVHD.

PRIMARY ENDPOINT 1. Serum AAT levels and activity, before myeloablative preconditioning, as well as on days (-3),0,7,14,28 from HSCT and every 21 days thereafter.

SECONDARY ENDPOINTS 1. Correlation between AAT patterns and:

Circulating immune cell activation profiles on day of ablation, 28 days from HSCT and once GVHD is diagnosed.
Patient survival
Liver function tests
GVHD grade: skin manifestations, weight, GI and liver histopathology
Graft-versus-leukemia effect

Full description

This study will focus on each individual patient from the early point of myeloablative conditioning through HSCT and GVHD. The rationale for this individualized approach is to account for the anticipated variability in patient age and primary disease, background pathology and individual therapeutic course, considering the enormous heterogeneity of this condition. To compensate for this limitation, we intend to create an individualized algorithm, based on a novel dynamic biomarker, i.e., AAT functionality, individualized per patient and placed on a timeline, with the aim of minimizing future occurrences of GVHD, and by using readily available laboratory measurements. The study is designed around patient sample collection, there is no change in standard of care, therefore there is no intervention as well.

Three types of sample tubes will be collected per indicated time point:

Serum tube for protein levels and enzymatic activity assays.
EDTA tube for isolation of peripheral blood mononuclear cells (PBMCs), cells will be stimulated and then analyzed by FACS and lysed for RT-PCR
EDTA tube for whole blood stimulation assay for further FACS analysis and cytokine production measurement.

After donor and recipient informed consent forms were signed, a single blood sample should be obtained from the donor on the day of transplant extraction. Time points for recipient's samples include the day of myeloablation and again immediately prior to HSCT (set as day 0 and possibly -3 in MUDs). Serum and lysed blood samples will be collected on days 7, 14, 28, and every 21 days thereafter, through the development and progression of GVHD (where relevant). Blood samples for FACS will be collected by days 0 and 28. Sample collection is planned to end within 1 year from HSCT, or two months after appearance of symptoms of GVHD, or two months after a change is introduced in the immunosuppressive therapy.

Enrollment

27 patients

Sex

All

Ages

18+ years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

Candidates for allogeneic transplantation for the first time, scheduled to receive HSCT from HLA-matched sibling or an unrelated matched donor
Signed informed consent by the donor(Healthy volunteers) and the patient

Exclusion criteria