Risk Stratification-directed NAC for Prevention of Poor Hematopoietic Reconstitution
Status:
Active, not recruiting
Trial end date:
2024-10-01
Target enrollment:
Participant gender:
Summary
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of
malignant hematopoietic diseases. However, poor hematopoietic reconstitution including poor
graft function (PGF) and prolonged isolated thrombocytopenia (PT), remains a life-threatening
complication after allo-HSCT. Especially with the increasing use of haploidentical allo-HSCT
(haplo-HSCT) in the past ten years, PGF and PT have become growing obstacles contributing to
high morbidity and mortality after allo-HSCT. Due to the limited mechanism studies, the
clinical management of PGF and PT is challenging.
Recent prospective case-control studies reported that the reduced and dysfunctional bone
marrow (BM) endothelial cells (ECs) after allo-HSCT are involved in the pathogenesis of PGF
and PT. Moreover, in vitro treatment with N-acetyl-L-cysteine (NAC) could enhance the
defective hematopoietic stem cell (HSC) function through repairing the dysfunctional BM ECs
of PGF and PT patients. The investigators performed a small-scale pilot cohort study and saw
encouraging clinical results that oral administration with NAC could partially repair the
dysfunctional BM ECs and improve megakaryocytopoiesis in PT patients, which suggests that NAC
is a promising drug in PT patients after allo-HSCT. In addition, prior prospective trial of
the investigators suggests that BM ECs<0.1% pre-HSCT is the risk factor for occurrence of the
PGF and PT two months following allo-HSCT. Previous single-arm clinical cohort studies of the
investigators showed that prophylactic use of NAC before allo-HSCT reduced the incidence of
poor hematopoietic reconstitution after allo-HSCT in patients with ECs <0.1% pre-HSCT.
Therefore, the investigators designed the study with acute leukemia patients who will be
scheduled to receive haplo-HSCT. The patients who are in the first complete remission at time
of haplo-transplant will be enrolled in the study. Exclusive criteria are bronchila asthma
and NAC allergy. The enrolled patients were risk-stratified into BM ECsā„0.1% group (low-risk
group) and BM ECs<0.1% group (high-risk group). Patients in high-risk group (ECs<0.1%) will
be randomized to 1 of 2 arms: (a) NAC 400 mg three times per day from 14 days pre-HSCT to 2
months post-HSCT, (b) No-NAC concurrent control according to a 2:1 schedule. The aim of the
trail is to assess the effects of NAC for prevention of poor hematopoietic reconstitution in
patients with acute leukemia undergoing haplo-HSCT.