Effect of NAC on the Hematopoietic Reconstitution After Haploidentical Hematopoietic Stem Cell Transplantation
Condition: Haploidentical Hematopoietic Stem Cell Transplantation
MeSH terms: Thrombocytopenia
Study type: Interventional
Phase: Phase 2

Summary: 
      The aim of the study is to evaluate the efficacy of the prophylactic administration of
      N-acetyl-L-cysteine (NAC) in acute leukemia patients with complete remission pre- and
      post-allotransplant on the occurrence of poor graft function (PGF) and prolonged isolated
      thrombocytopenia (PT) after haploidentical hematopoietic stem cell transplantation.
      Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment of
      malignant hematopoietic diseases. However, the delayed hematopoietic reconstitution,
      including PGF and PT, remain serious complication after allo-HSCT, and the effective
      therapeutic strategies are limited. In murine studies, endothelial cells have been identified
      as a key cellular component supporting hematopoietic stem cells in the bone marrow
      microenvironment. Our previous prospective nested case-control study suggested that the
      frequency of bone marrow endothelial cells was markedly reduced in patients with PGF or PT.
      Moreover, our recent study further identified reduced bone marrow endothelial cells (<0.1%)
      pre-allotransplant was associated with significant higher incidences of PGF or PT after
      allo-HSCT. In addition, NAC treatment in vitro could quantitatively and functionally improve
      bone marrow endothelial cells derived from the patients with PGF or PT. Therefore, bone
      marrow endothelial cells (<0.1%) pre-allotransplant can be used to identify patients with a
      higher incidence of PGF or PT to provide timely prophylactic intervention of NAC to prevent
      the occurrence of delayed hematopoietic reconstitution post-transplant. The study hypothesis:
      Prophylactic intervention of NAC pre- and post-allotransplant could reduce the incidence of
      PGF and PT in acute leukemia patients after haploidentical hematopoietic stem cell
      transplantation.
    

Detailed description: 
      Acute leukemia patients with complete remission, whose bone marrow endothelial cells were
      less than 0.1% detected before haploidentical hematopoietic stem cell transplantation,
      receive NAC (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days
      pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease
      progression or unacceptable toxicity. The effect of NAC on hematopoietic stem cells,
      megakaryocytes, immunologic subsets, and the elements of bone marrow microenvironment will be
      monitored pre- and post-allotransplant.

      Drug：N-acetyl-L-cysteine (NAC) is orally administrated at dosages of 400mg 3 times per day.
      NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant
      continuously in the absence of disease progression or unacceptable toxicity.

      Participant：Acute leukemia patients with CR, whose bone marrow endothelial cells were less
      than 0.1% detected before haploidentical hematopoietic stem cell transplantation.

      Eligibility Ages Eligible for Study: 15-60 Years Genders Eligible for Study: Both Accepts The
      trial will be terminated in following situation

        1. Severe toxicity occurrence

        2. Cumulative incidence of relapse increased) (≥ 30%)

        3. Cumulative incidence of mortality increased (≥ 30%)

        4. Cumulative incidence of severe graft-versus-host disease increased (≥ 30%)
    

Intervention name(s): N-acetyl-L-cysteine
Intervention type(s): Drug
Intervention description(s): Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation, receive N-acetyl-L-cysteine (NAC) (orally at dosages of 400mg 3 times per day). NAC treatment begins from 14 days pre-allotransplant to 2 months after-allotransplant continuously in the absence of disease progression or unacceptable toxicity.
Other intervention name(s): NAC
Intervention MeSH terms: Acetylcysteine; N-monoacetylcystine
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: haploidentical hematopoietic stem cell transplantation; poor graft function; prolonged isolated thrombocytopenia; bone marrow endothelial cells; N-acetyl-L-cysteine; Acute leukemia