Effect of NAC on the Hematopoietic Reconstitution After Haploidentical Hematopoietic Stem Cell Transplantation
- Conditions
- Haploidentical Hematopoietic Stem Cell Transplantation
- Interventions
- Registration Number
- NCT03236220
- Lead Sponsor
- Peking University People's Hospital
- Brief 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%)
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 35
Acute leukemia patients with complete remission, whose bone marrow endothelial cells were less than 0.1% detected before haploidentical hematopoietic stem cell transplantation；
- Bronchial asthma;
- Allergic to N-acetyl-L-cystein
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description N-acetyl-L-cysteine group N-acetyl-L-cysteine 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.
- Primary Outcome Measures
Name Time Method Incidence of poor graft function and prolonged isolated thrombocytopenia Participants will be followed for 2 months post-HSCT. Number of participants with poor graft function and prolonged isolated thrombocytopenia will be calculated at 2-month post-HSCT.
- Secondary Outcome Measures
Name Time Method Number of participants with treatment-related adverse events will be assessed by CTCAE v4.0 during oral administration of NAC. From 14 days pre-HSCT to 2 months post-HSCT. Participants will be closely observed for NAC-related toxicities during the NAC administration until 2-month post-HSCT.
Overall survival Participants will be followed for 1 year post-HSCT. Number of participants survived for 1 year post-HSCT will be calculated.
Effect of NAC on hematopoietic stem cells, megakaryocytes and the elements of bone marrow microenvironment. Participants will be followed for 100 days post-HSCT. Examine hematopoietic stem cells, megakaryocytes and the elements of bone
marrow microenvironment by flow cytometry and bone marrow histological examination.Non-relapse mortality Participants will be followed for 1 year post-HSCT. Number of participants with non-relapse mortality will be observed for 1 year post-HSCT.
Incidence of GVHD Participants will be followed for 100 days post-HSCT. Number of participants with I-IV aGVHD will be observed for 100 days post-HSCT.
Incidence of relapse Participants will be followed for 1 year post-HSCT. Number of participants with morphologic relapse will be calculated at one year post-HSCT.
Incidence of viral infection Participants will be followed for 100 days post-HSCT. Number of participants with viral infection(CMV,EBV,et al) will be observed for 100 days post-HSCT.
Progression-free survival Participants will be followed for 1 year post-HSCT. Number of participants survived with progression-free will be observed for 1 year post-HSCT.
Trial Locations
- Locations (1)
Peking University People's Hospital
🇨🇳Beijng, China