Severe Aplastic Anemia
Conditions
Keywords
Haploidentical, Hematopoietic stem cell transplantation, Severe aplastic anemia
Brief summary
This is a prospective case-control study on SAA patients treated with HSCT, order to further discuss and assess the safety, feasibility and effectiveness of HFD-HSCT which performed with reduced-intensity fludarabine-based conditioning regimen.Our findings would indicate that SAA patients who lack MSD benefited most if HFD-HSCT was performed with reduced-intensity fludarabine-based conditioning regimen, and our improved outcomes with HFD-HSCT may lead to a salvaged therapy and an expanded direct role for SAA in the future.
Interventions
OTHERMSD-HSCT
1. Conditioning regimens: (A) Patients had SAA and PNH, or heavy transfusion (RBC≥25U), or failed rabbit ATG therapy, and received 0.8 mg/kg/6h busulfan (days -7 to -6), 30mg/m2/day fludarabine (days -5 to -2), 25 mg/kg/day cyclophosphamide (days -5 to -2) and 2.5 mg/kg/day r-ATG (days -5 to -2). (B) The other patients with SAA or VSAA received same procedure but without busulfan; 2. Allogeneic HSC infusion: Doner BM cells were harvested to achieve a target mononuclear cell count (MNC) of 2-4 × 108 per kilogram of recipient weight. The target MNC from PB was 4-6× 108 per kilogram of recipient weight; 3. Prophylaxis and treatment of GVHD: GVHD prophylaxis consisted of intravenous CSP 2-3 mg/kg/day in divided doses beginning on the day before transplantation (day -5) and the target concentration was adjusted to 150-250 ng/ml. The oral MMF dose was 20 mg/kg/day from day -1 and was tapered off after 1 months if no aGVHD was observed.
OTHERHFD-HSCT
1. Conditioning regimens: (A) Patients had SAA and PNH, or heavy transfusion (RBC≥25U), or failed rabbit ATG therapy, and received 0.8 mg/kg/6h busulfan (days -7 to -6), 35mg/m2/day fludarabine (days -5 to -2), 25 mg/kg/day cyclophosphamide (days -5 to -2) and 2.5 mg/kg/day r-ATG (days -5 to -2). (B) The other patients with SAA or VSAA received same procedure but without busulfan; 2. Allogeneic HSC infusion: Doner BM cells were harvested to achieve a target mononuclear cell count (MNC) of 2-4 × 108 per kilogram of recipient weight. The target MNC from PB was 4-6× 108 per kilogram of recipient weight; 3. Prophylaxis and treatment of GVHD: GVHD prophylaxis consisted of intravenous CSP 2-3 mg/kg/day in divided doses beginning on the day before transplantation (day -5) and the target concentration was adjusted to 200-300 ng/ml. The oral MMF dose was 20 mg/kg/day from day -3 and was tapered off after 2 months if no aGVHD was observed.
Sponsors
Wu Xiaoxiong
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Masking description
no masking
Intervention model description
Patients with SAA
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
(i) Diagnosis of SAA, very SAA or SAA and paroxysmal nocturnal hemoglobinuria (PNH) according to the International Aplastic Anemia Study Group; (ii) SAA patients no response to previous IST; (iii) adequate performance status \[Eastern Cooperative Oncology Group (ECOG) score 0-2\].
Exclusion criteria
(i) Congenital forms of aplastic anemia; (ii)Patients with any severe pulmonary, cardiac, liver, or renal diseases or active infection.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Engraftment | In the first months after infusion | Neutrophil engraftment was defined as the first of three consecutive days in which the neutrophil counts (ANC) exceeded 0.50 × 109/L, and platelet engraftment was defined as the first of five consecutive days in which the platelet count exceeded 20 × 109/L without transfusion. GF was classified as follows: (1) primary non-engraftment (failure to reach a neutrophil count of 0.5×109/L after transplant); (2) rejection (decrease in blood counts to \< 0.5×109/L neutrophils, after achieving a neutrophil count of 0.5×109/L); (3) late graft failure (decrease of blood counts after day 100 to \< 1.0×109/L neutrophils and \< 30×109/L platelets). |
| Toxicity grading | TRT was defined as toxic effects occurring within 40 days after HSCT | The transplantation-related toxicity (TRT) was graded using the National Cancer Institute Common Toxicity Criteria for Adverse Events version 4.0. Organ damage due to GVHD or infectious complications were excluded. |
| Chimerism analyses +30 | Days +30 after HSCT | Chimerism would be evaluated in recipient BM cells usually on days +30 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors. |
| Chimerism analyses +100 | Days +100 after HSCT | Chimerism would be evaluated in recipient BM cells usually on days +180 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors. |
| Chimerism analyses +180 | Days +180 after HSCT | Chimerism would be evaluated in recipient BM cells usually on days +100 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors. |
| Chimerism analyses +365 | Days +365 after HSCT | Chimerism would be evaluated in recipient BM cells usually on days +365 after HSCT using cytogenetic G-banding or fluorescence in situ hybridization. Sex-matched donor-recipient chimerism was assessed using PCR-based analyses of polymorphic minisatellite or microsatellite regions. HLA typing was performed for patients with HLA-haploidentical donors. |
| OS 1-year | 1-year after HSCT | OS was defined as the time from transplantation to death from any cause or the last follow-up. |
| OS 2-year | 2-year after HSCT | OS was defined as the time from transplantation to death from any cause or the last follow-up. |
| OS 5-year | 5-year after HSCT | OS was defined as the time from transplantation to death from any cause or the last follow-up. |
| EFS 1-year | 1-year after HSCT | EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure. EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure. |
| EFS 2-year | 2-year after HSCT | EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure. |
| EFS 5-year | 5-year after HSCT | EFS was defined as survival with a response to therapy. Death, GF and relapse were considered as treatment failure. |
Countries
China
Outcome results
None listed