Haploidentical Transplantation in Severe Aplastic Anemia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: MSD-HSCT This group received treatment of matched sibling donor - hematopoietic stem cell transplantation (MSD-HSCT). |
Other: MSD-HSCT
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;
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;
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.
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| Experimental: HFD-HSCT This group received treatment of haploid family donor - hematopoietic stem cell transplantation (HFD-HSCT). |
Other: HFD-HSCT
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;
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;
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.
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Outcome Measures
Primary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Department of Hematology, 304th Clinical Division, Chinese PLA General Hospital | Beijing | China | 100048 |
Sponsors and Collaborators
- Wu Xiaoxiong
Investigators
- Study Director: Xiaoxiong WU, PhD, The First Affiliated Hospital of General Hospital of PLA
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 2016QX-KS008