Evaluation of an Optimized Allogeneic Hematopoietic Stem Cell Transplantation Protocol With Post-transplant Cyclophosphamide in Patients Aged 40 to 60 Years Old With Acquired Aplastic Anemia Refractory or in Relapse After Immunosuppression
Outcomes for adult patients with Severe Aplastic Anemia (SAA) aged more than 40 years who are refractory or in relapse after first-line IST remain poor. Hematopoietic stem cell transplantation (HSCT) is the unic valid therapeutic option but results have always been disappointing in patients aged 40 years or older. The first cause of death after HSCT in those refractory/relapse SAA patients is still graft versus host disease (GvHD). Recently, new strategies to prevent GvHD, including T-cell replete grafts with administration of post-transplantation cyclophosphamide (PTCy), have revolutionized the field, notably in haplo-identical donor setting. Using marrow as source of stem cells and a PTCy strategy not only in haplo-identical donor setting but also in case of an available matched sibling or unrelated donor might prevent drastically GvHD and eventually be practice changing. Evaluating this new strategy is the main objectives of APARR.
• Aged from 40 to 60 years old
• Suffering from acquired refractory severe idiopathic aplastic anemia after at least 6 months treatment with anti-thymocyte globulin, cyclosporine with Eltrombopag or in relapse
• Allograft validated in the National Multidisciplinary expertise meetings of the French reference centre for aplastic anemia
• With an available geno-identical donor or 10/10 matched donor or haploidentical donor
• With the absence of donor specific antibody detected in the patient with a MFI \< 1500 (antibodies to the distinct haplotype between donor and recipient)
• Usual criteria for HSCT:
‣ ECOG ≤ 2
⁃ No severe and uncontrolled infection
⁃ Cardiac function compatible with high dose of cyclophosphamide
⁃ With an adequate organ function ASAT and ALAT ≤ 3N, conjugated bilirubin ≤ 2N (or total bilirubin ≤ 2N if not available), clearance creatinine ≥ 50ml / min
• With health insurance coverage
• Women of childbearing potential and men must use contraceptive methods during their participation to the research and for 12 months and 6 months after the last dose of cyclophosphamide, respectively.
• Having signed a written informed consent
∙ NB: The authorized contraceptive methods are: For women of childbearing age and in absence of permanent sterilization:
• oral, intravaginal or transdermal combined hormonal contraception,
• oral, injectable or transdermal progestogen-only hormonal contraception,
• intrauterine hormonal-releasing system (IUS),
• sexual abstinence (need to be evaluated in relation to the duration of clinical trial and the preferred and usual lifestyle of the participants).
∙ For men in absence of permanent sterilization: sexual abstinence, condoms.
∙ Individuals must meet all of the inclusion criteria as verified at the screening / inclusion visit to be eligible to participate at the study.