Abstract
Introduction: As observed in myeloablative allograft, incidence of acute and chronic GVHD remains a major problem in patients receiving RIC HSCT in term of TRM and quality of life. So far, the best GVHD prophylaxis has not been yet established in this settings, as it could depend on the type of donor or of the RIC regimen. Thus, GVHD incidence is expected to be higher in patients receiving transplantation from unrelated donor compared to related donor. Here we have compared two GVHD prophylaxis regimen (Cyclosporine (CsA) alone vs CsA + Mycophenolate mofetil (MMF)) in patients receiving RIC allograft from unrelated donor in order to demonstrate the favourable impact of a stronger immmunosupressive treatment in term of overall survival (OS) due to less GVHD incidence.
Patients and Methods: We have studied retrospectively 40 successive patients from our institution who received RIC allogeneic HSCT from unrelated donor for haematological malignancies. Two GVHD prophylaxis regimen were administrated: CsA alone in Group 1 (n=19) from 2000 to 2005 and CsA +MMF in Group 2 (n=21) from 2005. Indeed, the observation of high incidence of acute GVHD in the former group conducted us to modify our strategy of GVHD prophylaxis. Almost all patients received a Slavin’s like RIC regimen associating Fludarabine, Busulfan and ATG. The graft consisted of peripheral blood stem cells for all patients except 4 patients in Group 1 who received bone marrow and 3 patients in Group 2 who received unrelated cord blood stem cells. The 2 groups were comparable in term of sex, status at transplant (CR1 vs others) and age at transplant (median age 49 years in Group 1 and 54 years in Group 2, p=0.05). Median follow-up for survival patients were 35 months and 12 months in Group 1 and 2 respectively. All patients have given informed consent.
Results: OS was significantly higher in Group 2: median 300 days (range: 36–2620 days) in group 1 versus median not reached (range: 181–812 days) in Group 2. OS was 40% at 1 year in group 1 compared to 92% in Group 2, p=0.0004. This discrepancy was due to the observation of a trend for higher acute GVHD grade III–IV occurrence in group 1 compared to Group 2 (75% vs 41%, p=0.21) and significant more deaths due to acute GVHD in Group 1 compared to Group 2 (4 patients vs 1, p<0.05). No difference was observed in term of relapse when comparing the 2 groups.
Conclusion: With restriction due to the short follow-up in Group 2, we demonstrated here the favourable impact of the combination of CsA + MMF as GVHD prophylaxis in patients receiving RIC transplant from unrelated donor as we demonstrate a significant benefit in term of overall survival due to less acute GVHD.
Author notes
Disclosure: No relevant conflicts of interest to declare.