EBMT 2019 | Incorporation of PT-Cy as standard-of-care prophylaxis in patients with an increased risk of GvHD

It is known that the administration of post-transplant cyclophosphamide (PT-Cy) effectively prevents graft-versus-host-disease (GvHD) after haploidentical stem cell transplantation (HSCT). Nonetheless, data in matched sibling and unrelated donor SCT are still scarce.

On Wednesday 27 March 2019, Oral Session 10 (OS10) took place at the 45^th Annual Meeting of the European Society of Blood and Marrow Transplantation (EBMT), Frankfurt, DE. During this session, abstract OS10-8 was presented by Irene García-Cadenas from the Hospital de la Santa Creu I Sant Pau, Barcelona, ES, discussed the role of incorporating PT-Cy-based prophylaxis as a standard-of-care (SoC) in HLA matched siblings or unrelated donor transplantation for patients with an increased risk of GvHD.

Patients and methods

Results

Median follow-up: 365 days (range: 64–959)

• Efficacy:
  • Median time to neutrophil (>500 cells/mm3) and platelet (>50 x 109/L)recovery: day 23 (12–36) and day 22 (10–50) days, respectively
  • One year overall survival (OS) was 76% and the estimated one-year disease-free survival (DFS) was 63.6%
  • All relapses occurred in patients with intermediate/high relapsed Disease Risk Index (rDRI)

• Safety:
  • There were 2 cases of drug-related renal failure (4.5%) and 1 case of possible VOD
  • Before the introduction of mini-thiotepa in the RIC protocols (FluBu/FluMel) there was:
  • One case of primary graft failure (GF)
  • Five cases of late graft failure (6/28; 21%)
  • Four cases were successfully re-grafted with the mini-thiotepa RIC protocol
  • Additional potential risk factors for GF were CD34⁺ status ≤ 3x10⁶/kg (P = 0.07) and a high lymphocyte count at stem cell infusion (P = 0.06)
  • Grade III-IV acute GvHD at day + 120 was 4% (95% CI, 14–48), with only two cases of refractoriness to steroids
  • One patient developed moderate chronic GvHD at one year ( 3%)
  • Non-relapse mortality (NRM) was 10.5% at one year, and relapses occurred in 31% of patients (95% CI, 21–40)
  • The median duration of the initial hospital stay was 36 days, readmissions occurred in 30 patients (68.2%)

Conclusion

Dr. García-Cadenas concluded the session by confirming the feasibility of RIC allo-SCT with PT-Cy in combination tacrolimus or sirolimus as immunosuppressive drugs for patients at high risk of GvHD. The data showed that there was a high rate of GF in period one where “classical” allo-RIC were performed, however, GF appears to be lower when mini-Thiotepa was introduced. Dr. García-Cadenas highlighted that these data are not representative and requires a larger cohort for validation. The current results suggest that PT-Cy could pave the way to improving the quality of life of transplant survivors by significantly reducing severe GvHD.