Cyclophosphamide is Effective GVHD Prophylaxis in Matched Related and Unrelated HCT

In patients with acute leukemia, post-transplant cyclophosphamide (PT-Cy) can effectively control GVHD after matched related and unrelated donor HCT, and is even more effective when combined with 1 or 2 immunosuppressive drugs.

Dr. Annalisa Ruggeri of the Hôpital Saint-Antoine, Paris, reported on outcomes of 423 patients with acute leukemia who received:

  • PT-Cy alone (n=78; group 1)
  • PT-CY with one immunosuppressive (IS) drug:
    • Cyclosporine A (CSA) or
    • Methotrexate (MTX) or
    • Mycophenolate mofetil (MMF) (n=204; group 2)
  • PT-Cy in combination with 2 IS drugs:
    • CSA+MTX or CSA+MMF (n=141; group 3)

Transplants were performed between 2007 and 2015, and had a median follow up of 16 months.

The cumulative incidence overall of grade II-IV acute GVHD was 27.9%, and the addition of immunosuppressive drugs to the PT-Cy did not affect the risk of acute GVHD.

The cumulative incidence overall of chronic GVHD was 33.4%, and the cumulative incidence of extensive chronic GVHD was 16.5%. In a multivariate analysis, the addition of 1 or 2 immunosuppressive drugs were associated with reduced risk of extensive chronic GVHD (PT Cy+ 1 drug, HR 0.25, p=0.02, PT Cy+ 2 drugs, HR 0.77, p=0.01) in comparison to PT-Cy alone.

Probability of overall survival at 2 years was comparable in all 3 patient cohorts: 50%, 52.2%, and 62.4%, for PT-Cy only patients, PT-Cy with MTX or MMF patients, and PT-Cy plus CSA+MTX or CSA+MMF patients, respectively, p=0.06. Increased overall survival was associated with disease status at the time of HCT (CR1 vs. CR2 HR 0.58, p=0.02; CR1 vs. advanced disease HR 0.40, p<0.001) and for patients with AML (HR 0.35, p=0.001).

The researchers concluded that PT-Cy is effective GVHD prophylaxis in matched related and unrelated donor HCT for acute leukemia. The addition of IS drugs, CSA+MTX or CSA+MMF, to the PT-Cy further decreases the risk of severe chronic GVHD, reducing transplant-related mortality and improving overall survival.

Ruggeri A, et al. Abstract oral presentation, 2017 ASH annual meeting

Related Resources