Post-transplantation cyclophosphamide reduces the incidence of acute graft-versus-host disease in patients with acute myeloid leukemia/myelodysplastic syndromes who receive immune checkpoint inhibitors after allogeneic hematopoietic stem cell transplantat

Journal Name
Journal for immunotherapy of cancer
Primary Author
Saberian C
Author(s)
Saberian C, Abdel-Wahab N, Abudayyeh A, Rafei H, Joseph J, Rondon G, Whited L, Gruschkus S, Fa'ak F, Daher M, Knape C, Safa H, Shoukier M, Suarez-Almazor ME, Marcotulli M, Ludford K, Gulbis AM, Konopleva M, Ohanian M, Ravandi F, Garcia-Manero G, Oran B,
Popat UR, Mehta R, Alousi AM, Daver N, Champlin R, Diab A, Al-Atrash G
Original Publication Date

Background: Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD): Also called GVHD, it is a common complication of bone marrow/stem cell transplantation. It is caused when the donor's immune cells, now in the patient, begin to see the the patient's body as foreign and mount an immune response. GVHD most commonly effects the recipient's skin, intestines, or liver… . We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT.

Methods: A retrospective study was performed in 21 patients with acute myeloid leukemia: (uh-KYOOT my-uh-LOYD loo-KEE-mee-uh) A cancer of the blood cells. It happens when very young white blood cells (blasts) in the bone marrow fail to mature. The blast cells stay in the bone marrow and become to numerous. This slows production of red blood cells and platelets. Some cases of MDS become… (n=16) or myelodysplastic syndromes: (my-eh-lo-diss-PLASS-tik SIN-dromez) A group of disorders where the bone marrow does not work well, and the bone marrow cells fail to make enough healthy blood cells. Myelo refers to the bone marrow. Dysplastic means abnormal growth or development. People with MDS have low blood cell count for at… (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte: see lymphocyte -associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed.

Results: Four patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide: Cyclophosphamide is in a class of medications called alkylating agents. When used to treat cancer, it works by slowing or stopping the growth of cancer cells in your body. When cyclophosphamide is used to treat bone marrow failure, it works by suppressing your body's immune system. (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2-4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01).

Conclusions: ICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

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