A pilot clinical trial explored the efficacy of posttransplant cyclophosphamide (PTCy) in graft-versus-host disease (GVHD) prophylaxis for patients who underwent mismatched unrelated donor (MMUD) hematopoietic stem cell transplantation (HCT). Overall survival (OS) and GVHD-free/relapse-free survival (GRFS) rates appeared to be promising with this approach. Trial results were reported in the journal Blood Advances.

“Given the increasing availability of alternative donors, finding a fully matched donor is not the key access barrier to HCT, even for patients among racial/ethnic minorities,” the study authors wrote in their report. However, they explained, outcomes with MMUD-HCT continue to be inferior when compared to HCT with other donor types.

The trial (ClinicalTrials.gov Identifier: NCT03128359) enrolled patients with hematologic malignancies who were undergoing MMUD-HCT with peripheral blood stem cells. Human leukocyte antigen (HLA) matching with unrelated donors was at a level of ≥6/8, and without donor-specific antibodies to mismatched HLA loci.

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Patients were assigned to receive either myeloablative conditioning (MAC) or reduced intensity conditioning (RIC). GVHD prophylaxis for both arms included PTCy, tacrolimus, and mycophenolate mofetil. GRFS was the primary study endpoint.

A total of 38 patients were enrolled. Patients had a median age of 53 years (range, 21-72) and a median of 2 HLA mismatches (range, 1-4) among 12 loci. Neutrophil engraftment occurred at a median of 16 days (range, 13-35) across the cohort.

The median study follow-up was 18.3 months (range, 4.3-25.0) among survivors. The 1-year GRFS rate was 68% (95% CI, 51-81) for the entire cohort. Patients in the MAC arm had a 1-year GRFS rate of 84% (95% CI, 59-95), and for patients in the RIC arm, this rate was 53% (95% CI, 29-72).

The 1-year OS rate was 84% (95% CI, 68%-93%) across the entire cohort. Additionally, for the entire cohort the 1-year progression-free survival rate was 76% (95% CI, 59-87). Nonrelapse mortality at 100 days occurred at a rate of 0% (95% CI, not applicable) and at 1 year in 13% (95% CI, 6-30) overall. The 1-year cumulative incidence of relapse or progression was 11% (95% CI, 4-27) for the overall population.

In the entire cohort, acute GVHD of grades 2 to 4 at 100 days occurred with a cumulative incidence of 50% (95% CI, 36-69). For grades 3 to 4, this rate was 18% (95% CI, 9-36). Chronic GVHD at 1 year occurred at a rate of 49% (95% CI, 35-69) for the overall cohort, with moderate to severe chronic GVHD occurring in 3% (95% CI, 0.4-19) of all patients.

The study authors considered the trial to not have excessive early toxicities. There was 1 patient who showed delayed engraftment, beyond day 30, with engraftment occurring on day 35. Cytokine release syndrome was seen in 71% of patients, and at grade 3 in 3%.

“Our data support further development of PTCy in the MMUD setting, which will likely expand the access and improve the HCT results in many patients without a matched donor, particularly in racial/ethnic minorities,” the study authors concluded in their report.


Al Malki MM, Tsai N, Palmer J, et al. Posttransplant cyclophosphamide as GVHD prophylaxis for peripheral blood stem cell HLA-mismatched unrelated donor transplant. Blood Adv. 2021;5(12):2650-2659. doi:10.1182/bloodadvances.2021004192