Post-Transplant Cyclophosphamide as Sole Graft-versus-Host Disease Prophylaxis Is Feasible in Patients Undergoing Peripheral Blood Stem Cell Transplantation for Severe Aplastic Anemia Using Matched Sibling Donors

Abstract

High-dose cyclophosphamide (PTCY) after allogeneic hematopoietic cell transplantation (HSCT) has been shown to be effective in preventing graft-versus-host disease (GVHD) after HLA-matched bone marrow transplantation. We performed a phase II study of PTCY given at 50 mg/kg i.v. on days 3 and 4 as the sole GVHD prophylaxis after HSCT for severe aplastic anemia (SAA) in patients receiving granulocyte colony-stimulating factor-mobilized peripheral blood stem cell (PBSC) grafts from HLA-matched related donors after conditioning with fludarabine, CY, and single-dose total body irradiation. Thirty patients with a median age of 29 years (range, 16 to 49) were enrolled in this study. Engraftment was seen in 27 patients (90%) at a median of 16 days (range, 12 to 21) post-HSCT. None of the patients developed veno-occlusive disease of the liver or hemorrhagic cystitis. Grades II to IV acute GVHD was seen in 22% of patients with grades III to IV GVHD in 11.1%. The 2-year cumulative incidence of chronic GVHD was 22.7%. Fourteen patients (46.6%) did not require any further immunosuppression after receiving PTCY. Comparing with 2 historical cohorts of 30 patients each who received cyclosporine and methotrexate (MTX; at 15 mg/m [MTX15] and 10 mg/m [MTX10]), the incidence of grades II to IV acute GVHD was lower, albeit not significantly, with the use of PTCY (PTCY, 22.2%, vs MTX15, 37.1%, vs MTX10, 53.8%; P = .056), whereas rates of chronic GVHD were significantly reduced (PTCY, 22.7%, vs MTX15, 63.6%, vs MTX10, 76.2%; P = .013). Viral infections including cytomegalovirus were significantly higher with the use of PTCY (60%) compared with cyclosporine and MTX (MTX15, 23.3%, vs MTX10, 33.3%; P = .008). Overall survival was similar between the 3 groups. We conclude that PTCY as the sole GVHD prophylaxis is associated with low rates of acute and chronic GVHD in patients undergoing PBSC transplant for SAA using HLA-matched donors. This trial is registered at CTRI/2010/091/001480.

Comparable Outcomes of First-Line Hematopoietic Stem Cell Transplantation from Unrelated and Matched Sibling Donors in Adult Patients with Aplastic Anemia: A Retrospective Single-Center Study

“…In the present study, in both the URD and MSD groups, all patients received 10.0 mg/kg ATG, which may have contributed to the high incidence of CMV viremia. Moreover, the PCR cutoff for positive CMV viremia was 500 copies/mL, lower than the cutoff in a previous study (1000 copies/mL) [46], and this low cutoff may also be an important contributing factor in the high rate of CMV viremia in our institution [47].…”

Low rates of acute and chronic GVHD with ATG and PTCy in matched and mismatched unrelated donor peripheral blood stem cell transplants

“…Post‐transplant cyclophosphamide (PTCy) for GVHD prophylaxis in the setting of matched related (MRD), matched and mismatched unrelated (MUD and MMUD), and haplo‐identical (HI) transplants has been associated with low rates of acute and chronic GVHD . Similarly, ATG has been used extensively for GVHD prophylaxis for MUD transplants with beneficial effects in reducing acute and chronic GVHD .…”

Allogeneic HSCT in Adolescents and Young Adults With Primary Immunodeficiencies

“…In up to date transplant practice, multiple agents in combination are typically used for GVHD prophylaxis either with or without PTCy (31) and T cell depleting serotherapy. Recent publications have also demonstrated that single agent PTCy can be effective as GVHD prophylaxis in pediatric and adult cohorts with non-malignant and malignant indications for HSCT (32, 33).…”