Single-Agent Post-Transplantation Cyclophosphamide as Graft-versus-Host Disease Prophylaxis after Human Leukocyte Antigen–Matched Related Bone Marrow Transplantation for Pediatric and Young Adult Patients with Hematologic Malignancies

Abstract

High dose cyclophosphamide given after HLA-matched related and unrelated allogeneic bone marrow transplantation (BMT) for patients with hematologic malignancies is effective single agent graft-versus-host disease (GVHD) prophylaxis in adults. Data describing outcomes for pediatric and young adult patients has not been reported. Between the years 2007-2013, 29 pediatric and young adult patients age ≤ 21 years of age treated at our institution for high-risk hematologic malignancies underwent myeloablative HLA-matched related T cell replete BMT. Eleven patients received post-transplant cyclophosphamide (PTCy) as single agent GVHD prophylaxis and were followed prospectively. Eighteen patients received calcineurin inhibitor (CNI)-based standard GVHD prophylaxis and were studied retrospectively as a control group. No acute GVHD developed in patients receiving PTCy, while patients receiving CNI-based GVHD prophylaxis had a cumulative incidence of grade II-IV and grade III-IV acute GVHD of 27% and 5% respectively. No patients receiving PTCy developed chronic GHVD, compared to one in the control group. Two-year overall survival was similar between the two groups (54% PTCy vs 58% CNI-based prophylaxis), as was event-free survival (42% PTCy vs 47% CNI-based). The 5 year cumulative incidence of relapse was 58% for PTCy and 42% for CNI-based GVHD prophylaxis (p=0.45). These results suggest that PTCy is a safe and efficacious method of GVHD prophylaxis following an HLA-matched related BMT in the pediatric and young adult population that affords patients to be off all post-transplant immunosuppression on day +5.

Development of Grade II Acute Graft-versus-Host Disease Is Associated with Improved Survival after Myeloablative HLA-Matched Bone Marrow Transplantation using Single-Agent Post-Transplant Cyclophosphamide

“…However, limiting the duration of immunosuppression has been associated in many platforms with an increased risk of severe aGVHD and cGVHD. We have previously shown that high-dose PTCy is an effective single-agent prophylactic strategy after HLA-matched BMT [10–13] and seems to reduce severe aGVHD and cGVHD without concomitant decreases in the incidence of grade II aGVHD. Similar to recent studies in haplo BMT with PTCy [9] and umbilical cord transplantation [30] we demonstrate that grade II aGVHD is associated with significantly improved OS and PFS in HLA-matched BMT with PTCy.…”

Allogenic peripheral stem cell transplantation from HLA-matched related donors for adult sickle cell disease: remarkable outcomes from a single-center trial

“…This procedure has been shown to eliminate proliferative allo-reactive T cells, while preserving resting, non-reactive T cells. Infection risk also decreases through preservation of virus-specific T cells [40]. Posttransplant Cy was reported to be used in allo-transplants in adult SCD patients and HLA-matched sibling donors by Bolanos-Meade et al [41].…”

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

“…The incidence of acute GVHD was low at 22.2%, with a low incidence of chronic GVHD of 22.7%. PTCY is increasingly used either alone or in combination with calcineurin inhibitors or sirolimus to reduce the incidence of GVHD after sibling donor transplants [18][19][20][21][22][23][24][25][26]. The combination of PTCY with calcineurin inhibitors has been associated with low rates of acute (17% to 40%) and, importantly, chronic GVHD (7% to 16%), but data on its single use have shown very conflicting rates of GVHD.…”

“…Although the above studies have described GVHD rates with PTCY in the setting of PBSCs as the graft source, the use of BM as the graft source while using PTCY has also shown conflicting data. Jacoby et al [25] in a study of 29 pediatric and young adult patients undergoing myeloablative HLAmatched related T cell-replete BM transplantation showed a 0% incidence of acute and chronic GVHD in those receiving PTCY (n = 11) compared with 27% and 5%, respectively, with the use of calcineurin inhibitor-based GVHD prophylaxis. However, Kanakry et al [26] in a multi-institutional study of 92 patients having allogeneic BM transplantation using myeloablative busulfan and fludarabine conditioning with PTCY as the single-agent GVHD prophylaxis showed acute and chronic GVHD rates of 51% and 14%, respectively.…”

“…The 2-year OS rates were 65.9% with PTCY compared with 63.9% with MTX15 and 69.8% with MTX10 (P = .922) (Figure 2A). The 2-year event-free survival rates were 15 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28) 15 (12)(13)(14)(15)(16)(17)(18)(19)(20) 16 (12)(13)(14)(15)(16)(17)(18)(19)(20)(21) .106 Median time to platelet engraftment, days (range)…”