Low-dose post-transplant cyclophosphamide and anti-thymocyte globulin as an effective strategy for GVHD prevention in haploidentical patients

Abstract

Background: Low-dose post-transplant cyclophosphamide (PTCy) in conjunction with anti-thymocyte globulin (ATG) appears as a potentially effective graft-versus-host disease (GVHD) prevention strategy in haploidentical hematopoietic cell transplant (haplo-HCT). Our study aims to assess the efficacy of this regimen. Methods:We extended our prospective study in patients treated with low-dose PTCy (14.5 mg/kg on days 3 and 4) in ATG/granulocyte colony-stimulating factor (G-CSF)-based regimen and compared the results to the contemporary cohort of patients without low-dose PTCy (ATG cohort). Both study cohort and control are transplanted from maternal donor or collateral relatives. Results: We identified 239 consecutive patients (ATG-PTCy cohort = 114; ATG cohort = 125). All patients but one in ATG cohort achieved myeloid engraftment by day 30 post-HCT. We found that both the cumulative incidence of 100-day grade III-IV aGvHD and non-relapse-mortality (NRM) in the ATG-PTCy cohort was significantly reduced than that in the ATG group (5% vs 18%; P = 0.003; and 6% vs 15%; P= 0.045); the 2-year cumulative incidences of relapse and overall survival were comparable between the two cohorts (13% vs 14%; P = 0.62; and 83% vs 77%; P = 0.18, respectively). Furthermore, GVHD-free, relapse-free survival (GRFS) was significantly improved in the ATG-PTCy arm (63% vs 48%; P = 0.039). In multivariate analysis, the joint treatment resulted in lower grade II-IV acute GVHD (HR 0.58; P = 0.036), grade III-IV aGvHD (HR 0.28; P = 0.006), chronic GVHD (HR 0.60; P = 0.047), NRM (HR 0.26; P = 0.014), and higher GRFS (HR 0.59; P = 0.021) but slower myeloid and platelet recovery (HR 0.29 and 0.30; both P < 0.001). Conclusions: These results suggested that ATG/PTCy (low-dose) can reduce both acute and chronic GVHD as compared with standard ATG-based prophylaxis using maternal donor or collateral relatives at particular high GVHD risk.

Post-transplantation Cyclophosphamide: From HLA-Haploidentical to Matched-Related and Matched-Unrelated Donor Blood and Marrow Transplantation

“…Similar results were reported by Bhamidipati et al following a nonmyeloablative preparative regimen (25). More recently, Wang et al showed that the addition of low dose PTCy (14.5 mg/kg on day +3 and +4), to the so-called Beijing protocol, reduced the incidence of grade II-IV aGvHD and improved GvHD-and relapse-free survival (GRFS) (26).…”

Haploidentical donor is preferred over matched sibling donor for pre-transplantation MRD positive ALL: a phase 3 genetically randomized study

“…Patients at high GVHD risk in the HIDT cohort received low-dose corticosteroid prophylaxis [19]. In addition, two doses of 14.5 mg/kg Cy was given on days 3 and 4 after HSCT from maternal donors during the trial period [20].…”

Grade 2 acute GVHD is a factor of good prognosis in patients receiving peripheral blood stem cells haplo-transplant with post-transplant cyclophosphamide

“…Among these strategies, the major one that emerged was to add ATG to PTCY. Several groups have demonstrated that this combination seems to be associated with a lower incidence of acute or chronic GVHD [21][22][23][24][25]. Here, the schedules used present the advantage, similarly to a recent publication [25], of comparing these two prophylaxis regimen (PTCY vs PTCY þ ATG 2.5 mg/kg, both with cyclosporine and mycophenolate mofetil) in a large cohort of patients.…”