Comparison of immune reconstitution between anti-T-lymphocyte globulin and posttransplant cyclophosphamide as acute graft-versus-host disease prophylaxis in allogeneic myeloablative peripheral blood stem cell transplantation.

Anti-T-cell lymphocyte globulin (ATLG) and posttransplant cyclophosphamide (PTCy) are now widely used strategies to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation. Data comparing immune reconstitution (IR) between ATLG and PTCy is scarce. This retrospective study conducted at the University Medical Center Hamburg-Eppendorf (UKE) compares PTCy (n=123) and ATLG (n=476) after myeloablative allogeneic peripheral blood stem cell transplant. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100 and 180 posttransplant. Incidence of infections, viral reactivations, GVHD and relapse were collected. Neutrophil engraftment was significantly delayed in the PTCy group (median day 12 vs. day 10, P<0.001) with a high incidence of infection before day+100 in the PTCy arm but a higher Epstein-Barr virus reactivation in the ATLG arm and comparable cytomegalovirus reactivation. Overall incidence of acute GVHD was similar but moderate/severe chronic GVHD was seen more often after PTCy (44% vs. 38%, P=0.005). ATLG resulted in a faster reconstitution of CD8+ T, NK, NKT and gdT cells while CD4 T cells and B cells reconstituted faster after PTCy. Similar reconstitution was observed for T-regulatory cells and B cells. Non-relapse mortality relapse incidence, disease-free survival, and overall survival did not differ significantly between both arms. Even though differences in IR were related to a decreased incidence of infection and moderate/severe cGVHD in the ATLG group they had no impact on any of the other long-term outcomes. However, it remains undetermined which regimen is better as GVHD prophylaxis.

Role of pre-transplant MRD level detected by flow cytometry in recipients of allogeneic stem cell transplantation with AML.

OBJECTIVES AND METHODS: We analyzed the impact of pretransplant MRD level in bone marrow measured by flow cytometry using "different from normal" method on outcomes for 189 AML patients (108 males; median age, 58 (21-80) years). All patients were subdivided into negative (n = 96), "low" (0.1%-0.5%, n = 32), and "high" MRD (>0.5%, n = 61) groups. RESULTS: In multivariate analysis, the hazard ratios for "high" and "low" MRD levels related to MRD negativity were 7.9 (95% CI 3.5-18.1, P < .001) and 5.4 (95% CI 2.1-14, P = .0058) for relapse; 2.3 (95% CI 1.3-4.1, P = .006) and 1.6 (95% CI 0.82-3.3, P = .16) for OS; and 2.8 (95% CI 1.7-4.7, P < .001) and 2.2 (95% CI 1.1-4.2, P = .02) for LFS, respectively. We found no significant impact of "low" MRD level on relapses (0.68, 95% CI 0.33-1.4, P = .30), OS (0.72, 95% CI: 0.36-1.5, P = .36) and LFS (0.79, 95% CI: 0.42-1.5, P = .46) related to "high" MRD group. CONCLUSIONS: Presence of detectable MRD was indicative for a high relapse risk, low LFS and OS. "Low" MRD level showed no significant impact on relapse, LFS and OS related to "high" MRD group.

Post-Transplantation Day +100 Minimal Residual Disease Detection Rather Than Mixed Chimerism Predicts Relapses after Allogeneic Stem Cell Transplantation for Intermediate-Risk Acute Myelogenous Leukemia Patients Undergoing Transplantation in Complete Remission.

Chimerism and minimal residual disease (MRD) are suggested to be prognostic for post-transplantation relapse in patients with acute myelogenous leukemia (AML). Nevertheless, the predictive value of both approaches in homogeneous populations remains underinvestigated. Here we suggest that MRD may have greater predictive value for relapse than mixed chimerism (MC) in intermediate-risk AML patients. Seventy-nine patients with intermediate-risk AML (40 males; median age, 57 years [range, 19 to 77 years]) were included. MRD detection on day +100 was performed in bone marrow via multiparameter flow cytometry (MFC) and quantitative real-time PCR (qPCR) for patients with an NPM1 mutation. Chimerism analysis was performed in peripheral blood. MC was defined as the persistence of <99.9% of donor alleles. The area under the receiver operating characteristic curve was highest for qPCR-MRD (.93), followed by MFC-MRD (.80) and MC (.65). The highest rate of relapse at 3 years was observed in day +100 qPCR-MRD-positive patients (100%), followed by MFC-MRD-positive patients (55%; P < .001). No patients with MC and without detectable MRD experienced relapse. The median 3-year overall survival (OS) and leukemia-free survival (LFS) for patients with MC without detectable MRD were both 86% (range, 61% to 96%), significantly higher than the values in day +100 MFC-MRD-positive patients (OS, 61% [range, 36% to 84%]; LFS: 30% [range, 11% to 59%]) and with day +100 qPCR-MRD-positive patients (OS: 17% [range, 3% to 56%], P = .001; LFS: 0%, P < .001). In patients with intermediate-risk AML, the qPCR-MRD on day +100 was highly predictive for relapse and long-term survival after allogeneic stem cell transplantation, followed closely by MFC-MRD. In contrast, chimerism status had limited predictive potential. Thus, molecular and flow cytometry MRD monitoring rather than MC in the first several months post-transplantation can identify patients at increased risk of relapse who may benefit from early post-transplantation preemptive intervention.

Impact of Anti-T-lymphocyte globulin dosing on GVHD and Immune reconstitution in matched unrelated myeloablative peripheral blood stem cell transplantation.

Data on the influence of different Anti-lymphocyte globulin (ATLG) doses on graft versus host disease (GVHD) incidence and immune reconstitution in matched unrelated (MUD) allogeneic Stem cell transplantation (allo-SCT) is limited. This retrospective study conducted at the University Medical-Center Hamburg compares GVHD and Immune reconstitution after myeloablative MUD (HLA 10/10) PBSC allogeneic stem cell transplant between 30 mg/Kg (n = 73) and 60 mg/Kg (n = 216) ATLG. Detailed phenotypes of T, B natural killer (NK), natural killer T (NKT) cells were analyzed by multicolor flow at day 30, 100, and 180 posttransplant. Neutrophil and platelet engraftments were significantly delayed in the 60 mg/kg group with a higher Cumulative incidence of Infections (67% vs 75% p = 0.049) and EBV (21% vs 41% p = 0.049) reactivation at day 100 in this group. In the 30 mg/kg group, we observed a faster reconstitution of naïve-B cells (p < 0.0001) and γδ T cells (p = 0.045) at day+30 and a faster naïve helper T-cell (p = 0.046), NK-cells (p = 0.035), and naïve B-cell reconstitution (p = 0.009) at day+180. There were no significant differences in aGVHD, cGVHD, NRM, RI, PFS, and OS between the groups. The choice of ATLG dose has significant impact on IR but not on GVHD after MUD-allo-SCT. Higher doses are associated with delayed engraftment and increased infections.