Comparable Results Between 8 and 12 Gray TBI in Combination With Fludarabine and Post-Transplant Cyclophosphamide in MRD-Negative but Not in MRD-Positive Acute Lymphoblastic Leukemia Patients Transplanted in First Complete Remission.

BACKGROUND: The optimal TBI dose for ALL patients undergoing allogeneic SCT is still not clearly defined. METHODS: Single-center retrospective analysis of high-risk ALL patients in CR1 treated with 8 Gy (n = 22) or 12 Gy (n = 50) TBI in combination with fludarabine and PTCy. Median patient age in the 8 Gy TBI cohort was 63 (37-79) and 37 (18-56) in the 12 Gy TBI cohort and median follow-up time was 21 months (range 1-92). RESULTS: OS and LFS at 2 years after 8 Gy were 65% and 55% versus 74% and 74% after 12 Gy (p = 0.3 and p = 0.2, respectively). CIR and NRM at 2 years were 27% and 14% after 8 Gy versus 4% and 20% after 12 Gy (p = 0.004 and p = 0.4, respectively). MRD-positive (+) patients (n = 26) receiving 12 Gy (n = 19) showed better OS (p = 0.01), LFS (p = 0.009), GRFS, lower CIR (p = 0.02), and similar NRM than did MRD+ patients receiving 8 Gy (n = 7). MRD-negative (-) patients (n = 38) receiving 12 Gy (n = 27) had similar OS, LFS, GRFS, lower CIR, and higher NRM (p = 0.04) than did MRD- patients receiving 8 Gy (n = 11). CONCLUSION: Our study demonstrates that 8 Gy TBI in comparison to 12 Gy TBI results in low NRM but a high relapse rate with similar OS, LFS, and GRFS. In MRD+ high-risk ALL patients, allogeneic SCT with 12 Gy TBI leads to improved OS, LFS, GRFS, and a low relapse rate. Prospective studies comparing the different treatment regimens with larger MRD patient cohorts are needed to confirm this data.

Anti-T-lymphocyte globulin (ATLG) compared to post-transplant cyclophosphamide as GvHD prophylaxis in ALL patients undergoing allogeneic stem cell transplantation.

We retrospectively analyzed high-risk ALL patients in CR1 receiving total body irradiation based conditioning regimen with ATLG (n = 74) or PTCy (n = 73) for GVHD prophylaxis. The 3-year OS and LFS were similar in both groups: 65 and 60% in the ATLG group and 64 and 67% in the PTCy group (p = 0.9 and 0.5, respectively). CIR and NRM rate at three years was 12 and 21% after PTCy and 19 and 20% after ATLG (p = 0.4 and p = 0.9, respectively). Acute GvHD grades II-IV and grades III/IV at 100 days was 46 and 19% after PTCy and 33 and 10% after ATLG (p = 0.08 and p = 0.9, respectively). Chronic GvHD of all grade at two years was higher after PTCy: 55% versus 26% (p < 0.001). Based on the propensity score matching (PSM) analysis, aGvHD grades II-IV was trending higher in the PTCy group compared to the ATLG group (p = 0.07). In contrast to the PSM analysis, on multivariate analysis the receipt of PTCy compared with ATLG was associated with a reduced CIR (p = 0.026). Our retrospective single-center analysis shows a lower incidence of acute and chronic GvHD while displaying similar LFS and OS after ATLG compared to PTCy in TBI based allogeneic stem cell transplantation for high-risk ALL.

Graft-versus-host disease and impact on relapse in myelofibrosis undergoing hematopoietic stem cell transplantation.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) remains the only curative treatment for myelofibrosis (MF). Relapse occurs in 10-30% and remains a major factor for dismal outcomes. Previous work suggested that graft-versus-host disease (GVHD) might be associated with risk of relapse. This study included 341 patients undergoing their first (n = 308) or second (n = 33) alloHSCT. Anti-T-lymphocyte or antithymocyte globulin was used for GVHD prophylaxis in almost all patients. Median time to neutrophile and platelet engraftment was 13 days and 19 days, respectively. The cumulative incidence of acute GVHD grade II-IV was 41% (median, 31 days; range, 7-112). Grade III-IV acute GVHD was observed in 22%. The cumulative incidence of chronic GVHD was 61%. Liver was affected in 23% of acute GVHD cases and 46% of chronic GVHD cases. Severe acute GVHD was associated with high non-relapse mortality. The development of acute GVHD grade II and moderate GVHD was an independent factor for reduced risk for relapse after transplantation without increased risk for non-relapse mortality, while especially acute GVHD grade IV was associated with high non-relapse mortality. Last, we identified that ongoing response to ruxolitinib, accelerated-phase MF at time of transplantation and splenectomy prior to transplantation were independent predictors for relapse.