0
selected
-
1.
Patterns of CMV Infection After Letermovir Withdrawal in Recipients of Post-Transplant Cyclophosphamide Based Transplant
Lin, A., Brown, S., Chinapen, S., Lee, Y. J., Seo, S. K., Ponce, D. M., Shahid, Z., Giralt, S. A., Papanicolaou, G. A., Perales, M. A., et al
Blood advances. 2023
Abstract
Reactivation of latent cytomegalovirus (CMV) is increased in CMV seropositive (CMV+) recipients of allogeneic hematopoietic cell transplantation (allo HCT) using post-transplant cyclophosphamide (PT-Cy) based graft versus host disease prophylaxis. Letermovir, a novel DNA terminase complex inhibitor, reduces the incidence of clinically significant CMV infection (csCMVi) in this population; however, parameters that predict csCMVi after letermovir withdrawal are not well described. Here, we examined clinical and immunological parameters in 294 recipients of PT-Cy based allo HCT, including 157 CMV+ patients of whom 80 completed letermovir prophylaxis without csCMVi, and subsequently stopped letermovir. In this population, the median duration of letermovir exposure was 203 days (interquartile range (IQR): 160 - 250 days). After letermovir withdrawal, the 90-day cumulative incidence of csCMVi was 23.0% (14.3 - 32.8). There were no episodes of CMV end-organ disease. Hypo-gammaglobulinemia prior to letermovir discontinuation was predictive of csCMVi (hazard ratio: 0.33, 95% confidence interval: 0.12-0.93, p = 0.03), whereas T-cell and B-cell reconstitution prior to letermovir withdrawal were not predictive of csCMVi. Higher numbers of NK cells were found prior to letermovir withdrawal in patients that experienced csCMVi (median 202 versus 160, p = 0.03). In CMV+ recipients, CD3+CD4-CD8+ T-cell reconstitution was faster in CMV+ patients regardless of letermovir exposure. Taken together, these data suggest that csCMVi after letermovir withdrawal was frequent in patients treated with PT-Cy, despite prolonged exposure. Strategies to boost CMV specific adaptive immunity in patients with persistent hypo-gammaglobulinemia is a logical pathway to reduce csCMVi after letermovir withdrawal.
-
2.
Improved GRFS after posttransplant cyclophosphamide-based vs ATG-based HLA-mismatched unrelated donor transplant
Jimenez Jimenez, A. M., Komanduri, K., Brown, S., Wang, T. P., Pereira, D. L., Goodman, M., Beitinjaneh, A., Lekakis, L. J., Chinapen, S., Devlin, S. M., et al
Blood advances. 2022
-
-
-
Free full text
-
Full text
-
Editor's Choice
Abstract
A common method to prevent graft versus host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) from an HLA-mismatched unrelated donor (MMUD) is tacrolimus, methotrexate and anti-thymocyte globulin (ATG). The use of post-transplant cyclophosphamide (PTCy) demonstrated promise in a prospective trial for MMUD HCT. We compared one-year GVHD-free, relapse-free survival (GRFS) in 128 recipients of tacrolimus/methotrexate/ATG (ATG group, N = 46) with PTCy, mycophenolate mofetil, and tacrolimus or sirolimus (PTCy group, N = 82) based prophylaxis after MMUD HCT. Patients receiving HCT from a MMUD mismatched at ≥ 1 locus among HLA-A, -B, -C, and -DRB1 were included. The two groups were well matched for HCT indication, high-risk disease, and HCT comorbidity index, whereas more patients on PTCy received bone marrow (50% versus 26%, P = 0.01) and >1 locus HLA-mismatched grafts (30.5% vs. 2.2%, P = 0.001). The one-year GRFS was 16% (95% confidence interval: 8% - 31%) versus 54% (44% - 66%, P < 0.001) in the ATG and PTCy groups, respectively. The multivariable-adjusted hazard ratio (HR) for GRFS was 0.34 (0.21 - 0.55, P < 0.001) with the use of PTCy. The one-year overall survival (OS) in the ATG group was 45% (32% - 62%) versus 75% (66% - 85%) in the PTCy group (P < 0.001). Relapse incidence was similar. One-year non-relapse mortality was greater after ATG-based prophylaxis: (38%, 23% - 52%; versus 16%, 9% - 25%; P < 0.001). In summary, PTCy based prophylaxis resulted in superior GRFS and OS in recipients of MMUD.
PICO Summary
Population
Adults from 11 centres in USA, transplanted from a mismatched unrelated donor, mismatched at ≥ 1 locus among HLA-A, -B, -C, and -DRB1.
Intervention
Methotrexate 5 to 15 mg/m2 IV, on days 1, 3, 6, and 11 post-HCT, peritransplant dose-adjusted tacrolimus, and 5 to 7.5 mg/kg rabbit ATG, before allograft infusion. (ATG group, n= 46)
Comparison
50 mg/kg IV cyclophosphamide on days 3 and 4, post-allograft infusion (PTCy group, n= 82)
Outcome
The one-year GRFS was 16% (95% confidence interval: 8% - 31%) versus 54% (44% - 66%,) in the ATG and PTCy groups, respectively. The multivariable-adjusted hazard ratio (HR) for GRFS was 0.34 (0.21 - 0.55) with the use of PTCy. The one-year overall survival (OS) in the ATG group was 45% (32% - 62%) versus 75% (66% - 85%) in the PTCy group. Relapse incidence was similar. One-year non-relapse mortality was greater after ATG-based prophylaxis: (38%, 23% - 52%; versus 16%, 9% - 25%).
-
3.
Impact of omitting post-transplant minidose-methotrexate doses in allogeneic hematopoietic cell transplantation
Lin, A., Brown, S., Maloy, M., Ruiz, J. D., Devlin, S., DeRespiris, L., Proli, A., Jakubowski, A. A., Papadopoulos, E. B., Sauter, C. S., et al
Leukemia & lymphoma. 2022;:1-8
Abstract
Given prophylactic methotrexate (MTX) is often held in the setting of toxicity we investigated the impact of omitting minidose-MTX dose(s). Outcomes were compared between patients who had 1-3 doses omitted and those who received all four planned doses of minidose-MTX. Of 370 consecutive patients, 50 had MTX dose(s) omitted. When MTX was omitted, initial management was mycophenolate mofetil (MMF; 36/50 patients) with or without corticosteroids (14/50 patients). Rates of grade 3-4 acute GVHD were similar between groups. Omission of minidose-MTX resulted in an increased risk of chronic GVHD (cGVHD; HR 2.27; p = .024) and decreased overall survival (HR 1.61; p = .024). However, other transplant-related outcomes were comparable. In summary, omission of minidose-MTX doses was not associated with an increased risk of acute GVHD when an alternative was added (e.g. MMF ± corticosteroids). This did not abrogate the increased risk of cGVHD or decreased overall survival.
-
4.
Haploidentical Transplantation with Post-Transplantation Cyclophosphamide for High-Risk Acute Lymphoblastic Leukemia
Srour, S. A., Milton, D. R., Bashey, A., Karduss-Urueta, A., Al Malki, M. M., Romee, R., Solomon, S., Nademanee, A., Brown, S., Slade, M., et al
Biology of Blood & Marrow Transplantation. 2017;23(2):318-324
Abstract
Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)-based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months. Thirty-two patients were in first complete remission (CR1), while the rest were beyond CR1. Neutrophil engraftment occurred in 95% of the patients. The cumulative incidences of grades II to IV and III and IV acute GVHD at day 100 after transplantation were 32% and 11%, respectively, whereas chronic GVHD, nonrelapse mortality, relapse rate, and disease-free survival (DFS) at 1 year after transplantation were 32%, 21%, 27%, and 51%, respectively. Patients in CR1 had 52% DFS at 3 years. These results suggest that haploidentical transplants performed with PTCy-based GVHD prophylaxis provide a very suitable alternative to HLA-matched transplantations for patients with ALL.