A Calcineurin Inhibitor Free Graft Versus Host Disease Prophylaxis for Patients Undergoing Matched Related and Matched Unrelated Donor Allogeneic Hematopoietic Cell Transplant.

Post-transplantation cyclophosphamide (PTCy) and calcineurin inhibitor (CNI)-based graft versus host disease (GVHD) prophylaxis has been associated with lower rates of acute and chronic GVHD compared with the traditional prophylaxis of CNI and methotrexate (MTX) in matched related donor (MRD) and matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT). The combination of PTCy with sirolimus (PTCy-Siro) as CNI-free GVHD prophylaxis has shown promising results, with cumulative rates of grade II-IV acute and chronic GVHD in the range of 15% to 27% and 20% to 27%, respectively, in patients undergoing MRD, MUD, and haploidentical allo-HCT. We report a single-center, nonrandomized comparison of patients undergoing matched donor allo-HCT receiving PTCy-Siro with those receiving the standard GVHD prophylaxis of tacrolimus and methotrexate (Tac-MTX). One hundred and sixteen consecutive patients who had undergone an MRD or MUD allo-HCT between January 2018 and January 2021 and received either PTCy-Siro (n = 29) or Tac-MTX (n = 87) as GVHD prophylaxis regimens were eligible for inclusion. Patients receiving PTCy-Siro had a significantly shorter median time to immunosuppression withdrawal than patients receiving Tac-MTX (138 days [range, 37 to 312 days] versus 232 days [range, 66 to 1120 days]; P < .001). There was no significant difference between the 2 arms in the incidence of grade II-IV acute GVHD, grade III-IV acute GVHD, steroid-refractory acute GVHD, or clinical infections. At a median follow-up of 1.1 years (range, 0 to 1.8 years), patients receiving PTCy-Siro were significantly less likely to have chronic GVHD, with 2-year freedom from GVHD of 75% (95% confidence interval [CI], 58% to 98%) versus 20% (95% CI, 10% to 40%) for those receiving Tac-MTX (P = .005).

Iqbal M ，Nieto FAM ，Brannick KM ，Li Z ，Murthy H ，Foran J ，Roy V ，Kharfan-Dabaja MA ，Ayala E ... -  《-》

Severity and organ distribution of chronic graft-versus-host disease with posttransplant cyclophosphamide-based versus methotrexate/calcineurin inhibitor-based allogeneic hematopoietic cell transplantation.

Chhabra S ，Jerkins JH ，Monahan K ，Szabo A ，Shah NN ，Abedin S ，Runaas L ，Fenske TS ，Pasquini MC ，Shaw BE ，Drobyski WR ，Saber W ，D'Souza A ，Dhakal B ，Mohan M ，Longo W ，Hamadani M ... -  《-》

Post-Transplantation Cyclophosphamide Versus Tacrolimus and Methotrexate Graft-Versus-Host Disease Prophylaxis for HLA-Matched Donor Transplantation.

The use of post-transplantation cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is increasing in patients undergoing HLA-matched sibling (MSD) or unrelated (MUD) donor hematopoietic cell transplantation (HCT), but data about its comparative efficacy against the traditional GVHD prophylaxis are scarce. Two broad questions assessed in this study were (a) comparison of PTCy-based GVHD prophylaxis versus Tac/MTX (without ATG) in the MSD and (b) comparison of PTCy-based GVHD prophylaxis versus Tac/MTX (with ATG) in the MUD group. This retrospective single-center study analyzed the outcomes of 964 patients who received Tac/MTX (n = 578) versus PTCy-based (n = 386) GVHD prophylaxis. All MUD recipients in the Tac/MTX group also received ATG; thus separate analyses were conducted for MSD (n = 412) and MUD (n = 552) cohorts. In the MUD cohort, 306 patients received Tac/MTX/ATG and 246 received PTCy-based GVHD prophylaxis. In the MSD cohort, 272 received Tac/MTX and 140 received PTCy-based prophylaxis. Both PTCy groups included somewhat older patients than the Tac/MTX groups and more patients had myeloid malignancy (85%-90% versus 59%-64%, respectively). A majority of patients in all groups received myeloablative conditioning and peripheral blood graft. Both PTCy groups had a significantly delayed neutrophil engraftment, higher risk of hemorrhagic cystitis, and higher risk of bacterial infections than the Tac/MTX groups. The risks of viral infections and related deaths were significantly higher in Tac/MTX group in the MUD cohort. In multivariate analysis, the risk of grade III-IV acute GVHD was similar in PTCy and Tac/MTX groups in both MSD and MUD cohorts, but the risk of chronic GVHD was significantly lower with PTCy in the MSD cohort. PTCy was associated with a significantly lower risk of non-relapse mortality and better progression-free survival in the MUD. PTCy was associated with improved GVHD-free relapse-free survival in both MSD and MUD groups. Our data suggest a benefit of using PTCy-based GVHD prophylaxis in both MSD (versus Tac/MTX) and MUD (versus Tac/MTX/ATG) HCT.

Mehta RS ，Saliba RM ，Rondon G ，Al-Atrash G ，Bashir Q ，Hosing CM ，Kebriaei P ，Khouri I ，Nieto Y ，Oran B ，Popat UR ，Qazilbash MH ，Ramdial J ，Srour SA ，Champlin RE ，Rezvani K ，Shpall EJ ，Alousi AM ... -  《-》

Sirolimus Is an Acceptable Alternative to Tacrolimus for Graft-versus-Host Disease Prophylaxis after Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide.

Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy), tacrolimus (Tac), and mycophenolate mofetil (MMF) for allogeneic haploidentical donor (haplo) hematopoietic cell transplantation (HCT) results in comparable outcomes to matched unrelated donor HCT. A phase II study from the Moffitt Cancer Center substituting sirolimus (Siro) for Tac in this prophylactic regimen reported comparable rates of grade II-IV acute GVHD (aGVHD). Many centers have substituted Siro for Tac in this setting based on a preferable side effect profile, although comparative data are limited. In this study, we retrospectively compared outcomes in haplo-HCT with PTCy/Siro/MMF versus haplo-HCT with PTCy/Tac/MMF. The study cohort included all consecutive patients receiving haploidentical donor T cell-replete peripheral blood stem cell (PBSC) HCT for hematologic malignancies at Moffitt Cancer Center or the City of Hope National Medical Center between 2014 and 2019. A total of 423 patients were included, of whom 84 (20%) received PTCy/Siro/MMF and 339 (80%) received PTCy/Tac/MMF. The median age for the entire cohort was 54 years (range, 18 to 78 years), and the median follow-up was 30 months. The Siro group had a higher proportion of patients age ≥60 years (58% versus 34%; P < .01), and the groups also differed in diagnosis type, conditioning regimen, and cytomegalovirus serostatus. There were no significant differences in the rates of grade II-IV aGVHD (45% versus 47%; P = .6) at day +100 or chronic GVHD (cGVHD) (47% versus 54%; P = .79) at 2 years post-HCT. In multivariate analysis, neutrophil engraftment at day +30 was significantly better in the Tac group (odds ratio, .30; 95% confidence interval, .1 to .83; P = .02), with a median time to engraftment of 17 days versus 18 days in the Siro group, but platelet engraftment was similar in the 2 groups. Otherwise, in multivariate analysis, GVHD prophylaxis type had no significant influence on aGVHD or cGVHD, nonrelapse mortality, relapse, GVHD-free relapse-free survival, disease-free survival, or overall survival after PBSC haplo-HCT. These findings suggest that Siro is a comparable alternative to Tac in combination with PTCy/MMF for GVHD prophylaxis, with overall similar clinical outcomes despite delayed engraftment after peripheral blood stem cell haplo-HCT. Although Tac remains the standard of care, Siro may be substituted based on the side effect profile of these medications, with consideration of patient medical comorbidities at HCT.

Elmariah H ，Otoukesh S ，Kumar A ，Ali H ，Arslan S ，Shouse G ，Pourhassan H ，Nishihori T ，Faramand R ，Mishra A ，Khimani F ，Fernandez H ，Lazaryan A ，Nieder M ，Perez L ，Liu H ，Nakamura R ，Pidala J ，Marcucci G ，Forman SJ ，Anasetti C ，Locke F ，Bejanyan N ，Al Malki MM ... -  《-》

Post-transplant cyclophosphamide, calcineurin inhibitor, and mycophenolate mofetil compared to anti-thymocyte globulin, calcineurin inhibitor, and methotrexate combinations as graft-versus-host disease prophylaxis post allogeneic stem cell transplantation

Post-transplant cyclophosphamide plus calcineurin inhibitor (CNI)(tacrolimus or cyclosporine A) plus mycophenolate mofetil (PTCy/TAC or CSA/MMF) and anti-thymocyte globulin plus CNI (tacrolimus or cyclosporine A) plus methotrexate (ATG/TAC or CSA/MTX) are common graft-versus-host disease (GVHD) prophylaxis regimens. We compared the two regimens in patients with acute myeloid leukemia (AML) undergoing allogeneic transplantation from matched siblings or unrelated donors. 402 received PTCy/TAC or CSA/MMF and 5648 received ATG/TAC or CSA/MTX. Patients in the PTCy-based group were younger (48.7 vs. 51.5 years, p = 0.024) and there was a higher frequency of patient cytomegalovirus seropositivity and female donor to male patient combination in this group (77.8% vs. 71.8%, p = 0.009 and 18.4% vs. 14.4%, p = 0.029, respectively). More patients in the PTCy-based group received reduced-intensity conditioning (51.5% vs. 41%, p < 0.0001). No differences were observed in the incidence of acute GVHD grade II-IV and III-IV (21.2% vs. 20.4%, p = 0.92 and 8.1% vs. 6%, p = 0.1) or 2-year total and extensive chronic GVHD (33.7% vs. 30%, p = 0.09 and 10.7% vs. 11.2%, p = 0.81) between the groups. In the multivariate analysis, all transplant outcomes did not differ between the groups. PTCy/CNI/MMF and ATG/CNI/MTX are alternative regimens for GVHD prophylaxis in AML patients.

Nagler A ，Labopin M ，Swoboda R ，Schroeder T ，Hamladji RM ，Griskevicius L ，Salmenniemi U ，Rambaldi A ，Mielke S ，Kulagin A ，Passweg J ，Luft T ，Gedde-Dahl T ，Forcade E ，Helbig G ，Stelljes M ，Castilla-Llorente C ，Spyridonidis A ，Brissot E ，Ciceri F ，Mohty M ... -  《-》