Corticosteroids as graft-versus-host disease prophylaxis for allogeneic hematopoietic cell transplant recipients with calcineurin inhibitor intolerance.

Although calcineurin inhibitors (CNIs) have a well-established role in the prevention of graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT), their use can be limited by significant toxicities, which may result in premature treatment discontinuation. The optimal management of patients with CNI intolerance is unknown. The objective of this study was to determine the effectiveness of corticosteroids as GVHD prophylaxis for patients with CNI intolerance. This retrospective single-center study included consecutive adult patients with hematologic malignancies who underwent myeloablative peripheral blood allogeneic HCT with anti-thymocyte globulin, CNI, and methotrexate GVHD prophylaxis in Alberta, Canada. Multivariable competing-risks regression was used to compare cumulative incidences of GVHD, relapse, and non-relapse mortality between recipients of corticosteroid versus continuous CNI prophylaxis, and multivariable Cox proportional hazards regression was applied to compare overall survival, relapse-free survival (RFS) and moderate-to-severe chronic GVHD and RFS. Among 509 allogeneic HCT recipients, 58 (11%) patients developed CNI intolerance and were switched to corticosteroid prophylaxis at median 28 days (range 1-53) after HCT. Compared with patients who received continuous CNI prophylaxis, recipients of corticosteroid prophylaxis had significantly greater cumulative incidences of grade 2-4 acute GVHD (subhazard ratio [SHR] 1.74, 95% confidence interval [CI] 1.08-2.80, P = 0.024), grade 3-4 acute GVHD (SHR 3.22, 95% CI 1.55-6.72, P = 0.002), and GVHD-related non-relapse mortality (SHR 3.07, 95% CI 1.54-6.12, P = 0.001). There were no significant differences in moderate-to-severe chronic GVHD (SHR 0.84, 95% CI 0.43-1.63, P = 0.60) or relapse (SHR 0.92, 95% CI 0.53-1.62, P = 0.78), but corticosteroid prophylaxis was associated with significantly inferior overall survival (hazard ratio [HR] 1.77, 95% CI 1.20-2.61, P = 0.004), RFS (HR 1.54, 95% CI 1.06-2.25, P = 0.024), and chronic GVHD and RFS (HR 1.46, 95% CI 1.04-2.05, P = 0.029). Allogeneic HCT recipients with CNI intolerance are at increased risks of acute GVHD and poor outcomes despite institution of corticosteroid prophylaxis following premature CNI discontinuation. Alternative GVHD prophylaxis strategies are needed for this high-risk population.

Puckrin R ，Kwan ACF ，Blosser N ，Leyshon C ，Duggan P ，Daly A ，Zepeda V ，Stewart D ，Chaudhry A ，Storek J ，Jamani K ... -  《-》

Calcineurin Inhibitors Replacement by Ruxolitinib as Graft-versus-Host Disease Prophylaxis for Patients after Allogeneic Stem Cell Transplantation.

Graft-versus-host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT) that carries a high mortality. Although calcineurin inhibitors (CNIs) have been widely used in GVHD prophylaxis, the incidence of acute GVHD (aGVHD) remains at roughly 30% to 50%. Moreover, some allo-SCT recipients cannot tolerate CNI. Thus, improved GVHD prevention methods are needed. Our study aimed to determine the prophylactic value of ruxolitinib for GVHD in CNI-intolerant patients after allo-SCT. Between September 2017 and March 2019, 10 patients with hematopoietic malignancies after allo-SCT who were intolerant to CNI at our center were enrolled in this study. The regimens were based on a myeloablative busulfan and cyclophosphamide regimen. Antithymocyte globulin was administered to patients with an HLA-haploidentical related donor (HRD) at a dosage of 6 mg/kg. All received ruxolitinib to replace CNI as GVHD prophylaxis. Ruxolitinib was initiated at 5 to 10 mg twice daily until 2 to 3 months post-transplantation and then tapered gradually, and in the absence of GVHD, discontinued by day +180. Eight patients had acute leukemia, 1 patient had myeloproliferative neoplasm, and 1 patient had natural killer T cell (NK/T) lymphoma. The donor type was a matched sibling donor in 3 patients and an HLA-haploidentical related donor (HRD) in 7 patients. All patients received CNI plus short-course of methotrexate as GVHD prophylaxis, but showed intolerance to CNI within 45 days post-transplantation. After ruxolitinib replacement, only 1 patient (10%) developed grade II skin aGVHD within 100 days, and only 1 patient developed severe aGVHD after 100 days. Two patients developed moderate/severe chronic GVHD (cGVHD) after tapering or stopping ruxolitinib, resulting in a 1-year cumulative incidence of moderate/severe cGVHD of 21.4%. Cytomegalovirus (CMV) reactivation occurred in 4 patients (40%), and Epstein-Barr virus (EBV) reactivation occurred in 3 patients (30%). None of the patients developed CMV disease or EBV post-transplantation lymphoproliferative disorder. After a median follow-up of 11 months (range, 2 to 15.5 months), 2 patients (20%) relapsed and 7 (70%) were alive, of whom 6 (60%) were negative for minimal residual disease and 4 were off immunosuppressant therapy. The prophylactic application of ruxolitinib for CNI-intolerant patients after allo-SCT appears to be safe and effective in preventing GVHD, but this awaits further study in larger cohorts.

Zhao Y ，Shi J ，Luo Y ，Gao F ，Tan Y ，Lai X ，Yu J ，Wei G ，Huang H ... -  《-》

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 ... -  《-》

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 ... -  《-》

Mycophenolate mofetil versus methotrexate for prevention of graft-versus-host disease in people receiving allogeneic hematopoietic stem cell transplantation.

Kharfan-Dabaja M ，Mhaskar R ，Reljic T ，Pidala J ，Perkins JB ，Djulbegovic B ，Kumar A ... -  《-》