Background:

Umbilical cord blood transplantation (UCBT) is associated with a slightly lower incidence and severity of acute graft-versus-host disease (aGVHD) compared to other donor sources. While aGVHD following UCBT tends to respond relatively well to corticosteroids, steroid-refractory (SR) aGVHD still occurs at a notable frequency, with reported treatment-related mortality rates of 10–20%. Although the efficacy of the JAK1/2 inhibitor ruxolitinib (RUX) has been demonstrated, most reports have focused on peripheral blood or bone marrow transplant recipients, and data on its use in the UCBT setting remain limited. We retrospectively evaluated the efficacy and safety of RUX in patients who developed SR-aGVHD after UCBT.

Methods:

This retrospective analysis included patients who underwent UCBT at Toranomon Hospital between August 2023 and December 2024 and received RUX for SR-aGVHD.

Results:

A total of 55 patients were analyzed. The median age at transplantation was 59 years (range, 22–74), with 31 males and 24 females. Underlying diseases included myeloid malignancies in 44 patients, lymphoid malignancies in 10, and other diseases in 1. Disease status at transplantation was complete remission in 25 patients and non-remission in 30. Conditioning regimens included myeloablative conditioning in 39 and reduced-intensity conditioning in 16. GVHD prophylaxis consisted of tacrolimus (Tac) plus mycophenolate mofetil in 54 patients and Tac plus short-term methotrexate in 1. The median time to aGVHD onset was 25 days post-transplant (range, 9–122). All patients initially received corticosteroids. RUX was introduced as second-line therapy in 44 patients, third-line in 6, and fourth-line in 5. The median interval from steroid initiation to RUX was 13 days (range, 1–271), with a median steroid dose of 0.6 mg/kg (prednisolone equivalent) at RUX initiation. Initial RUX doses were 5 mg in 3 patients, 10 mg in 37, and 20 mg in 15. The median duration of RUX treatment was 166 days (range, 8–663). At RUX initiation, GVHD severity was Grade II in 18 patients, Grade III in 29, and Grade IV in 8. Active infections were present in 11 patients (20.0%). Best overall response included complete response (CR) in 33 patients (60.0%), partial response (PR) in 3 (5.5%), no change in 10 (18.2%), and progressive in 9 (16.3%). The median time to response (CR or PR) was 10 days (range, 2–36). On Day 28, 20 patients (36.4%) achieved CR and 6 (23.1%) achieved PR; on Day 56, CR was observed in 18 patients (32.7%) and PR in 9 (33.3%). Among those receiving RUX as second-line therapy, CR and PR were achieved in 28 (63.6%) and 3 (6.8%) patients, respectively; in third-line or later cases, CR was seen in 3 (27.2%). Overall response rates (ORR: CR + PR) by GVHD grade were 16/18 (88.9%) for Grade II, 16/29 (55.2%) for Grade III, and 4/8 (50.0%) for Grade IV. Organ-specific ORR were 15/15 (100%) in skin, 15/25 (60.0%) in the upper gastrointestinal tract, 28/45 (62.2%) in the lower gastrointestinal tract, and 1/5 (20.0%) in the liver. One-year overall survival from RUX initiation was 55.9% (95% CI: 41.1–68.4%), and one-year failure-free survival was 29.8% (95% CI: 17.8–42.8%).Grade ≥3 adverse events included neutropenia in 12 patients (21.8%), anemia in 37 (67.3%), and thrombocytopenia in 36 (65.5%). New infections occurred in 45 patients (81.8%), with 22 involving multiple pathogens. Bloodstream infections were observed in 22 cases, including septic shock in 6. Fungal infections were noted in 6 patients (5 candidemia, 1 probable invasive pulmonary aspergillosis). CMV reactivation occurred in 30 patients, EBV reactivation in 1, CMV enteritis in 1, HHV-6 encephalitis in 4, and VZV meningitis in 2. Viral pneumonias included SARS-CoV-2 in 2, influenza in 2, and parainfluenza in 1.Reasons for RUX discontinuation included insufficient response (n=2), cytopenia (n=1), infection (n=1), difficulty with oral intake (n=2), intracranial hemorrhage (n=1), sinusoidal obstruction syndrome (n=1), and death (n=18: 2 disease relapse, 8 infections, 3 idiopathic pneumonia syndrome, 5 other complications).

Conclusion:

RUX therapy for SR-aGVHD following UCBT showed a meaningful response rate, with sustained benefit observed in responders. Although cytopenias and infections were frequently encountered, most patients were able to continue treatment. RUX may represent a viable treatment option for SR-aGVHD in the UCBT setting, with careful attention to adverse events.

This content is only available as a PDF.
2025
Sign in via your Institution