Introduction
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the most successful curative therapy for a wide variety of hematological malignancies, but half of the patients would eventually develop disease relapse. Although donor lymphocyte infusion (DLI) is one of the effective options in the treatment of relapsed hematological malignancies after allo-HSCT, preemptive DLI alone may not be effective for all patients equally, and other potential alternatives are still needed. It has been reported that, compared with steady-state DLI, DLI after granulocyte colony stimulating factor (G-CSF) mobilization (modified donor lymphocyte infusion, mDLI) shows an increase of neutrophils engraftment and can exert a stronger graft-versus-leukemia (GVL) effect, complicated with mild graft versus host disease (GVHD) only, and show an improved overall survival (OS) rate. Severe acute graft versus host disease (aGVHD) can induce the occurrence of an inflammatory cytokine storm, while chronic graft versus host disease (cGVHD) is controllable.
Skillfully balancing immunosuppression and relapse after transplantation or DLI to minimize aGVHD and maximize GVL is a challenge, and the discussion regarding the best approach is still ongoing. Ruxolitinib is an inhibitor of Janus kinase 1 (JAK1) and Janus kinase 2 (JAK2), first used in the treatment of myelofibrosis, where it was associated with a reduction in inflammatory cytokines and markers of inflammation and improvements in metabolic and nutritional status. Acting on the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, ruxolitinib increases forkhead box P3 (FOXP3)+ T regulatory cells related to immune tolerance influences the migration of T cells, and regulates immune function on many levels, which might be a promising aid in the treatment of steroid-refractory GVHD. Moreover, ruxolitinib demonstrated not only immunosuppressive but also antileukemic effects, and now a clinical trial for ruxolitinib and B-cell lymphoma-2 (BCL2) inhibitors synergism to treat relapsed/refractory leukemia is under trial.
Methods
We retrospectively included patients with relapsed leukemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received ruxolitinib prophylaxis between October 2018 and April 2020. The incidence of aGVHD, disease-free survival (DFS), overall survival (OS), and treatment safety were evaluated.
Results
Seventeen patients were followed up for a median time of 8 months (range: 1–26 months). The incidence of aGVHD on Day 30 after mDLI was 41.2% and ranged from Grade 1 to 4; ten of 17 patients (58.8%) achieved a complete response (CR), and two (11.8%) had a partial response (PR). Cytomegalovirus (CMV) reactivation rate was 23.5%, and the median time from mDLI to CMV reactivation was 48.5 days. The mean DFS and OS after mDLI were 1.0 (95% CI 0.0–3.5) and 9.0 (95% CI 1.2–16.8) months, respectively. The causes of death for 10 patients were leukemia relapse (n = 5), aGVHD and septic shock (n = 3), intracranial lesion (n = 1), and COVID-19 (n = 1).
Conclusions
We reported encouraging results of ruxolitinib monotherapy in the prevention of aGVHD and maintenance of GVL for post-transplantation relapsed patients, even though being at high risk with poor initial prognosis.
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