Graft-versus-host disease (GVHD) is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), significantly affecting survival and quality of life. Acute GVHD (aGVHD) typically occurs within 100 days post-transplant, commonly involving skin, gastrointestinal tract, and liver. Chronic GVHD (cGVHD) can appear months to years later.
Despite prophylaxis with calcineurin inhibitors (e.g., cyclosporine or tacrolimus), methotrexate, mycophenolate mofetil, and post-transplant cyclophosphamide (PTCy), patients receiving haploidentical transplantation from parous female donors remain at high risk for moderate-to-severe aGVHD.
JAK1-dependent cytokine signaling (IL-6, IFN-γ) is central to GVHD pathogenesis. Selective JAK1 inhibition may attenuate T cell-mediated inflammation while preserving hematopoiesis. Ivarmacitinib (SHR0302) is a highly selective oral JAK1 inhibitor, showing favorable safety and preliminary efficacy in autoimmune and GVHD settings, making it a candidate for early GVHD prophylaxis.
Age 18-70 years, any gender. Recipients must be diagnosed with hematologic malignancies, such as acute leukemia, myelodysplastic syndrome, or malignant lymphoma, and are planned to undergo haploidentical peripheral blood stem cell transplantation (Haplo-PBSCT).
The donor must be a haploidentical relative within three degrees of kinship and a parous female (having given birth; number of pregnancies not limited), aged 18-55 years, in good health, and cleared by donor screening.
Karnofsky performance status ≥70. The recipient is expected to tolerate transplant-related toxicity. Major organ functions must meet transplantation requirements: cardiac and pulmonary function essentially normal; liver function: ALT/AST <2× upper limit of normal, total bilirubin <1.5× upper limit of normal; renal function: creatinine clearance >50 mL/min.
No active infection prior to transplantation (or infection effectively controlled). Chronic infections such as HBV, HCV, or syphilis must be stable under treatment; HBV DNA negative or receiving antiviral therapy is acceptable.
History of prior hematopoietic stem cell transplantation (including autologous or allogeneic transplant).
Presence of donor-specific antibodies (DSA) with a mean fluorescence intensity (MFI) ≥5000.
History of severe hypersensitivity or allergy to JAK inhibitors or the investigational drug.
Prior treatment with JAK1/2 inhibitors.