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.
Single group
Low-dose ATG + PTCy + Ivarmacitinib
DrugPatients will receive rabbit ATG 2.5 mg/kg on Day -2 and -1 (total 5 mg/kg), post-transplant cyclophosphamide 50 mg/kg on Day +3, cyclosporine/MMF starting Day +4, and Ivarmacitinib 4 mg PO daily from Day -3 to +45, reduced to 2 mg PO daily from Day +46 to +60
Number of Participants With Grades II-IV Acute GVHD
Acute graft-versus-host disease (aGVHD) will be assessed according to standard criteria (Glucksberg or MAGIC). The primary measure is the occurrence of grade II-IV aGVHD in any organ (skin, liver, gastrointestinal tract) within 180 days after haploidentical peripheral blood stem cell transplantation. Severity will be graded based on clinical manifestations, laboratory results, and endoscopic or biopsy findings where applicable.
Number of Participants With Graft Failure
Primary graft failure is defined as failure to achieve sustained neutrophil engraftment (ANC ≥ 0.5 × 10⁹/L for 3 consecutive days) and/or platelet engraftment (Platelet ≥ 20 × 10⁹/L without transfusion for 7 consecutive days) by Day 28 post-transplant. Assessment is based on peripheral blood counts and confirmed by the study team.
Number of Participants With Non-Relapse Mortality by Day +180
NRM is defined as death occurring after allogeneic hematopoietic stem cell transplantation without evidence of relapse of the underlying hematologic malignancy. Causes include transplant-related complications such as acute or chronic GVHD, severe infections, organ toxicity, or graft failure. All deaths will be adjudicated by the study team based on clinical, laboratory, and imaging data.
Number of Participants With Chronic Graft-Versus-Host Disease by 1 Year
The cumulative incidence of chronic GVHD will be measured as the occurrence of chronic GVHD (limited or extensive) diagnosed according to NIH consensus criteria within 1 year after transplantation. cGVHD will be assessed clinically using standardized criteria, including organ involvement and requirement for systemic immunosuppressive therapy.
Number of Participants With Relapse by 1 Year
Relapse rate is defined as the proportion of patients who develop recurrence of the underlying hematologic malignancy after achieving initial engraftment. Relapse will be confirmed by bone marrow examination, cytogenetic/molecular criteria, or imaging evidence consistent with disease recurrence. Competing risk analysis will treat non-relapse mortality as a competing event.
Number of Participants Alive at 1 Year
Overall survival (OS) is defined as the time from the date of transplantation to death from any cause. Patients alive at the end of the follow-up period will be censored at the last known date alive. OS will be estimated using Kaplan-Meier methods.
Number of Participants Alive and Disease-Free at 1 Year
Disease-free survival (DFS) is defined as the time from transplantation to the first occurrence of relapse or death from any cause. Patients without relapse or death at the end of the follow-up period will be censored at last follow-up. DFS will be estimated by Kaplan-Meier analysis.
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