Gecacitinib in the Treatment of Steroid-Refractory/Dependent Chronic Graf Versus Host Disease (cGVHD).

Inclusion criteria

• Age ≥ 18 years, regardless of gender.
• Underlying hematologic malignancies or non-malignant disorders having received allogeneic hematopoietic stem cell transplantation.
• Diagnosis of active cGVHD according to the 2014 NIH consensus criteria, meeting the definition of steroid-refractory or steroid-dependent cGVHD. Prior lines of cGVHD therapy are not restricted. Definitions are as follows:

• Steroid-refractory cGVHD is defined as meeting any of the following criteria: disease progression despite the use of prednisone ≥1 mg/kg/day (or equivalent dose of corticosteroids) for at least 1 week; OR, persistent disease symptoms with no improvement despite the use of prednisone ≥0.5 mg/kg/day or ≥1 mg/kg every other day (or equivalent dose of corticosteroids) for at least 4 weeks.
• Steroid-dependent cGVHD is defined as the requirement for a maintenance dose of prednisone >0.25 mg/kg/day or >0.5 mg/kg every other day (or equivalent dose of corticosteroids) to prevent disease flare or progression, and failure to successfully taper the dose to a lower level in at least 2 separate attempts spaced ≥8 weeks apart.
• Platelet count ≥50 × 10⁹/L and absolute neutrophil count (ANC) ≥0.5 × 10⁹/L, without the use of colony-stimulating factors, androgens, erythropoietin, thrombopoietin, or platelet transfusion within 7 days prior to screening.
• Adequate major organ function, defined as meeting the following criteria: ALT and AST ≤ 2.5 × upper limit of normal (ULN); direct and total bilirubin ≤ 2.0 × ULN; serum creatinine ≤ 1.5 × ULN.
• Stable underlying disease without evidence of progression or relapse.
• Karnofsky Performance Status (KPS) ≥ 60%.
• Voluntarily participate in this study, provide signed informed consent, demonstrate good compliance, and be able to adhere to the study and follow-up procedures

Exclusion criteria

• Post-transplant lymphoproliferative disorder, or loss of full donor chimerism due to other reasons.
• Previous use of, or current treatment with, other JAK inhibitors at the time of screening.
• History or presence of major diseases or clinically significant organ dysfunction that cannot be adequately controlled by treatment and may interfere with study completion:

• Congestive heart failure of New York Heart Association (NYHA) class III-IV, or documented history of diastolic or systolic dysfunction (e.g., left ventricular ejection fraction <40% by echocardiography), or uncontrolled/unstable angina or myocardial infarction.
• Uncontrolled diabetes (blood glucose >250 mg/dL or >13.9 mmol/L).
• Hypertension that cannot be adequately controlled to systolic blood pressure <160 mmHg and diastolic blood pressure <100 mmHg despite combination antihypertensive therapy.
• Peripheral neuropathy (Grade 2 or higher per NCI-CTCAE v5.0 criteria).
• Patients with any uncontrolled bacterial, viral, or fungal infection.
• Positive for HIV at screening, or active hepatitis B virus infection (HBsAg positive and HBV-DNA positive or above the upper limit of normal), or positive for HCV antibody with detectable HCV-RNA.
• History of tuberculosis or positive interferon-γ release assay at screening.
• Concurrent use of strong CYP3A4 inhibitors.
• History of progressive multifocal leukoencephalopathy.
• Known or suspected hypersensitivity to Gecacitinib hydrochloride, drugs of the same class, or any of their excipients.
• Pregnant or lactating women, or patients unwilling to use effective contraception during Gecacitinib treatment and for 1 week after the last dose.
• Inability to swallow oral tablets.