Platelet transfusion refractoriness (PTR) is a common complication in patients with hematological malignancies. It not only prolongs the duration of platelet transfusion dependence and significantly increases the risk of bleeding, but is also strongly associated with graft failure and reduced survival after transplantation. HLA class I antibody-mediated alloimmunization is recognized as the most important immunological cause of PTR. HLA antibodies are directly secreted by plasma cells, which are derived from B cells. Therefore, targeting B cells to reduce antibody production is a crucial step in eliminating HLA antibodies. Bruton's tyrosine kinase (BTK) is expressed throughout B cell development from the pre-B cell stage to maturity and supports B cell development, maturation, survival, proliferation, and antibody production by acting as a downstream kinase in the B cell receptor signaling pathway. Bortezomib, a proteasome inhibitor, can selectively induce apoptosis in long-lived plasma cells. The investigators' preliminary exploratory use of a BTK inhibitor in the treatment of PTR with HLA antibodies significantly reduced the mean fluorescence intensity (MFI) of HLA antibodies, improved platelet transfusion outcomes, and demonstrated a favorable safety profile. Based on these findings, the investigators are conducting a prospective, multicenter, randomized controlled two-arm study to investigate the efficacy and safety of acalabrutinib and bortezomib in eliminating HLA antibodies in hematological malignancies patients with PTR.

Inclusion Criteria:

• Patients with hematological malignancies and platelet transfusion refractoriness (24-hour CCI < 4.5×10⁹/L or PPR < 20%), and with the highest MFI of HLA antibodies > 8000 ;
• Age 18-65 years, both male and female;
• ECOG performance status 0-3;
• Expected survival > 6 months;
• Patients must be able to understand and be willing to participate in this study, and sign an informed consent form.

Exclusion Criteria:

• Hypersensitivity to acalabrutinib, bortezomib, or excipients;
• Major organ bleeding (central nervous system, lung, intestines) or grade ≥3 bleeding;
• Hypersplenism;
• Concurrent use of drugs that may cause excessive platelet consumption (amphotericin B, vancomycin, ATG, interferon, etc.);
• Disseminated intravascular coagulation, microangiopathic hemolytic anemia;
• Underlying diseases of vital organs: such as malignant arrhythmia, myocardial infarction, chronic cardiac insufficiency, decompensated liver insufficiency, renal insufficiency, severe coagulation abnormalities, etc.; persistent fever (>38.0°C) for more than 3 days; clinically uncontrolled active infection (including bacterial, fungal, or viral infections), but patients under effective drug therapy are not excluded;
• Concurrent other progressive malignancies;
• Patients with cardiac insufficiency: ejection fraction (EF) <30%, NYHA class ≥III cardiac insufficiency;
• Pregnant or lactating women;
• Expected survival <60 days;
• Currently participating in other clinical drug trials.