Early recognition and optimized management of tafro syndrome: A 10-year experience from a single center in China

Abstract

Abstract Background: TAFRO syndrome (Thrombocytopenia, Anasarca/serositis, Fever, Renal impairment, Organomegaly) is a rare systemic disorder and distinct subtype of idiopathic multicentric Castleman disease (iMCD), first described by Japanese researchers in 2010. Since then, most published data and clinical experience have originated from Japan. The disease is marked by clinical heterogeneity and extremely poor early prognosis. Early diagnosis remains challenging and is often delayed or missed, especially in rapidly progressing cases. Moreover, no standardized treatment regimen has been established to date, and conventional iMCD protocols yield complete response (CR) rates of only 40–50%. As a result, early mortality remains high. Therefore, establishing reliable early warning strategies and developing standardized first-line treatment protocols are critical to improving patient outcomes in TAFRO syndrome. Methods: We retrospectively reviewed clinical, pathological, therapeutic, and survival data of 16 TAFRO patients diagnosed and treated at Shenzhen People's Hospital (January 2014 to December 2024), aiming to optimize diagnostic and management strategies. Results: The median age was 37.5 years (range 18–80; F:M=10:6). All patients presented with fever, thrombocytopenia, and polyserositis-related symptoms. Initial consultations included pulmonology (6/16), hematology (5/16), infectious diseases (2/16), and other specialties (3/16). ECOG scores ≥2 were observed in all cases, with 10/16 scoring ≥3; ICU admission occurred in 10/16. All patients exhibited the diagnostic “TAF” triad: thrombocytopenia (median platelet 11×10⁹/L), serositis (16/16 pleural effusion, 14/16 polyserositis), and fever (median CRP 144.6 mg/L). Subcutaneous edema was present in 7/16 cases. All patients underwent peripheral blood cytomorphological examination, consistently demonstrating leukocytosis with neutrophil hypo-segmentation, toxic granulation, abnormal erythrocytes (hypochromic, fragmented, teardrop-shaped), and thrombocytopenia accompanied by giant platelets. Diagnosis was definitive during initial hospitalization in only 2/16; retrospective confirmation of diagnosis occurred in 14/16. Among 9 patients with lymphadenopathy, biopsy-confirmed iMCD was achieved in 6/9 cases, with a median diagnostic time of 18.5 days after hospital admission. Bone marrow aspirates were performed in 15 patients, all demonstrating distinctive megakaryocyte atypia: ET-like “staghorn” morphology (4/15), PMF-like “cloud-/balloon-shaped” morphology with abnormal nuclear-cytoplasmic ratios, hyper-condensed chromatin, and hyperchromasia (3/15), or mixed ET/PMF morphology (8/15). Bone marrow evaluation thus achieved 100% diagnostic sensitivity (15/15), significantly reducing diagnostic time compared to lymph node biopsy (median 7 vs. 18.5 days, p<0.001). Eight patients received only supportive therapy and all experienced rapid mortality, primarily due to multi-organ failure (5 cases) or sepsis (3 cases). Among patients receiving active treatment, glucocorticoid treatment alone and CTD (combined cyclophosphamide, thalidomide, and dexamethasone) regimen were almost universally unsuccessful. In contrast, IL-6 inhibitor-based therapies (tocilizumab or siltuximab combined with CTD ± rituximab) achieved a CR rate of 100% (4/4), with sustained remission maintained through subsequent maintenance therapy with IL-6 inhibitors or thalidomide. Non-recipients of IL-6-targeted therapy had a 91.7% mortality rate (11/12). Factors correlating with poor prognosis included advanced age, severe renal impairment, and markedly elevated D-dimer levels. Conclusion: Based on our 10-year single-center experience, we emphasize two critical recommendations. First, combining the classical “TAF” triad with specific morphological abnormalities observed in bone marrow megakaryocytes and peripheral blood cytomorphology constitutes an effective early diagnostic tool for TAFRO syndrome. Second, we strongly advocate for an IL-6 inhibitor-containing R-CTD regimen as the standard first-line therapy due to its substantial impact on improving patient outcomes. Nonetheless, further validation through broader clinical practice and prospective studies is necessary to confirm and refine these strategies.