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1917 Characteristics of Autoimmune Hemolytic Anemia Associated with Khsv/HHV-8 Multicentric Castleman Disease

Program: Oral and Poster Abstracts
Session: 652. MGUS, Amyloidosis, and Other Non-Myeloma Plasma Cell Dyscrasias: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Viral, Autoimmune hemolytic anemia, Plasma Cell Disorders, Diseases, Immune Disorders, Infectious Diseases, Immunology, Lymphoid Malignancies, Biological Processes
Saturday, December 7, 2024, 5:30 PM-7:30 PM

Yannick Dieudonné1*, Clement Gourguechon2*, Romain Stammler, MD3*, Florence Delestre4*, Boris Sorin5*, Bertrand Dunogué4*, Guillaume Dumas6*, Guillemette Fouquet, MD, PhD7*, Anne Marie Ronchetti8*, Romain Paule9*, Pascal Meliani10*, Nathalie Pansu11*, Rodolphe Buzele12*, Robin Noel, MD13*, Jehane Fadlallah14*, Emilie Corvilain, MD15*, Marion Malphettes16*, Laurence Gerard, MD17*, Veronique Meignin18*, Constance Guillaud19*, Antoine Dossier20*, Jeremie Dion21*, Eric Oksenhendler14*, Lionel Galicier22* and David Boutboul, MD, PhD3,23*

1Strasbourg University Hospital, Strasbourg, FRA
2Amiens University Hospital, Amiens, France
3Department of Hematology, Hôpital Cochin, AP-HP, Université Paris Cité, Paris, France
4Internal Medicine, Hopital Cochin Université Paris Cité, Paris, France
5Internal Medicine, Hopital Cochin Université Paris Cité, Paris, FRA
6Intensive Care Unit, CHU Grenoble, Grenoble, France
7Hematology Department, Hospital Sud Francilien, Corbeil-Essonnes, France
8CH Sud Francilien, Hematology Department, Corbeil Essonne, France
9Hopital Foch, Suresnes, FRA
10CH Mayotte, Mayotte, France
11Tropical and Infectious Diseases University Hospital, Montpellier Cedex 5, Franc, Montpellier, FRA
12Centre Hospitalier de Saint-Brieuc, Saint-Brieuc, France
13Institut Paoli-Calmettes, Marseille, FRA
14Service d'Immunopathologie Clinique, Saint Louis hospital, AP-HP, Paris, France
15Hôpital Saint-Louis, APHP, Paris, France
16Saint Louis Hospital, Paris, France
17Hôpital Saint-Louis, Paris, France
18Assistance Publique - Hôpitaux de Paris (APHP), Pathology; Paris University. Paris, Paris, France
19Hôpital Henri Mondor, Créteil, France
20Internal Medicine, Hôpital Bichat, Paris, France
21Toulouse University Hospital, Toulouse, France
22Centre de Réference National Maladie de Castleman, Paris, France
23Laboratory of Lymphocyte Activation and Susceptibility to EBV Infection, Imagine Institute, Paris, France

Introduction Castleman disease is a rare lymphoproliferative disorder that encompasses distinct clinicopathological entities. The multicentric form (MCD) related to KSHV (Kaposi Sarcoma Associated Virus or Human Herpesvirus 8) mainly occurs in the immunocompromised host and its diagnosis relies on lymph node biopsy. Life-threatening complications such as hemophagocytic lymphohistiocytosis (HLH) and KSHV-related lymphomas may develop during the natural history of the disease. Standard of care of KSHV MCD currently includes the use of etoposide and rituximab.

Autoimmunity also belongs to the spectrum of KSHV MCD-related complications and encompasses autoimmune hypoglycemia, autoimmune thrombotic thrombocytopenic purpura (TTP) and autoimmune cytopenias, including autoimmune hemolytic anemia (AIHA). Despite having been described in case reports, the characteristics, evolution, and prognosis of AIHA was not fully addressed. Moreover, management of this complication is not well-defined although corticosteroids and rituximab are commonly used by analogy to other AIHA situations, increasing the risk of Kaposi sarcoma. The present work focuses on a comprehensive description of the characteristics of AIHA related to KHSV MCD.

Methods Patients with biopsy-proven MCD included in the French national reference center for CD between 2000 and 2023 were included in the study. Patients were included in the AIHA+ MCD subgroup if they met all following criteria: 1) Hemoglobin (Hb) <10 g/dL, 2) hemolysis defined by elevated LDH and free bilirubin, associated to undetectable haptoglobin, 3) positivity for Direct Antiglobulin Test (DAT). Patients with confounding causes of hemolysis were excluded from further analysis. Other patients were included in the AIHA- MCD subgroup. Complete response (CR) was defined by Hb >12 g/dL with no signs of hemolysis.

Results. Three hundred and twenty-three patients with a diagnosis of KSHV MCD were identified. Fifty-seven patients (17%) fulfilled AIHA criteria. In this subgroup, the male to female ratio was 3.8, with a median (min-max) age at MCD diagnosis of 45 (19-83) years. Thirty-seven patients (65%) were positive for HIV. AIHA occurred during the first flare-up of MCD in most of the cases (n = 54, 95%). As compared to AIHA- MCD patients, AIHA + MCD patients displayed lower median Hb level (5.2 g/dL (2.6-9.8) vs Hb 9.0g/dL (3.2-14.1), P <0.001) and higher LDH level (499 U/L (300-1300) vs 172U/L, P <0.001). DAT was strongly positive for IgG and C3 in 53 patients, for IgG only in 4 patients. No cold agglutinin was found. AIHA+ MCD patients presented more frequently with autoimmune thrombocytopenia (11% vs 4%, P = 0.07), but no other autoimmune complications including TTP were diagnosed. There were no differences between AIHA+ and AIHA- MCD patients regarding HLH frequency (36% vs 28%, P = 0.2), HIV positivity (64% vs 75%, P = 0.1), KSHV blood viral load (5.2 vs 5.3 log copies/ml) or Kaposi sarcoma (44% vs 48%, P = 0.9). White cell counts (including CD4+ T-cells in patients living with HIV), CRP, or immunoglobulin levels were comparable between the two groups.

Management and follow-up data were available for 50 AIHA+ patients (median follow-up 48 months). Sixteen patients (32%) had AIHA relapse associated with MCD flare. Three patients (6%) had multiple relapses. Nine patients died in AHAI+ patients (18% vs 23% in AIHA- patients, P = 0.06).

Twenty-nine patients (58%) were treated with steroids (ST), associated with etoposide in 25 (VP16 ST+, 50%). Twenty-one were treated with etoposide without steroids (VP16 ST-, 42%). Forty-three (86%) were treated with rituximab. While Hb level was similar in VP16 ST+ and VP16 ST- patients (median 5,2 vs 5,3g/dL respectively), the frequency of CR at day 30 was comparable between the two subgroups (n = 17, 59% vs n = 13, 62%, P = 0.9) as well as the median time to transfusion independence (6 (0-40) vs 6 days (0-16)), and the number of transfusion packages (5 (0-7) vs 5 (0-17)). These results were not modified when patients were stratified on rituximab use. Only three patients relapsed AIHA in the VP16 ST- group (14% vs n = 12, 41% in the VP16 ST+ group, P = 0.09), at least two years after the first episode.

Conclusion. AIHA is a frequent complication of KSHV MCD. Steroid-free therapeutic strategy appears efficient in inducing a complete and durable response of AIHA and should be considered in this setting to reduce the risk of Kaposi sarcoma development.

Disclosures: Oksenhendler: Eusapharma: Honoraria. Galicier: Eusapharma: Honoraria.

*signifies non-member of ASH