-Author name in bold denotes the presenting author
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795 Pediatric Autoimmune Hemolytic Anemia Is Associated with a High Incidence of an Underlying Immune Disorder and High Mortality Rate

Program: Oral and Poster Abstracts
Type: Oral
Session: 905. Outcomes Research: Non-Malignant Conditions Excluding Hemoglobinopathies: Innovative Approaches to Improve Care for Understudied Non-Malignant Hematologic Diseases
Hematology Disease Topics & Pathways:
Research, Autoimmune disorders, Epidemiology, Autoimmune hemolytic anemia, Clinical Research, Pediatric, Diseases, Immune Disorders, Immunodeficiency, Real-world evidence, Study Population, Human
Monday, December 9, 2024: 11:00 AM

Rachael F Grace, MD1, MacGregor Steele, MD2*, Tatiana Kalashnikova2*, Ellis Bloom, DO3*, Aila Khan3*, Sherif M. Badawy, MD, MS, MBA4, Hannah Elkus, MD5*, Vicky R. Breakey, MD, BSc, FRCPC, MEd6, Sureka Pavalagantharajah, MD7*, Stephanie A. Fritch Lilla, MD8, John Leister, DO9*, Manpreet Kochhar, MD, MS10*, Kirsty Hillier, MD11*, Lia Phillips, MD12*, Jessica Chumsky, MD11*, Robert J. Klaassen, MD, FRCPC13, Dana Ghanem14*, Danielle Charland, BScH14*, Taizo A. Nakano, MD15, Joshua Kalter, MD16*, Allison Remiker, MD17*, Jennifer A. Rothman, MD18, Caitlyn McComb, MD18*, Brian Guedes, MD18*, Sanjay J. Shah, MBBS19, Cassandra J. Everly20*, Kristin A. Shimano, MD21, Alison Matsunaga, MD22*, Gerald C Tiu, MD, PhD22*, Russell P Valle, MD, MS22*, Shilpa Nataraj, MD22*, Stacey Rifkin-Zenenberg, DO23, Erika Tavares24*, Caitlin Montcrieff, MSN, CPNP24*, Emily M Harris, MD25, Nan Chen, MS26*, Wendy B. London, PhD26* and Michele P. Lambert, MD27

1Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Harvard Medical School, Boston, MA
2Alberta Children’s Hospital, Calgary, Alberta, Canada
3Division of Hematology, The Children's Hospital of Philadelphia, Philadelphia, PA
4Ann & Robert Lurie Children's Hospital, Chicago, IL
5Ann and Robert H. Lurie Children’s Hospital of Chicago, Chicago, IL
6McMaster Children's Hospital, Hamilton, ON, CAN
7McMaster University, Hamilton, ON, Canada
8Children's Minnesota, Minneapolis, MN
9University of Minnesota, Minneapolis, MN
10The Warren Alpert Medical School at Brown University, Hasbro Children's Hospital, Providence, RI
11NYU Langone Children’s Hospital, New York, NY
12Department of Pediatrics, NYU Grossman Long Island School of Medicine, Mineola, NY
13Division of Hematology/Oncology, Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
14Children's Hospital of Eastern Ontario, Ottawa, ON, Canada
15Children's Hospital Colorado, Denver, CO
16Children’s Hospital Colorado, Denver, CO
17Children's Wisconsin, Medical College of Wisconsin, Milwaukee, WI
18Duke University Medical Center, Durham, NC
19Department of Child Health, Phoenix Children’s Hospital, University of Arizona College of Medicine, Chandler, AZ
20Phoenix Children’s Hospital, University of Arizona College of Medicine, Phoenix, AZ
21Pediatric Allergy, Immunology, and Bone Marrow Transplant Division, University of California San Francisco Benioff Children's Hospital, San Francisco, CA
22UCSF Benioff Children's Hospital, San Francisco, CA
23Pediatric Hematology/Oncology Division, Hackensack Meridian Health, Hackensack, NJ
24Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA
25Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Brookline, MA
26Dana Farber/Boston Children's Cancer and Blood Disorders Center, Boston, MA
27Children's Hospital of Philadelphia, Philadelphia, PA

Background: Autoimmune hemolytic anemia (AIHA) is a rare pediatric autoimmune disease in which there is limited guidance for evaluation and treatment and a poor understanding of the characteristics that influence prognosis and clinical course.

Aim: To characterize the clinical features, laboratory findings, and treatment outcomes of children with AIHA over a 10-year period.

Methods: An IRB-approved multicenter observational cohort study included patients (pts) from 15 institutions from the ITP Consortium of North America (ICON) who were 3 mo to 21 y and had hematology consultation between Jan 2011 and Dec 2020 with a diagnosis of AIHA. Post-stem cell transplant AIHA was excluded. Demographic, medical history, laboratory, and treatment data were collected. Continuous variables are summarized as mean (SD) or median (range) and compared with a two-sided t-test. Categorical variables are summarized as counts or percentages and compared with a two-sided chi-squared test.

Results: A total of 402 pts were included: median age at diagnosis 7 y (n=397, range: 0-22) with median length of follow up 2.7 years (n=390, range: 0.1-19.2). 45% (180/398) were female. Warm AIHA (wAIHA) was the predominant subtype in 64% (252/395). Most pts (58%, 217/374) had a single AIHA episode that remitted; others had two episodes that remitted (8%, 29/374), multiple relapsing episodes (7%, 26/374), chronic course that remitted (13%, 48/374), or chronic ongoing course (14%, 54/374). Cold agglutinin disease (CA) was present in 12% (47/395), paroxysmal cold hemoglobinuria (PCH) in 6% (24/395), and mixed/unspecified AIHA in 18% (72/395).

Secondary AIHA was common with 15% (57/389) with an underlying primary immunodeficiency, most commonly CVID (49%, 28/57), ALPS (33%, 19/57), and 22q11.2DS (16%, 9/57); and 16% (61/391) with another autoimmune disorder, most commonly SLE (49%, 30/61), neurologic disease (36%, 22/61), or APLA (16%, 10/61). Immune testing was sent in 100% (402/402) and abnormal in 60% (240/402). An immunologist was consulted in 136/342 (40%). Infectious testing was sent in 71% (260/366).

Family history (1st or 2nd degree) was positive for immune cytopenias, immunodeficiency, or autoimmunity in 19% (78/402). Genetic testing (sent in 30%, 106/349), was most often a gene panel (67%, 71/106) or WES (28%, 30/106) with pathogenic findings identified in 30% (30/100).

Evans syndrome (ES) was common (37%, 142/385) including ITP (92%, 131/142) and/or immune neutropenia (43%, 57/133) and most likely in those with wAIHA (47%, 113/241) compared with PCH (0%, 0/23) or CA (4%, 2/45). Compared with pts without ES (n=243), those with ES (n=142) were more likely to be older at first episode (9 y vs 5 y, p=0.010), have genetic testing (54% vs 18%, p<0.001), pathogenic gene findings (13% vs 5%, p=0.002), and treatment with steroid-sparing agents at first episode (35% vs 19%, p<0.001). There was no difference in response to steroids at first episode (77% vs 75%, p=0.748) or incidence of another autoimmune disorder (18% vs 14%, p=0.306).

Similarly, those with secondary AIHA were more likely to be older at first episode (8 y vs 6 y, p=0.007) and have wAIHA (77% vs 62%, p=0.035). Secondary AIHA did not impact steroid response (77% vs 74%, p=0.653) or treatment with steroid-sparing agents at first episode (26% vs 24%, p=0.756). Pts with multiple episodes of AIHA were also more likely to have wAIHA (82% vs 52%, p<0.001), genetic testing (50% vs 19%, p<0.001), and treatment with steroid-sparing agents at first episode (34% vs 18%, p<0.001) but did not have a different age at presentation of 1st episode [8 y vs 5 y, p=0.203] or proportion with pathogenic gene findings (10% vs 6%, p=0.268).

Of those with ongoing follow up, 68/249 (27%) of pts with wAIHA had active disease on treatment, 7/249 (3%) had active disease and were being observed, and 174/249 (70%) were in remission. Overall, mortality was 9.4%. Mortality was not associated with a diagnosis of ES, immunodeficiency or autoimmunity, number of AIHA episodes, or type of AIHA.

Conclusion: AIHA is associated with significant morbidity in children with a high rate of secondary AIHA (~30%), 37% with ES, and 34% with a chronic or relapsing course. In this recently diagnosed cohort, there was a 9.4% mortality rate. These high morbidity and mortality rates require expanded testing, monitoring, and additional treatment approaches in this pediatric population.

Disclosures: Grace: Sobi: Consultancy, Research Funding; Agios: Consultancy, Research Funding; Novartis: Research Funding; Sanofi: Consultancy. Fritch Lilla: Sobi: Honoraria; Agios: Honoraria; Chiesi: Speakers Bureau; Octapharma: Consultancy. Klaassen: Takeda: Consultancy; Octapharma AG: Consultancy; Novo Nordisk: Consultancy; Hoffman La Roche: Consultancy; Amgen Inc: Consultancy; Agios Pharmaceuticals: Consultancy; Sanofi: Consultancy; Bayer Canada: Consultancy. Remiker: Bluebird Bio: Membership on an entity's Board of Directors or advisory committees; Horizon therapeutics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; X4: Speakers Bureau. Rothman: Agios: Consultancy, Research Funding; Blue Bird Bio: Research Funding; Dova: Research Funding; Novartis: Research Funding; Pfizer: Research Funding; Sobi: Research Funding. Shah: Sobi: Honoraria. Shimano: Sobi: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Sanofi: Research Funding; Daiichi Sankyo: Research Funding. Rifkin-Zenenberg: Vertex: Honoraria, Membership on an entity's Board of Directors or advisory committees. Montcrieff: Takeda Pharmaceuticals USA: Current Employment, Current holder of stock options in a privately-held company. London: Y-mAbs Therapeutics, Inc: Membership on an entity's Board of Directors or advisory committees; Merck: Consultancy; Jubilant Draximage Inc: Consultancy. Lambert: FWGBD, PDSA, NIH, Sysmex, Novartis, Principia, Argenx, Dova, Octapharma and Sanofi: Research Funding; Octapharma, Dova, Principia, Rigel, Argenx, PDSA, 22qSociety and CdLS Foundation: Membership on an entity's Board of Directors or advisory committees; Novartis Dova, Principia, Argenx, Rigel, Sobi, Sanofi and Janssen: Consultancy.

*signifies non-member of ASH