When All Else Fails - Complete Remission with Bortezomib in a Child with Life-Threatening Refractory Autoimmune Hemolytic Anemia

Oct 4, 2026

Uploaded by dhado

Letter to the editor describing a 3-year-old boy with life-threatening, refractory autoimmune hemolytic anemia (AIHA) who achieved rapid, complete, and sustained hematological remission after failure of multiple immunosuppressive regimens. After presenting with profound anemia and positive direct antiglobulin testing, the patient received bortezomib on days 1, 4, 8, and 11, with hemoglobin recovery after the third dose, transfusion discontinuation, and normalization of LDH. Adverse effects were not observed during follow-up; immune dysregulation workup and genetic findings were discussed.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages3

Reading Time8 min

AccessFree to download

Letter to the Editor

Clinical presentation and prior therapies

Bortezomib treatment course and outcomes

Discussion and literature context

Conclusion and future directions

LETTER TO THE EDITOR Turk J Hematol 2026;43:296-298 When All Else Fails: Complete Remission with Bortezomib in a Child with Life-Threatening Refractory Autoimmune Hemolytic Anemia Her Şey Başarısız Olduğunda: Hayatı Tehdit Eden, Refrakter Otoimmün Hemolitik Anemili Bir Çocukta Bortezomib ile Tam Remisyon Sağlanması Fatih Demircioğlu1, Zekai Avcı2, İbrahim Akalın3, Ayşe Sena Demircioğlu4, Betül Tavil1 1 Private Kavacık Medistate Hospital, Clinic of Pediatric Hematology-Oncology, İstanbul, Türkiye 2 Okan University Faculty of Medicine, Department of Pediatric Hematology-Oncology, İstanbul, Türkiye 3 Private Metagentech Center for Genetic Diseases, Clinic of Medical Genetics, İstanbul, Türkiye 4 Kocaeli University Faculty of Medicine, İzmit, Kocaeli, Türkiye To the Editor, Autoimmune hemolytic anemia (AIHA) is a rare but potentially life-threatening condition in childhood, with an incidence of approximately 0.2 cases per 1,000,000 children per year [1] . Corticosteroids remain the frontline therapy with a response rate of 50%-80%, but sustained remission is achieved in only 20%-30% of cases [2] . Second-and third-line agents including intravenous immunoglobulin (IVIG), rituximab, cyclosporine, mycophenolatemofetil, and plasmapheresis are frequently insufficient in the most refractory cases [3] . Here we describe a 3-year-old boy who, following failure of multiple immunosuppressive regimens including rituximab, achieved complete and sustained hematological remission with bortezomib. The patient presented with pallor, jaundice, and hemoglobin (Hb) of 4 g/dL, with lactate dehydrogenase (LDH) of 1935 U/L and direct antiglobulin test (DAT) score of 3+ . He had experienced 5 to 6 severe hemolytic relapses since infancy, most commonly following upper respiratory tract infections. Previous treatments administered at referring centers and our institution included corticosteroids, pulse methylprednisolone, IVIG, plasmapheresis, mycophenolate mofetil, tacrolimus, and multiple erythrocyte transfusions, resulting only in transient or partial responses. Rituximab (375 mg/m2 weekly x4) had been completed 6 weeks before bortezomib initiation without clinical improvement. Secondary etiologies (e.g., autoimmune, infectious, immunodeficiency) were excluded. Given the unusually early onset and refractory disease course, immune dysregulation was investigated. Immunoglobulin levels, lymphocyte subsets, and double-negative T-cell percentage (0 .75%) were normal. Whole- exome sequencing identified a rare heterozygous PIK3R1 variant of uncertain significance (c. 1202T>C; p.V401A) . However, the absence of recurrent severe infections, lymphoproliferation, or laboratory evidence of immune dysregulation precludeda diagnosis of activated PI3Kδ syndrome type 2 (APDS2) . Bone marrow biopsy showed erythroid hyperplasia without dysplasia. Given the life-threatening, multi-refractory course, bortezomib was initiated at 1.3 mg/m2 on days 1, 4, 8, and 11. Hb began rising after the third dose and complete normalization of blood counts with reticulocytosis was achieved within 1 month. Erythrocyte transfusions were discontinued. The patient was dischargedon a tapering course of methylprednisolone (stopped within 2 weeks), tacrolimus, and mycophenolate mofetil. At 1 month, Hb was 13.4 g/dL, reticulocyte count was 1. 1%, the DAT score had decreased to +1, and LDH had normalized (Figure 1) . The DAT became negative at 6 months, with no further transfusion requirements over 10 months of follow-up. No adverse effects, including peripheral neuropathy, were observed. Bortezomib is a selective, reversible 26S proteasome inhibitor approved for multiple myeloma that depletes antibodyproducing plasma cells and suppresses NF-κB-mediated inflammation [4,5] . Its use in pediatric refractory AIHA and autoimmune cytopenias is emerging: among 24 cases reported in the literature, hematological response was achieved in 18 (75%), predominantly in post-he

FAQs

What condition is highlighted in the letter, and why is it considered high risk in children?

The letter focuses on autoimmune hemolytic anemia (AIHA), described as rare but potentially life-threatening in childhood due to its severity and the limited rate of sustained remission with standard therapy.

Which treatments had failed before bortezomib, and what was the key treatment change?

The patient had multiple prior immunosuppressive regimens, including corticosteroids, IVIG, plasmapheresis, mycophenolate mofetil, tacrolimus, and erythrocyte transfusions. Rituximab was completed 6 weeks before bortezomib initiation without clinical improvement, after which bortezomib was started on a defined schedule.

What outcomes were achieved after starting bortezomib?

Hemoglobin began rising after the third dose, complete normalization of blood counts with reticulocytosis occurred within 1 month, transfusions were discontinued, and the direct antiglobulin test became negative by 6 months, with no further transfusion needs over 10 months.

Oct 4, 2026

Uploaded by dhado