Early hematopoietic cell transplantation for familial hemophagocytic lymphohistiocytosis in a regional treatment network in Japan

Ishimura, M; Eguchi, K; Sonoda, M; Tanaka, T; Shiraishi, A; Sakai, Y; Yasumi, T; Miyamoto, T; Voskoboinik, I; Hashimoto, K; Matsumoto, S; Ozono, S; Moritake, H; Takada, H; Ohga, S

Author(s): Ishimura, M; Eguchi, K; Sonoda, M; Tanaka, T; Shiraishi, A; Sakai, Y; Yasumi, T; Miyamoto, T; Voskoboinik, I; Hashimoto, K; Matsumoto, S; Ozono, S; Moritake, H; Takada, H; Ohga, S;
Details: Publication Year 2024-05,Volume 119,Issue #5,Page 592-602
Journal Title: International Journal of Hematology
Publication Type: Research article
Abstract: Familial hemophagocytic lymphohistiocytosis (FHLH) is a fatal hyperinflammation syndrome arising from the genetic defect of perforin-mediated cytolysis. Curative hematopoietic cell transplantation (HCT) is needed before development of central nervous system (CNS) disease. We studied treatment outcomes of 13 patients (FHLH2 n = 11, FHLH3 n = 2) consecutively diagnosed from 2011 to 2022 by flow cytometric screening for non-myeloablative HCT in a regional treatment network in Kyushu, Japan. One patient with a novel PRF1 variant escaped screening, but all patients with FHLH2 reached diagnosis and 8 of them received HCT until 3 and 9 months of age, respectively. The earliest HCT was conducted 65 days after birth. Three pretransplant deaths occurred in newborns with liver failure at diagnosis. Ten posttransplant patients have remained disease-free, 7 of whom had no neurological involvement. Time from first etoposide infusion to HCT was shorter in patients without CNS disease or bleeding than in patients with those factors (median [range] days: 62 [50-81] vs. 122 [89-209], p = 0.016). Six of 9 unrelated patients had a PRF1 c.1090_1091delCT variant. These results suggest that the critical times to start etoposide and HCT are within 3 months after birth and during etoposide control, respectively. Newborn screening may increase the percentage of disease-free survivors without complications.
Publisher: Springer Nature
Keywords: Humans; *Lymphohistiocytosis, Hemophagocytic/therapy/diagnosis/etiology; *Hematopoietic Stem Cell Transplantation; Japan; Infant; Female; Male; *Perforin/genetics; Infant, Newborn; Treatment Outcome; Child, Preschool; Etoposide/therapeutic use/administration & dosage; Hematopoietic cell transplantation; Hyperinflammation; Perforin; Rapid diagnosis
Department(s): Laboratory Research
Publisher's Version: https://doi.org/10.1007/s12185-024-03721-3
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-07-11 01:41:16

Last Modified: 2024-07-11 01:48:04