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Phagocyte Biology & its Disorders
Treatment outcomes and prognostic factors in adult patients with secondary hemophagocytic lymphohistiocytosis
not associated with malignancy
Jae-Ho Yoon, Sung-Soo Park, Young-Woo Jeon, Sung-Eun Lee, Byung-Sik Cho, Ki-Seong Eom, Yoo-Jin Kim, Hee-Je Kim, Seok Lee, Chang-Ki Min, Seok-Goo Cho and Jong Wook Lee
Department of Hematology, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
ABSTRACT
Hemophagocytic lymphohistiocytosis is an overwhelming sys- temic inflammatory process that is life-threatening if not treated appropriately. We analyzed prognostic factors in patients with secondary hemophagocytic lymphohistiocytosis excluding malignancy. In this retrospective study, we analyzed 126 adult cases between 2001 and 2017. Treatment was based on dexamethasone with or without etoposide and cyclosporine. Patients who achieved a complete response by 4 weeks were defined as early stable responders, those who failed to achieve a complete response but showed continuous improvement until 8 weeks were defined as late responders, and those whose conditions waxed and waned until 8 weeks were defined as unstable responders. Patients with hemophagocytic lymphohistiocytosis caused by Epstein- Barr virus had a worse 5-year overall survival compared to those whose disease was secondary to autoimmune disease, other infections, or unknown causes (25.1% versus 82.4%, 78.7% and 55.5%, respectively; P<0.001). We observed that the overall response rate at 4 weeks was similar, but decreased at 8 weeks in the Epstein-Barr virus subgroup from 75.5% to 51.0%, and finally decreased to 30.6%. Multivariate analysis revealed that 8-week treatment response was the most relevant factor for overall survival. Excluding 8-week response, the presence of Epstein- Barr virus, old age, hyperferritinemia, and thrombocytopenia were asso- ciated with poor survival. We established a prognostic model with the parameters: low-risk (score 0-1), intermediate-risk (score 2), and high- risk (score ≥3). These groups had 5-year overall survival rates of 92.1%, 36.8%, and 18.0%, respectively (P<0.001). We found that 8-week treat- ment response was a good predictor for overall survival, and that Epstein-Barr virus, old age, thrombocytopenia, and hyperferritinemia were associated with poor survival outcomes. Physicians should take care to identify high-risk patients for appropriate treatment strategies.
Introduction
Secondary hemophagocytic lymphohistiocytosis (HLH) without a family history or known genetic predisposition is considered a rare clinical condition and its underlying pathophysiological mechanisms have not yet been well elucidated. The distinction between primary HLH and secondary HLH is not clear because of the emergence of new gene defects, and the diagnosis is difficult because the symptoms and signs of HLH overlap with those of other severe conditions such as sepsis, multi-organ failure, and progression of malignancies or rheumatologic disorders.1,2 The incidence and prevalence of HLH may, therefore, be under- or overestimated if clinicians lack suspi- cion of and specific knowledge about HLH, especially in adult patients.3
HLH is a life-threatening inflammatory disease, and therefore early diagnosis and urgent treatment, including dexamethasone, cyclosporine, and etoposide, are
Ferrata Storti Foundation
Haematologica 2019 Volume 104(2):269-276
Correspondence:
jwlee@catholic.ac.kr
Received: May 27, 2018.
Accepted: September 11, 2018. Pre-published: September 13, 2018.
doi:10.3324/haematol.2018.198655
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/2/269
©2019 Ferrata Storti Foundation
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