Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
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Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study. / Bergsten, Elisabet; Horne, AnnaCarin; Hed Myrberg, Ida; Aricó, Maurizio; Astigarraga, Itziar; Ishii, Eiichi; Janka, Gritta; Ladisch, Stephan; Lehmberg, Kai; McClain, Kenneth L; Minkov, Milen; Nanduri, Vasanta; Rosso, Diego A; Sieni, Elena; Winiarski, Jacek; Henter, Jan-Inge.
In: BLOOD ADV, Vol. 4, No. 15, 11.08.2020, p. 3754-3766.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Stem cell transplantation for children with hemophagocytic lymphohistiocytosis: results from the HLH-2004 study
AU - Bergsten, Elisabet
AU - Horne, AnnaCarin
AU - Hed Myrberg, Ida
AU - Aricó, Maurizio
AU - Astigarraga, Itziar
AU - Ishii, Eiichi
AU - Janka, Gritta
AU - Ladisch, Stephan
AU - Lehmberg, Kai
AU - McClain, Kenneth L
AU - Minkov, Milen
AU - Nanduri, Vasanta
AU - Rosso, Diego A
AU - Sieni, Elena
AU - Winiarski, Jacek
AU - Henter, Jan-Inge
N1 - © 2020 by The American Society of Hematology.
PY - 2020/8/11
Y1 - 2020/8/11
N2 - We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged <18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P = .035). For children with verified FHL (family history/genetically verified, n = 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n = 53) was significantly lower (52%; 95% CI, 38-65) (P = .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival. This trial was registered at www.clinicaltrials.gov as #NCT00426101.
AB - We report the largest prospective study thus far on hematopoietic stem cell transplantation (HSCT) in hemophagocytic lymphohistiocytosis (HLH), a life-threatening hyperinflammatory syndrome comprising familial/genetic HLH (FHL) and secondary HLH. Although all patients with HLH typically need intensive anti-inflammatory therapy, patients with FHL also need HSCT to be cured. In the international HLH-2004 study, 187 children aged <18 years fulfilling the study inclusion criteria (5 of 8 diagnostic criteria, affected sibling, or molecular diagnosis in FHL-causative genes) underwent 209 transplants (2004-2012), defined as indicated in patients with familial/genetic, relapsing, or severe/persistent disease. Five-year overall survival (OS) post-HSCT was 66% (95% confidence interval [CI], 59-72); event-free survival (EFS) was 60% (95% CI, 52-67). Five-year OS was 81% (95% CI, 65-90) for children with a complete response and 59% (95% CI, 48-69) for those with a partial response (hazard ratio [HR], 2.12; 95% CI, 1.06-4.27; P = .035). For children with verified FHL (family history/genetically verified, n = 134), 5-year OS was 71% (95% CI, 62-78) and EFS was 62% (95% CI, 54-70); 5-year OS for children without verified FHL (n = 53) was significantly lower (52%; 95% CI, 38-65) (P = .040; HR, 1.69; 95% CI, 1.03-2.77); they were also significantly older. Notably, 20 (38%) of 53 patients without verified FHL had natural killer cell activity reported as normal at diagnosis, after 2 months, or at HSCT, suggestive of secondary HLH; and in addition 14 (26%) of these 53 children had no evidence of biallelic mutations despite having 3 or 4 FHL genes analyzed (natural killer cell activity not analyzed after 2 months or at HSCT). We conclude that post-HSCT survival in FHL remains suboptimal, and that the FHL diagnosis should be carefully investigated before HSCT. Pretransplant complete remission is beneficial but not mandatory to achieve post-HSCT survival. This trial was registered at www.clinicaltrials.gov as #NCT00426101.
U2 - 10.1182/bloodadvances.2020002101
DO - 10.1182/bloodadvances.2020002101
M3 - SCORING: Journal article
C2 - 32780845
VL - 4
SP - 3754
EP - 3766
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
IS - 15
ER -
