The outcome of hematopoietic stem cell transplantation in Korean children with hemophagocytic lymphohistiocytosis

Abstract

Chemoimmunotherapy-based treatments have improved the survival of patients with HLH, but outcomes of the patients are still unsatisfactory. We report here the outcome of Korean children with HLH who underwent HSCT, which was analyzed from the data of a nation-wide HLH registry. Retrospective nation-wide data recruitment for the pediatric HLH patients diagnosed between 1996 and 2008 was carried out by the Histiocytosis Working Party of the Korean Society of Hematology. Nineteen patients who received HSCT among the total of 148 enrolled children with HLH were analyzed for the transplant-related variables and events. The probability of five-yr survival after HSCT was 73.3% with a median follow-up of 57. Two months compared to 54.3% for the patients who were treated with chemoimmunotherapy only (p = 0.05). The reasons for HSCT were active disease after eight wk of initial treatment (n = 9), relapsed disease (n = 5), and FHL (n = 5). Fourteen patients are currently alive without disease after HSCT, four patients died of treatment-related events (infection in two and graft failure in two) at early post-transplant period, and one patient died of relapse at one yr post transplantation. The survival of patients who were transplanted because of active disease after eight wk of initial treatment was worse compared to those patients who had inactive state at that time (60.6% vs. 100%, respectively, p = 0.06). Of the four patients who received transplants using cord blood, three died of graft failure (n = 2) and relapse (n = 1). The five-yr probability of survival after HSCT according to the donor type was 85.7% for the MRDs (n = 6), 87.5% for the MUDs (n = 8), and 40% for the MMUDs (n = 5) (p = 0.03). Other variables such as age, CNS involvement at the time of diagnosis, the etiology of HLH (familial or secondary), and the conditioning regimens had no influence on the five-yr OS of the HLH patients who underwent HSCT. HSCT improved the survival of the patients who had familial, relapsed, or severe and persistent SHLH in the Korean nation-wide HLH registry. Although numbers were small, these results are similar to other reports in the literature. The disease state after initial treatment, the stem cell source of the transplant, and the donor type were the important prognostic factors that affected the OS of the HLH patients who underwent HSCT.

X-linked lymphoproliferative disease due to SAP/SH2D1A deficiency: a multicenter study on the manifestations, management and outcome of the disease

“…This may reflect the effects of HLH itself or HLH chemotherapy and immunosuppression on the transplant process, including increased organ related toxicity and increased susceptibility to pathogens. In comparison to data reported on cohorts of patients undergoing transplant for HLH associated with other gene defects (eg, perforin and munc 13-4) [39][40][41] it appears that the outcome for HLH associated with XLP1 is worse and may relate to the multiple immune deficits associated with SAP deficiency. By contrast all XLP1 patients who had no HLH manifestations (n ϭ 27) survived the HSCT procedure.…”

Reduced‐intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis

“…The causal genes of FHL account for the structure, function, and metabolism of cytotoxic granules, such as PRF1 (FHL2), UNC13D (FHL3), STX11 (FHL4), and STXBP2 (FHL5) [2]. A potential risk of developing HLH is also a part of the clinical expressions of X-linked lymphoproliferative disease (XLP1 and XLP2), Chediak-Higashi syndrome, and Griscelli syndrome [3].Recent advances in SCT procedures have improved the survival rate of patients with FHL who undergo SCT after myeloablative conditioning, which now range from 45 to 65% [4][5][6][7][8][9][10][11]. However, there remain critical problems with SCT for FHL; early death from treatment-related events often associated with venoocclusive disease, and neurological sequelae in survivors.…”

Autoimmune-Associated Hemophagocytic Syndrome/Macrophage Activation Syndrome

“…A recent Japanese survey revealed a curative effect of alloSCT on sHLH in 7 out of 11 patients (64%) with refractory EBV-HLH (Ogha et al, 2010). Similarly, Yoon et al reported that alloSCT could be a curative treatment not only for FHL, but also for relapsed/refractory sHLH (Yoon et al, 2010). Anecdotal reports have also shown the efficacy of alloSCT in M-HLH therapy (Chang et al, 2009;Goi et al, 1999;Kelly et al, 2011;Machaczka et al, 2011b).…”