Encouraging Results of Low-Dose Etoposide in the Treatment of Early-Onset Hemophagocytic Syndrome Following Allogeneic Hematopoietic Stem Cell Transplantation

Koyama, M.; Sawada, Akihisa; Yasui, Masayoshi; Inoue, Masami; Kawa, Keisei

doi:10.1007/bf02984009

Cited by 28 publications

(27 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reported incidence of secondary HLH after HSCT for malignancies in adults ranges from 4% to 17% in the first 9 months. [24][25][26][27] To account for this uncertainty, we separately analyzed HLH events that occurred during and events that occurred after the phase of most profound immune suppression, with a cutoff at 180 days after HSCT.…”

Section: Discussionmentioning

confidence: 99%

The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis

Hartz

Marsh

Rao

et al. 2016

Blood

View full text Add to dashboard Cite

Key Points• Donor chimerism .20%-30% usually protects against late disease reactivation after day 180 post stem cell transplantation for primary HLH.• Lower levels do not inevitably result in reactivations. The risks of intervention must be weighed against the risk of reactivation.Reduced-intensity conditioning has improved survival after hematopoietic stem cell transplantation (HSCT) for hemophagocytic lymphohistiocytosis (HLH) at the cost of more frequent mixed chimerism. The minimum level of donor chimerism (DC) required to prevent HLH reactivation in humans remains to be determined. In a multicenter retrospective study, 103 patients transplanted for hereditary HLH (2000HLH ( -2013 and DC permanently or transiently <75% (overall, CD3 1 , CD56 1 ) were analyzed regarding DC, specific immunologic function, occurrence of systemic reactivations ( ‡5/8 HLH criteria), partial systemic flares (<5 criteria and HLH-directed treatment), isolated central nervous system reactivations, and management. Recurrence was reported in 18 patients (systemic reactivation n 5 11, partial flare n 5 3, isolated central nervous system reactivation n 5 4). Ten events occurred during profound immune suppression before day 180 (median DC, 10%; range, 1-100%; CD3 1 if available, otherwise overall DC), which renders a differentiation between secondary post-HSCT HLH and HLH related to the genetic defect difficult. Eight events occurred between 0.5 and 6.7 years post-HSCT (median DC, 13%; range, 0-30%). In 5 patients, overall and lineage-specific DC were £10% for >6 months (median, 5.1; range, 1.1-10 years) without reactivation. A second HSCT was performed in 18 patients (median, DC 4%; range, 0-19%). Death from reactivation occurred in 4 patients (22% of recurrences). Six patients died of transplant complications following a second HSCT (33% of second HSCT). We conclude that a DC >20%-30% is protective against late reactivation. Lower levels do not, however, inescapably result in recurrences. The decision for or against second HSCT must be based on a thorough risk assessment. (Blood. 2016;127(25):3281-3290)

show abstract

Section: Discussionmentioning

confidence: 99%

The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis

Hartz

Marsh

Rao

et al. 2016

Blood

View full text Add to dashboard Cite

show abstract

“…[6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] The frequency of HLH after SCT was reported as 4.1% in patients who had undergone autologous and allogeneic SCT 6 and was reported as 16.8% in patients who underwent CBT. 7 In the present study, the cumulative incidence of HLH was 4.3% in all patients and was 5.8% in patients who underwent CBT.…”

Section: Discussionmentioning

confidence: 99%

“…Because etoposide is known as a therapeutic agent for HLH, we think it is very interesting that a conditioning regimen containing etoposide resulted in a reduction in the development of HLH after SCT. 8,9 The manuscript as risk factor including use of etoposide about HLH was never seen until now. The clear reason conditioning regimen containing etoposide controls development of HLH is not known.…”

Section: Discussionmentioning

confidence: 99%

“…Previous studies of HLH after SCT have not included many patients who received an etoposide-containing condition regimen. 8,[10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] Indeed, none of the patients in the report by Takagi et al received an etoposide-containing condition regimen. 6 These facts may also serve to support our speculation.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT

Kobayashi

Tanaka

Hashino

et al. 2013

Bone Marrow Transplant

View full text Add to dashboard Cite

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening disease of severe hyperinflammation caused by uncontrolled proliferation of activated lymphocytes and macrophages that secrete high amounts of inflammatory cytokines. HLH occurring after SCT is difficult to diagnose. It is characterized by severe clinical manifestations and high mortality. Despite current therapeutic approaches, outcomes remain poor. We analyzed the incidence and risk factors of HLH after SCT and the response to treatment and prognosis of 554 patients with HLH after SCT. The cumulative incidence of HLH after SCT was 4.3% (24/554). Use of etoposide in the conditioning regimen was only factor that reduced HLH after SCT (P ¼ 0.027). All patients who received autologous transplantation were successfully treated. Patients with liver dysfunction (for example, high total bilirubin level, prolonged prothrombin time and high level of fibrinogen degradation products) had a poor response to treatment for HLH. Physicians should be cautious of HLH, while not using etoposide for conditioning regimen.

show abstract

“…The potential therapeutic options targeting macrophages could include anti-TNFa agents, etoposide or liposomal corticosteroids. [28][29][30][31] As we cannot rule out the possibility that early macrophage activation is the result rather than the cause of inflammatory processes, prospective trials are warranted to examine whether macrophage-targeted therapies for early macrophage activation can lower NRM rates.…”

Section: Tablementioning

confidence: 99%

Clinical significance of hemophagocytosis in BM clot sections during the peri-engraftment period following allogeneic hematopoietic SCT

Imahashi¹,

Inamoto²,

Ito³

et al. 2011

Bone Marrow Transplant

View full text Add to dashboard Cite

The effects of macrophage activation on the outcome of allogeneic hematopoietic SCT (allo-HSCT) have yet to be fully examined. A total of 70 adult patients who received a first allo-HSCT for hematological diseases were studied. We counted the number of hemophagocytic cells in BM clot sections on day þ 14±7, and analyzed its impact on subsequent outcome. In all, 23 patients were diagnosed as having increased numbers of hemophagocytic cells (HP group), whereas 47 were not (non-HP group). The HP group was not associated with an increased incidence of acute or chronic GVHD, but was associated with worse hematopoietic recovery than the non-HP group. The 2-year OS for the HP group and the non-HP group was 30 and 65% (Po0.01), respectively, and 2-year nonrelapse mortality was 48% and 27% (Po0.01), respectively. Multivariate analysis confirmed that the HP group was associated with a lower OS (hazard ratio (HR) ¼ 2.3; 95% confidence interval (CI), 1.0-5.4; P ¼ 0.048) and higher non-relapse mortality (HR ¼ 4.0; 95% CI, 1.6-9.9; Po0.01). The HP group had higher incidences of death due to graft failure (Po0.01) and endothelial complications, such as sinusoidal obstruction syndrome and transplant-associated microangiopathy (P ¼ 0.01). Macrophage activation is a previously unrecognized complication with negative impact on outcome of allo-HSCT.

show abstract

Encouraging Results of Low-Dose Etoposide in the Treatment of Early-Onset Hemophagocytic Syndrome Following Allogeneic Hematopoietic Stem Cell Transplantation

Cited by 28 publications

References 5 publications

The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis

The minimum required level of donor chimerism in hereditary hemophagocytic lymphohistiocytosis

Etoposide-containing conditioning regimen reduces the occurrence of hemophagocytic lymphohistiocytosis after SCT

Clinical significance of hemophagocytosis in BM clot sections during the peri-engraftment period following allogeneic hematopoietic SCT

Contact Info

Product

Resources

About