Improved outcome in haemophagocytic lymphohistiocytosis after bone marrow transplantation from related and unrelated donors: a single‐centre experience of 12 patients

Abstract

Summary. Haemophagocytic lymphohistiocytosis (HLH) isan autosomal recessive disease with histiocytic and lymphocytic in®ltrations in multiple organs. Cure seems possible only by allogeneic bone marrow transplantation (BMT), but matched sibling donors (MSD) are restricted and high mortality rates are associated with BMT from unrelated donors (URD). We report on 12 consecutive HLH patients with an improved outcome following URD transplants. Eight patients received BMT from URD, four from MSD. Five patients had signs of active HLH at the time of BMT. The conditioning regimen consisted of 20 mg/kg busulphan, 60 mg/kg VP-16 and 120 mg/kg cyclophosphamide and, in case of URD, 90 mg/kg antithymocyte globulin. The doses of busulphan and VP-16 were reduced during the programme to 16 mg/kg and 30 mg/kg, respectively. Using a ®vefold graft-versus-host disease (GVHD) prophylaxis, GVHD was absent or mild in 10, and moderate or severe in two patients undergoing unrelated transplants. One patient with URD experienced graft failure and was retransplanted on day 37. Major toxicities were hepatic veno-occlusive disease in ®ve, capillary leak syndrome in two, pneumonia in three, sepsis in one, severe mucositis in one and seizures in two patients. All patients are alive without HLH after a median follow-up of 24´5 months. One patient has chronic GVHD, another patient has severe retardation. Three patients show slight to moderate development delay. These results indicate that in HLH, BMT from matched unrelated donors should be performed. Incomplete resolution of disease activity need not impede a successful outcome.

Patients with early relapse of primary hemophagocytic syndromes or with persistent CNS involvement may benefit from immediate hematopoietic stem cell transplantation

“…Our data also indicate that CNS disease may become permanently controlled after successful HSCT. Similar encouraging experience has previously been reported in a study by Du¨rken et al, 24 where all the five FHLH patients with manifestations of active disease survived after HSCT.…”

Allogeneic bone marrow transplantation for children with histiocytic disorders: use of TBI and omission of etoposide in the conditioning regimen

“…13 However, the results of BMT for patients with active disease and for recipients of alternative-donor grafts have been discouraging, with significant morbidity and mortality because of toxicity, GvHD, and graft failure. 12,14,[27][28][29] Some reports associate graft failure with autologous reconstitution, 12,30 and disease recurrence was observed in the single patient with autologous reconstitution in our series. However, other reports do not confirm this observation.…”

“…14,20,[27][28][29][30][31][32][33] Results from larger published series are summarized in Table 3. However, our center reports favorable outcomes in a small number of patients using a TBI-containing conditioning regimen that omits etoposide.…”

“…Recipients of non-T-cell depleted grafts tend to have lower rates of graft failure, countered by higher rates of acute and chronic GvHD when compared to recipients of T-cell-depleted grafts. 14,20,[27][28][29][30][31][32][33] In the largest series of HLH patients receiving non-T-cell-depleted grafts, 20 GvHD was a significant cause of morbidity and mortality.…”

Autoimmune-Associated Hemophagocytic Syndrome/Macrophage Activation Syndrome

“…Since then, information regarding the role of alloSCT in the treatment of HLH has mostly concerned FHL (Janka, 2009;Marsh et al, 2010 (Baker et al, 1997;Cesaro et al, 2008;Dürken et al, 1999;Horne et al, 2005;Imashuku et al, 1999;Jabado et al, 1997;Ouachèe-Chardin et al, 2006), and 75-92% with reduced-intensity conditioning (RIC) (Cooper et al, 2006;Marsh et al, 2010). So far, alloSCT has been performed only occasionally in cases of acquired HLH and its role in the treatment of sHLH is not yet established.…”