Stem cell transplantation with reduced-intensity conditioning for hemophagocytic lymphohistiocytosis

Abstract

Allogeneic stem cell transplantation (SCT) is curative for hemophagocytic lymphohistiocytosis (HLH). However, patients frequently have significant morbidity before transplantation and there is high transplant-related mortality (TRM). Because first-degree HLH is caused by immune dysregulation, a reduced-intensity conditioned (RIC) regimen might be sufficient for cure while decreasing the TRM. Twelve patients with HLH underwent RIC SCT from a matched family/unrelated or haploidentical donor. Eleven were conditioned with fludarabine/melphalan with additional busulphan for haploidentical grafts. One received fludarabine and 2-Gy total body irradiation (TBI). All patients showed engraftment at a median of 14 days. Nine of 12 (75%) are alive and in complete remission (CR) a median of 30 months (range, 9-73 months) after SCT. Two patients died from pneumonitis and one from hepatic rupture. Four patients developed acute graft-versus-host disease (GVHD) and 3 have chronic GVHD. Three of 9 survivors have mixed chimerism but remain free of disease. In summary, RIC compares favorably to conventional SCT with long-term disease control in surviving patients despite a significant incidence of mixed chimerism.

Hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis: a journey of a thousand miles begins with a single (big) step

“…Although therapy with chemo and/or immunotherapy is effective in achieving clinical remission of symptoms, HLH will inexorably (and fatally) recur in individuals with intrinsic, severe deficiencies of cytotoxic function. 7 In recent years, HCT treatment results have been reported in two multicenter, 14,15 and two single institution, 16,17 series of patients ( Table 2). Although limited, these four series are the largest ones reported to date for this rare disorder.…”

“…a Adapted from Henter et al 4 b In addition, in the case of familial HLH, no evidence of malignancy should be apparent. 17 Most patients in these reports received CYA and MTX for GVH prophylaxis. The incidence of grades II-IV GVHD was reported as 32%, 14 41%, 15 17% 16 and 33%.…”

“…Most patients in these three series received similar conditioning regimens: (standard) BU, cytoxan and etoposide, with or without ATG (antithymocyte globulin). Cooper et al 17 described a small series of patients (with a variety of donor types) from a single institution, who received a campath/fludarabine/melphalan-based reduced intensity conditioning (RIC) regimen. In all these series (except Baker et al who did not specify) at least half of the patients had primary (or familial) HLH, with the remainder suffering from secondary HLH.…”

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

“…Cooper et al [12] first indicated the utility of reduced-intensity conditioning (RIC) for SCT in 12 patients with primary HLH. Recently, Marsh et al [13] reported a survival advantage for 26 patients who underwent RIC-SCT compared with myeloablative conditioning SCT.…”

“…However, acute rejection and late graft failure following mixed donor chimerism occurred. In Cooper's [12] and Marsh's protocols [13], 30 and 65% of patients showed mixed donor chimerism after RIC-BM/PBSCT, respectively. All patients with mixed chimerism needed stem cell boost and/or donor lymphocyte infusion to promote stable chimerism.…”