Haematopoietic stem cell transplantation in haemophagocytic lymphohistiocytosis

Abstract

Summary Haemophagocytic lymphohistiocytosis (HLH) poses major therapeutic challenges, and the primary inherited form, familial haemophagocytic lymphohistiocytosis (FHL), is usually fatal. We evaluated, including Cox regression analysis, survival in 86 children (29 familial) that received HLH‐94‐therapy (etoposide, dexamethasone, ciclosporin) followed by allogeneic stem cell transplantation (SCT) between 1995 and 2000. The overall estimated 3‐year‐survival post‐SCT was 64% [confidence interval (CI) = ±10%] (n = 86); 71 ± 18% in those patients with a matched related donor (MRD, n = 24), 70 ± 16% with a matched unrelated donor (MUD, n = 33), 50 ± 24% with a family haploidentical donor (haploidentical, n = 16), and 54 ± 27% with a mismatched unrelated donor (MMUD, n = 13). After adjustment for potential confounding factors, estimated odds ratios (OR) for mortality were 1·93 (CI =0·61–6·19) for MUD, 3·31 (1·02–10·76) for haploidentical, and 3·01 (0·91–9·97) for MMUD, compared with MRD. In children with active disease after 2‐months of therapy (n = 43) the OR was 2·75 (1·26–5·99), compared with inactive disease (n = 43). In children with active disease at SCT (n = 37), the OR was 1·80 (0·80–4·06) compared with inactive disease (n = 49), after adjustment for disease activity at 2‐months. Mortality was predominantly transplant‐related. Most HLH patients survived SCT using MRD or MUD, and survival with partially mismatched donors was also acceptable. Patients that responded well to initial pretransplant‐induction therapy fared best, but some persisting HLH activity should not automatically preclude performing SCT.

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

“…Others have also reported on the unusual high incidence of this complication in transplanted FHLH patients, indistinguishable from an accelerated phase and thus suggesting recurrence of the disease. 15 Control of this complication requires aggressive management including the use of chemotherapy, as documented in one of our patients who improved dramatically following treatment with VP16 and who is a long-term survivor.…”

“…11,[15][16][17][18][19] In patients with active disease due to either incomplete treatment responses or relapses, treatment strategies are not well defined and commonly consist of intensification of immunosuppressive treatment in an attempt to reach a second remission.…”

“…14 The curative potential of HSCT was initially demonstrated by Fischer et al, 14 and has subsequently been confirmed by a number of groups. [15][16][17][18][19] HSCT is currently the only available treatment to cure primary hemophagocytic syndromes and thus represents the treatment of choice in all patients. Interestingly, lasting remissions have also been observed in patients with stable mixed donor-cell chimerism, 19 indicating that even a limited level of immune reconstitution by donor cells is sufficient to control the dysfunctional immune system in patients.…”

Elements of confusion

“…However, those who do not receive early etoposide therapy fare much worse, with a mortality rate of 92%. 10 This patient was not able to receive etoposide because of his decompensated liver disease.…”

“…9,10 Those who survive this initial phase are recommended for hematopoetic stem cell transplantation producing an overall 3-year survival rate of 64%. However, those who do not receive early etoposide therapy fare much worse, with a mortality rate of 92%.…”