Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis

TY - JOUR

T1 - Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis

AU - Lehmberg, Kai

AU - Albert, Michael H

AU - Beier, Rita

AU - Beutel, Karin

AU - Gruhn, Bernd

AU - Kröger, Nicolaus-Martin

AU - Meisel, Roland

AU - Schulz, Ansgar

AU - Stachel, Daniel

AU - Woessmann, Wilhelm

AU - Janka, Gritta

AU - Müller, Ingo

PY - 2014/1/1

Y1 - 2014/1/1

N2 - In hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis, high transplant-related mortality after busulfan-based myeloablative regimens has been observed. Conditioning regimens with reduced toxicity based on melphalan or treosulfan are promising alternatives. We retrospectively analyzed hematopoietic stem cell transplantations in 19 hemophagocytic lymphohistiocytosis patients after conditioning with fludarabine, treosulfan, alemtuzumab, with or without thiotepa. Overall and disease-free survivals were 100% (follow up 7-31 months). Two patients required second transplant (1 after haploidentical transplantation). In 6 patients, overall donor chimerism dropped below 75% and prompted donor lymphocyte infusions. Administration of donor lymphocytes or second transplantation were significantly more frequent after transplantation from a human leukocyte antigen mismatched (9/10) versus matched (10/10) donor (P=0.018). The toxicity profile was favorable, with one veno-occlusive disease, one grade 3 graft-versus-host disease after donor lymphocyte infusion, and 2 severe viral infections (1 influenza, 1 Epstein Barr virus). In conclusion, the treosulfan-based regimen in hemophagocytic lymphohistiocytosis is effective with low toxicity and gives excellent overall and disease-free survival rates. In the future, the incidence of mixed chimerism, particularly after human leukocyte antigen mismatched donor transplants, needs to be addressed.

AB - In hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis, high transplant-related mortality after busulfan-based myeloablative regimens has been observed. Conditioning regimens with reduced toxicity based on melphalan or treosulfan are promising alternatives. We retrospectively analyzed hematopoietic stem cell transplantations in 19 hemophagocytic lymphohistiocytosis patients after conditioning with fludarabine, treosulfan, alemtuzumab, with or without thiotepa. Overall and disease-free survivals were 100% (follow up 7-31 months). Two patients required second transplant (1 after haploidentical transplantation). In 6 patients, overall donor chimerism dropped below 75% and prompted donor lymphocyte infusions. Administration of donor lymphocytes or second transplantation were significantly more frequent after transplantation from a human leukocyte antigen mismatched (9/10) versus matched (10/10) donor (P=0.018). The toxicity profile was favorable, with one veno-occlusive disease, one grade 3 graft-versus-host disease after donor lymphocyte infusion, and 2 severe viral infections (1 influenza, 1 Epstein Barr virus). In conclusion, the treosulfan-based regimen in hemophagocytic lymphohistiocytosis is effective with low toxicity and gives excellent overall and disease-free survival rates. In the future, the incidence of mixed chimerism, particularly after human leukocyte antigen mismatched donor transplants, needs to be addressed.

U2 - 10.3324/haematol.2013.094730

DO - 10.3324/haematol.2013.094730

M3 - SCORING: Journal article

C2 - 24162790

VL - 99

SP - 180

EP - 184

JO - HAEMATOLOGICA

JF - HAEMATOLOGICA

SN - 0390-6078

IS - 1

ER -