Fludarabine/Melphalan 100 mg/m ² Conditioning Therapy Followed by Allogeneic Hematopoietic Cell Transplantation for Adult Patients with Secondary Hemophagocytic Lymphohistiocytosis.

Publisher: Carden Jennings Publishing Country of Publication: United States NLM ID: 9600628 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1523-6536 (Electronic) Linking ISSN: 10838791 NLM ISO Abbreviation: Biol Blood Marrow Transplant Subsets: MEDLINE

Publication: Charlottesville, VA : Carden Jennings Publishing
Original Publication: Charlottesville, VA : Kluge Carden Jennings Publishing, Co., Ltd., [1995-

Hematopoietic Stem Cell Transplantation/*methods ; Lymphohistiocytosis, Hemophagocytic/*drug therapy ; Melphalan/*therapeutic use ; Myeloablative Agonists/*therapeutic use ; Transplantation Conditioning/*methods ; Transplantation, Homologous/*methods ; Vidarabine/*analogs & derivatives; Adolescent ; Adult ; Female ; Humans ; Lymphohistiocytosis, Hemophagocytic/mortality ; Male ; Melphalan/pharmacology ; Middle Aged ; Myeloablative Agonists/pharmacology ; Survival Analysis ; Vidarabine/pharmacology ; Vidarabine/therapeutic use ; Young Adult

Our previous research indicated that a reduced-intensity conditioning regimen (fludarabine and melphalan at 100 mg/m ² ) was useful in allogeneic hematopoietic cell transplantation (HCT) for patients with lymphoma. This retrospective study evaluated the reduced-intensity conditioning regimen in allogeneic HCT for adult patients with hemophagocytic lymphohistiocytosis (HLH). Sixteen patients with HLH were evaluated, including 6 patients who were enrolled in a prospective clinical trial (NCT00772811) and 10 patients who received the same conditioning regimen (fludarabine at 30 mg/m ² /day on days -6 to -2 and melphalan at 100 mg/m ² on day -2). The median age was 42 years (range, 18 to 64), and 12 patients had Epstein-Barr virus (EBV)-associated HLH. Donors were an HLA matched sibling for 10 patients, an unrelated matched volunteer for 4 patients, and a mismatched family member for 2 patients. After excluding 3 patients who died soon after HCT, 12 patients achieved an engraftment (neutrophil median, day 12; platelet median, day 16). Five patients experienced acute graft-versus-host disease (GVHD), including 1 case of grade II and 4 cases of grades III to IV. Chronic GVHD occurred in 3 patients (moderate, 1 case; severe, 2 cases). After a median follow-up of 33.8 months 1 patient progressed, 3 patients relapsed, and 9 patients died. Five deaths were unrelated to relapse or progression and were caused by infection (n = 3), bleeding (n = 1), and GVHD (n = 1). No deaths or relapses were observed at >124 days post-transplant. The overall survival rate was 48.6%, and significant differences were observed according to pretransplant ferritin level (P = .007) and cytopenia lineage (P = .021). Before allogeneic HCT 10 of 12 patients still tested positive for EBV DNA: 6 patients tested negative for EBV DNA after HCT, 2 patients had persistent EBV DNA, and 2 patients were unassessable because of early death. Conditioning therapy using a lower dose of melphalan combined with fludarabine appears to be promising in allogeneic HCT for adults with HLH. However, strategies are needed to reduce the risk of early death.
(Copyright © 2018 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.)

Keywords: Allogeneic hematopoietic cell transplantation; Epstein-Barr virus; Hemophagocytic lymphohistiocytosis; Reduced-intensity conditioning regimen

0 (Myeloablative Agonists)
FA2DM6879K (Vidarabine)
P2K93U8740 (fludarabine)
Q41OR9510P (Melphalan)

Date Created: 20181204 Date Completed: 20200406 Latest Revision: 20200408

20221213

10.1016/j.bbmt.2018.11.032

30508593