title: Successful engraftment and stable full donor chimerism after myeloablation with thiotepa, fludarabine, and melphalan and CD34-selected peripheral allogeneic stem cell transplantation in hemophagocytic lymphohistiocytosis.
abstract: Allogeneic hematopoietic stem cell transplantation (HSCT) represents the only curative option for primary hemophagocytic lymphohistiocytosis (HLH), a rare disease of infants and young children, characterized by recurrent fever, hepatosplenomegaly, and cytopenia. We report a case of successful engraftment and stable full-donor chimerism in a patient with HLH who underwent peripheral allogeneic CD34-selected HSCT. The donor was his 1-antigen-HLA-mismatched grandmother. After a conditioning regimen based on the combination of thiotepa, fludarabine, melphalan, and rabbit antilymphocyte serum, the patient received a megadose of 26.3 x 10(6)/kg of CD34(+) peripheral blood cells. Neutrophil (>0.5 x 10(9)/L) and platelet (>50 x 10(9)/L) engraftment was observed on days +16 and +12, respectively, and the patient was discharged home on day +24. No acute or chronic GVHD was observed. Infectious complications were the main causes of re-hospitalization in the first year after transplantation, but no significant morbidity was observed thereafter. Thirty-two months after HSCT, the patient is alive and well, still in complete clinical remission of his underlying disease with a durable engraftment, normal NK activity and full donor chimerism. This case suggests that a fludarabine-based conditioning regimen and CD34-selected peripheral allogeneic HSCT may be a feasible option in case of unavailability of a fully HLA-matched related or unrelated donor.
authors.affiliation: Clinic of Pediatric Oncology-Hematology, Department of Pediatrics, University of Padua, Via Giustiniani 3, 35128 Padua, Italy. simone.cesaro@unipd.it
authors.forename: Simone
authors.initials: S
authors.lastname: Cesaro
authors.forename: Maria Vittoria
authors.initials: MV
authors.lastname: Gazzola
authors.forename: Piero
authors.initials: P
authors.lastname: Marson
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Calore
authors.forename: Luciana
authors.initials: L
authors.lastname: Caenazzo
authors.forename: Roberta
authors.initials: R
authors.lastname: Destro
authors.forename: Giustina
authors.initials: G
authors.lastname: De Silvestro
authors.forename: Stefania
authors.initials: S
authors.lastname: Varotto
authors.forename: Marta
authors.initials: M
authors.lastname: Pillon
authors.forename: Luigi
authors.initials: L
authors.lastname: Zanesco
authors.forename: Chiara
authors.initials: C
authors.lastname: Messina
mesh_terms: D018952:Antigens, CD34; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018572:Disease-Free Survival; D006085:Graft Survival; D015616:Histiocytosis, Non-Langerhans-Cell / Q000628:therapy*; D006801:Humans; D007223:Infant; D008558:Melphalan; D019653:Myeloablative Agonists / Q000008:administration & dosage*; D036102:Peripheral Blood Stem Cell Transplantation / Q000379:methods*; D012074:Remission Induction / Q000379:methods; D013852:Thiotepa; D018183:Transplantation Chimera; D019172:Transplantation Conditioning / Q000379:methods; D014184:Transplantation, Homologous / Q000379:methods; D014740:Vidarabine / Q000008:administration & dosage* / Q000031:analogs & derivatives*
chemical_list: D018952:Antigens, CD34; D019653:Myeloablative Agonists; D013852:Thiotepa; D014740:Vidarabine; C024352:fludarabine; D008558:Melphalan