Thymosin alpha1 to harness immunity to pathogens after haploidentical hematopoietic transplantation.
We designed a phase I/II clinical study to determine safety and efficacy of thymosin alpha1 (Talpha1) administration in recipients of one HLA haplotype (haploidentical) stem cell transplants for hematologic malignancies. Talpha1 administration did not cause acute or chronic graft versus host disease and was associated with significant improvement in polymorphonuclear (phagocytosis) and dendritic cell (phagocytosis, expression of costimulatory molecules, and cytokine production) functions. It was also associated with increased T-cell counts and earlier appearance of functional pathogen-specific T cell responses (by a sensitive limiting dilution assay that detects frequency of T cells specific for Aspergillus, Candida, CMV, ADV, VZV, HSV, Toxoplasma). Five of six haploidentical transplant recipients who received Talpha1 are alive and disease free at a median follow-up of 10 months after transplantation (range: 5-20). They experienced only a single nonlethal infectious episode and one patient developed fatal immune hemolytic anemia. At this very early stage of the clinical trial, we conclude Talpha1 administration is safe and may impact favorably on immune function. Larger numbers of patients and longer follow-up are, of course, needed to assess its impact on survival.
Division of Hematology and Clinical Immunology, University of Perugia, Perugia, Italy.
Katia
K
Perruccio
Pierluigi
P
Bonifazi
Fabiana
F
Topini
Antonella
A
Tosti
Silvia
S
Bozza
Teresa
T
Aloisi
Alessandra
A
Carotti
Franco
F
Aversa
Massimo F
MF
Martelli
Luigina
L
Romani
Andrea
A
Velardi
D001230:Aspergillus / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000503:physiopathology; D006239:Haplotypes; D019337:Hematologic Neoplasms / Q000150:complications / Q000276:immunology* / Q000628:therapy*; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000276:immunology; D007239:Infections / Q000150:complications / Q000276:immunology; D018139:Simplexvirus / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use
D013947:Thymosin; D000077596:Thymalfasin