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A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing

Grosso, Dolores ; Carabasi, Matthew ; Filicko-O'Hara, Joanne ; Kasner, Margaret ; Wagner, John L. ; Colombe, Beth ; Cornett Farley, Patricia ; O'Hara, William ; Flomenberg, Phyllis ; Werner-Wasik, Maria ; Brunner, Janet ; Mookerjee, Bijoyesh ; Hyslop, Terry ; Weiss, Mark ; Flomenberg, Neal

Blood, 2011-10, Vol.118 (17), p.4732-4739 [Periódico revisado por pares]

Washington, DC: Elsevier Inc

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Título:
A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing
Autor: Grosso, Dolores ; Carabasi, Matthew ; Filicko-O'Hara, Joanne ; Kasner, Margaret ; Wagner, John L. ; Colombe, Beth ; Cornett Farley, Patricia ; O'Hara, William ; Flomenberg, Phyllis ; Werner-Wasik, Maria ; Brunner, Janet ; Mookerjee, Bijoyesh ; Hyslop, Terry ; Weiss, Mark ; Flomenberg, Neal
Assuntos: Adult ; Aged ; Biological and medical sciences ; Calibration ; Cell Count ; Female ; Graft vs Host Disease - epidemiology ; Graft vs Host Disease - etiology ; Haplotypes ; Hematologic and hematopoietic diseases ; Hematologic Neoplasms - immunology ; Hematologic Neoplasms - mortality ; Hematologic Neoplasms - therapy ; Hematopoietic Stem Cell Transplantation - adverse effects ; Hematopoietic Stem Cell Transplantation - methods ; Hematopoietic Stem Cell Transplantation - standards ; Humans ; Male ; Medical sciences ; Middle Aged ; Myeloablative Agonists - adverse effects ; Myeloablative Agonists - therapeutic use ; T-Lymphocytes - cytology ; Transplantation Conditioning - adverse effects ; Transplantation Conditioning - methods ; Transplantation, Homologous ; Young Adult
É parte de: Blood, 2011-10, Vol.118 (17), p.4732-4739
Descrição: Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 108/kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes, especially in good-risk patients, and can serve as the basis for further exploration and optimization of this 2-step approach. This study is registered at www.clinicaltrials.gov as NCT00429143.
Editor: Washington, DC: Elsevier Inc
Idioma: Inglês

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A 2-step approach to myeloablative haploidentical stem cell transplantation: a phase 1/2 trial performed with optimized T-cell dosing

Grosso, Dolores ; Carabasi, Matthew ; Filicko-O'Hara, Joanne ; Kasner, Margaret ; Wagner, John L. ; Colombe, Beth ; Cornett Farley, Patricia ; O'Hara, William ; Flomenberg, Phyllis ; Werner-Wasik, Maria ; Brunner, Janet ; Mookerjee, Bijoyesh ; Hyslop, Terry ; Weiss, Mark ; Flomenberg, Neal

Washington, DC: Elsevier Inc

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