Post-transplantation Cyclophosphamide and Sirolimus after Haploidentical Hematopoietic Stem Cell Transplantation Using a Treosulfan-based Myeloablative Conditioning and Peripheral Blood Stem Cells

被引：116

作者：

Cieri, Nicoletta ^{[1
,2
]}

Greco, Raffaella ^{[1
]}

Crucitti, Lara ^{[1
,3
]}

Morelli, Mara ^{[1
]}

Giglio, Fabio ^{[1
]}

Levati, Giorgia ^{[1
]}

Assanelli, Andrea ^{[1
]}

Carrabba, Matteo G. ^{[1
]}

Bellio, Laura ^{[4
]}

Milani, Raffaella ^{[4
]}

Lorentino, Francesca ^{[1
]}

Stanghellini, Maria Teresa Lupo ^{[1
]}

De Freitas, Tiago ^{[1
]}

Marktel, Sarah ^{[1
]}

Bernardi, Massimo ^{[1
]}

Corti, Consuelo ^{[1
]}

Vago, Luca ^{[1
,3
]}

Bonini, Chiara

Ciceri, Fabio ^{[1
,3
]}

Peccatori, Jacopo ^{[1
]}

机构：

[1] Ist Sci San Raffaele, Hematol & Bone Transplantat Unit, Div Regenerat Med Stem Cells & Gene Therapy, I-20132 Milan, Italy

[2] Ist Sci San Raffaele, Expt Hematol Unit, Div Immunol Transplantat & Infect Dis, I-20132 Milan, Italy

[3] Ist Sci San Raffaele, Mol & Funct Immunogenet Unit, Div Regenerat Med Stem Cells & Gene Therapy, I-20132 Milan, Italy

[4] Ist Sci San Raffaele, Immunohematol & Transfus Med Unit, Div Regenerat Med Stem Cells & Gene Therapy, I-20132 Milan, Italy

来源：

BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION | 2015年 / 21卷 / 08期

关键词：

Post-transplantation cyclophosphamide; Sirolimus; Peripheral blood stem cell transplantation; Allogeneic stem cell transplantation; Haploidentical transplantation; VERSUS-HOST-DISEASE; BONE-MARROW-TRANSPLANTATION; HUMAN-LEUKOCYTE ANTIGEN; REGULATORY T-CELLS; HIGH-RISK; ACUTE-LEUKEMIA; HEMATOLOGIC MALIGNANCIES; MISMATCHED HLA; PHASE-II; RAPAMYCIN;

D O I：

10.1016/j.bbmt.2015.04.025

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Haploidentical hematopoietic stem cell transplantation (HSCT) performed using bone marrow (BM) grafts and post-transplantation cyclophosphamide (PTCy) has gained much interest for the excellent toxicity profile after both reduced-intensity and myeloablative conditioning. We investigated, in a cohort of 40 high-risk hematological patients, the feasibility of peripheral blood stem cells grafts after a treosulfan-melphalan myeloablative conditioning, followed by a PTCy and sirolimus-based graft-versus-host disease (GVHD) prophylaxis (Sir-PTCy). Donor engraftment occurred in all patients, with full donor chimerism achieved by day 30. Post-HSCT recovery of lymphocyte subsets was broad and fast, with a median time to CD4 > 200/mu L of 41 days. Cumulative incidences of grade II to IV and III-IV acute GVHD were 15% and 7.5%, respectively, and were associated with a significant early increase in circulating regulatory T cells at day 15 after HSCT, with values < 5% being predictive of subsequent GVHD occurrence. The 1-year cumulative incidence of chronic GVHD was 20%. Nonrelapse mortality (NRM) at 100 days and 1 year were 12% and 17%, respectively. With a median follow-up for living patients of 15 months, the estimated 1-year overall and disease-free survival (DFS) was 56% and 48%, respectively. Outcomes were more favorable in patients who underwent transplantation in complete remission (1-year DFS 71%) versus patients who underwent transplantation with active disease (DFS, 34%; P = .01). Overall, myeloablative haploidentical HSCT with peripheral blood stem cells (PBSC) and Sir-PTCy is a feasible treatment option: the low rates of GVHD and NRM as well as the favorable immune reconstitution profile pave the way for a prospective comparative trial comparing BM and PBSC in this specific transplantation setting. (C) 2015 American Society for Blood and Marrow Transplantation.

引用

页码：1506 / 1514

页数：9

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