Your browser doesn't support javascript.
loading
Low Nonrelapse Mortality after HLA-Matched Related 2-Step Hematopoietic Stem Cell Transplantation Using Cyclophosphamide for Graft-versus-Host Disease Prophylaxis and the Potential Impact of Non- Cyclophosphamide-Exposed T Cells on Outcomes.
Grosso, Dolores; Carabasi, Matthew; Filicko-O'Hara, Joanne; Wagner, John L; O'Hara, William; Sun, Michael; Colombe, Beth; Shi, W; Werner-Wasik, Maria; Rudolph, Shannon; Alpdogan, Onder; Binder, Adam; Kasner, Margaret; Klumpp, Thomas; Martinez-Outschoorn, Ubaldo; Palmisiano, Neil; Wilde, Lindsay; Porcu, Pierluigi; Gergis, Usama; Flomenberg, Neal.
Affiliation
  • Grosso D; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania. Electronic address: lorigrosso@gmail.com.
  • Carabasi M; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Filicko-O'Hara J; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Wagner JL; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • O'Hara W; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Sun M; Blood and Marrow Transplant Cell Processing Lab, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Colombe B; Department of Pathology, Tissue Typing, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Shi W; Department of Radiation Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Werner-Wasik M; Department of Radiation Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Rudolph S; Clinical Research Office, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Alpdogan O; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Binder A; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Kasner M; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Klumpp T; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Martinez-Outschoorn U; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Palmisiano N; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Wilde L; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Porcu P; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Gergis U; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
  • Flomenberg N; Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania.
Biol Blood Marrow Transplant ; 26(10): 1861-1867, 2020 10.
Article in En | MEDLINE | ID: mdl-32629157
The use of cyclophosphamide (CY) for bidirectional tolerization of recipient and donor T cells is associated with reduced rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after HLA-matched hematopoietic stem cell transplantation (HSCT). However, recurrent disease remains the primary barrier to long-term survival. We extended our 2-step approach to HLA-matched related HSCT using a radiation-based myeloablative conditioning regimen combined with a high dose of T cells in an attempt to reduce relapse rates while maintaining the beneficial effects of CY tolerization. After conditioning, patients received their grafts in 2 components: (1) a fixed dose of 2 × 108/kg T cells, followed 2 days later by CY, and (2) a CD34-selected graft containing a small residual amount of non-CY-exposed T cells, at a median dose of 2.98 × 103/kg. Forty-six patients with hematologic malignancies were treated. Despite the myeloablative conditioning regimen and use of high T cell doses, the cumulative incidences of grade II-IV acute GVHD, chronic GVHD, and NRM at 1 year and 5 years were very low, at 13%, 9%, and 4.3%, respectively. This contributed to a high overall survival of 89.1% at 1 year and 65.8% at 5 years. Relapse was the primary cause of mortality, with a cumulative incidence of 23.9% at 1 year and 45.7% at 5 years. In a post hoc analysis, relapse rates were significantly lower in patients receiving greater than versus those receiving less than the group median of non-CY-exposed residual T cells in the CD34 product (19.3% versus 58.1%; P = .009), without a concomitant increase in NRM. In its current form, this 2-step regimen was highly tolerable, but strategies to reduce relapse, potentially the addition of T cells not exposed to CY, are needed.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hematopoietic Stem Cell Transplantation / Hematologic Neoplasms / Graft vs Host Disease Limits: Humans Language: En Journal: Biol Blood Marrow Transplant Journal subject: HEMATOLOGIA / TRANSPLANTE Year: 2020 Type: Article

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Hematopoietic Stem Cell Transplantation / Hematologic Neoplasms / Graft vs Host Disease Limits: Humans Language: En Journal: Biol Blood Marrow Transplant Journal subject: HEMATOLOGIA / TRANSPLANTE Year: 2020 Type: Article