Successful one antigen mismatched bone marrow transplant for chronic myeloid leukemia (CML) after two failed syngeneic transplants

Abstract

Summary:In May 1989, a 43-year-old woman with chronic myelocytic leukemia diagnosed in 1988 underwent a syngeneic bone marrow transplant (BMT), conditioned with cyclophosphamide-TBI while in chronic phase. Three years later, because of both cytogenetic and hematological relapse, she was treated with interferon-␣ (IFN-␣) and hydroxyurea (HU) for 3 years. In 1994 while still in chronic phase, she was conditioned with busulfan-cyclophosphamide (BU-CY) and underwent a second syngeneic BMT. In 1996, following a further cytogenetic and hematological relapse, she was again placed on IFN-␣ and HU therapy for 13 months, when she was referred to our hospital in accelerated phase. In October 1997 following thiotepa, CY and anti-thymocyte globulin conditioning, she underwent an allogeneic BMT from her 1-Ag mismatched brother. She became Ph1 negative with full chimerism and normal hematological parameters; acute graft-versus-host disease (GVHD) grade 3 of the skin and chronic GVHD of the liver occurred. At 11 months follow-up she is in good clinical condition and with a Karnofsky score of 90%. The role of a graft-versus-leukemia (GVL) effect in securing and maintaining the complete remission is discussed. Keywords: chronic myeloid leukemia; graft-versusleukemia Allogeneic bone marrow transplantation (BMT) is the only curative treatment for chronic myeloid leukemia (CML), 1 even though the leukemic clone may not always be eradicated by the preparative regimen. Therefore, an alloreactive T cell-mediated GVL effect is considered important in controlling the leukemic clone, thus preventing relapse. 2,3 A GVL effect was initially postulated on the basis of the lower rate of leukemia relapse in patients with GVHD. 4 Well-identified risk factors for relapse of CML following transplant include the use of T cell-depleted or syngeneic

Flagellin, a TLR5 Agonist, Reduces Graft-versus-Host Disease in Allogeneic Hematopoietic Stem Cell Transplantation Recipients While Enhancing Antiviral Immunity

“…Using an established murine CMV model, which has similarities to the pathogenicity of human CMV infection (67, 68), we observed that flagellin-treated recipients successfully recovered from sub-lethal dose of mCMV infection with faster viral clearance and higher anti-viral cellular immunity compared with PBS-treated control recipients. In addition to opportunistic infections, disease relapse is another major clinical problem in allogeneic HSCT (69) and it possible that full donor chimerism with improved immune reconstitution (Figure 2 and Table 1) will protect recipients from disease relapse. Although, we did not test the antitumor activity of flagellin in allogeneic HSCT recipients in the current study, we are currently testing whether flagellin may also enhance the antitumor immunity of donor T cells.…”