TY - JOUR

T1 - Graft-versus-leukaemia activity associated with CMV-seropositive donor, post-transplant CMV infection, young donor age and chronic graft-versus-host disease in bone marrow allograft recipients

AU - Jacobsen, N.

AU - Badsberg, J. H.

AU - Lönnqvist, B.

AU - Ringdén, O.

AU - Volin, L.

AU - Rajantie, J.

AU - Nikoskelainen, J.

AU - Keiding, N.

AU - The Nordic Bone Marrow Transplantation Group

PY - 1990

Y1 - 1990

N2 - Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogeneic bone marrow transplantation for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma in first to fourth remission or during relapse. Multifactorial analysis was performed according to Cox with fixed pretransplant covariates and post-transplant cytomegalovirus (CMV) infection and graft-versus-host disease (GVHD) as time-dependent covariates. Advanced stage of leukaemia at the time of transplantation was an important risk factor for subsequent relapse. Furthermore, the study confirmed a graft-versus-leukaemia (GVL) activity associated with chronic GVHD, including de novo chronic GVHD (intensity factor 0.08, p = 0.004). In a model excluding chronic GVHD, female donor-to-male recipient (a risk factor for GVHD), was associated with decreased post-transplant relapse risk (intensity factor 0.3, p = 0.008), suggesting that an alloreaction against a minor transplantation antigen (Hy) may mediate antileukaemic activity. A decrease of the relapse risk by a factor 0.18 was observed in recipients with AML as well as ALL when the donor was CMV seropositive (p = 0.0002). This effect was restricted to patients who had laboratory evidence of post-transplant CMV infection. When CMV infection occurred and donor was seropositive the relapse risk was reduced by a factor 0.035. The effect was not mediated through an increased occurrence of grade 2-4 acute or chronic GVHD and could not be explained by a statistical bias due to censoring of patients who died in remission. Rather, donor CMV immunity was associated with GVHD independent GVL activity. Finally, this study demonstrated a 3.7-fold increased risk of relapse when the donor was more than 20 years of age.

AB - Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogeneic bone marrow transplantation for acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL) or lymphoblastic lymphoma in first to fourth remission or during relapse. Multifactorial analysis was performed according to Cox with fixed pretransplant covariates and post-transplant cytomegalovirus (CMV) infection and graft-versus-host disease (GVHD) as time-dependent covariates. Advanced stage of leukaemia at the time of transplantation was an important risk factor for subsequent relapse. Furthermore, the study confirmed a graft-versus-leukaemia (GVL) activity associated with chronic GVHD, including de novo chronic GVHD (intensity factor 0.08, p = 0.004). In a model excluding chronic GVHD, female donor-to-male recipient (a risk factor for GVHD), was associated with decreased post-transplant relapse risk (intensity factor 0.3, p = 0.008), suggesting that an alloreaction against a minor transplantation antigen (Hy) may mediate antileukaemic activity. A decrease of the relapse risk by a factor 0.18 was observed in recipients with AML as well as ALL when the donor was CMV seropositive (p = 0.0002). This effect was restricted to patients who had laboratory evidence of post-transplant CMV infection. When CMV infection occurred and donor was seropositive the relapse risk was reduced by a factor 0.035. The effect was not mediated through an increased occurrence of grade 2-4 acute or chronic GVHD and could not be explained by a statistical bias due to censoring of patients who died in remission. Rather, donor CMV immunity was associated with GVHD independent GVL activity. Finally, this study demonstrated a 3.7-fold increased risk of relapse when the donor was more than 20 years of age.

UR - http://www.scopus.com/inward/record.url?scp=0025188236&partnerID=8YFLogxK

M3 - Journal article

C2 - 2164434

AN - SCOPUS:0025188236

VL - 5

SP - 413

EP - 418

JO - Bone Marrow Transplantation

JF - Bone Marrow Transplantation

SN - 0268-3369

IS - 6

ER -