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. The Nordic Bone Marrow Transplantation Group.
Risk factors for post-transplant relapse were analysed retrospectively in 163 patients treated with allogenic 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 (GVHD) as time-dependent covariates. Advanced stage of leukemia 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 allo-reaction 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Jacobsen
N
N
Department of Infectious Diseases, Rigshospitalet, Denmark.
Badsberg
J H
JH
Lönnqvist
B
B
Ringdén
O
O
Volin
L
L
Rajantie
J
J
Nikoskelainen
J
J
Keiding
N
N
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D003587:Cytomegalovirus / Q000145:classification; D003586:Cytomegalovirus Infections / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D006086:Graft vs Host Disease / Q000150:complications* / Q000453:epidemiology / Q000401:mortality; D006801:Humans; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D012008:Recurrence; D012307:Risk Factors; D012703:Serotyping; D013223:Statistics as Topic; D014184:Transplantation, Homologous / Q000009:adverse effects