Prognostic factors for long-term survival in leukemic marrow recipients with special emphasis on age and prophylaxis for graft-versus-host disease.
Long-term survival of 182 leukemic patients after allogeneic bone marrow transplantation (BMT) was analyzed retrospectively regarding the type of graft-versus-host disease (GvHD) prophylaxis and patient age. Monotherapy with either methotrexate (MTX) (n = 59) or cyclosporin (CSA) (n = 40) was given to 79 patients less than 30 years of age and to 20 older patients. These patients were compared to those receiving a combination of MTX+CSA (n = 55) or T-cell depletion (TCD) (n = 28) (38 patients < or = 30 and 45 > 30 years of age). Patient characteristics were similar in the two pairs of groups. The median follow-up time was between 4.7 and 9.6 years in the different groups. In younger patients, the incidence of grade II-IV acute GvHD was 38% amongst those treated with MTX or CSA and 14% in the MTX+CSA/TCD group (p = 0.008). Forty percent of older patients on monotherapy developed grade II-IV acute GvHD compared to 26% of those over 30 treated with MTX+CSA/TCD (ns). As a consequence, mortality from GvHD among younger patients was 19% in the monotherapy group and 3% in the MTX+CSA/TCD group (p = 0.03) with 37% and 10% (p = 0.04) in the older patient groups. The cumulative incidence of chronic GvHD was similar amongst treatments in the younger patients (39% in monotherapy and 39% in MTX+CSA/TCD), but was significantly lower in the MTX+CSA/TCD group among patients > 30 (55% vs 25%, p = 0.05). The actuarial overall survival at 5 years was unchanged in patients < or = 30, 49% and 43% in the monotherapy and MTX+CSA/TCD groups, respectively. However, in older patients survival increased from 25% to 46% (p = 0.04). An increase in leukemic relapse associated with MTX+CSA/TCD among both younger (26% vs 48%, p = 0.05) and older patients (0% vs 46%, p = 0.05) influenced the relapse-free survival, 48% vs 39% (ns) in younger and 25% vs 37% (ns) in older patients. Risk-factors for survival were dependent on the type of GvHD prophylaxis used. Using monotherapy, in contrast to combination therapy or TCD, multivariate analysis showed that recipient age > 30 years and HLA disparity between donor and recipient were correlated with poor outcome. In patients receiving MTX + CSA or TCD, a female donor to a male recipient correlated significantly with poor survival, which was not the case with monotherapy. Disease status beyond 1st complete remission (1 CR) or 1st chronic phase (1 CP), grade II-IV acute GvHD and recipient CMV seropositivity were significant risk-factors among all patients regardless of the type of GvHD prophylaxis.
Aschan
J
J
Department of Clinical Immunology, Huddinge Hospital, Stockholm, Sweden.
Ringdén
O
O
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D016026:Bone Marrow Transplantation; D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000601:surgery*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000601:surgery; D015470:Leukemia, Myeloid, Acute / Q000601:surgery; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000601:surgery; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate
D016572:Cyclosporine; D008727:Methotrexate