title: Risk factors in bone marrow transplant recipients with leukaemia. Increased relapse risk in patients treated with ciprofloxacin for gut decontamination.
abstract: Three hundred and six patients with low- and intermediate-risk leukaemias undergoing allogeneic BMT between 1980 and March 1996 were studied regarding transplantation-related mortality (TRM), relapse, and leukaemia-free survival (LFS). Among the patients were 262 recipients of marrow from HLA-identical siblings and 44 patients receiving marrow from HLA-A, -B, and -DR identical unrelated donors. Between 1986 and 1993, 153 adult patients received ciprofloxacin continuously during Cy conditioning, but since November 1993 ciprofloxacin has not been given until after Cy treatment. TRM at 5 yr showed an incidence of 30%. Significant risk factors in Cox regression multivariate analysis comprised acute GVHD grades II-IV (p < 0.0001), seropositivity for 3-4 herpes viruses prior to BMT (p = 0.002), intermediate risk disease (p = 0.008), female donor to male recipient (p = 0.015), and a donor age over 17 yr (p = 0.025). The risk of relapse was studied from 90 d after BMT, and the overall 5-yr incidence was 32%. Significant risk factors comprised acute leukaemia, as compared to CML (p = 0.003), total body irradiation (TBI) compared to busulphan treatment (p = 0.011), gram-negative prophylaxis with ciprofloxacin during cyclophosphamide (Cy) conditioning (p = 0.024), GVHD prophylaxis using a combination of methotrexate (MTX) and cyclosporine (CSA), compared to monotherapy (p = 0.037) and absence of chronic GVHD (p = 0.050). The 5-yr probability of relapse in patients receiving ciprofloxacin prophylaxis during Cy conditioning was 40%, compared to 24% in patients not receiving this treatment (p = 0.01). Overall, LFS at 5 yr was 49%. LFS was evaluated from day 30 after BMT until relapse or death of the patient. We found no difference in TRM, relapse or LFS between recipients of HLA-identical sibling or unrelated bone marrow, risk factors significantly associated with an inferior LFS included acute GVHD grades II-IV (p = 0.0002), intermediate risk disease (p = 0.003), donor seropositivity for 3-4 herpes viruses (p = 0.046), and TBI conditioning (p = 0.048).
authors.affiliation: Department of Transplantation Surgery, Huddinge University Hospital, Karolinska Institute, Sweden.
authors.forename: S
authors.initials: S
authors.lastname: Carlens
authors.forename: O
authors.initials: O
authors.lastname: Ringdén
authors.forename: J
authors.initials: J
authors.lastname: Aschan
authors.forename: H
authors.initials: H
authors.lastname: Hägglund
authors.forename: P
authors.initials: P
authors.lastname: Ljungman
authors.forename: J
authors.initials: J
authors.lastname: Mattsson
authors.forename: M
authors.initials: M
authors.lastname: Remberger
mesh_terms: D000328:Adult; D000890:Anti-Infective Agents / Q000627:therapeutic use*; D016026:Bone Marrow Transplantation; D002939:Ciprofloxacin / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology; D006566:Herpesviridae Infections / Q000453:epidemiology; D006648:Histocompatibility; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000401:mortality / Q000628:therapy*; D015470:Leukemia, Myeloid, Acute / Q000401:mortality / Q000628:therapy*; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000401:mortality / Q000628:therapy*; D016016:Proportional Hazards Models; D012008:Recurrence; D012189:Retrospective Studies; D012307:Risk Factors; D019172:Transplantation Conditioning / Q000379:methods
chemical_list: D000890:Anti-Infective Agents; D007166:Immunosuppressive Agents; D002939:Ciprofloxacin; D003520:Cyclophosphamide