Patient cytomegalovirus seropositivity with or without reactivation is the most important prognostic factor for survival and treatment‐related mortality in stem cell transplantation from unrelated donors using pretransplant in vivo T‐cell depletion with anti‐thymocyte globulin

• Published in: British journal of haematology 2001-06, Vol.113 (4), p.1060-1071
• Main Authors: Kröger, Nicolaus, Zabelina, Tatjana, Krüger, William, Renges, Helmut, Stute, Norbert, Schrum, Johanna, Kabisch, Hartmut, Schafhausen, Philippe, Jaburg, Nicole, Löliger, Cornelius, Schäfer, Peter, Hinke, Axel, Zander, Axel R.
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Adult; Antilymphocyte Serum - administration & dosage; anti‐thymocyte globulin; Child; Child, Preschool; Cytomegalovirus; Cytomegalovirus Infections - complications; Female; Hematopoietic Stem Cell Transplantation - mortality; Humans; Infant; Leukemia - therapy; Leukemia - virology; Leukemia, Myeloid - therapy; Leukemia, Myeloid - virology; Leukemia, Myeloid, Accelerated Phase - therapy; Leukemia, Myeloid, Accelerated Phase - virology; Leukemia, Myeloid, Chronic-Phase - therapy; Leukemia, Myeloid, Chronic-Phase - virology; Leukemia, Myelomonocytic, Acute - therapy; Leukemia, Myelomonocytic, Acute - virology; Lymphoma - therapy; Lymphoma - virology; Male; Middle Aged; Multiple Myeloma - therapy; Multiple Myeloma - virology; Multivariate Analysis; Myelodysplastic Syndromes - therapy; Myelodysplastic Syndromes - virology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - therapy; Precursor Cell Lymphoblastic Leukemia-Lymphoma - virology; Risk Factors; Survival Rate; Transplantation Conditioning - methods; Transplantation, Homologous; unrelated bone marrow transplantation
• ISSN: 0007-1048; 1365-2141
• DOI: 10.1046/j.1365-2141.2001.02849.x

We evaluated the cytomegalovirus (CMV) serostatus as a risk factor for survival and treatment‐related mortality (TRM) in 125 patients allografted from an unrelated donor between 1994 and 1999. All patients received pretransplant in vivo T‐cell depletion using rabbit anti‐thymocyte globulin (ATG). Only one patient had primary graft failure and severe grade III/IV graft‐versus‐host disease occurred in 14% of the patients. The overall survival (OS) at 3 years was 70% for CMV‐negative patients (n = 76) and 29% in the seropositive cohort (n = 49) (P > 0·001). In multivariate analyses, CMV seropositivity remained an independent negative prognostic factor for OS (RR: 2·1; CI: 1·2–3·8; P = 0·014), apart from age > 20 years (RR: 2·74; CI: 1·2–3·8; P = 0·004) and late leucocyte engraftment (RR: 2·4; CI: 1·2–4·9; P = 0·015). The TRM for all patients was 27%. Despite monitoring for CMV antigenaemia and preemptive therapy with ganciclovir when reactivation occurred, seropositive patients had a three times higher risk of fatal treatment‐related complications than seronegative patients. In multivariate analyses, CMV seropositivity remained the strongest independent negative factor for TRM (RR: 5·3; CI: 1·9–14·6; P = 0·002), followed by age > 20 years (RR: 4·8; CI: 1·3–18·1; P = 0·02) and delayed leucocyte engraftment (RR: 3·6; CI: 1·2–11; P = 0·02). The TRM was identical in seropositive patients with (n = 27) or without (n = 22) CMV reactivation (44% versus 50%). We conclude that CMV seropositivity, despite preemptive ganciclovir therapy and even without reactivation, is a major negative prognostic factor for survival as well as for TRM in unrelated stem cell transplantation using pretransplant in vivo T‐cell depletion with ATG.