Summary:Among 551 consecutive recipients of allogeneic bone marrow transplants, 451 survived more than 3 months and were evaluated for chronic graft-versus-host disease (GVHD). Most of the donors were HLA-identical siblings or parents (n = 334). Patients with HLA-mismatched donors (n = 30) and matched unrelated donors (MUD) (n = 87) were also included in the study. In the analysis of all patients, the 5-year cumulative incidence of chronic GVHD was 45%. We analysed 34 risk factors. High recipient age was the single most important risk factor (P Ͻ 0.001). Other significant risk factors in multivariate analysis were: acute GVHD grades I-IV (P Ͻ 0.001), immune female donor to male recipient (P = 0.006) and chronic myelogenous leukaemia (CML), compared with all other diagnoses (P = 0.014). The cumulative 5-year incidence of chronic GVHD, with no significant risk factors present, was 9%, 29% with one risk factor, 53% with two, 68% with three and 75% with all four risk factors present. In patients with HLAidentical sibling donors and GVHD prophylaxis consisting of a combination of methotrexate (MTX) and cyclosporin A (CsA) (n = 208), increasing recipient age (P Ͻ 0.001) and CML (P = 0.007), were found to be significant risk factors for chronic GVHD. Finally, a multivariate analysis in recipients of bone marrow from unrelated donors (n = 89) showed recipient age alone (P = 0.006) to be significantly associated with chronic GVHD.
After myeloablative treatment and allogeneic stem cell transplantation (SCT), patients are kept in isolation rooms in the hospital to prevent neutropenic infections. During a 3-year period, patients were given the option of treatment at home after SCT. Daily visits by an experienced nurse and daily phone calls from a physician from the unit were included in the protocol. We compared 36 patients who wished to be treated at home with 18 patients who chose hospital care (control group 1). A matched control group of 36 patients treated in the hospital served as control group 2. All home care patients had hematologic malignancies and 19 were in first remission or first chronic phase. Of the donors, 25 were unrelated. The patients spent a median of 16 days at home (range, 0-26 days). Before discharge to the outpatient clinic after SCT, patients spent a median of 4 days (range, 0-39 days) in the hospital. In the multivariate analysis, the home care patients were discharged earlier (relative risk [RR] 0.33, P ؍ .03), had fewer days on total parenteral nutrition (RR 0.24, P < .01), less acute graft-versus-host disease (GVHD) grades II-IV (RR 0.25, P ؍ .01), lower transplantationrelated mortality rates (RR 0.22, P ؍ .04), and lower costs (RR 0.37, P < .05), compared with the controls treated in the hospital. The 2-year survival rates were 70% in the home care group versus 51% and 57% (not significant) in the 2 control groups, respectively (P < .03). To conclude, home care after SCT is a novel and safe approach. This study found it to be advantageous, compared with hospital care. (Blood. 2002;100: 4317-4324)
Summary:Three different types of anti-T cell antibody were used in patients undergoing haematopoietic stem cell transplantation (HSCT) with an HLA-A, -B and -DR compatible unrelated donor: ATG-Fresenius (ATG-F) (n = 26), Thymoglobuline (TMG) (n = 61) and OKT-3 (n = 45). The groups were comparable regarding diagnosis, stage, age, conditioning and GVHD prophylaxis, Adverse events were less frequent after ATG-F treatment. Levels of IL-2, IL-6, IFN-␥, TNF-␣ and GM-CSF were increased after OKT-3 infusion. In multivariate analysis OKT-3 treatment (P = 0.01), G-CSF treatment (P = 0.02) and a cell dose у2.7 ؋ 10 8 /kg (P = 0.03) gave a faster engraftment. Acute GVHD grades II-IV occurred in 25% of the ATG-F patients, 12% of the TMGpatients and 43% (P Ͻ 0.001 vs TMG) of the OKT-3 patients. OKT-3 was associated with acute GVHD in multivariate analysis. TRM was 26% using TMG as compared to 43% in the OKT-3 group (P = 0.03). Patient survival at 4 years was 63%, 50% and 45% in the ATG-F, TMG and OKT-3-treated patients, respectively (NS). Relapses were 8%, 49% and 34%, respectively (ATG-F vs TMG, P = 0.03). Relapse-free survivals were 61%, 40% and 37% (NS). Among CML patients the probability of relapse was 61% in TMG-treated patients, while no patients relapsed in the other two groups. To conclude, the type of anti-T cell antibody affects GVHD and relapse after HSCT using unrelated donors.
We analyzed the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) over the past 2 decades. Between 1992 and 2009, 953 patients were treated with HSCT, mainly for a hematologic malignancy. They were divided according to 4 different time periods of treatment: 1992 to 1995, 1996 to 2000, 2001 to 2005, and 2006 to 2009. Over the years, many factors have changed considerably regarding patient age, diagnosis, disease stage, type of donor, stem cell source, genomic HLA typing, cell dose, type of conditioning, treatment of infections, use of granulocyte-colony stimulating factor (G-CSF), use of mesenchymal stem cells, use of cytotoxic T cells, and home care. When we compared the last period (2006-2009) with earlier periods, we found slower neutrophil engraftment, a higher incidence of acute graft-versus-host disease (aGVHD) of grades II-IV, and less chronic GVHD (cGHVD). The incidence of relapse was unchanged over the 4 periods (22%-25%). Overall survival (OS) and transplant-related mortality (TRM) improved significantly in the more recent periods, with the best results during the last period (2006-2009) and a 100-day TRM of 5.5%. This improvement was also apparent in a multivariate analysis. When correcting for differences between the 4 groups, the hazard ratio for mortality in the last period was 0.59 (95% confidence interval [CI]: 0.44-0.79; P < .001) and for TRM it was 0.63 (CI: 0.43-0.92; P = .02). This study shows that the combined efforts to improve outcome after HSCT have been very effective. Even though we now treat older patients with more advanced disease and use more alternative HLA nonidentical donors, OS and TRM have improved. The problem of relapse still has to be remedied. Thus, several different developments together have resulted in significantly lower TRM and improved survival after HSCT over the last few years.
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