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ATG in myelofibrosis patients
Figure 1. Acute and chronic graft-versus-host disease. The top panels show the incidences of grade II-IV and grade III-IV acute chronic graft-versus-host disease (GvHD). The bottom panels show the incidences of chronic GvHD and chronic extensive GvHD.
29% in ATG patients. The 5-year overall survival (54.7% versus 52.8%), disease-free survival (49% versus 44.7%), and GRFS (29.3% versus 23.6%) rates were not significant- ly different between the two groups on univariate analysis (Table 2).
Effects of antithymocyte globulin
Due to disparities between the ATG and non-ATG groups, univariate analysis gave no clues on the effects of ATG. A multivariable model was generated to analyze the potential role of ATG on outcomes (Online Supplementary Table S1). Age was the strongest variable significantly associated with overall survival, disease-free survival and non-relapse mortality. Adjustments were made for age at transplantation, Lille score, Karnofsky Performance Status score, splenectomy before transplant, intensity of condi- tioning regimen (reduced intensity versus myeloablative) and source of stem cells (bone marrow versus peripheral blood). There was no effect of center on any outcome (Online Supplementary Table S2). Table 3 shows the effect of ATG for each outcome. The hazard ratio (HR) showed a benefit from ATG on overall survival (HR: 0.66, 95% CI: 0.43-1.00; P=0.05) and non-relpase mortality (HR: 0.64, 95% CI: 0.39-1.07; P=0.09). The incidence of grade II-IV acute GvHD was significantly lower following the use of
ATG (HR: 0.54, 95% CI: 0.34-0.86; P=0.01) but this was not the case for either grade III-IV acute GvHD or chronic extensive GvHD. In this model, ATG did not have a sig- nificant impact on disease-free survival, GRFS or relapse risk (see values in Table 3). Figure 2 shows the overall sur- vival, disease-free survival and GRFS taking into account variables of the adjusted model.
Discussion
While there is some evidence that in vivo ATG can pro- tect against the occurrence of acute and chronic GvHD, which may translate into a higher probability of GRFS in patients transplanted from an HLA matched related donor,19 there are no specific data from patients with myelofibrosis undergoing HSCT, because of the small numbers of such patients. In this retrospective study on behalf of the EBMT, we analyzed the impact of ATG in the largest documented cohort of patients with myelofi- brosis transplanted with an HLA-matched related donor. Approximately half of the patients received ATG which is higher percentage than that previously reported by the Center for International Blood and Marrow Transplant Research (CIBMTR), according to which only 11% of
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