Relapse of aplastic anaemia after immunosuppressive treatment: a report from the European Bone Marrow Transplantation Group SAA Working Party

Abstract

This study was designed to determine the incidence of relapse and factors predictive for relapse in 719 patients with severe aplastic anaemia (SAA) after immunosuppressive treatment (IS). Patients developing myelodysplasia or acute leukaemia after IS, and patients receiving a transplant, were excluded from this analysis. Response was defined as reaching complete independence from transfusions, relapse was defined as becoming again transfusion dependent. This criteria was validated by similar figures when using other 'relapse criteria' such as drop in neutrophil or platelet counts. Of 358 patients responding to IS. 74 patients relapsed after a mean time of 778 d after treatment. The actuarial incidence of relapse is 35.2% at 14 years after IS. The risk for relapse was higher in patients responding within 120 d from IS (48%) compared to patients responding between 120 and 360 d (40%) and only 20% for slow responders (> 360 d from IS) (P < 0.00001). In multivariate analysis this factor still proved significant (P < 0.0001). The mean time between diagnosis and treatment was significantly longer in patients relapsing compared to patients who did not relapse (260 v 134 d, P = 0.037). Relapse was not predicted by the severity of the disease, age, and sex. In 39 of the 74 relapsing patients a second response could be achieved. Responses after relapse were associated in univariate analysis with early response to previous IS and early occurrence of relapse. The actuarial survival of patients not relapsing is significantly better than survival of patients relapsing (79.8% v 67.1%, P = 0.0024). However, the actuarial survival of 39 relapsing patients who responded again to IS was similar to patients not relapsing (86%) and significantly better than in 35 patients not reaching a second response after relapse (49.3%, P = 0.0015). This study indicates that relapse is a relevant problem in the treatment of aplastic anaemia, and does have an impact on overall survival. Prospective studies of immunosuppressive regimens, looking at responses, should also address this problem in the future.

Treatment of severe aplastic anemia with antithymocyte globulin and cyclosporin A with or without G-CSF in adults: a multicenter randomized study in Japan

“…14 A European group reported that the actuarial risk for relapse after IST was 35% at 10 years, and the relapse occurred at any time from a few months to 10 years after IST without a particular period of higher occurrence. 23 Because the median follow-up period of our study was not so long, the possibility that G-CSF only delays the time of relapse cannot be excluded. To elucidate whether G-CSF actually prevents relapse or only delays the time of relapse, further follow-up is required…”

“…14,15 It has been reported that the overall survival in patients who do not relapse is better than that of patients who relapse. 23 Therefore, better survival in the G-CSFϩ group will be expected because of the low incidence of relapse in the G-CSFϩ group. Further follow-up is necessary to conclude whether a difference in overall survival exists between the G-CSFϩ and the G-CSFϪ group.…”

Quality-adjusted survival analysis shows differences in outcome after immunosuppression or bone marrow transplantation in aplastic anemia

“…Therefore, one might want to take additional endpoints such as eventfree survival, the ability to tolerate treatment, and quality of life during different sequences of relevant health states into account in the decision making process, when different treatment options result in similar long-term survival. In aplastic anemia, quality of life outcomes are affected by treatment toxicity, graft rejection, infections, and graft-versus-host disease (GvHD) after BMT [13][14][15], and by persisting cytopenia due to slow or incomplete responses, relapse of aplastic anemia, or the development of clonal disorders such as myelodysplastic syndrome (MDS) or paroxysmal nocturnal hemoglobinuria (PNH) after immunosuppression [16][17][18].…”

Aplastic anaemia in childhood. Description of two cases and review of the literature

“…Overall survival at 5 years is estimated at about 80%, but the eventfree survival rate is lower as a result of non response or relapse. Relapse, defined as requirement for platelet or erythrocyte transfusions in patients having been transfusion-independent for at least 3 months, occurs in about 30% of patients [27]. In addition, these patients have an increased risk of developing solid tumors and clonal disorders such as myelodysplastic syndromes (most frequently involving chromosomes 7 or 8), acute myeloid leukaemia and paroxysmal nocturnal hemoglobinuria [28].…”