Outcome after relapse of myelodysplastic syndrome and secondary acute myeloid leukemia following allogeneic stem cell transplantation: a retrospective registry analysis on 698 patients by the Chronic Malignancies Working Party of the European Society of Blood and Marrow Transplantation

Abstract

No standard exists for the treatment of myelodysplastic syndrome relapsing after allogeneic stem cell transplantation. We performed a retrospective registry analysis of outcomes and risk factors in 698 patients, treated with different strategies. The median overall survival from relapse was 4.7 months (95% confidence interval: 4.1-5.3) and the 2-year survival rate was 17.7% (95% confidence interval: 14.8-21.2%). Shorter remission after transplantation (P<0.001), advanced disease (P=0.001), older age (P=0.007), unrelated donor (P=0.008) and acute graft-versus-host disease before relapse (P<0.001) adversely influenced survival. At 6 months from relapse, patients had received no cellular treatment, (i.e. palliative chemotherapy or best supportive care, n=375), donor lymphocyte infusion (n=213), or a second transplant (n=110). Treatment groups were analyzed separately because of imbalanced characteristics and difficulties in retrospectively evaluating the reason for individual treatments. Of the patients who did not receive any cellular therapy, 109 were alive at 6 months after relapse, achieving a median overall survival from this landmark of 8.9 months (95% confidence interval: 5.1-12.6). Their 2-year survival rate was 29.7%. Recipients of donor lymphocytes achieved a median survival from first infusion of 6.0 months (95% confidence interval: 3.7-8.3) with a 2-year survival rate of 27.6%. Longer remission after first transplantation (P<0.001) and younger age (P=0.009) predicted better outcome. Among recipients of a second transplant, the median survival from second transplantation was 4.2 months (95% confidence interval: 2.5-5.9), and their 2-year survival rate was 17.0%. Longer remission after first transplantation (P<0.001), complete remission at second transplant (P=0.008), no prior chronic graft-versus-host disease (P<0.001) and change to a new donor (P=0.04) predicted better outcome. The data enabled identification of patients benefiting from donor lymphocyte infusion and second transplantation, and may serve as a baseline for prospective trials.

Figure 1.

Overall survival from relapse in 698 patients. Overall survival (OS) from relapse of the entire cohort (gray area denotes 95% confidence interval, CI, over time) The median overall survival was 4.7 months (95% CI: 4.1–5.3 months).

Figure 2.

Cumulative incidence of treatments applied during the first 6 months. The plots are stacked: the distance between two lines (and, for the uppermost curve, the distance from the curve to 100%) indicates the cumulative incidence as a function of time. At 6 months after relapse, the cumulative probability of having received a DLI (bottom group) was 31% (95% CI: 28–35%) and that of having undergone HCT2 (second group from the bottom) was 17% (95% CI: 14–19%). Thirty-five percent had died without having received DLI or HSCT2 (second group from top), whereas 18% (95% CI: 15–21%) of patients were still in the cellular treatment-free group (uppermost group).

Figure 3.

Overall survival after second transplant. (A) Within the entire cohort of 110 patients (gray area denotes 95% confidence interval, CI, over time; 2-year overall survival: 17.0, 95% CI: 10.7–27.1%). (B) As of remission duration after first transplantation, (>12 months, solid line, 2-year overall survival 36.6%, 95% CI: 21.9–61.0; 6–12 months, dashed line, 2-year overall survival 14.9%, 95% CI: 6.3–35.7; <6 months, dotted line, 2-year overall survival 5.9%, 95% CI: 15.7–22.3) P=0.002. (C) As of remission status at time of second transplant (complete remission, solid line, 2-year overall survival 59.3%, 95% CI: 32.2–100%; active disease, dotted line, 2-year OS 11.1%, 95% CI: 5.5–22.4%) P=0.022.

Figure 4.

Overall survival after first therapeutic donor lymphocyte infusion. (A) Within the entire cohort of 213 patients, 2-year overall survival was 27.6%, 95% confidence interval (CI): 21.1–34.1.0%. Grey area denotes 95% CI, over time (B) As of remission duration after HSCT1 (>12 months, solid line, 2-year overall survival 51.3%, 95% CI: 39.1–67.2%; 6–12 months, dashed line, 2-year overall survival 30.8%, 95% CI: 20.2–46.8%; <6 months, dotted line, 2-year overall survival 11.0%, 95% CI: 5.9–20.4%) P<0.001.