Outcome of Second Allogeneic SCT Following Relapse of Hematological Malignancies After a First Allogeneic SCT

Disease relapse is the most frequent cause of treatment failure following allogeneic haematopoietic cell transplantation (allo-HCT), and carries a very poor prognosis. A second allo-HCT may be the only curative option for the majority of these patients. Patient and transplant factors that may associate with the outcome of a second allo-HCT are required for clinical-decision making in such high-risk patients.

We performed a retrospective analysis of patients receiving a second allo-HCT for disease relapse after a prior allo-HCT reported by GETH centres. Our aim is to analyze our experience in this setting, and to identify factors associated with patient outcome.

We present data on 189 patients who underwent a second allo-HCT for disease relapse in Spain up to December 2010 (median year 2004), with a median follow-up for survivors of 54 months (3–224): median age 35 years (range 4–69); 113 male (60%); initial diagnosis AML 77, ALL 45, MDS/MPD 28, CML 23, lymphoprolipherative disorder 12, and others 4. Seventy-five (40%) received myeloablative conditioning. Donors for second allo-HCT were related in 158 cases (84%), and in 33 cases (17%) were new donors different from the donors in the previous allo-HCT. Only 23 cases (12%) had T-cell depletion. Median time from the first to the second allo-HCT was 19 months (1–151). The cumulative incidence of non-relapse mortality was 37%. Median overall survival (OS) was 297 days, with an OS at 1, 3 and 5 years of 39%, 28% and 25%, respectively. Type of donor (related versus unrelated and new donor versus same donor) and type of conditioning (myeloablative versus non-myeloablative) had no association with patient outcome. However, OS was significantly poorer in patients who underwent second allo-HCT in active relapse or progression than in those with low disease burden (complete response, good partial response, or chronic phase; 29% vs 52% at 1 year, 21% vs 39% at 3 years, 17% vs 35% at 3 years, respectively; p=0.001). Also, patients with early relapse after the first allo-HCT who underwent a second allo-HCT <1 year after first HCT also had a poorer OS than those with a later relapse and second allo-HCT (13% vs 53% at 1 year, 7% vs 40% at 3 years, and 5% vs 35% at 5 years, respectively; p<0.001). The impact of these two clinical factors in the outcome remained independent in the multivariate analysis (disease status at second allo-HCT: HR 1.8, 95% CI 1.2–2.6, p=0.002; time to second allo-HCT: HR 3.2, 95% CI 2.2–4.6, p<0.001). Time to second allo-HCT and disease status also have an independent association with the probability of progression free survival in this series (p <0.001 and p =0.001, respectively). In fact, while patients with late relapse who received a second allo-HCT in good response had a very encouraging probability of OS of 49% at 5 years, patients who had an early relapse and required a second allo-HCT in less than 1 year from their first allo-HCT and also had active disease at the time of second allo-HCT had very poor OS of only 8% at 1 year and no one survived beyond 3 years after the second allo-HCT.

25% of patients who relapse after an allo-HCT can achieve long-term survival of 5 or more years following a second allo-HCT. Donor type does not appear to influence the outcome. On the contrary, our data suggest that disease status at HCT and time to relapse between first and second HCT are two significant prognostic factors with independent impact on patient outcome. The indication of a second allo-HCT in this context should be thoroughly discussed for individual cases, in particular for patients with early relapse and refractory disease arriving to second allo-HCT, for whom the probability of prolonged survival is extremely low.

No relevant conflicts of interest to declare.