Outcomes of Adults with Acute Lymphoblastic Leukemia (ALL) Following Relapse After First Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Abstract

AbstractAbstract 4215 Background:Outcomes of SCT in adult ALL have improved over the past decade. However, for patients (pts) who relapse after SCT, the prognosis is poor and treatment options are limited; the clinical course and prognostic factors affecting these pts are not well characterized. Methods:We retrospectively analyzed the outcomes of relapsed adult ALL pts who underwent first SCT between 1993–2011. The objectives of the study were to assess outcome after salvage therapy in these pts and to investigate the prognostic factors affecting outcome. Out of 365 ALL pts who underwent first SCT, 123 pts relapsed and received further treatment. Outcome was assessed since the date of relapse until death or last follow-up. Results:The median time to relapse was 4.4 months (mo.) (0.4–38.5 mo.) from first SCT. With a median follow up of 11 mo. (0.1 mo. -9 years) from time of relapse, the actuarial OS at 6 mo. was 35% (27–44%). First salvage treatments and median OS after relapse were: second SCT (n=19, OS 10 mo.) or donor lymphocyte infusion (DLI) (n=11, OS 6.5 mo.) with or without prior chemotherapy, radiation therapy for extramedullary only relapse (n=6, OS 3 mo.), cytoreductive chemotherapy (n=30, OS 4 mo.), mild chemotherapy (n=27, OS 4 mo.) and palliative care (n=23, OS 1 mo.). Mild chemotherapy was defined as combinations of steroids and vincristine, single cytotoxic agents such as clofarabine or nelarabine, tyrosine kinase inhibitors, hypomethylating agents, or monoclonal antibody therapies. Seven pts were lost to follow-up. Following the first salvage treatment, 47 pts (38%) went into complete remission (CR). The CR rate was higher in the HSCT, radiotherapy and DLI groups (84%, 83% and 64% respectively) compared with the mild chemotherapy (41%) and cytoreductive chemotherapy (27%) groups.In a univariate analysis for survival (Table 1), adverse factors included active disease at time of first SCT and short time to relapse from first SCT (<6 mo.). In pts who were not in active disease at SCT (n=83), the EBMT prognostic score (Spyridonidis et al, Leukemia 2012) was found to be highly prognostic of OS. Patients with 2/3 adverse factors (first SCT at CR2/3, relapse in <6.9 mo. and peripheral blast >10% at relapse) had significantly worse 6-mo. OS compared to pts with 0/1 adverse factor (p=0.009). Presence of isolated extra-medullary relapse was not associated with improved OS compared to pts with systemic relapse.Second SCT was found to be correlated with improved outcome compared with cytoreductive chemotherapy (p=0.003). Among the pts who received treatment and were evaluable for response (n=86), achievement of CR after first salvage was the most significant predictor of survival (p=0.001). In bivariate analysis, this benefit was shown to be independent of performing second SCT. Conclusion:Prognosis of ALL pts who relapse following SCT remains poor. However, second SCT may allow long term survival in a small subset of pts. Longer time to progression after first SCT and successful induction of CR following first salvage treatment are associated with improved survival post relapse. We corroborated the EBMT prognostic score for pts experiencing relapse after HSCT.Table 1Univariate analysis of factors influencing 6-month post relapse OSCovariatesN (123)HR95% CIP valueAge at HSCT (years)<=3055Ref.>30680.70.5–1.10.2SexFemale39Ref.Male841.71.01–2.80.05LineageB-cell85Ref.T-cell2810.6–1.70.99CytogeneticPh-71Ref.Ph+280.70.4–1.30.2Status at HSCTCR120Ref.PIF/CR2/CR3632.020.9–4.30.07Active disease403.11.4–6.70.005Preparative regimenRIC32Ref.HD911.10.6–1.80.8AllotypeMatched unrelated45Ref.Matched related650.70.5–1.20.2Cord blood70.80.3–2.20.6Haploidentical61.60.6–4.20.3Time to relapse (months)>642Ref.<=6812.051.2–3.40.007Site of relapseSystemic99Ref.Isolated extramedullary240.80.4–1.40.4First line salvage*Cytoreductive chemotherapy30Ref.Second SCT190.20.1–0.60.003Chemotherapy + DLI110.50.2–1.30.1Mild chemotherapy270.990.5–1.90.9Radiation therapy only60.90.3–3.10.9Response to first salvage**CR47Ref.NR392.91.6–5.40.001CR indicates complete remission; PIF, primary induction failure; RIC, reduced intensity conditioning; HD, high dose conditioning; NR, no response.*Palliative group was excluded.**Palliative group and non-evaluable pts excluded. Disclosures:No relevant conflicts of interest to declare.