Abstract

Abstract 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 1.

Univariate analysis of factors influencing 6-month post relapse OS

CovariatesN (123)HR95% CIP value
Age at HSCT (years) 
    <=30 55 Ref.   
    >30 68 0.7 0.5–1.1 0.2 
Sex 
    Female 39 Ref.   
    Male 84 1.7 1.01–2.8 0.05 
Lineage 
    B-cell 85 Ref.   
    T-cell 28 0.6–1.7 0.99 
Cytogenetic 
    Ph- 71 Ref.   
    Ph+ 28 0.7 0.4–1.3 0.2 
Status at HSCT 
    CR1 20 Ref.   
    PIF/CR2/CR3 63 2.02 0.9–4.3 0.07 
    Active disease 40 3.1 1.4–6.7 0.005 
Preparative regimen 
    RIC 32 Ref.   
    HD 91 1.1 0.6–1.8 0.8 
Allotype 
    Matched unrelated 45 Ref.   
    Matched related 65 0.7 0.5–1.2 0.2 
    Cord blood 0.8 0.3–2.2 0.6 
    Haploidentical 1.6 0.6–4.2 0.3 
Time to relapse (months) 
    >6 42 Ref.   
    <=6 81 2.05 1.2–3.4 0.007 
Site of relapse 
    Systemic 99 Ref.   
    Isolated extramedullary 24 0.8 0.4–1.4 0.4 
First line salvage* 
    Cytoreductive chemotherapy 30 Ref.   
    Second SCT 19 0.2 0.1–0.6 0.003 
    Chemotherapy + DLI 11 0.5 0.2–1.3 0.1 
    Mild chemotherapy 27 0.99 0.5–1.9 0.9 
    Radiation therapy only 0.9 0.3–3.1 0.9 
Response to first salvage** 
    CR 47 Ref.   
    NR 39 2.9 1.6–5.4 0.001 
CovariatesN (123)HR95% CIP value
Age at HSCT (years) 
    <=30 55 Ref.   
    >30 68 0.7 0.5–1.1 0.2 
Sex 
    Female 39 Ref.   
    Male 84 1.7 1.01–2.8 0.05 
Lineage 
    B-cell 85 Ref.   
    T-cell 28 0.6–1.7 0.99 
Cytogenetic 
    Ph- 71 Ref.   
    Ph+ 28 0.7 0.4–1.3 0.2 
Status at HSCT 
    CR1 20 Ref.   
    PIF/CR2/CR3 63 2.02 0.9–4.3 0.07 
    Active disease 40 3.1 1.4–6.7 0.005 
Preparative regimen 
    RIC 32 Ref.   
    HD 91 1.1 0.6–1.8 0.8 
Allotype 
    Matched unrelated 45 Ref.   
    Matched related 65 0.7 0.5–1.2 0.2 
    Cord blood 0.8 0.3–2.2 0.6 
    Haploidentical 1.6 0.6–4.2 0.3 
Time to relapse (months) 
    >6 42 Ref.   
    <=6 81 2.05 1.2–3.4 0.007 
Site of relapse 
    Systemic 99 Ref.   
    Isolated extramedullary 24 0.8 0.4–1.4 0.4 
First line salvage* 
    Cytoreductive chemotherapy 30 Ref.   
    Second SCT 19 0.2 0.1–0.6 0.003 
    Chemotherapy + DLI 11 0.5 0.2–1.3 0.1 
    Mild chemotherapy 27 0.99 0.5–1.9 0.9 
    Radiation therapy only 0.9 0.3–3.1 0.9 
Response to first salvage** 
    CR 47 Ref.   
    NR 39 2.9 1.6–5.4 0.001 
*

Palliative group was excluded.

**

Palliative group and non-evaluable pts excluded.

CR indicates complete remission; PIF, primary induction failure; RIC, reduced intensity conditioning; HD, high dose conditioning; NR, no response.

Disclosures:

No relevant conflicts of interest to declare.

Author notes

*

Asterisk with author names denotes non-ASH members.