Clofarabine-Based Chemotherapy for Relapsed/Refractory Adult Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma. the Spanish Experience

Patients with relapsed/refractory acute lymphoblastic leukemia (ALL) have a very poor outcome with limited therapeutic options available. Clofarabine (Clo) is a second generation purine nucleoside analogue increasingly used in these patients, mainly in the pediatric setting.

To evaluate the toxicity profile and outcome of Clo-based chemotherapy regimens used in adult ALL in the Spanish PETHEMA centers.

Sixteen of the 22 PETHEMA centers to have used Clo in adult patients (≥16 years) with a definitive diagnosis of ALL (n=25) or lymphoblastic lymphoma (LL) (n=5) participated in the study. Patient-, disease-, toxicity- and outcome-related data were retrospectively collected and analyzed.

Thirty patients received Clo-based regimens from January 2007 to May 2011. Median age at diagnosis was 33 years (range 16–73). B- and T- lineage diseases were found in 20 (67%) and 10 (33%) patients, respectively. Median number of treatment regimens before Clo was 3 (range 1–7) and median time of follow-up for survivors was 5 months (range 2–25). Clo-based combinations included Clo-cyclofosfamide (Cy) (n=11, 36%), Clo-Cy-etoposide (n=8, 27%) Clo-cytarabine (n=6, 20%) and Clo monotherapy (n=5, 17%) for a median of 1 (range 1–3) cycle. Clo total dose/cycle in most patients was 200mg/m². Hematological and infectious grade III-IV toxicities were found in 30 (100%) and 20 (67%) patients, while hepatic, gastrointestinal and renal grade III-IV toxicities were less common (17%, 17% and 0%, respectively). Eight (27%) and 2 (7%) patients achieved CR (complete remission) and CRi, respectively (overall CR rate 33%), while 7 patients died before disease evaluation. CRs were observed in B- (n=8, 40%) and T- (n=2, 20%) lineage diseases and in patients with normal and adverse cytogenetics (including the only Ph+ case). Younger patients (median age 25 years vs 36 years, p=0.1) and those who received a previous allogeneic hematopoietic cell transplantation (allo-HCT) (67% vs 29%, p=0.1) showed a non-significant trend for a higher overall CR achievement. Six (20%) patients (5 in CR) underwent allo-HCT after Clo-based treatment. Five (17%) patients were alive at 5 months of Clo treatment for an overall survival probability of 10% (95%CI 4–16). The most frequent death causes were disease progression (n= 16, 64%) and infections (n= 3, 12%).

Despite their toxicity, Clo-based chemotherapy regimens may allow CR achievement in heavily pretreated relapsed/refractory ALL and LL patients.

Barba:Genzyme: Consultancy.