Burkitt lymphoma (BL) and B-cell acute lymphoblastic leukemia (B-ALL) are very aggressive malignancies with poor prognosis unless treated with highly specific intensive programs. The German Multicenter Study Group for Adult ALL piloted a short intensive rituximab (R)-chemotherapy program that improved outcome compared to the prior regimen (Hoelzer et al, Blood 110:abstr 518, 2007). The Northern Italy Leukemia Group adopted the same protocol to treat 105 consecutive, unselected adult patients with BL and B-ALL.
To assess long-term outcome and toxicity according to pre-therapy risk factors predominantly identified by higher age and/or performance status (PS) according to the Eastern Cooperative Oncology Group score.
Between December 2002 and June 2010, 55 BL (stage III-IV 53%, bulky 45%, extranodal involvement 64%) and 50 B-ALL patients were treated. Median age was 47 years (range 17–78), 31% were >55 years, 15% had a PS >2, and 15% were HIV+. Treatment consisted of 6 R-chemotherapy courses (4 in stage I-II disease without mediastinal/extranodal involvement), two additional R doses at completion of chemotherapy and local radiotherapy in case of mediastinal/CNS disease or residual tumor. R-chemotherapy blocks were as follows: A) prednisone-cyclophosphamide prephase (course 1 only), R plus dexamethasone, vincristine, ifosphamide, HD-methotrexate, teniposide [or etoposide], Ara-C, intrathecal therapy [IT]; B) R plus dexamethasone, vincristine, cyclophosphamide, HD-methotrexate, adriamycin, IT; C) R plus dexamethasone, vindesine, HD-methotrexate, etoposide, HD-Ara-C. The A-C sequence was repeated once. Patients aged >55 years received only courses A and B with methotrexate 0.5 g/m2.
Eighty-three total patients (79%) achieved CR, 8 were refractory and 14 died of complications. All early deaths occurred in patients older than 40 years, correlated with stage III-IV BL or B-ALL (n=13), PS ≥1 (n=10), and were mainly caused by infections. Among CR patients, 67 (81%) received all planned therapy and 16 did not (toxicity/CR death 11, early relapse 3, other 2). The mean intercycle time (MIT) between chemotherapy courses was 29 days (range 22–52). After a median follow-up of 23.8 months (range 0.7–99), 65 patients (61%) were alive in 1st CR, 19 (18%) died of complications (7 in CR, including 2 late deaths due to secondary AML and cardiovascular accident), and 19 had refractory or recurrent disease. Ten of 67 patients treated with MIT >25 days relapsed within 6 months (15%), compared to one of 15 treated with MIT ≤25 days (7%, P=.34). Projected 3-year overall and disease-free survival and were 67% (OS) and 75% (DFS), respectively. In univariate analysis age, normal LDH, ECOG PS <2 and lack of CNS involvement were favorable prognostic factors, whereas MIT was of borderline significance. In multivariate analysis, age and PS were highly predictive for OS and DFS. In a cumulative analysis, patients aged >55 years with PS ≥1 had the worst outcome (n=24; OS 28% and DFS 36%), those with PS=0 fared as well as patients aged ≤55 years with PS=0–1 (n=55; OS 89% and DFS 89%) and the younger patients with PS >1 represented an intermediate-good risk category (n=26; OS 61% and DFS 77%) (P=.0000). The incidence of TRM and relapse varied significantly among the 3 groups, each contributing almost equally to the final outcome.
The excellent therapeutic potential of this treatment (89% cure rate) was confirmed in patients with PS=0, regardless of age, and in younger patients with PS=0–1, whereas the results were still good, though significantly inferior, with PS >1 (61% cure rate). Prompt diagnosis and referral of BL and B-ALL patients is essential for exploiting the prognostic advantage associated with a better PS, together with maximized anti-infectious measures and rapid re-cycling of chemo-immunotherapy blocks.
No relevant conflicts of interest to declare.
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