Experience of a Brazilian Institution with Adult Acute Lymphoblastic Leukemia: Clinical, Laboratory and Prognosis in 102 Patients.

Abstract

ALL is an aggressive bone marrow neoplasm, mainly associated with a poor outcome in adult patients. The aim of this study is to describe clinical, laboratory and prognostic factors in 102 patients treated in one institutional department from 1990 to 2005, retrospectively. Adult ALL subtype L3 (FAB) or B-IV (EGIL) was excluded. Statistical analysis was done by SPSS 10.0.The association of features and prognosis was assessed by Pearson’s chi-square. OS and DFS curves were constructed by Kaplan-Meier method and the differences were analyzed by the log-rank test. Mean age was 30,6 (12 to 82) years and 55,9% was male. Clinical findings, at diagnosis, were fatigue (55,9%), splenomegaly (56,9%), hepatomegaly (54,6%), lymphadenopathy (52,6%), fever (38,8%), bone pain (28,6%), bleeding (27,5%) and headache (15,3%). Involvement of CNS was detected in 11(10,8%) patients and testicular involvement was observed in one patient. Cutaneous infiltration occurred in one patient immunophenotyping T-IV(group b). Kidney and pulmonary infiltration, documented by biopsy, was found in 2 and 1 patients respectively. At diagnosis; mean blood values were 8,5g/dl, 84.341/mm3 and 76.275/mm3 for hemoglobin, leukocytes and platelets respectively. 98,7% of the patients presented with lymphoblasts in peripheral blood. FAB classification was L1 and L2, 50% each. B and T-ALL was observed in 69,7% and 30,2% respectively. One case was identified as biphenotypic B and T leukemia. Karyotype analysis was performed in 40 cases, Ph chromosome was identified in 20% (8/40) of the cases. Others abnormalities were hyperdiploid karyotype (6/40); t(4;11) in 2 cases; t (1;19) and t(10;11) each one with 1 case. Patients were treated with different protocols: BFM 86 modified (BFM 86M) in 47,1% (48/102) of the patients, OPAL86 and OPAL87 protocols (Linker e cols) in 45,1% (46/102) and CHOP in 7,8% (8/102). Ten patients died in early induction phase and 70,6% (65/92) were in complete remission after induction treatment. Age less than 35 years (p=0.021), CNS not infiltrated (p= 0.022) and immunophenotyping B1 and B3 (p=0.018) were associated with a better induction response in a univariated analysis. The first two parameters were associated with a high probability of complete response (p=0.041 and 0.034, respectively) in a multivariate analysis. In a median follow up of 49 months, we have observed a four-years OS of 30,4% (median 19 months). Univariate analysis of OS showed that age less than 35 and mainly less than 18 years (p=0.01), absent bleeding and hepatomegaly at diagnosis (p=0.0022; p=0.029), early time to complete remission (p=0.0001) and treatment protocol BFM 86M (p=0.0034) were associated with better survival. In a multivariate analysis age >35y, presence of hepatomegaly or bleeding at diagnosis were associated with poor OS, and were used to created a prognosis score. Patients with none to one adverse factor have a significantly better survival than patients with more than one (p=0.0001). We have observed in our population a DFS of 27% in 4 years with a median DFS of 18,9 months. Only fever, at diagnosis, was an adverse factor related to DFS in univariate analysis (p=0.0057).