Prognostic Factors

Determining prognostic factors in lymphoblastic disease has been difficult, partly because of the rarity of this disease, and the limited sample size in most published reports, and partly because of the variable criteria for distinguishing between LBL and lymphoblastic leukemia.

Retrospective studies of patients with LBL have identified adverse clinical prognostic factors for overall and disease-free survival.19-21 Few of these have been consistent across different series.

Coleman et al.8 identified favorable and unfavorable risk groups in a series of 44 patients treated at Stanford University on the basis of Ann Arbor stage IV, bone marrow or CNS involvement, and serum lactate dehydrogenase (LDH) level <300 IU/L (normal = 200 IU/L). Patients with these factors were considered poor risk, with a 5-year freedom from relapse of only 19%. Good-risk patients, who lacked these factors, had a 5-year freedom from relapse rate of 94%.

The applicability of the International Prognostic Index (IPI) for aggressive NHLs has also been investigated. A retrospective series of 62 patients from France concluded that the IPI did not have prognostic significance in adults with LBL.22 Similarly, a retrospective analysis of 26 patients with LBL was reported by the

Non-Hodgkin's Lymphoma Classification Project.23 The number of IPI risk factors was not predictive of overall or failure-free survival.

The utility of the IPI was also investigated in a European randomized trial in adult patients,7 representing the only prospectively collected data set in an unselected population. This study showed a statistically significant trend for lower overall survival with an increasing number of adverse factors according to the age-adjusted IPI (p = 0.016). However, although there was a clearly inferior survival in patients with three adverse factors, there was little distinction between those with zero, one, or two factors, and the value of the IPI as a prognostic model remains unclear.

Data regarding immunophenotypic and genetic risk factors in precursor lymphoblastic disease have been exclusively derived from patients with lymphoblastic leukemias. In adult patients with T-cell ALL, expression of T-cell antigens including CD1, CD2, CD4, and CD5 has been associated with a favorable prognosis. In the Cancer and Leukemia Group B 8364 study, overall and disease-free survival correlated with the number of T-cell antigens expressed. 24

Gene expression profiles have identified subtypes of precursor T-cell lymphoblastic disease characterizing different stages in thymocyte maturation, which may identify prognostic subgroups.18 Patients with HOX11 expression show a pattern of gene expression corresponding to the early cortical thymocyte. This group has a favorable clinical outcome. These cells are apparently developmentally arrested at a stage at which they are particularly sensitive to drug-induced apoptosis.

In contrast, those samples with gene expression profiles associated with TAL1 or LYL1 expression resemble late cortical and early pro-T thymocytes, respectively, and show more drug resistance and correspondingly higher levels of bcl-2.

For patients with B-cell disease, most studies have been reported from childhood B-cell ALL series. Translocations involving the MLL gene at 11q23 predict for unfavorable outcome, as does the t(9;22)(q34;q11.2). Hyperdiploid karyotype, trisomy 4, 10, and 17 are favorable risk factors.

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