A Long-Term Study on Indolent Adult T-Cell Leukemia/Lymphoma (ATLL).

Background: Previous report on the subclassification and the clinical course of ATLL with maximum follow-up duration of 7 years revealed that the prognosis of indolent (smouldering or chronic) type was much better than that of aggressive (lymphoma or acute) types. (Shimoyama M, et al. Brit J Haematol, 1991). The median survival time (MST) was 6.2, 10.2 and 24.3 months for acute, lymphoma and chronic types, respectively. A MST has not been established for the smouldering type. However, long-term prognosis of the indolent types has not been elucidated.

Method: The diagnosis of ATLL was made based on seropositivity for HTLV-1 and histologically- and/or cytogically-proven peripheral T-cell malignancy. Subclassification of ATLL was based on the Shimoyama’s criteria. A total of 90 patients with indolent ATLL (65 chronic type and 25 smouldering type) with a median age of 61 years, newly diagnosed from 1974 to 2003 at Nagasaki University, were analyzed for the clinical course and prognostic factors.

Results: MST for the patients was 4.5 years with 12 patients alive for more than 10 years. Projected 5-, 10- and 15-yr survival rates were 47%, 23% and 13%, respectively, with first steep slope and sequential slow slope without plateau phase of the survival curve. Sixty-three of the patients died; 46 died of ATLL, 11 of other disease, 2 of transplantation related death and 4 of unknown. Unfavorable prognostic factor for survival included advanced performance status (PS) (p=0.005), high LDH value (p=0.004), more than 4 total involved lesions (p=0.03), more than 3 extranodal lesions (p=0.004), the presence of neutrophilia (p=0.02) by univariate analyses. In multivariate analysis, advanced PS was significant. There was no significant survival-difference in relation to age, subtypes of ATLL or lymphocyte count. Thirty-five patients with complications at diagnosis tended to be poor prognostic, especially those with active multiple cancers (n=7) or opportunistic infections (n=9). Most patients were treated as a subtype of chronic lymphoid leukemia (CLL) with watchful waiting until disease progression to acute ATLL. Twelve patients, who were treated with chemotherapy immediately after diagnosis of indolent ATLL, showed poorer prognosis as compared to the others. Five patients with at least one of the following 4 factors: alteration in tumor suppressor genes, p14ARF, p16 INK4a or p53, or aneuploidy >1 chromosomal locus by Comparative Genomic Hybridization analysis in ATLL cells, showed extremely poor prognosis.

Conclusions: The long-term prognosis of indolent ATLL was not good without plateau phase in the survival curve, similar to the findings in B-CLL. Advanced PS and genetic alterations in ATLL cells were poor prognostic factors.