The enigma of testicular leukemia: a critical review

Isolated testicular relapse (T.R.) in acute lymphoblastic leukemia (ALL) has an overall incidence of 10% and affects mainly patients off therapy. Multivariate analysis of pretreatment characteristics has shown that lymphadenopathy and splenomegaly are independently associated with increased risk of T.R. during maintenance and off therapy, respectively. Sequential biopsy studies have demonstrated that testicular biopsies are unable to detect scanty infiltrates and have no practical utility. Prophylactic gonadal irradiation produced equivocal results and should not be used because of its sterilizing effect. Intensive multi-drug regimens or prolonged maintenance were unable to substantially reduce T.R. rate. On the contrary, intermediate-dose methotrexate (IDM) early in remission has almost abolished T.R. These findings strongly support the hypothesis that testicular interstitium is a very peculiar site where blasts are partially protected from the drug action; high drug concentrations are required for the optimal cytocidal effect. There are sufficient clues of a link between the excess of late marrow relapse in male sex and the capacity of testes of harboring blasts. Therefore IDM early in remission should be routinely adopted for prevention of testicular leukemia and its potential of late spread.