LONG-TERM FOLLOW-UP OF MINIMAL RESIDUAL DISEASE IN LEUKEMIA PATIENTS BY MONITORING WT1 (WILMS-TUMOR GENE) EXPRESSION LEVELS

Thirty-one patients (27 with acute myeloid leukemia [AML], 2 with acut e lymphocytic leukemia [ALL], and 2 with acute mixed lineage leukemia [AMLL]) treated with conventional chemotherapy (CHT) and 23 patients ( 13 AML, 5 ALL, and 5 with chronic myeloid leukemia [CML]) treated with allogeneic bone marrow transplantation (BMT) were monitored or WT1 ex pression levels in BM and peripheral blood (PB) by reverse transcripta se-polymerase chain reaction over a long-term period (mean, 29 months for CHT and 24 months for BMT). Sixteen of the patients in the CHT gro up and 3 in the BMT group who had achieved complete remission Suffered clinical relapse. In 10 of these patients, WT1 expression that had re turned to normal BM levels (<10(-3); the WT1 expression level of K562 cells was defined as 1.0) after complete remission (CR) either gradual ly or rapidly increased again to abnormal levels 1 to 18 months (mean, 7 months) before clinical relapse became apparent. In another 9 patie nts, WT1 expression never returned to normal BM levels even after CR a nd the subsequent relapse was accompanied by a rapid increase in WT1 e xpression to levels higher than 10(-2) (10(-3) levels in PB). On the o ther hand, the remaining 35 patients (15 CHI and 20 BMI) maintained th eir CR. In 29 of these patients (11 CHT and 18 BMT), WT1 expression ei ther gradually or rapidly decreased to normal BM levels, whereas in th e other 6 (4 CHT and 2 BMT), low or very low levels of WT1 mRNAs (10(- 3) to 10(-2) in BM and 10(-5) to 10(-3) in PB) remain detectable, but without any clinical signs of relapse. A clear correlation was found t o exist between the minimal residual disease (MRD) detected in the pai red BM and PB samples for all types of leukemias (AML, ALL, and CML), with MRD in PB being approximately one-tenth of that in BM. WT1 quanti tation of 168 paired BM and PB samples showed that PB samples were sup erior to BM samples for the detection of MRD. We conclude that monitor ing of WT1 expression levels in BM and PB makes it possible to rapidly assess the effectiveness of individual treatment and diagnose clinica l relapse in the early stage for all leukemia patients regardless of t he presence or absence of tumor-specific DNA markers. (C) 1996 by The American Society of Hematology.