Therapy-related acute lymphoblastic leukaemia with MLL rearrangements following DNA topoisomerase II inhibitors, an increasing problem: report on twonew cases and review of the literature since 1992

A highly increased risk of myelodysplasia (MDS) and acute myeloid leukaemia (AML) is well established in patients previously treated for other maligna ncies with alkylating agents or topoisomerase II inhibitors. More recently, single cases of acute lymphoblastic leukaemia (ALL), often presenting bala nced translocations involving chromosome band 11q23, have been observed. We present two such cases with t(4;11)(q21;q23), one of whom had previously r eceived only single-agent chemotherapy with 4-epi-doxorubicin. A review of the literature since 1992 including these two patients reveals a total of 2 3 cases of ALL or lymphoblastic lymphoma after chemotherapy presenting bala nced translocations to 11q23. All 23 patients had previously received at le ast one topoisomerase II inhibitor, and in two patients 4-epi-doxorubicin h ad been administered as single-agent chemotherapy for breast cancer. The la tency period to development of t-ALL was 24 months or less in 20 out of 22 cases. The MLL gene was found to be rearranged in 14 out of 14 cases, and i n three out of six cases the breakpoint was at the telomeric part of the ge ne, as observed in most cases of AT AML following therapy with topoisomeras e II inhibitors. These results indicate that patients with ALL and balanced translocations to chromosome band 11q23 following chemotherapy with topois omerase II inhibitors in the future should be included with cases of MDS or AML in calculations of risk of leukaemia.