Therapy-Related PML-RARα Leukemia: An Emerging Disease. Report of 10 Cases From One Department of Hematology.

Therapy-related acute myeloid leukemia (t-AML) following chemotherapy is a distinct diagnostic entity in the WHO classification of hematopoietic malignacies. t-AML with monosomy 5 and 7 (or 5q-/7q-) usually occur late after exposure to alkylating agents, whereas those with balanced translocations, especially involving 11q 23 are associated with exposure to epipodophyllotoxin and shorter latency. The occurrence of acute promyelocytic leukaemia (APL) with PML-RARa rearrangement after treatment of a preceding malignancy is a rare event. APL constitutes 10 % of all AML but only 2.7% are t-APL.

We reported on a single-center experience about of 10 cases of t-APL; patients were observed between October of 1997 until Abril of 2007. There were 6 males and 4 females. Previous diseases were: 6 solid organ malignancies (3 breast cancer, 1 colon cancer, 1 prostate adenocarcinoma and 1 oral cancer), 3 hematologic malignancies (1 Hodgkin disease, 1 follicular lymphoma and 1 polycytemia vera), and 1 multiple sclerosis. Treatment: all of 6 solid tumors received radiotherapy, besides, 3 breast cancers were treated with topoisomerase II inhibitors and anthracyclines, the prostate adenocarcinoma got hormonal therapy and antimetabolite, two lymphomas and the oral cancer received alkylants agents, polycytemia vera was treated with phosphorus 32 and hydroxiurea, and multiple sclerosis with mitoxantrone. Mean age at diagnosis of first cancer was 52.2 years (range: 19-74) and 59.7 years (range: 34-80) at the second. The mean time between the treatment and diagnosis of t-APL was 69.6 months (range: 12-180) being longer in patients treated with alkylants agents (mean: 84 months). Morphologically, all patients presented with hypergranular or typical promyelocytic leukaemia; moreover, two showed Chèdiak granulation and only in one patient bundles of Auer rods (faggot cells) were not observed. By conventional cytogenetics, 3 out of 10 patients presented with complex karyotype: +4, ider(17)(q10) and del(3)(q23q26),t(9;22) (p24;q12),del(14)(q23q32). In all patients the presence of PML/RARa fusion gene was confirmed by RT-PCR. Patients were treated according to Spanish PHETEMA protocol. Regarding to the prognosis they were classified as: high- risk 2, intermediate-risk: 7 and low-risk: 1 (Sanz et al, Blood 2000; 96:1247). A complete remission (CR) was achieved in 8 patients that received treatment. Two patients died of bleeding at diagnosis. Only one patient had molecular relapse and received arsenic trioxide; currently he is in complete remission.

Therapy-related AML has poor prognosis because of the short duration of response. In contrast, several retrospective studies have described that responses to chemotherapy and prognosis of t-APL is similar to that of de novo APL. Last years, we have observed an increment of t-APL diagnosis, 6 out of 10 of our patients were diagnosed over period of 24 months.

Guerra-Moreno:Celgene: Research Funding.