A therapy-related myelodysplastic syndrome with unusual features in a patient treated for acute promyelocytic leukemia.

MDS in patients treated for APL are rare events; we report a case that shows some traits that are unusual among therapyrelated stem cell disorders. A 51-year old woman presented in May 1997 with fatigue and dyspnea. Her peripheral blood cell count showed pancytopenia with 2% abnormal promyelocytes; coagulation tests showed signs of disseminated intravascular coagulation. Bone marrow revealed 50% hypergranular promyelocytes; cytogenetic analysis showed the classical translocation t(15;17) while molecular biology studies confirmed the presence of PML/RARα gene rearrangement type bcr3. A diagnosis of hypergranular APL was made. The patient was treated according to the Gimema AIDA protocol; she received induction therapy with ATRA 45 mg/m2/day plus idarubicin 12 mg/m2/day for 4 days, achieving complete remission after one month. Consolidation therapy consisted of three courses as follows: cytosine arabinoside (Ara-C) plus idarubicin; mitoxantrone plus etoposide; idarubicin plus Ara-C plus 6-thioguanine. In January 1998 the patient started maintenance therapy consisting of courses of methotrexate plus 6-mercaptopurine alternating with courses of ATRA. Therapy was stopped in July 1999 owing to the appearance of progressive pancytopenia. In September 1999 the bone marrow examination revealed hypocellularity with trilineage dysplasia; 4% of nucleated cells were blasts; Perls’ staining revealed the presence of 11% ring sideroblasts. No abnormal promyelocytes were seen. Karyotype was 46, XX, -5, add (6) (p2325), +8, add (17) (p13) in 10/10 metaphases. The molecular biology study showed that the PML-RARα gene rearrangement was absent. A diagnosis of MDS was made. In December 1999 the MDS evolved into M6 acute myeloid leukemia (AML) refractory to polychemotherapy, and the patient died four months later from infectious complications (Table 1). Seven cases of MDS and seven cases of AML in patients with a previous diagnosis of APL have been reported in the literature (Table 2):1-10 although several mechanisms have been hypothesized – coexistence of MDS/AML and APL with initial superimposition of APL, MDS/AML as a clonal evolution from the original APL – most of the authors agree in considering these cases as therapy-related secondary MDS and AML (t-MDS and t-AML). The case we report shows features that are unusual among therapy-related stem cell disorders. The patient developed a hematologic disease usually associated with previous treatment Table 1. Laboratory findings during disease evolution.