A case of chronic chronic lymphocytic leukemia developing chronic myeloid leukemia with high platelets and followed by acute myeloid leukemia

Chronic lymphocytic leukemia (CLL) is the most common leukemia in Western Countries, with an incidence of 4.2/100.000/year. During the disease course there is a greater incidence of secondary malignancies compared to general population, possibly related to the known CLLassociated immunodeficiency and/or its therapy. Chronic myeloid leukemia (CML), concomitant, preceding or following CLL, is an extremely rare event (25 cases reviewed by the GIMEMA), with a different clonal origin of these neoplasms demonstrated in most cases. We describe a patient with CLL, who developed two different hematologic malignancies, namely CML and AML. A 69 year-old woman was diagnosed with CLL in 2004 at our Institution (67% CD20+CD5+CD23+ peripheral lymphocytes, 78% lymphocytes at marrow aspirate, 45% CLL interstitial and nodular infiltrate at marrow biopsy). Karyotype was normal in 24/31 metaphases and non-clonal chromosome abnormalities (not further identified) in 7/31. FISH analysis was negative for typical CLL abnormalities. CD38 and Zap-70 were positive and VHIg status unmutated. The patient was classified in stageA/0 Binet/Rai, intermediate risk. For the appearance of constitutional symptoms, splenomegaly and progressive lymphocytosis (LDT=9 months) she was treated from Nov 2005 to Sept 2009 with chlorambucil (overall dose 1060 mg) and then she underwent 4 FCR cycles, obtaining disease remission. On may 2012 an abrupt increase of platelets (1,365,000/mL) and basophils (1,009/mL) was observed. Bone marrow aspiration and biopsy displayed increased cellularity (90-95%), with granulocytes series hyperplasia and prevalence of intermediate and mature forms and eosinophilia. Megakaryocytes were increased, small and with hypolobated nuclei. Karyotype showed t(9:22)(q34;q11) [19/22]. RT-PCR was positive for BCR-ABL p210 b3a2. A diagnosis of CML Ph+ (HR Sokal) was established and CLL was confirmed to be in remission (CLL infiltrated 5%). Imatinib therapy was then started and after 3 months a CCyR was obtained. Two months later, clinical conditions rapidly worsened and peripheral blood showed 20% of myeloid blasts (CD34+, CD33+, CD117+/-), consistent with the diagnosis of AML although she was still in CCyR. The patient was then hospitalized but after few days died because of MOF. Based on clinical and biological data, we suggest that in this case the three haematological neoplasms had an independent origin.