Secondary acute myeloid leukaemia after peptide receptor radionuclide therapy

Abstract

Dear Editor, Peptide receptor radionuclide therapy (PRRT) with YDOTATOC or Lu-DOTATATE has demonstrated its efficacy in the treatment of neuroendocrineand somatostatin-receptor expressing tumours [1, 2]. Several clinical trials have confirmed that adverse effects are represented by possible renal impairment [3] and low but not absent haematological toxicity. We report on a patient who developed acute myeloid leukaemia (AML) following peptide receptor radionuclide therapy for a well-differentiated neuroendocrine carcinoma. He was a 50-year-old man with a past medical history of alcoholism, oesophagitis, arterial hypertension, thalassemia β-minor and deep venous thrombosis of left popliteal vein. He was also a heavy smoker. In November 2005 following repeated episodes of upper abdominal pain, he underwent a thoracic and abdominal CT-scan which showed a pancreatic lesion of 20 mm and another lesion in the Vater papilla of 30 mm in size. An Octreoscan® showed high uptake on the upper right renal pole and on the fifth and seventh hepatic segments. An oesophagoduodenoscopy revealed a duodenal neoformation of 20 mm. The ampullary lesion and peripancreatic lymph node were surgically removed in April 2006, and a fine needle biopsy of the liver was performed. Histology of the ampullary lesion showed a low-grade neuroendocrine carcinoma with extension to the duodenal submucosa, mucosa and focal angioinvasion. Immunohistochemistry was positive for chromogranin A, synaptophisin, neuron-specific enolase and for cytokeratins AE1–AE3 focally. Ki67 was expressed in less than 1% of nuclei. Insulin and glucagone himmunoistochemistry was negative. Histology of the lymph node demonstrated metastasis of the neuroendocrine carcinoma, whereas the liver biopsy showed necrosis without vital tumour cells. Between November 2005 and June 2007, the patient was closely monitored by repeated abdominal CT-scans. In October 2006 an Octreoscan® was repeated on the patient which showed a focal uptake in the pancreatic region. In June 2007, two new small suprarenal lesions were detected; the peri-pancreatic lesion was unchanged. On the basis of the neuroendocrine carcinoma and the increased uptake in receptor scintigraphy, the patient was started on PRRT. From June 2007 to February 2009, he received 6 cycles of PRRT with a cumulative activity of 20.16 GBq (545 mCi) of LuDOTATATE and 5.55 GBq (150 mCi) of Y-DOTATOC. A CT scan performed in October 2008 after 2 cycles of PRRT showed no increase in the size of peri-pancreatic and surrenalic lesions. This finding was confirmed by a subsequent CT-scan in January 2009. The patient completed his PRRT treatment in February 2009. A follow-up CT-scan performed in December 2009 documented that the disease was stable. In January 2010 pancytopenia was observed with Hb 9.1 g/dl, white cell count 6,400/μl, neutrophils 70% and platelets 157,000/μl. A bone marrow aspirate showed hypocellularity with trilineage dysplasia and blasts count <5%, suggestive of alcohol-induced myelodysplastic syndrome A. Piccin (*) : I. Pusceddu : S. Cortelazzo Haematology Department and Bone Marrow Transplant Unit, San Maurizio Regional Hospital, Bolzano, South Tyrol, Italy e-mail: apiccin@gmail.com