Acute Leukemias Following a Diagnosis of Colorectal Cancer: Are They Therapy-Related?

Abstract

Abstract 1453▪▪This icon denotes a clinically relevant abstractApproximately 140,000 patients per year are diagnosed with colorectal cancer in the United States. Historically, treatment modalities have included surgery, 5-fluourouracil (5-FU) and/or radiation. Over the past ten years standard treatment has evolved and now includes platinum compounds such as Oxaliplatin, the topoisomerase I inhibitor Irinotecan, and the oral analogue of 5-FU, Capecitabine. Rectal cancer often utilizes these agents in a neoadjuvant fashion with concomitant radiation therapy, followed by surgery and postoperative chemotherapy. The incidence of therapy related acute myeloid leukemia (t-AML) has been well described after treatment for breast cancer and lymphoma and occurs most commonly in patients previously treated with alkylating agents or topoisomerase II-active agents (epipodophylotoxins or anthracyclines). However, the occurrence of acute leukemia after a diagnosis of colorectal cancer has never been systematically investigated in a large clinical database.Using ICD-9 codes for leukemia and colorectal cancer, we identified 37 patients seen at Memorial Sloan-Kettering Cancer Center since 1970 with colon cancer, rectal cancer, or anal cancer who were subsequently diagnosed with leukemia or a myelodysplastic syndrome (MDS). Of these 37 patients, 23 had colon cancer, 13 had rectal cancer and 1 had anal cancer. Treatments for the primary malignancy included: external beam radiation alone (2), chemotherapy alone (10), chemotherapy in combination with radiation (12) and surgery alone (13). The most common leukemia was acute myeloid leukemia (20) followed by MDS (8), Pre-B cell acute lymphoblastic leukemia (ALL) (4), acute promyelocytic leukemia (APL) (3), T-ALL (1) and T- cell prolymphocytic leukemia (PLL) (1). Of the 8 patients with MDS, 4 had chronic myelomonocytic leukemia. Among patients who received chemotherapy or combined chemoradiation the most common chemotherapeutic agents were 5-Fluorouracil (19) followed by Oxaliplatin (8), intrahepatic Floxuridine (2), Irinotecan (1) and Mitomycin (1). The median time from treatment with chemotherapy and/or radiation to diagnosis of acute leukemia or MDS was 41 months (range 10 months – 135 months). The most common cytogenetic abnormalities of the patients with MDS or AML were monosomies and deletions in chromosomes 5, 7, and 12. Of the 4 patients with Pre B-ALL, 3 had t(9;22). Interestingly of the 23 patients with myeloid leukemia, 3 (13%) patients developed the APL subtype with the disease defining t(15;17). Two of these three patients had received neo-adjuvant external beam radiation and 5-FU, one received adjuvant treatment with Oxaliplatinand one was treated with surgery alone. The latency period between diagnosis or treatment of colorectal cancer and the development of APL ranged from 10 to 20 years.Table 1Patient CharacteristicsM/F23/14Type of Lower GI MalignancyColon23Rectal13Anal1TreatmentSurgery Alone13Radiation Alone2Chemo-radiation12Chemotherapy Alone105-Fluorouracil19Oxaliplatin8Intrahepatic Floxuridine2Irinotecan1Mitomycin1Median Latency period (range)41 months (10-135 months)Type of leukemiaAML (non-APL)20APL3MDS4CMMOL4ALL Ph pos3ALL Ph neg1T-ALL1T-PLL1In conclusion, to our knowledge this is among the first uses of a comprehensive clinical database to investigate the occurrence of acute leukemia and MDS after the diagnosis and/or treatment of a colorectal or anal malignancy. Our finding that the most common chromosomal abnormalities seen in patients who developed MDS or AML involve chromosomes 5 and 7, similar to t-AML suggests, that some of these leukemias are therapy related. It may be that the widespread adoption of newer platinum compounds will precipitate t-AML. Future studies of larger databases of patients may help establish if the acute leukemias seen after colorectal cancer are related to prior exposure to anti-cancer therapy. Disclosures:Douer:Teva: Consultancy.