Chloroma of the Bladder: A Case Report of Leukemia Progression Presenting as Hematuria.

Myeloid sarcoma (MS) is a rare extramedullary manifestation of acute myelogenous leukemia (AML). The mass is composed of primitive myeloid cells that can occur in a variety of organs, most commonly the skin, lymph nodes, GI tract, bone, breast, and CNS. Involvement of the genitourinary tract is rare. Consensus on treatment of MS has not been established, but management typically involves systemic therapy, such as chemotherapy or allogeneic hematopoietic stem cell transplant as well as palliative local therapies such as radiation or surgery. Outcomes of MS using novel AML therapies, such as BCL-2 inhibitors or IDH inhibitors, remain undescribed. We describe a rare case of a 70-year-old man presenting with MS of the urinary bladder complicating known secondary AML (RUNX1 and IDH2 mutated). Prior to development of bladder MS, the patient had received decitabine, enasidenib, and venetoclax. Following diagnosis, he was treated with cytarabine and venetoclax. To our knowledge, this is the first case of bladder MS treated with a BCL-2 inhibitor.

Alternative chemoradiotherapy in anal carcinoma patients with mutations in thymidylate synthase and dihydropyrimidine dehydrogenase genes.

BACKGROUND: 5-fluorouracil (5-FU) and mitomycin-C (MMC) with radiotherapy (RT) remain an established treatment for patients with anal cancer (AC). Genetic mutations in two major metabolizing enzymes for 5-FU; dihydropyrimidine dehydrogenase (DPYD and thymidylate synthetase (TYMS), have been associated with clinical response and toxicity. However, their place in the treatment of AC remains undetermined. METHODS: We retrospectively reviewed 21 patients with AC, including T2-4, N0-1, M0 or T1-4, N2-3, and M0 treated between 2012 and 2018. All patients were treated with 5-FU 1,000 mg/m2/day via continuous intravenous (IV) infusion 1-4 and 29-32, MMC 10 mg/m2 IV bolus days 1 and 29 plus RT. Patients who developed ⩾3 grade toxicities were tested for the DPYD and TYMS genes. Treatment was either modified with reduced doses or changed to MMC 10 mg/m2 day 1 and 29 with cisplatin 25 mg/m2/week plus RT. Toxicities and responses were collected. RESULTS: Six out of 21 patients who developed ⩾3 grade toxicities including pancytopenia, neutropenia, thrombocytopenia, mucositis, nausea, rash, and nephritis were found to have genetic mutations: TYMS 2RG/3RC (n = 2), 3RG/3RC (n = 1), 2R/2R (n = 2), TYMS 3'UTR del/Ins (n = 2), and DPYD c.2864A > T heterozygous (n = 1). Two patients received 5-FU at a 50% reduced dose on days 29-32; one patient refused to receive 5-FU (continued with MMC and RT); one patient received only radiation therapy due to persistent pancytopenia despite the use of growth factors; two patients received an alternative regimen consisting of MMC 10 mg/m2 on day 29 with cisplatin (CDDP) 25 mg/m2/week plus RT; and two patients received cisplatin/MMC with RT from the beginning as they were prospectively detected to have TYMS abnormalities prior to dosing the chemotherapy. These patients tolerated treatment very well with only grade 2 toxicities. All the patients (4/4) on cisplatin/MMC achieved clinical complete response (cCR), while four patients (4/15) on 5-FU/MMC reached cCR at the first assessment. Radiological response showed complete response at the end of 24 weeks assessment. CONCLUSIONS: Molecular testing for DPYD and TYMS genes can allow us to identify patients who are most likely to respond or face severe toxicity to 5-FU in a potentially curable cancer. Combining radiation with CDDP with MMC in patients with AC is feasible. A prospective study based on pharmacogenetic testing comparing MMC/cisplatin with MMC/5-FU is indicated in patients with AC.