Renal cell carcinoma and acute promyelocytic leukemia: A nonrandom association?
Authors: Ritesh Parajuli, Jessica Altman, Timothy Kuzel, Maria Perdekamp, Martin Tallman
Journal: American Journal of Hematology (2010)

Renal cell carcinoma (RCC) may develop as a second malignancy after the treatment of acute promyelocytic leukemia (APL), Wilms tumor and non-Hodgkin's lymphoma. We report two adults who developed APL and RCC in close temporal proximity. While it is possible that the two malignancies were unrelated and may be coincidental, we speculate that there is a nonrandom association. This association, to the best of our knowledge, has not been reported previously in adults. A 64-year-old woman was diagnosed with APL in July 2006. She was treated with daunorubicin, doxorubicin, and all-trans retinoic acid (ATRA). A computed tomography (CT) scan of the chest showed an incidental left renal mass. A radical nephrectomy performed in December 2006 showed a RCC. Cytogenetics confirmed the t(15;17) translocation. The consolidation therapy consisted of daunorubicin and ATRA in October 2006. She achieved a complete molecular remission. A colonoscopy done for diarrhea revealed a polyp with adenocarcinoma. No additional therapy for APL was considered because of the time needed for the recovery from colon cancer. She remains disease free, from both APL and RCC. A 58-year-old man underwent a bone marrow biopsy for pancytopenia in December 2005 that revealed hypercellularity, promyelocytes, and Auer rods. A diagnosis of APL was made. Cytogenetics confirmed the t(15;17) translocation. The induction chemotherapy consisted of cytarabine, idarubicin, and ATRA. A CT of the abdomen in January 2006 identified an incidental left renal mass which was absent 2 years previously. He received two cycles of consolidation chemotherapy with Idarubicin in March and May 2006 and attained a complete molecular remission. He was started on ATRA, 6-mercaptopurine and methotrexate as maintenance therapy. In January 2007, a CT scan of the chest showed pulmonary nodules. Biopsy confirmed adenocarcinoma consistent with metastatic RCC. He was treated with sunitinib without nephrectomy. Subsequent imaging showed that the lung disease had resolved, the renal abnormality had regressed and the APL was in complete remission. RCC in Case 1 was detected 2 months after the diagnosis of APL. In the second case, RCC was diagnosed during the induction phase of the treatment of APL and a CT scan done 2 years earlier demonstrated the absence of a renal mass. In both the cases, ATRA was a part of the initial therapy. The occurrence of second malignancies after chemotherapy has been postulated to be due to mutations induced by cytotoxic chemotherapy. Taking into account the immunology of RCC and the effect of ATRA on the immune system, it is possible that ATRA or the chemotherapeutic regimen for APL has a role in the development or RCC in a short period of time. It seems less likely that the RCCs observed here were therapy-related because of the short time from treatment to diagnosis. An alternative explanation may be that the altered immunologic milieu provided fertile ground for the development of both diseases. A literature review reveals that RCC developing after the treatment of APL has been reported only by Huang et al. [1]. The cases reported here add to the growing body of evidence that RCC can occur as a second malignancy during or after the treatment of APL or can be related to the progression of APL and highlights the need for close monitoring after the treatment of either cancer. Alternatively, the expression and secretion of pro-angiogenic and proliferative cytokines by the renal tumor may play a role in the development of the leukemia. Ritesh Parajuli*, Jessica K. Altman*, Timothy Kuzel*, Maria Perdekamp , Martin S. Tallman , * Northwestern University Feinberg School of Medicine, Hematology-Oncology, Chicago, IL, Decatur Memorial Hospital, Hematology-Oncology, Decater, IL, Memorial Sloan Kettering Cancer Center, Leukemia Service, Division of Hematologic Oncology, New York, NY.