A 41-year-old man presented with pancytopenia and disseminated intravascular coagulation (DIC) at our institution in June 2002. He was diagnosed with morphologically classical hypergranular t (15; 17)(q22; q12)–positive acute promyelocytic leukemia (APL). Although conventional cytogenetic studies revealed a normal 46, XY karyotype, the PML-RARA fusion of the t (15; 17) was detected by both fluorescent in situ hybridization and qualitative reverse-transcription polymerase chain reaction (RT-PCR), with a breakpoint in break cluster region 3 (bcr3) of the PML gene. All-trans-retinoic acid (ATRA) therapy was initiated, and a differentiation syndrome (formerly called retinoic acid syndrome) developed. Hematologic remission was attained 1 month after induction therapy with cytarabine, daunorubicin, and ATRA, with subsequent attainment of molecular remission. After three cycles of consolidation chemotherapy with idarubicin alternating with mitoxantrone, he remained in hematologic and molecular remission for approximately 2 years.

In May 2004, a routine follow-up bone marrow RT-PCR for a PML-RARA fusion was positive. This molecular-only relapse was treated with arsenic, followed by autologous stem-cell transplantation and prophylactic intrathecal chemotherapy in March 2005; molecular remission was attained. He relapsed again in October 2005, with morphologic evidence of both peripheral blood and CNS involvement. This was treated with ATRA, intrathecal cytarabine, and CNS radiation. After the attainment of a second remission (by RT-PCR), he underwent nonmyeloablative 9/10 allele-matched unrelated-donor stem-cell transplantation in March 2006. However, he relapsed for a third time in December 2006, with morphologic evidence of bone marrow involvement, and was treated into molecular remission with ATRA and donor lymphocyte infusion. Afterward, his bone marrow showed full engraftment for a period of approximately 15 months, paralleled by RT-PCR negativity for the PML-RARA fusion. In April 2008, the patient presented to an outside hospital with a small-bowel obstruction and was found to have a mass involving the colon and small bowel. A colon biopsy revealed extramedullary APL (myeloid sarcoma), reflecting a fourth relapse. Of note, peripheral blood engraftment studies at this time still showed 100% donor DNA. The next month, he underwent a hemicolectomy and small-bowel resection at our institution to remove a 4.2-cm mass, which confirmed the presence of a myeloid sarcoma involving the full thickness of the bowel wall and extending into periappendiceal and small-bowel fat (Fig 1, hematoxylin and eosin stain, 5). Flow cytometry performed on the mass confirmed the presence of CD33, CD34, HLA-DR-, MPO blasts/leukemic promyelocytes. Concurrent bone marrow did not reveal any morphologic or