The patient is presenting with acute promyelocytic leukemia that results from a 15;17 translocation.
Acute promyelocytic leukemia (APL) results from a 15;17 translocation that produces a disruption in the retinoic acid receptor required for myeloblast maturation, producing the fusion gene PML/RARalpha. This neoplastic proliferation of myeloblasts (>20%) results in a decrease of mature leukocytes, as it crowds out the bone marrow, preventing the growth and maturation of other RBC and WBCs; in turn, this leads to bone marrow failure. APL typically occurs in the 5th-6th decades of life. Patients present with recurrent infections, bleeding, and fatigue. On exam, many have hepatosplenomegaly and lymphadenoapthy, which is secondary to leukemic infiltrate. CBC will demonstrate decreased levels of RBCs, mature WBCs, and platelets. Bone marrow aspiration will show >20% myeloblasts with Auer rods, and they will be myeloperoxidase positive.
Watts and Tallman review the treatment of APL. What once was a death sentence is now highly curable with two medications - all-trans retinoic acid (ATRA) and arsenic trioxide (ATO). Many patients do not even have to undergo chemotherapy if their WBC count is less than 10,000/ul. They demonstrate that survival is as high as 90%. If patients do relapse, they can be cured with ATO and autologous hematopoietic cell transplantation.
Kutny et al. describe the similarities and differences of pediatric and adult patients with APL. Although there are similarities between pediatric and adult patients, pediatric patients typically present with elevated WBCs or the microgranular variant. The early death rate from APL is lower in pediatric patients, but the very young do have a much higher risk of relapse than adults. In pediatric patients, ATRA in combination with chemotherapy has made APL quite curable. Although there is less data on the use of ATRA and ATO in pediatric patients, the use in adults has shown considerable promise in treating without the use of chemotherapy; however, further research on the use of these drugs in the pediatric population is needed.
Illustration A demonstrates a myeloblast with two visible Auer rods, which are crystal aggregates of myeloperoxidase. Illustration B demonstrates myeloblasts that have been stained with an antibody against myeloperoxidase. Illustration C shows a karyotype displaying the 15;17 translocation; notice that the second 15th chromosome is slightly longer and the second 17th chromosome is shorter.
Answer 2: The 9;22 translocation results in the bcr:abl fusion gene causing CML.
Answer 3: The 14;18 translocation results in follicular and undifferentiated lymphomas.
Answer 4: The 11;14 translocation results in mantle cell lymphoma.
Answer 5: The 8;14 translocation results in Burkitt's lymphoma.
Watts JM, Tallman MS. Acute promyelocytic leukemia: What is the new standard of care? Blood Rev. 2014 Sep;28(5):205-212.
PMID:25107311 (Link to Abstract)
Kutny MA, Gregory J Jr, Feusner JH. Treatment of paediatric APL: how does the therapeutic approach differ from adults? Best Pract Res Clin Haematol. 2014 Mar;27(1):69-78.
PMID:24907019 (Link to Abstract)