A Patient with Pancytopenia

Peter W. Marks, MD

Yale University School of Medicine, New Haven, CT

Copyright of the American Society of Hematology, 2012. ISSN: 1931-6860.


Acute promyelocytic leukemia (APL) is a favorable risk leukemia that is now generally associated with an approximately 80% five-year survival. However, because of the coagulopathy with disseminated intravascular coagulation (DIC) that is commonly associated with it, the highest risk for morbidity and mortality is during the initial presentation and treatment. Note that any type of AML may present with concomitant DIC, though APL is most commonly associated with this complication.

Because of the risk of bleeding complications, particularly hemorrhage into the brain, whenever there is even a small suspicion from features of the presentation that a leukemia may be APL, it is recommended that all trans retinoic acid (ATRA) be started empirically pending confirmation of the diagnosis. Treatment with ATRA is associated with reduction or resolution of the DIC in APL. One complication of its use is an infiltrate that may occur in the lungs, causing hypoxia. This finding is a well-described complication, as the myeloid blasts undergo maturation induced by ATRA, and is called differentiation syndrome. It may be prevented by concomitant treatment of patients with corticosteroids. Following initial treatment with ATRA, initial chemotherapy, called induction chemotherapy, is administered. This may consist of an anthracycline chemotherapy drug such as daunorubicin or idarubicin, in combination with continuation of the ATRA, until the patient achieves a complete remission, which usually takes about a month. Following this, several additional cycles of chemotherapy are given to try to eliminate any remaining leukemic cells. This is called consolidation. Finally, to further reduce the risk of recurrence, patients are often treated with oral maintenance chemotherapy for two years. Note that APL is the only type of acute myeloid leukemia for which maintenance chemotherapy has been shown to be of benefit. For the rest, induction and consolidation chemotherapy is followed either by observation or treatment with hematopoietic stem cell transplant.

This patient is treated with ATRA at presentation and receives induction chemotherapy. Within a few days of starting chemotherapy, there are no more blasts present in the peripheral blood, and the DIC resolves completely. About two weeks after starting chemotherapy, her white blood cell count is barely detectable, and she develops a fever. Blood cultures are obtained, and she is empirically started on broad spectrum antibiotics. After 2 days, her fever resolves; however, no organism is ever identified from the blood cultures. Four weeks after starting treatment, her blood counts recover toward normal. A bone marrow aspirate and biopsy is performed to assess her response to the chemotherapy, and she is found to be in remission. She is then treated with three cycles of consolidation chemotherapy over the next three months, followed by two years of maintenance chemotherapy. When she returns to the clinic a year after completing all of her treatments, she feels well and has no complaints. A molecular diagnostic test performed reveals no evidence of the PML-RARA gene fusion.

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