- © 2005 by American Society of Clinical Oncology
Side Effects Related to Cancer Treatment
CASE 2. Splenic Rupture Following Pegfilgrastim
A 51-year-old man noticed fatigue in December 2003. His hemoglobin was 5 g/dL, WBC count 4,000/mm3 with a normal differential, and platelet count was 122,000/mm3. Bone marrow aspiration showed RAEB-2, with 16% blasts and normal cytogenetics. The patient was treated on a phase II study of cytarabine and gemtuzumab ozogamicin. He received filgrastim, and later, one dose of pegfilgrastim following that treatment. The patient had an uneventful course and achieved a complete remission. He received his second cycle of cytarabine and gemtuzumab ozogamicin followed by pegfilgrastim in March 2004. He was well until July 2004, when his hemoglobin dropped to 7.3 g/dL; the WBC was 3,100/mm3 with a normal differential, and the platelet count was 214,000/mm3. Bone marrow aspiration showed low-grade myelodysplasia (RA) with normal cytogenetics. He received one dose of darbepoetin alfa 200 μg. Eight days later the WBC was 2,200/mm3, with 27% neutrophils, 47% lymphocytes, and 26% monocytes. Pegfilgrastim 6 mg was administered. On the next day, the patient experienced low-grade fever, severe fatigue, headache, nausea, and muscle aches. He was admitted to the hospital for further evaluation. His WBC was 88,000/mm3 with 83% neutrophils, 3% bands, 2% lymphocytes, 5% monocytes, 1% eosinophils, and 5% metamyelocytes. Two days later, the patient experienced left upper quadrant pain that radiated to the rest of the abdomen. Computed tomography scan of the abdomen and pelvis showed mild splenomegaly with an anteroposterior diameter of 16 cm and perisplenic fluid that extended to the perihepatic space and lower abdomen and pelvis (Fig 1). Emergency laparotomy revealed 1,500 mL of blood in the abdomen, and splenic rupture. Splenectomy was performed. The patient recovered completely from his surgery. Grossly, the spleen weighed 523 g and measured 14 × 12 × 4 cm. There was an 8-cm irregular linear defect near the hilum and another 2.5-cm defect over the lateral surface. Histology showed marked expansion of the red pulp secondary to infiltration of the splenic cords, and sinusoids by mature granulocytic cells, including neutrophils and band forms (Fig 2A). A few scattered immature myeloid precursors, occasional megakaryocytes, and macrophages containing hemosiderin and nuclear debris were noted. No erythroid precursors were seen. The white pulp was attenuated to small lymphoid aggregates around the arterioles. The myeloperoxidase stain supported the presence of myeloid cells (Fig 2B). Splenic rupture is a life-threatening emergency that is most often the result of trauma. Splenic rupture has also been reported in patients with infections1,2 and hematologic malignancies.3,4 Rare cases of splenic rupture have been reported following administration of filgrastim, including fatalities of normal donors undergoing stem-cell collection.5,6 Recently, pegfilgrastim was approved to decrease the incidence of infection in patients with nonmyeloid malignancies receiving immunosuppressive anticancer drugs associated with a clinically significant incidence of febrile neutropenia. Pegylation of granulocyte colony-stimulating factor results in a prolongation of drug half-life such that a single subcutaneous injection is equivalent to 10 daily injections of the nonpegylated parent compound. Although pegfilgrastim is not US Food and Drug Administration–approved in patients with myelodysplastic syndrome (MDS), it is currently being used in patients with MDS in an off-label use. Here, to the best of our knowledge, we report the first published case of a patient who developed splenic rupture 3 days after treatment with pegfilgrastim. Splenic rupture has been reported rarely in other patients with MDS. One group reported splenic rupture in a patient receiving anabolic steroids for myelodysplasia.7 At autopsy, the spleen had numerous cavities containing fresh blood or organized thrombi (peliosis) without any infiltration of myeloblasts. Another group reported fatal splenic rupture in a patient with MDS who received filgrastim for refractory cytopenias.8 At autopsy, the spleen showed massive congestion of the red pulp by immature myeloid elements in both cords and sinuses. Most of the cells were myelocytes. Histologic evaluation of the spleen in the current case revealed marked granulocytic hyperplasia. In our patient, most of the cells were mature neutrophils. These findings are in contrast to the typical histologic findings in the spleen in patients with MDS. The histologic findings of the current case are more akin to the case of one study,9 in which a patient with systemic lupus erythematosus developed marked granulocytic hyperplasia in the spleen following treatment with filgrastim. Our patient received two prior doses of pegfilgrastim without incident. However, both doses were given after intensive chemotherapy that likely prevented a rapid rise in the patient’s WBC. Alternatively, the possibility that the darbepoetin alfa the patient received before the last dose of pegfilgrastim had a synergistic effect cannot be ruled out. Many cases of splenic rupture in the literature report a fatal outcome. With the increased use of hematopoietic growth factors for a wider range of indications, it is important for all physicians to be aware of this life-threatening complication. Early recognition of this condition can result in improved survival.
Authors’ Disclosures of Potential Conflicts of Interest
The authors indicated no potential conflicts of interest.
