Spontaneous rupture of the spleen is a rare but serious and life-threatening complication of treatment with granulocyte colony-stimulating factor (G-CSF). A few case reports address the occurrence of splenic rupture after filgrastim therapy, mostly in healthy donors of peripheral blood stem cells, but also in patients with acute myelogenous leukemia, myelodysplastic syndrome and amyloidosis.1, 2, 3, 4, 5 A recent article by Arshad et al.6 describes a case of splenic rupture in a patient with myelodysplastic syndrome following administration of pegfilgrastim. The compound has recently been approved to shorten neutropenia and decrease the incidence of infection in patients with non-myeloid malignancies receiving myelosuppressive anticancer drugs. We report a case of splenic rupture in a completely different clinical situation after the use of pegfilgrastim in a patient with multiple myeloma undergoing autologous peripheral blood stem cell transplantation (PBSCT).
A 43-year-old woman was diagnosed with multiple myeloma. At presentation, free κ light chain was identified in the patient's serum, and urine immunofixation electrophoresis showed bence-jones-proteinuria. A bone-marrow biopsy showed 90% plasma cells and a normal karyotype. She had osteolytic lesions of both humeri and femora, anemia (hemoglobin 9.8 g/dl) and mild thrombocytopenia (138.000/μl). No lymphadenopathy or hepatosplenomegaly were evident at the time of diagnosis. Spleen size, determined by ultrasonography, was 11.6 × 4.2 cm. The patient was initially treated with three cycles idarubicin and dexamethasone. For stem cell mobilization, she received 6 mg pegfilgrastim on day 5 after the administration of cyclophosphamide (4 g/m2). This treatment was well tolerated, induced a partial remission and led to successful collection of stem cells.
The patient received a PBSCT in May 2005. Myeloablation was induced by high-dose melphalan (200 mg/m2) followed by PBSCT. On day +1, pegfilgrastim (6 mg) was administered. On the morning of day +9, the patient complained of vertigo and abdominal pain. The blood count revealed acute worsening of anemia (hemoglobin 3.7 g/dl compared to 8.8 g/dl on day 8), the beginning of neutrophil regeneration (900/μl, on the same evening the WBC was 2.600/μl) and thrombocytopenia (26.000/μl). Abdominal ultrasound demonstrated considerable free fluid in the abdomen, which we confirmed to be blood by aspiration. She underwent an emergency laparotomy that showed splenic rupture. The spleen was of normal size (10 × 7 × 3.5 cm3), weighed 116 g and a subcapsular hematoma was present. Histopathologically, the white pulp was atrophic. No proliferation of myeloid CD34+ cells, infiltration with myeloma cells or amyloidosis could be demonstrated. Myeloperoxidase-positive cells were numerous, but not obviously increased when compared to the normal spleen. The postoperative course was free of complications. The patient was vaccinated against Pneumococci and Haemophilus influenza B and was discharged on day +18.
The use of G-CSF has proven beneficial in a variety of clinical settings. Common side effects include musculoskeletal pain, headache and rash, but splenic rupture has also been described with filgrastim, as a rare complication of growth factor administration in healthy donors of PBSC,1, 2 myeloid malignancies3, 4 and amyloidosis.5 Previous studies in humans and animals have shown splenomegaly and extramedullary hematopoiesis induced by G-CSF.7, 8, 9 Pre-existing splenomegaly and disease infiltration, for example, in myeloproliferative and myelodysplastic syndrome or amyloidosis, could be a risk factor for splenic rupture after administration of myeloid growth factors.
Interestingly, our patient had no splenomegaly or infiltration by disease. However, occurrence of splenic rupture during sleep without any previous trauma supports a relationship between regeneration of the neutrophil count after administration of the growth factor and the adverse event. Spleen size after surgery may not reflect the true size at the time of rupture as the considerable blood loss may decrease both the size and weight of the spleen. In our opinion, this case supported by a few other cases,2, 4 indicates, that absolute splenic size may be less important than rapid volume changes during G-CSF-induced hematopoietic expansion.
Splenic rupture must be considered as a possible complication with use of all myeloid growth factors, for all indications, including stem cell mobilization, chronic severe neutropenia or after administration of myelosuppressive anticancer drugs. It is important to amass cases of splenic rupture after growth factor administration in order to identify potential risk factors for this rare but life-threatening complication.
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Kuendgen, A., Fenk, R., Bruns, I. et al. Splenic rupture following administration of pegfilgrastim in a patient with multiple myeloma undergoing autologous peripheral blood stem cell transplantation. Bone Marrow Transplant 38, 69–70 (2006). https://doi.org/10.1038/sj.bmt.1705382
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