1. The role of partial splenic embolization in the management of chemotherapy-induced thrombocytopenia Ohinata A 1, Wallace M 2, Overman M 1, Wolff RA 1, Phillips JK 1, Eng C 1 The Department of Gastrointestinal Medical Oncology 1, Diagnostic Radiology 2, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

2. Background Partial splenic embolization (PSE) has been preformed to treat hypersplenism and to improve hematologic parameters related to this sequela. 1 Splenomegaly induced thrombocytopenia associated with liver cirrhosis, portal hypertension, and chronic idiopathic thrombocytopenic purpura have shown to benefit from PSE. 2-4 Chemotherapy-induced splenomegaly is a relatively known treatment complication 5, where the clinical sequela of hypersplenism is persistent thrombocytopenia due to splenic sequestration. For cancer patients (patients) undergoing chemotherapy, thrombocytopenia may result in a dose delay or dose reduction, thus reducing dose intensity.

3. PSE for cancer patients with thrombocytopenia has been previously evaluated. One retrospective study evaluated 28 patients who underwent PSE at a single institution for the purpose of achieving improved platelet count to continue with their systemic therapy. 96.3 % of the patients were able to see platelet count increase >150 K/UL and 95.7% of patients were able to resume or initiate chemotherapy. 1 While long-term outcome of undergoing PSE has proven to be reasonably safe 6, there are potential complications including hematoma, fever, pneumonia/atelectasis, pain, splenic abscess, thrombosis, and splenic infarction resulting in death. 2-4, 7 The impact of refinement in technique with limited volume embolization of the spleen (30-70%) upon morbidity and mortality has not been well studied.

4. Aim To assess post-PSE platelet count and the rate of successful re-initiation of chemotherapy. Additionally, periprocedural laboratory values, adverse events, and mortality/morbidity were recorded.

5. Methods Study Design and Population A retrospective review of gastrointestinal cancer patients undergoing PSE at our institution for thrombocytopenia to facilitate the initiation or resumption of systemic chemotherapy between January 2008 and March 2011 was completed. Appropriate waivers of informed consent were obtained. Pre- and post-PSE platelet counts were recorded, within 30 days of the procedure, and evaluated for benefit of treatment. Post-PSE platelet count >150 K/UL was considered beneficial. Electronic medical records were reviewed for patient demographics, tumor factors, lab values, and clinical outcomes including: Disease history, prior systemic treatments received, pre- and post- PSE platelet count, duration of hospitalization, subsequent lines of therapy tolerated, adverse events, and overall survival (OS). Statistical Analysis OS was calculated using the Kaplan-Meier method.

6. Demographics (Table 1) N=79 (%) Mean Age (Std dev)50 (11.7) Gender Male51 (65) Female28 (35) Ethnicity White64 (81) Black2 (3) Hispanic8 (10) Asian/Pacific Islander5 (6) Primary Tumor Colon38 (48) Pancreas17 (21) Rectal6 (8) Other15 (19) Unknown3 (4) Median Prior Lines of Therapy (Range) 2 (1-5)

7. Results PSE was performed in 79 patients. The median follow-up was 12 months. Mean pre-PSE platelet count was 80 K/UL (3-196). Re-initiation of chemotherapy was achieved in 49 patients (62%). Lack of re-initiation in remaining patients was due to continued thrombocytopenia. Post-PSE platelet count of >150 K/UL was achieved in 43 patients (54%), with a mean peak platelet count of 219 K/UL. Median duration of subsequent chemotherapy: 8 months (95% CI 4.2-14.2). Median overall survival after PSE: 30 months (95% CI: 14-46) (Figure 1). Six patients (8%) underwent repeat PSE for recurrent thrombocytopenia after re-initiation of systemic therapy. Median duration until repeat PSE was 4 months.

8. Adverse events are shown in Table 2. Median length of hospital stay = 3 days (interquartile range 1-5 days). 60-day mortality was 9% (7 of 79 patients). N=79 (%) Post-procedure fever7 (9%) Pleural effusion, atelectasis, or consolidation 8 (10%) Grade 1 hyperbilirubinemia17 (21%) Periprocedural Adverse Events (Table 2)

9. Figure 1. OS

10. Conclusions Partial splenic embolization is a safe and effective method of managing thrombocytopenia secondary to chemotherapy induced hypersplenism to facilitate re-administration of systemic therapy in cancer patients. Partial splenic embolization may be considered as a potential option in patients with good PS to facilitate further systemic chemotherapy.

11. References 1. Kauffman C, Mahvash A, Kopetz S, et al. Partial Splenic Embolization for Cancer Patients With Thrombocytopenia Requiring Systemic Chemotherapy. Cancer 2008; 112: 2283-8. 2. Palsson B, Hallen M, Forsberg, AM et al. Partial splenic embolization: long-term outcome. Langenbecks Arch Surg 2003; 387: 421-6. 3. Amin MA, el-Gendy MM, Dawoud IE, et al. Partial splenic embolization versus splenectomy for the management of hypersplenism in cirrhotic patients. World J Surg 2009 Aug; 33(8): 1702-10. 4. Kimura F, Itoh H, Ambiru S, et al. Long-term results of initial and repeated partial splenic embolization for the treatment of chronic idiopathic thrombocytopenic purpura. AJR Am J Roentgenol 2002 Nov; 179(5): 1323-6. 5. Overman M, Maru D, Charnsangavej C. Oxaliplatin-mediated increase in spleen size as a biomarker for the development of hepatic sinusoidal injury. J Clin Oncol. 2010 May 20;28(15):2549-55. Epub 2010 Apr 20. 6. Naber AH, Van Haelst U, Yap SH. Nodular regenerative hyperplasia of the liver: an important cause of portal hypertension in non-cirrhotic patients. J Hepatol 1991 Jan; 12 (1):94-9. 7. Lee SS. “Portal hypertension.” First Principles of Gastroenterology. Ed. Thomson ABR, Shaffer EA. Canada: AstraZeneca, 2000. 525-30.