Hematological toxicities associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Abstract

Introduction Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been found to prolong survival in selected patients with peritoneal disease, but the extent of cytoreduction and chemoperfusion can result in systemic toxicities. We evaluate the incidence of perioperative hematological complications and its associated risk factors. Methods Retrospective analysis of a prospectively collected database of CRS‐HIPEC cases between April 2001 and October 2016 was performed. Patients were stratified based on the clinicopathological characteristics, perioperative incidence, grade, and duration of leukopenia (white blood cells < 4000/mm3), neutropenia (absolute neutrophils < 2000/mm3), and thrombocytopenia (platelets < 140 000/mm3). Results Two hundred and thirty‐five CRS‐HIPEC were performed in 220 patients with peritoneal metastasis of colorectal, ovarian, primary peritoneal, appendiceal, or mesothelioma origins. The incidences of leukopenia, neutropenia, and thrombocytopenia were 15.3%, 3.8%, and 37.9%, respectively. Median time to onset was 1 day (0‐16 days), 0 day (0‐2 days), and 1 day (1‐2 days), respectively, after operation. Median duration of leukopenia, neutropenia, and thrombocytopenia was 1 day (1‐3 days), 1 day (1‐2days), and 3 days (range 0‐16 days), respectively. Age > 60 (odds ratio [OR] 0.229 [95% CI: 0.105‐0.502], P < .001) and the use of prior chemotherapy (OR 2.46 [95% CI: 1.24, 4.83], P = .010) were independent risk factors for thrombocytopenia on multivariable logistic regression. Conclusion Hematological toxicities are common after hyperthermic intraperitoneal chemotherapy with thrombocytopenia being most common. Patients with age > 60, and who have undergone chemotherapy, are at risk of these toxicities and should be closely monitored post CRS‐HIPEC.

Pancytopenia after administration of hyperthermic intraperitoneal chemotherapy with mitomycin-C: local therapy and systemic toxicity

“…Contrary to previously published reports, we present a case of pancytopenia in a patient who underwent splenectomy as part of CRS and subsequent MMC-HIPEC. One retrospective analysis by Wong et al, [13] showed that while neutropenia and thrombocytopenia can occur postoperatively, the median duration was only 1 and 3 days, respectively, which is significantly shorter than that seen in our patient.…”

Hematological Alterations after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

“…We also found a trend towards a longer ICU stay in patients who developed leukopenia, as already described by other authors [24,31].…”

“…Only two studies— one involving 18 patients treated with intravenous ifosfamide and HIPEC and the other involving 50 patients treated with CRS and HIPEC—described an incidence of 61.1 and 36%, respectively, with a cut-off of 150,000/mm 3 as in our study [ 22 , 23 ]. Another described an incidence of thrombocytopenia (defined as lower than 140,000/mm 3 ) of 37.9% in 235 CRS and HIPEC patients; these authors found that increased age (>60 years) and previous chemotherapy were independent risk factors associated with the development of thrombocytopenia [ 24 ]. Although we did not reach such a finding, severe thrombopenia (less than 50,000/mm 3 ) is described in 0.6–11% of patients [ 7 , 19 , 25 ].…”

“…Hakeam et al [ 22 ] found an incidence of 11.1% of leukopenia, which recovered spontaneously within 48 h without a need for filgrastim use. Wong et al [ 24 ] found an incidence of leukopenia of 15.3% that recovered after 1–3 days and a 3.8% incidence of neutropenia (<2000/mm 3 ), which was related to ICU stay; through a univariate analysis, they found that patients that received more intraoperative blood transfusions had a higher risk of postoperative leukopenia. Fefermann [ 31 ] found a 7% incidence of leukopenia (defined as <2000/mm 3 ) in 242 patients treated with CRS and HIPEC with mitomycin C, with a median nadir on day 5 postoperatively, who had a significantly longer ICU stay with respect to patients who did not develop leukopenia (11 vs. 6 days, p < 0.05).…”