Life-threatening capillary leak syndrome after G-CSF mobilization and collection of peripheral blood progenitor cells for allogeneic transplantation

Abstract

Summary:We report a case of capillary leak syndrome in a 37-year-old female PBPC donor who received G-CSF 900 g/day for 4 days and underwent leukapheresis. This lady had remained well and stable despite marked leukocytosis during G-CSF treatment, but developed hypotension during leukapheresis, quickly followed by hypoxemia, ascites, pericardial and pleural effusion, shock, edema, neurologic changes and hepatocellular injury. Upon G-CSF withdrawal, dopamine and crystalloid infusion, methylprednisolone treatment and suspension of apheresis, the clinical situation fully reversed. We hypothesize that leukapheresis, in the presence of marked leukocytosis and high doses of G-CSF, may have triggered neutrophil activation and the release of inflammatory mediators, resulting in tissue damage and systemic manifestations of increased capillary permeability. Bone Marrow Transplantation (2001) 28, 311-312. Keywords: G-CSF; capillary leak syndrome; leukapheresis; peripheral blood progenitor cell transplantation A 37-year-old white female agreed to donate allogeneic G-CSF-mobilized PBPC for her brother. She was asymptomatic, in good health, and used no medications. Her past medical history was unremarkable. Physical examination was normal except for moderate obesity and bradycardia. She had a normal chest film and echocardiogram. ECG showed sinus bradycardia. Serum biochemistry and coagulation tests were normal, Hb was 12.9 g/dl, hematocrit 38%, WBC 6.4 × 10 9 /l (ANC 3.1 × 10 9 /l) and platelets 322 × 10 9 /l. She received G-CSF 900 g s.c. daily in two divided doses for 4 days (10 g/kg/day). On the fifth day, the WBC count was 90.5 × 10 9 /l. Her only symptom thus far had been moderate headache which subsided with acetaminophen. A last dose of G-CSF was given. Three hours after the start of apheresis, she was pale and hypotensive, complaining of respiratory discomfort, nausea and weakness. Intravenous saline and calcium gluconate were given, with partial improvement. Apheresis was stopped after 5 h and she received another dose of G-CSF, because the number of CD34 + cells collected had been insufficient. Returning in the next morning, she complained of dyspnea, pleuritic pain and 'tightness in the chest'. Hematocrit was 33% and WBC 74.7 × 10 9 /l. Minutes later, she fainted and was admitted to the emergency room with severe hypotension, pallor, pulmonary rales, hypoxemia, cyanosis and confusion. A CT scan showed ascites, pericardial fluid and bilateral pleural effusion (Figures 1 and 2). Pericardiocentesis yielded clear fluid with 65 cells/mm 3 (77% neutrophils), 4.2 g/dl protein and LDH 512 U/l. Pleural fluid had the same characteristics. Her hemodynamic status improved with i.v. saline and dopamine. She remained confused and agitated for the next 12 h, normalizing her mental status gradually thereafter. A CT scan of the head was normal. Her weight was 8 kg above baseline. Her previously normal alanine aminotransferase peaked at 568 U/l (normal: Ͻ37 U/l). Bilirubin and alkaline phosphatase were unchanged. Hypoalbuminemia (3....

PBSC mobilization in newly diagnosed patients with POEMS syndrome: outcomes and prognostic factors

“…2 The use of G-CSF might increase the release of pro-inflammatory cytokines and enhance this imbalance, which could worsen certain clinical symptoms closely associated with pro-inflammatory cytokines, for example, extravascular volume overload, similar to capillary leak syndrome induced by G-CSF. 16,17 Studies have showed that CY is one of the drugs that can effectively decrease the pro-inflammatory cytokine network. It is reported that combination of CY and prednisone is an effective treatment regimen for patients with POEMS syndrome.…”

PBSC collection from family donors in Japan: a prospective survey

“…The stem cell harvest procedure is more convenient for both donors and medical teams, 1-3 the speed of post-transplant, hematological recovery is faster in recipients, [4][5][6][7] and outcomes are similar compared to that of BMT. [8][9][10] However, there have been occasional reports of mortalities [11][12][13][14][15] and severe complications such as splenic rupture. 16,17 Most of these severe adverse events (SAE) occurred with family donors, appeared as anecdotal or were based on retrospective analyses.…”

Excessive fluid accumulation during stem cell mobilization: a novel prognostic factor of first-year survival after stem cell transplantation in AL amyloidosis patients

“…18,19 Although cytotoxics are often thought to be important, they are by no means a prerequisite. 20 Most agree that CLS is the result of activation of proinflammatory cytokines. 21 The incident may be higher with GM-SCF than G-CSF.…”