Treatment of severe neutropenic sepsis with granulocyte transfusion in the current era – experience from an adult haematology unit in Singapore

Abstract

Granulocyte transfusion's (GT) efficacy among adult severe neutropenic sepsis (SNS) patients remains uncertain. We assessed GT's efficacy and its determinants among SNS patients in an adult haematology unit. The feasibility and safety of granulocyte donation (GD) and determinants of granulocyte yield were also evaluated. Retrospective analysis of granulocyte donors and recipients from March 2008 to October 2009. Donors: Sixty GDs with a median WBC yield (WBCY) of 65·49 (31·30-131·72) × 10(9) were collected from 48 donors (9 repeat donors) using hydroxyethyl starch and intermittent flow centrifugation aphaeresis after receiving 8 mg dexamethasone and 300 mcg granulocyte colony-stimulating factor, with no serious adverse reactions (SAR). Six donations were urgently collected <3 h after pre-medication, the median WBCY of which was not significantly different from donations collected >12 h after pre-medication [59·18 (45·68-62·90) × 10(9) vs 67·45 (31·30-131·72) × 10(9) , P = 0·140]. Only pre-GD absolute neutrophil count (ANC) correlated with WBCY. Fifteen patients (12 acute leukaemias, 1 severe AA, 1 myelodysplastic syndrome and 1 lymphoma) received median 3 (2-9) ABO/RhD-matched GTs over 2-24 (median 7) days at 3-61 (median 28) days from severe neutropenia (SN) onset without SAR. They received intensive chemotherapies (N = 9), allogeneic transplant (N = 3), autologous stem cell rescue (N = 1) or immunosuppressants (N = 2). Fourteen had bacterial (N = 1) infections, fungal (N = 3) infections or both (N = 10) and one had severe viral pneumonitis; 63·6 and 30·8% of bacterial and fungal infections responded, respectively. Median ANC increase (ANC(increase) ) was 1·26 (0-9·25) × 10(9) at 5-20 (median 11) h post-GT. On multivariate analysis, each patient's median ANC(increase) only significantly correlated positively with median WBC dose/kg (P = 0·013). Five (33·3%) patients survived to discharge; the rest had infection-related mortality (IRM). IRM was significantly associated with inotropic requirement (P = 0·004), ventilatory requirement (P = 0·017) and persistent SN (P = 0·007). GD is safe and feasible with good WBCY obtainable using our protocol. The effect of shortening pre-medication interval on WBCY which may prevent delay in initiating GT is worth evaluating. GT most likely benefits SNS patients with prospects of neutrophil recovery before haemodynamic deterioration. Large randomised trials investigating the role and timing of GT among such patients are required.