Role of granulocyte transfusions in combating life-threatening infections in patients with severe neutropenia: Experience from a tertiary care centre in North India

Abstract

Bacterial and fungal infections still remain an important cause of mortality in patients with hematological malignancies and in recipients of hematopoietic stem cell transplants (HSCT) especially in developing countries like India. Granulocyte transfusions (GTX) from healthy donors may lead to early clearance of index infection and thus prevent mortality. The aim of the present study was to evaluate the efficacy of GTX in combating life-threatening infections and preventing mortality in patients of hematological disorders/recipients of HSCT with severe neutropenia. This study was a prospective, observational analysis of patients with different hematological disorders/recipients of HSCT, who received GTX from January 2014 to December 2017. All patients had an Absolute neutrophil Count (ANC) < 0.5 x 109/L and a life threatening sepsis defined by presence of hemodynamic instability/ impending septic shock/ continuous high fever despite the use of the highest line of antimicrobials. A total of 143 granulocyte collections were done for 66 infectious episodes (IEs) in 60 patients. Multidrug resistant organisms (MDROs) were observed in 47/66 IEs (71.2%) and fungal infections were seen in 9/66 IEs (13.6%). Resolution of index infection after GTX was seen in 45/66 IEs (68.2%), and the 30 day overall survival (OS) was 67.7%. OS was significantly higher in patients who received GTX within 7 days of neutropenic sepsis (p = 0.01). Patients with MDROs who received early GTX therapy had a better OS as compared to those who received late GTX (p = 0.02). GTX were well tolerated and only 6 patients’ developed mild features of transfusion related acute lung injury (TRALI) which was managed conservatively, and 1 patient demonstrated hypocalcemic tetany. GTX may be of particular relevance in countries like India, where the incidence of infections is very high in neutropenic patients and there is an increasing emergence of MDROs.

Clinical Experience of Granulocyte Transfusion Therapy in Pediatric Patients for Management of Neutropenia-related Infections in a Tertiary Care Center in India

“…12 In another study, it has been observed that patients receiving median doses of 1.5-3.0 × 10 8 granulocytes/kg had reduced infection-related mortality. 13 Also, Garg et al 14 demonstrated in their study that doses >10 × 10 8 / kg though associated with a higher total leucocyte count (TLC) increment at 6 hours post-infusion had no significant impact on survival at 30 days.…”

“…The infection-related survival was 82.4% while overall survival (OS) was 77% at day 30. 17 Garg et al 14 also analyzed the efficacy of granulocyte therapy in combating life-threatening infections in patients of hematological disorders/ recipients of hematopoietic stem cell transplant (HSCT) with severe neutropenia. A total of 143 granulocyte transfusions in 60 patients were included.…”

Granulozytentransfusion: Update 2020

“…So erzielten Teofili et al die besten Ergebnisse mit einer Konzentration von 1,5-3 × 10 8 Zellen/kg Körpergewicht, während sie bei einer darüber hinausgehenden Zellzahl sogar einen Anstieg der Sterblichkeit verzeichneten [51]. Die Gruppe um Garg et al schlägt ein Plateau des maximal erreichbaren Effekts bei einer Konzentration von 5 × 10 9 Zellen pro transfundierter Einheit vor [52]. Ein weiterer zu berücksichtigender Faktor ist die Art der Infektion, unter der ein Patient leidet.…”

“…B. im Gewebe, besser mit GKs therapieren lassen als eine Sepsis [53]. Die Ansprechraten decken sich dabei mit den Zahlen von Garg et al [52]. Prinzipiell ist die Wirksamkeit davon abhängig, in welchem Ausmaß die transfundierten Immunzellen unterschiedliche Infektionsorte erreichen.…”

“…Wichtig für die Praxis ist außerdem noch die Überlegung, wann im Verlauf einer Infektion eine Therapieeskalation erfolgen sollte. Hier scheinen möglichst frühe Transfusionen wirksamer zu sein als spätere [52].…”