ii. Granulocyte Transfusion Page 2

I. Single center experience with collection and administration of G-CSF-mobilized, irradiated granulocyte transfusions from directed donors to support patients at high risk for infections undergoing unrelated donor blood and marrow transplantation. Allison J, Stephens C, Waters-Pick B, et al. Biol Blood and Marrow Transplant 2005;11(2, Suppl.1):90.

Over the past 7.5 years the authors supported patients at increased risk for infection for 4-10 weeks posttansplantation with G-CSF primed, irradiated granulocyte transfusions harvested from a healthy family member. After clearance and placement of a central venous catheter, donors were injected with G-CSF (10µg/kg) 12-15 hours before donation, twice weekly, 3 days apart. Granulocytes were divided into 3 equal aliquots to be administered on the day of collection and the next 2 days. They were stored at 4°C on a blood rotator until warming to room temperature before infusion.

A total of 82 patients (32 with fungal infections, 26 undergoing second transplant, 22 with other infections, and 2 with surgical wounds) received >2,800 granulocyte transfusions from 91 donors harvested in 939 separate donation procedures. The average number of donations per donor was 10 over 5 weeks. Donor complications included line infection in 14% of donors requiring central venous line removal in 5%, pruritis in 2.5% and hypoproteinemia in 1%. There were no serious complications in recipients.

Less than 10% of patients with active infections experienced progression or recurrence of infection on granulocyte support and, on that basis, the authors conclude that patients with invasive fungal disease, prolonged neutropenia, and surgical wounds can be maintained infection-free during marrow aplasia after allogeneic hematopoietic cell transplantation with regular transfusions of irradiated granulocytes.

(This is an encouraging report, but does not satisfy the need for a prospective controlled study as called for by Robinson et al (citation iiD on previous page). Surprisingly, there is not even a mention of a comparison with historical controls. The difficulties encountered in performing a prospective controlled study in this population of patients are considerable.)

J. Prophylactic and interventional granulocyte transfusions in patients with haematological malignancies and life-threatening infections during neutropenia. Mousset S, Hermann S, Klein SA, Bialleck H, Duchscherer M, Bomke B, Wassmann B, Bohme A, Hoelzer D, Martin H. Ann Hematol. 2005;84:734-41.

Interest in granulocyte transfusions (GTX) has been revived as a result of the use of G-CSSF for donor leukocyte stimulation. Subsequently, several phase I and II studies have demonstrated the feasibility and good safety of GTX in neutropenic patients. There are four uncontrolled studies and one historical matched pair analysis of GTX in adult patients with acute life-threatening infections. The uncontrolled trials revealed encouraging results but, in the matched pair analysis, the group with GTX had no better outcome than their historical matched controls.

This article reports the results of a prospective, non-randomized study of GTX to control acute life-threatening infections ("interventional" GTX, 44 episodes), and to prevent recurrence of severe fungal infections during HCT or intensive chemotherapy ("prophylactic" GTX, 23 episodes).

Patients with leukemia or lymphoma and profound documented or anticipated neutropenia due to chemotherapy or stem cell transplantation were eligible if they met one of the following inclusion criteria: (1) life-threatening infection with rapid progress despite antimicrobial therapy for more than 48 hours or (2) severe (fungal or bacterial) infections during a previous neutropenic interval with a high risk of recurrence during subsequent neutropenias. Patients were scheduled to receive three GTX per week if feasible.

GTX achieved control in 82% (36/44) of acute life-threatening infections. No single reactivation of a previous infection occurred under prophylactic GTX (0/23). However, at the end of the observation period, a total of 42 patients (42/52 - 81%) had died. The causes of death were relapse (n=23), continuing aplasia (n=3) and other complications such as GVHD or infections (n=16). Median survival was 170 days in the interventional group and 185 days in the prophylactic group.

The authors concluded that their results indicated good clinical efficacy in the interventional and prophylactic setting, and that the use of GTX seems to be justified in acute life-threatening infections in high-risk patients. On the other hand, GTX remains a very costly treatment and demands a high workload. Alternative approaches to secondary prophylaxis for patients undergoing allogeneic transplantation or intensive chemotherapy despite preceding fungal infections include the use of antifungal prophylaxis with voriconazole. Finally, until the results of randomized prospective trials are available, GTX have to be considered an experimental treatment.

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