Abstract
Patients with haematological malignancies and prolonged periods of neutropenia after chemotherapy are at high risk for severe bacterial and fungal infections. Those infections have long time been considered as a contraindication for subsequent haematopoietic stem cell transplantation (HCT). We conducted a prospective, non-randomized study of granulocyte transfusions (GTX) to control acute life-threatening infections (44 episodes) and to prevent recurrence of severe fungal infections during HCT or intensive chemotherapy (23 episodes). 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). Median survival was 170 days in the interventional group and 185 days in the prophylactic group; death in both patient groups was mainly due to underlying progressive malignant disease. We conclude that under GTX, the infection-related mortality even in high-risk patients is low. Due to a secondary prophylaxis with GTX, haematopoietic allografts can be safely given to patients with previous fungal infections.
Similar content being viewed by others
References
Adkins DR, Goodnough LT, Moellering J, Brown R, Khoury H, Vij R, DiPersio J (1999) Reduction in antibiotic utilization and of febrile days by transfusion of G-CSF mobilized prophylactic granulocyte components: a randomised study. Blood 94:590a
Adkins DR, Goodnough LT, Shenoy S, Brown R, Moellering J, Khoury H, Vij R, DiPersio J (2000) Effect of leukocyte compatibility on neutrophil increment after transfusion of granulocyte colony-stimulating factor-mobilized prophylactic granulocyte transfusions and on clinical outcomes after stem cell transplantation. Blood 95:3605–3612
Ascioglu S, Rex JH, de Pauw B, Bennett JE, Bille J, Crokaert F, Denning DW, Donnelly JP, Edwards JE, Erjavec Z, Fiere D, Lortholary O, Maertens J, Meis JF, Patterson TF, Ritter J, Selleslag D, Shah PM, Stevens DA, Walsh TJ (2002) Defining opportunistic invasive fungal infections in immunocompromised patients with cancer and haematopoietic stem cell transplants: an international consensus. Clin Infect Dis 34:7–14
Bensinger WI, Price TH, Dale DC, Appelbaum FR, Clift R, Lilleby K, Williams B, Storb R, Thomas ED, Buckner CD (1993) The effects of daily recombinant human granulocyte colony-stimulating factor administration on normal granulocyte donors undergoing leukapheresis. Blood 81:1883–1888
Blum W, Hallem C, Vij R, Shenoy S, Goodnough L, Brown R, Khoury H, Westervelt P, DiPersio J, Adkins D (2001) Improved survival in allogeneic peripheral blood stem cell (PBSC) transplant recipients who received prophylactic granulocyte transfusions from HLA-matched donors: long-term follow-up. Blood 98:58a
Bodey GP, Buckley M, Sathe YS, Freireich EJ (1966) Quantitative relationships between circulating leukocytes and infection in patients with acute leukemia. Ann Intern Med 64:328–340
Bux J, Dielschneider T, Duscherer M, Edel E, Eichler H, Haas C, Moog R, Peschke H, Peters C, Ryzenkov I, Schlenke P, Ullrich H, Wiesneth M (2003) Tolerance of granulocyte donors towards granulocyte colony-stimulating factor stimulation and of patients towards granulocyte transfusions: results of a multicentre study. Vox Sang 85:322–325
Caspar CB, Seger RA, Burger J, Gmür J (1993) Effective stimulation of donors for granulocyte transfusions with recombinant methionyl granulocyte colony-stimulating factor. Blood 81:2866–2871
Cordonnier C, Maury S, Pautas C, Bastié JN, Chehata S, Castaigne S, Kuentz M, Bretagne S, Ribaud P (2004) Secondary antifungal prophylaxis with voriconazole to adhere to scheduled treatment in leukemic patients and stem cell transplant recipients. Bone Marrow Transplant 33:943–948
Denning DW (1998) Invasive aspergillosis. Clin Infect Dis 26:781–803
Dignani MC, Anaissie EJ, Hester JP, O’Brien S, Vartivarian SE, Rex JH, Kantarjian H, Jendiroba DB, Lichtiger B, Nadersson BS, Freireich EJ (1997) Treatment of neutropenia-related fungal infections with granulocyte colony-stimulating factor-elicited white blood cell transfusions : a pilot study. Leukemia 11:1621–1630
Freireich EJ, Levin RH, Whang J, Carbone PP, Bronson W, Morse EE (1964) The function and fate of transfused leukocytes from donors with chronic myelocytic leukemia in leukopenic patients. Ann NY Acad Sci 113:1081–1090
Herbrecht R, Denning DW, Patterson TF, Bennett JE, Greene R, Oestmann JW, Kern WV, Marr KA, Ribaud P, Lortholary O, Sylvester R, Rubin RH, Wingard JR, Stark P, Durand C, Caillot D, Thiel E, Chandrasekar PH, Hodges MR, Schlamm HAT, Troke PF, De Pauw B (2002) Voriconazole versus amphotericin B for primary therapy of invasive aspergillosis. N Engl J Med 347:408–415
Hermann S, Klein SA, Jacobi V, Thalhammer A, Bialleck H, Duchscherer M, Wassmann B, Hoelzer D, Martin H (2001) Older patients with high-risk fungal infections can be successfully allografted using non-myeloablative conditioning in combination with intensified supportive care regimens. Br J Haematol 113:446–454
Hübel K, Carter RA, Liles WC, Dale DC, Price TH, Bowden RA, Rowley RD, Chauncey TR, Bensinger WI, Boeckh M (2002) Granulocyte transfusion therapy for infections in candidates and recipients of HPC transplantation: a comparative analysis of feasibility and outcome for community donors versus related donors. Transfusion 42:1414–1421
Illerhaus G, Wirth A, Dwenger A, Waller CF, Garbe A, Brass V, Lang H, Lange W (2002) Treatment and prophylaxis of severe infections in neutropenic patients by granulocyte transfusions. Ann Hematol 81:273–281
Kerr JP, Liakopolou E, Brown J, Cornish JM, Fleming D, Massey E, Oakhill A, Pamphilon DH, Robinson SP, Totem A, Valencia AMP, Marks DI (2003) The use of stimulated granulocyte transfusions to prevent recurrence of past severe infections after allogenic stem cell transplantation. Br J Haematol 123:114–118
Klein SA, Hermann S, Dietrich CF, Hoelzer D, Martin H (2002) Transplantation-related toxicity and acute intestinal graft-versus-host disease after conditioning regimens intensified with Rhenium 188-labeled anti-CD66 monoclonal antibody. Blood 99:2270–2271
Lee JJ, Chung IJ, Park MR, Kook H, Hwang TJ, Ryang DW, Kim HJ (2001) Clinical efficacy of granulocyte transfusion therapy in patients with neutropenia-related infections. Leukemia 15:203-207
Offner F, Cordonnier C, Ljungmann P, Prentice HG, Engelhard D, De Bacquer D, Meunier F, De Pauw B (1998) Impact of previous aspergillosis on the outcome of bone marrow transplantation. Clin Infect Dis 26:1098–1103
Peters C, Minkov M, Matthes-Martin S, Pötschger U, Witt V, Mann G, Höcker P, Worel N, Stary J, Klingebiel T, Gadner H (1999) Leucocyte transfusions from rhG-CSF or prednisolone stimulated donors for treatment of severe infections in immunocompromised patients. Br J Haematol 106:689–696
Price TH, Raleigh AB, Boeckh M, Bux J, Nelson K, Liles C, Dale DC (2000) Phase I/II trial of neutrophil transfusions from donors stimulated with G-CSF and dexamethasone for treatment of patients with infections in hematopoietic stem cell transplantation. Blood 95:3302–3309
Robinson SP, Marks DI (2004) Granulocyte transfusions in the G-CSF era. Where do we stand? Bone Marrow Transplant 34:839–846
Rutella S, Pierelli L, Piccirillo N, Sica S, Serafini R, Chiusolo P, Paladini U, Leone F, Zini G, D’Onofrio G, Leone G (2003) Efficacy of granulocyte transfusions for neutropenia-related infections: retrospective analysis of predictive factors. Cytotherapy 5:19–30
Strauss RG (1995) Clinical perspectives of granulocyte transfusions: efficacy to date. J Clin Apher 10:114–118
Vamvakas EC, Pineda AA (1996) Meta-analysis of clinical studies of the efficacy of granulocyte transfusions in the treatment of bacterial sepsis. J Clin Apher 11:1–9
Vij R, DiPersio JF, Venkatraman P, Trinkaus K, Goddnough LT, Brown RA, Khoury HJ, Devine SM, Oza A, Shenoy S, Blum W, Adkins D (2003) Donor CMV serostatus has no impact on CMV viremia or disease when prophylactic granulocyte transfusions are given following allogenic peripheral blood stem cell transplantation. Blood 101:2067–2069
Acknowledgements
This work was supported by Knochenmarktransplantation/Gentherapie Frankfurt (KGF) e.V. The authors thank the haematology nursing staff for their excellent patient care.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Mousset, S., Hermann, S., Klein, S.A. et al. Prophylactic and interventional granulocyte transfusions in patients with haematological malignancies and life-threatening infections during neutropenia. Ann Hematol 84, 734–741 (2005). https://doi.org/10.1007/s00277-005-1055-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-005-1055-z