Occurrence and severity of adverse events after autologous hematopoietic progenitor cell infusion are related to the amount of granulocytes in the apheresis product
Boris Calmels
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorClaude Lemarié
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorBenjamin Esterni
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorCaroline Malugani
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorAude Charbonnier
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorDiane Coso
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorJean-Marc Schiano de Colella
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorEric Deconinck
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorDenis Caillot
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorFrédéric Viret
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorPatrick Ladaique
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorValérie Lapierre
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorChristian Chabannon
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorBoris Calmels
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorClaude Lemarié
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorBenjamin Esterni
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorCaroline Malugani
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorAude Charbonnier
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorDiane Coso
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorJean-Marc Schiano de Colella
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorEric Deconinck
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorDenis Caillot
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorFrédéric Viret
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorPatrick Ladaique
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorValérie Lapierre
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorChristian Chabannon
From the Paoli-Calmettes Institute, Marseille; Establissement Français du Sang, Besançon; CHU Jean Minjoz, Besançon; and CHU Bocage, Dijon, France.
Search for more papers by this authorAbstract
BACKGROUND: Adverse events (AEs) after hematopoietic progenitor cell (HPC) infusion are rare but might be life-threatening. These reactions have traditionally been associated with the amount of infused cryoprotectant, but persistence of such events after dimethyl sulfoxide (DMSO) depletion has questioned this assumption.
STUDY DESIGN AND METHODS: The incidence of AEs on a cohort of 460 patients (490 HPC infusions) undergoing autologous DMSO-reduced HPC transplantation was prospectively evaluated. HPCs were collected from adult patients with various hematologic or solid malignancies. After quality control (QC) on fresh apheresis products and subsequent cryopreservation, HPC grafts were thawed and washed at the cell therapy facility. QC was performed on each graft after washing, and clinical data were collected for each infusion.
RESULTS: AEs were reported in 66 cases (13.5%) and were graded according to the NCI-CTC scale from 1 to 4. Although none of the factors associated with patient characteristics or infusion procedure were different between the two groups (no AE vs. occurrence of AE), it was found that the absolute number of granulocytes measured before freezing was considerably higher in the AE group. Furthermore, within this group, there was a strong correlation between the amount of granulocytes and the grading of the reaction.
CONCLUSION: This survey demonstrates that AEs occurring in the setting of DMSO-reduced HPC grafts are directly related to the amount of granulocytes and thus emphasizes the need for high-quality apheresis products so as to improve the safety of HPC infusion.
REFERENCES
- 1 Ljungman P, Urbano-Ispizua A, Cavazzana-Calvo M, et al. Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe. Bone Marrow Transplant 2006; 37: 439-49.
- 2 Corso S, Vukelja SJ, Wiener D, Baker WJ. Diffuse alveolar hemorrhage following autologous bone marrow infusion. Bone Marrow Transplant 1993; 12: 301-3.
- 3 Miniero R, Vai S, Giacchino M, et al. Severe respiratory depression after autologous bone marrow infusion. Haematologica 1992; 77: 98-9.
- 4 Higman MA, Port JD, Beauchamp NJ Jr, Chen AR. Reversible leukoencephalopathy associated with re-infusion of DMSO preserved stem cells. Bone Marrow Transplant 2000; 26: 797-800.
- 5 Windrum P, Morris TC. Severe neurotoxicity because of dimethyl sulphoxide following peripheral blood stem cell transplantation. Bone Marrow Transplant 2003; 31: 315.
- 6 Dhodapkar M, Goldberg SL, Tefferi A, Gertz MA. Reversible encephalopathy after cryopreserved peripheral blood stem cell infusion. Am J Hematol 1994; 45: 187-8.
- 7 Nishihara G, Sakemi T, Ikeda Y, et al. Multiple organ failure associated with dimethylsulfoxide and hydroxyethyl starch in autologous blood stem cell transplantation. Nephron 1996; 72: 356-7.
- 8 Bauwens D, Hantson P, Laterre PF, et al. Recurrent seizure and sustained encephalopathy associated with dimethylsulfoxide-preserved stem cell infusion. Leuk Lymphoma 2005; 46: 1671-4.
- 9 Zenhausern R, Tobler A, Leoncini L, et al. Fatal cardiac arrhythmia after infusion of dimethyl sulfoxide-cryopreserved hematopoietic stem cells in a patient with severe primary cardiac amyloidosis and end-stage renal failure. Ann Hematol 2000; 79: 523-6.
- 10 Hoyt R, Szer J, Grigg A. Neurological events associated with the infusion of cryopreserved bone marrow and/or peripheral blood progenitor cells. Bone Marrow Transplant 2000; 25: 1285-7.
- 11 Sauer-Heilborn A, Kadidlo D, McCullough J. Patient care during infusion of hematopoietic progenitor cells. Transfusion 2004; 44: 907-16.
- 12 Stroncek DF, Fautsch SK, Lasky LC, et al. Adverse reactions in patients transfused with cryopreserved marrow. Transfusion 1991; 31: 521-6.
- 13 Zambelli A, Poggi G, Da Prada G, et al. Clinical toxicity of cryopreserved circulating progenitor cells infusion. Anticancer Res 1998; 18: 4705-8.
- 14 Davis JM, Rowley SD, Braine HG, et al. Clinical toxicity of cryopreserved bone marrow graft infusion. Blood 1990; 75: 781-6.
- 15 Ferrucci PF, Martinoni A, Cocorocchio E, et al. Evaluation of acute toxicities associated with autologous peripheral blood progenitor cell reinfusion in patients undergoing high-dose chemotherapy. Bone Marrow Transplant 2000; 25: 173-7.
- 16 Abrahamsen JF, Bakken AM, Bruserud O. Cryopreserving human peripheral blood progenitor cells with 5-percent rather than 10-percent DMSO results in less apoptosis and necrosis in CD34+ cells. Transfusion 2002; 42: 1573-80.
- 17 Martino M, Morabito F, Messina G, et al. Fractionated infusions of cryopreserved stem cells may prevent DMSO-induced major cardiac complications in graft recipients. Haematologica 1996; 81: 59-61.
- 18 Martin-Henao GA, Torrico C, Azqueta C, et al. Cryopreservation of hematopoietic progenitor cells from apheresis at high cell concentrations does not impair the hematopoietic recovery after transplantation. Transfusion 2005; 45: 1917-24.
- 19 Beaujean F, Hartmann O, Kuentz M, et al. A simple, efficient washing procedure for cryopreserved human hematopoietic stem cells prior to reinfusion. Bone Marrow Transplant 1991; 8: 291-4.
- 20 Rodriguez L, Velasco B, Garcia J, Martin-Henao GA. Evaluation of an automated cell processing device to reduce the dimethyl sulfoxide from hematopoietic grafts after thawing. Transfusion 2005; 45: 1391-7.
- 21 Lemarie C, Calmels B, Malenfant C, et al. Clinical experience with the delivery of thawed and washed autologous blood cells, with an automated closed fluid management device: CytoMate. Transfusion 2005; 45: 737-42.
- 22 Calmels B, Houze P, Hengesse JC, et al. Preclinical evaluation of an automated closed fluid management device: Cytomate, for washing out DMSO from hematopoietic stem cell grafts after thawing. Bone Marrow Transplant 2003; 31: 823-8.
- 23 Syme R, Bewick M, Stewart D, et al. The role of depletion of dimethyl sulfoxide before autografting: on hematologic recovery, side effects, and toxicity. Biol Blood Marrow Transplant 2004; 10: 135-41.
- 24 Hequet O, Dumontet C, El Jaafari-Corbin A, et al. Epileptic seizures after autologous peripheral blood progenitor infusion in a patient treated with high-dose chemotherapy for myeloma. Bone Marrow Transplant 2002; 29: 544.
- 25 Olivero S, Alario T, Ladaique P, et al. CD34+ cell enumeration in peripheral blood and apheresis samples, using two laboratory diagnostic kits or an institutional protocol. Bone Marrow Transplant 1999; 23: 387-94.
- 26 Windrum P, Morris TC, Drake MB, et al. Variation in dimethyl sulfoxide use in stem cell transplantation: a survey of EBMT centres. Bone Marrow Transplant 2005; 36: 601-3.
- 27 Lopez-Jimenez J, Cervero C, Munoz A, et al. Cardiovascular toxicities related to the infusion of cryopreserved grafts: results of a controlled study. Bone Marrow Transplant 1994; 13: 789-93.
- 28 Thome S, Craze J, Mitchell C. Dimethylsulphoxide-induced serum hyperosmolality after cryopreserved stem-cell graft. Lancet 1994; 344: 1431-2.
- 29 Keung YK, Lau S, Elkayam U, et al. Cardiac arrhythmia after infusion of cryopreserved stem cells. Bone Marrow Transplant 1994; 14: 363-7.
- 30 Frim J, Mazur P. Approaches to the preservation of human granulocytes by freezing. Cryobiology 1980; 17: 282-6.
- 31 Tsvetkov T, Nickolov C, Buckureshtliev A, et al. Aggregate formation in cryopreserved leukocyte suspensions. Cryobiology 1985; 22: 35-9.
- 32 Price TH. Granulocyte transfusion therapy. J Clin Apher 2006; 21: 65-71.
- 33 Strauss RG, Connett JE, Gale RP, et al. A controlled trial of prophylactic granulocyte transfusions during initial induction chemotherapy for acute myelogenous leukemia. N Engl J Med 1981; 305: 597-603.
- 34 Price TH, Bowden RA, Boeckh M, et al. 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 2000; 95: 3302-9.
- 35 Moraes TJ, Zurawska JH, Downey GP. Neutrophil granule contents in the pathogenesis of lung injury. Curr Opin Hematol 2006; 13: 21-7.
- 36 David NA. The pharmacology of dimethyl sulfoxide. Annu Rev Pharmacol 1972; 12: 353-74.
- 37 Rowley SD, Prather K, Bui KT, et al. Collection of peripheral blood progenitor cells with an automated leukapheresis system. Transfusion 1999; 39: 1200-6.
- 38 Wilke R, Brettell M, Prince HM, et al. Comparison of COBE Spectra software version 4.7 PBSC and version 6.0 auto PBSC program. J Clin Apher 1999; 14: 26-30.
- 39 Milone G, Pinto V, Mercurio S, et al. Adverse events after infusions of cryopreserved hematopoietic stem cells depend on non-mononuclear cell in infused suspension and on patient age. Blood 2006; 108: 402b.
Citing Literature
