Original Articles
Vol. 18 No. 1 (2026): Mediterranean Journal of Hematology and Infectious Diseases
EFFECT OF FRESH VERSUS CRYOPRESERVED GRAFTS ON FEBRILE NEUTROPENIA AND INFECTIONS IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION: FACTORS DETERMINING MORTALITY.
Fresh vs Frozen Grafts: Infection and Outcome
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: February 28, 2026
711
Views
360
Downloads
68
HTML
Authors
Background: The study aimed to compare the incidence and course of febrile neutropenia (FN) and factors affecting mortality in hematologic patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either fresh or cryopreserved grafts.
Methods: The clinical data of 155 patients who underwent allo-HSCT at our hematology clinic between 2010 and 2023 were retrospectively analyzed. The incidence of bloodstream infection (BSI) and FN-related mortality were analyzed in these patients. Factors affecting FN-related mortality were examined using a Cox regression model.
Results: A total of 143 patients who developed FN were included in the study. Ninety-eight patients underwent transplantation with fresh stem cells and 45 patients with cryopreserved stem cells. The duration of FN episodes was similar between groups (p = 0.077); however, the duration of deep neutropenia (neutrophils < 100/mm³) was significantly longer in the cryopreserved group (11.56 ± 4.84 vs. 7.78 ± 3.03; p < 0.001). GNB infections and invasive fungal infections were more frequent in the cryopreserved group (p = 0.009 and p < 0.001, respectively). In the Cox regression model, the most important determinants of FN-related mortality were duration of the FN episode (HR 1.18; 95% CI 0.99–1.41; p = 0.046) and higher hematopoietic cell transplantation comorbidity index (HCT-CI) score (score 1; p = 0.014 and score 2; p = 0.039).
Conclusions: This study demonstrated that irrespective of the graft type, prolonged FN duration and high HCT-CI score are the primary determinants of mortality. Therefore, clinical management of patients should also address these risk factors.
Downloads
Download data is not yet available.
Citations
Yang, M., Xin, L., Li, H., Lu, X., Pan, X., Lei, S., Li, Y., Zhu, L., Zhu, Q., Jiang, R., Jia, Z., Cheng, G., Zeng, L., & Zhang, L. Risk factors for bloodstream infection in paediatric haematopoietic stem cell transplantation: a systematic review and meta-analysis. J Hosp Infect 2023; 139: 11–22. http://doi.org/10.1016/j.jhin.2023.06.003
Giaccone L, Faraci DG, Butera S, Lia G, Di Vito C, Gabrielli G, Cerrano M, Mariotti J, Dellacasa C, Felicetti F, Brignardello E, Mavilio D, Bruno B. Biomarkers for acute and chronic graft versus host disease: state of the art. Expert Rev Hematol 2021; 14(1): 79–96. http://doi.org/10.1080/17474086.2021.1860001
Bembnista E, Stawicka P, Matuszak P, Łojko-Dankowska A, Dytfeld D, Matuszak M, Wache A, Kaźmierska K, Majewska E, Lewandowski K, Gil L Should we cryopreserve allogenic hematopoietic stem cell grafts? In Vivo 2025; 39(2): 870–876. http://doi.org/10.21873/invivo.13890
Strzelec A, Gawlik-Rzemieniewska N, Klima A, Panek K, Helbig G. The impact of cryopreservation on hematopoietic stem cell engraftment and post-transplant outcome during the COVID-19 pandemic. In Vivo 2024; 38(3): 1271–1277. http://doi.org/10.21873/invivo.13565
Ersal T, Özkocaman V, Yalçın C, Orhan B, Candar Ö, Çubukçu S, Koca TG, Pınar İE, Hunutlu FÇ, Özkalemkaş F. The effect of cryopreservation on engraftment kinetics in fully matched allogeneic stem cell transplantation: Real-life data and literature review. Transfus Apher Sci 2023; 62(6): 103821. http://doi.org/10.1016/j.transci.2023.103821
Medd P, Nagra S, Hollyman D, Craddock C, Malladi R. Cryopreservation of allogeneic PBSC from related and unrelated donors is associated with delayed platelet engraftment but has no impact on survival. Bone Marrow Transplant 2013; 48(2): 243–248. http://doi.org/10.1038/bmt.2012.118
Hsu JW, Farhadfar N, Murthy H, Logan BR, Bo-Subait S, Frey N, Goldstein SC, Horowitz MM, Lazarus H, Schwanke JD, Shah NN, Spellman SR, Switzer GE, Devine SM, Shaw BE, Wingard JR. The effect of donor graft cryopreservation on allogeneic hematopoietic cell transplantation outcomes: a center for international blood and marrow transplant research analysis. Implications during the COVID-19 pandemic. Transplant Cell Ther 2021; 27(6): 507–516. http://doi.org/10.1016/j.jtct.2021.03.015
Yan CH, Wang Y, Mo XD, Sun YQ, Wang FR, Fu HX, Chen Y, Han TT, Kong J, Cheng YF, Zhang XH, Xu LP, Liu KY, Huang XJ. Incidence, risk factors, mic2robiology and outcomes of pre-engraftment bloodstream infection after haploidentical hematopoietic stem cell transplantation and comparison with HLA-identical sibling transplantation. Clin Infect Dis 2018; 67(suppl 2): S162–S173. http://doi.org/10.1093/cid/ciy658
Freifeld AG, Bow JE, Sepkowitz KA, Boeckh MJ, Ito J, Mullen CA, Raad I, Rolston KV, Young JH, Wingard JR; Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis 2011; 52(4): e56–e93. http://doi.org/10.1093/cid/cir073
Kikuchi M, Akahoshi Y, Nakano H, Ugai T, Wada H, Yamasaki R, Sakamoto K, Kawamura K, Ishihara Y, Sato M, Ashizawa M, Terasako-Saito K, Kimura S, Yamazaki R, Kanda J, Kako S, Nishida J, Kanda Y. Risk factors for pre- and post-engraftment bloodstream infections after allogeneic hematopoietic stem cell transplantation. Transpl Infect Dis 2015; 17(1): 56–65. http://doi.org/10.1111/tid.12345
Mori Y, Yoshimoto G, Nishida R, Sugio T, Miyawaki K, Shima T, Nagasaki Y, Miyake N, Harada Y, Kunisaki Y, Kamezaki K, Numata A, Kato K, Shiratsuchi M, Maeda T, Takenaka K, Iwasaki H, Shimono N, Akashi K, Miyamoto T. Gastrointestinal graft-versus-host disease is a risk factor for postengraftment bloodstream infection in allogeneic hematopoietic stem cell transplant recipients. Biol Blood Marrow Transplant 2018; 24(11): 2302–2309. http://doi.org/10.1016/j.bbmt.2018.06.002
Zhang R, Xiong Y, Zhang L, Liu L. Epidemiology, microbiology, and risk factors of bacterial bloodstream infections in patients after allogeneic hematopoietic stem cell transplantation. Infect Drug Resist 2024; 17: 1561–1569. http://doi.org/10.2147/IDR.S451781
Lee SJ, Kim JH, Han SB, Paik JH, Durey A. Prognostic factors predicting poor outcome in cancer patients with febrile neutropenia in the emergency department: usefulness of qsofa. J Oncol 2018; 2018: 2183179. http://doi.org/10.1155/2018/2183179
Coyne CJ, Castillo EM, Shatsky RA, Chan TC. Procalcitonin as a predictive tool for death and icu admission among febrile neutropenic patients visiting the emergency department. Medicina (Kaunas) 2022; 58(8): 985. http://doi.org/10.3390/medicina58080985
Al-Anazi KA. Autologous hematopoietic stem cell transplantation for multiple myeloma without cryopreservation. Bone Marrow Res 2012; 2012: 917361. http://doi.org/10.1155/2012/917361
Berz D, McCormack EM, Winer ES, Colvin GA, Quesenberry PJ. Cryopreservation of hematopoietic stem cells. Am J Hematol 2007; 82(6): 463–472. http://doi.org/10.1002/ajh.20707
Yalçın C, Özkalemkaş F, Özkocaman V, Ersal T, Pınar İE, Orhan B, Candar Ö, Çubukçu S, Koca TG, Akyol MN, Ada NG, Özakın C, Kazak E, Akalın H, Ali R. Evaluation of using empiric glycopeptides in accordance with the IDSA guideli4nes in hematologic malignancy patients with febrile neutropenia. Mediterr J Hematol Infect Dis 2022; 14(1): e2022039. http://doi.org/10.4084/MJHID.2022.039
Donnelly JP, Chen SC, Kauffman CA, Steinbach WJ, Baddley JW, Verweij PE, Clancy CJ, Wingard JR, Lockhart SR, Groll AH, Sorrell TC, Bassetti M, Akan H, Alexander BD, Andes D, Azoulay E, Bialek R, Bradsher RW, Bretagne S, Calandra T, Caliendo AM, Castagnola E, Cruciani M, Cuenca-Estrella M, Decker CF, Desai SR, Fisher B, Harrison T, Heussel CP, Jensen HE, Kibbler CC, Kontoyiannis DP, Kullberg BJ, Lagrou K, Lamoth F, Lehrnbecher T, Loeffler J, Lortholary O, Maertens J, Marchetti O, Marr KA, Masur H, Meis JF, Morrisey CO, Nucci M, Ostrosky-Zeichner L, Pagano L, Patterson TF, Perfect JR, Racil Z, Roilides E, Ruhnke M, Prokop CS, Shoham S, Slavin MA, Stevens DA, Thompson GR, Vazquez JA, Viscoli C, Walsh TJ, Warris A, Wheat LJ, White PL, Zaoutis TE, Pappas PG. Revision and update of the consensus definitions of invasive fungal disease from the European organization for research and treatment of cancer and the mycoses study group education and research consortium. Clin Infect Dis 2020; 71(6): 1367–1376. http://doi.org/ 10.1093/cid/ciz1008
Sorror ML, Maris MB, Storb R, Baron F, Sandmaier BM, Maloney DG, Storer B. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood 2005; 106(8): 2912–2919. http://doi.org/10.1182/blood-2005-05-2004
European Committee on Antimicrobial Susceptibility Testing (EUCAST). Breakpoint tables for interpretation of MICS and zone diameters. Version 14.0, 2024. https://www.eucast.org/clinical_breakpoints. Accessed January 1, 2025.
Centers for Disease Control and Prevention (CDC). Healthcare-Associated Infections (HAIs). Carbapenem-resistant Enterobacterales (CRE) Technical Information. https://www.cdc.gov/cre/hcp/infection-control/index.html. Accessed April 12, 2024.
Tomblyn M, Chiller T, Einsele H, Gress R, Sepkowitz K, Storek J, Wingard JR, Young JA, Boeckh MJ. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant 2009; 15(10): 1143–1238. http://doi.org/10.1016/j.bbmt.2009.06.019
Styczyński J, Tridello G, Koster L, Iacobelli S, van Biezen A, van der Werf S, Mikulska M, Gil L, Cordonnier C, Ljungman P, Averbuch D, Cesaro S, de la Camara R, Baldomero H, Bader P, Basak G, Bonini C, Duarte R, Dufour C, Kuball J, Lankester A, Montoto S, Nagler A, Snowden JA, Kröger N, Mohty M, Gratwohl A. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant 2020; 55(1): 126–136. http://doi.org/10.1038/s41409-019-0624-z
Islas-Muñoz B, Volkow-Fernández P, Silva-Zamora J, Ramírez-Ibarguen A, Cornejo-Juárez P. Mortality in patients with hematological malignancies, febrile neutropenia, and septic shock. J Infect Dev Ctries 2024; 18(2): 235–242. http://doi.org/10.3855/jidc.17451
Cao W, Guan L, Li X, Zhang R, Li L, Zhang S, Wang C, Xie X, Jiang Z, Wan D, Chi X. Clinical analysis of bloodstream infections during agranulocytosis after allogeneic hematopoietic stem cell transplantation. Infect Drug Resist 2021; 14: 185–192. http://doi.org/10.2147/IDR.S280869
Nesher L, Rolston KVI. Febrile neutropenia in transplant recipients. In: Safdar A (ed). Principles and Practice of Transplant Infectious Diseases. 1st ed. New York: Springer; 2018: 185–198. http://doi.org/10.1007/978-1-4939-9034-4_9
Zhang R, Xiong Y, Zhang L, Liu L. Epidemiology, microbiology, and risk factors of bacterial bloodstream infections in patients after allogeneic hematopoietic stem cell transplantation. Infect Drug Resist 2024; 17: 1561–1569. http://doi.org/10.2147/IDR.S451781
Herrera F, Torres D, Laborde A, Jordán R, Berruezo L, Roccia Rossi I, Mañez N, Tula L, Pereyra ML, Nenna A, Costantini P, Benso J, González Ibañez ML, Eusebio MJ, Baldoni N, Barcán LA, Lambert S, Luck M, Pasterán F, Corso A, Rapoport M, Nicola F, García Damiano MC, Monge R, Carbone R, Reynaldi M, Greco G, Blanco M, Chaves ML, Bronzi M, Carena A. Epidemiology of bacteremia in patients with hematological malignancies and hematopoietic stem cell transplantation and the impact of antibiotic resistance on mortality: data from a multicenter study in Argentina. Pathogens 2024; 13(11): 933. http://doi.org/10.3390/pathogens13110933
Girmenia C, Bertaina A, Piciocchi A, Perruccio K, Algarotti A, Busca A, Cattaneo C, Raiola AM, Guidi S, Iori AP, Candoni A, Irrera G, Milone G, Marcacci G, Scimè R, Musso M, Cudillo L, Sica S, Castagna L, Corradini P, Marchesi F, Pastore D, Alessandrino EP, Annaloro C, Ciceri F, Santarone S, Nassi L, Farina C, Viscoli C, Rossolini GM, Bonifazi F, Rambaldi A. Incidence, risk factors and outcome of pre-engraftment gram-negative bacteremia after allogeneic and autologous hematopoietic stem cell transplantation: an Italian prospective multicenter survey. Clin Infect Dis 2017; 65(11): 1884–1896. http://doi.org/10.1093/cid/cix690
Gill J, Busca A, Cinatti N, Passera R, Dellacasa CM, Giaccone L, Dogliotti I, Manetta S, Corcione S, De Rosa FG. Bacterial bloodstream infections after allogeneic hematopoietic stem cell transplantation: etiology, risk factors and outcome in a single-center study. Microorganisms 2023; 11(3): 742. http://doi.org/10.3390/microorganisms11030742
Ogura S, Kimura M, Takagi S, Mitsuki T, Yuasa M, Kageyama K, Kaji D, Nishida A, Taya Y, Ishiwata K, Yamamoto H, Asano-Mori Y, Yamamoto G, Uchida N, Wake A, Taniguchi S, Araoka H. Characteristics of gram-negative bacteremia during febrile neutropenia am10ong allogeneic hematopoietic stem cell transplant recipients on levofloxacin prophylaxis. Eur J Clin Microbiol Infect Dis 2021; 40(5): 941–948. http://doi.org/10.1007/s10096-020-04096-z
Pagano L, Caira M, Nosari A, Van Lint MT, Candoni A, Offidani M, Aloisi T, Irrera G, Bonini A, Picardi M, Caramatti C, Invernizzi R, Mattei D, Melillo L, de Waure C, Reddiconto G, Fianchi L, Valentini CG, Girmenia C, Leone G, Aversa F. Fungal infections in recipients of hematopoietic stem cell transplants: results of the SEIFEM B-2004 study--Sorveglianza Epidemiologica Infezioni Fungine Nelle Emopatie Maligne. Clin Infect Dis 2007; 45(9): 1161–1170. http://doi.org/10.1086/522189
Neofytos D, Horn D, Anaissie E, Steinbach W, Olyaei A, Fishman J, Pfaller M, Chang C, Webster K, Marr K. Epidemiology and outcome of invasive fungal infection in adult hematopoietic stem cell transplant recipients: analysis of multicenter prospective antifungal therapy (PATH) alliance registry. Clin Infect Dis 2009; 48(3): 265–273. http://doi.org/10.1086/595846
Biyun L, Yahui H, Yuanfang L, Guo X, Wang D. Risk factors for invasive fungal infections after haematopoietic stem cell transplantation: a systematic review and meta-analysis. Clin Microbiol Infect 2024; 30(5): 601–610. http://doi.org/10.1016/j.cmi.2024.01.005
Acosta-Medina AA, Baranwal A, Johnson IM, Kharfan-Dabaja MA, Murthy H, Palmer JM, Sproat L, Mangaonkar A, Shah MV, Hogan WJ, Litzow MR, Tefferi A, Alkhateeb HB. Comparison of pretransplantation prediction models for nonrelapse mortality in patients with myelofibrosis undergoing allogeneic stem cell transplantation. Transplant Cell Ther 2023; 29(6): 360.e1–360.e8. http://doi.org/10.1016/j.jtct.2023.02.002
Bayraktar UD, Shpall EJ, Liu P, Ciurea SO, Rondon G, de Lima M, Cardenas-Turanzas M, Price KJ, Champlin RE, Nates JL. Hematopoietic cell transplantation-specific comorbidity index predicts inpatient mortality and survival in patients who received allogeneic transplantation admitted to the intensive care unit. J Clin Oncol 2013; 31(33): 4207–4214. http://doi.org/10.1200/JCO.2013.50.5867
How to Cite
“EFFECT OF FRESH VERSUS CRYOPRESERVED GRAFTS ON FEBRILE NEUTROPENIA AND INFECTIONS IN ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION: FACTORS DETERMINING MORTALITY.: Fresh vs Frozen Grafts: Infection and Outcome” (2026) Mediterranean Journal of Hematology and Infectious Diseases, 18(1). doi:10.4084/MJHID.2026.032.
Copyright (c) 2026 Cumali Yalçın, Bedrettin Orhan, Tuba Ersal, Mümin Şentürk, Vildan Özkocaman, Halis Akalın, Fahir Özkalemkaş
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
