Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide

Aim: Dimethylsulfoxide (DMSO) is the most frequently used agent for hematopoietic cell (HC) graft cryopreservation. This study aimed to monitor blood pressure and heart rate (HR) during HC graft infusion and assess the impact of cryopreservation with DMSO. Methods: 153 HC graft infusions in 153 co...

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Datum:2009
Hauptverfasser: Horacek, J.M., Jebavy, L., Jakl, M., Zak, P., Mericka, P., Maly, J.
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Sprache:English
Veröffentlicht: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2009
Schriftenreihe:Experimental Oncology
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Online Zugang:http://dspace.nbuv.gov.ua/handle/123456789/135722
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Zitieren:Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide / J.M. Horacek, L. Jebavy, M. Jakl, P. Zak, P. Mericka, J. Maly // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 121–122. — Бібліогр.: 15 назв. — англ.

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spelling irk-123456789-1357222018-06-16T03:11:09Z Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide Horacek, J.M. Jebavy, L. Jakl, M. Zak, P. Mericka, P. Maly, J. Short communications Aim: Dimethylsulfoxide (DMSO) is the most frequently used agent for hematopoietic cell (HC) graft cryopreservation. This study aimed to monitor blood pressure and heart rate (HR) during HC graft infusion and assess the impact of cryopreservation with DMSO. Methods: 153 HC graft infusions in 153 consecutive hematological patients (mean age 49.1 ± 12.6 years; 80 males) were evaluated. Cryopreservation with DMSO was used in 133 grafts (DMSO group). Twenty grafts were infused directly without cryopreservation (control group). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were measured immediately before and after HC graft infusion. Results: SBP and DBP increased significantly after graft infusions cryopreserved with DMSO (p < 0.0001 for SBP; p < 0.01 for DBP). Increases (> 10 mmHg) in SBP were seen in 42 (31.6%) patients; in DBP in 31 (23.3%) patients. Changes in HR were non-significant in DMSO group. Increases in BP and HR correlated with increasing DMSO dose (p < 0.01; p < 0.05, respectively). Changes in SBP, DBP and HR were non-significant in control group. Conclusion: HC graft infusions cryopreserved with DMSO could cause statistically significant increases in SBP and DBP, without changes in HR. These changes were mostly transient and asymptomatic, not requiring therapeutic intervention. However, they might cause complications, especially in patients with preexisting cardiovascular disease, who should be monitored closely during HC transplantation. 2009 Article Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide / J.M. Horacek, L. Jebavy, M. Jakl, P. Zak, P. Mericka, J. Maly // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 121–122. — Бібліогр.: 15 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/135722 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Short communications
Short communications
spellingShingle Short communications
Short communications
Horacek, J.M.
Jebavy, L.
Jakl, M.
Zak, P.
Mericka, P.
Maly, J.
Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide
Experimental Oncology
description Aim: Dimethylsulfoxide (DMSO) is the most frequently used agent for hematopoietic cell (HC) graft cryopreservation. This study aimed to monitor blood pressure and heart rate (HR) during HC graft infusion and assess the impact of cryopreservation with DMSO. Methods: 153 HC graft infusions in 153 consecutive hematological patients (mean age 49.1 ± 12.6 years; 80 males) were evaluated. Cryopreservation with DMSO was used in 133 grafts (DMSO group). Twenty grafts were infused directly without cryopreservation (control group). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were measured immediately before and after HC graft infusion. Results: SBP and DBP increased significantly after graft infusions cryopreserved with DMSO (p < 0.0001 for SBP; p < 0.01 for DBP). Increases (> 10 mmHg) in SBP were seen in 42 (31.6%) patients; in DBP in 31 (23.3%) patients. Changes in HR were non-significant in DMSO group. Increases in BP and HR correlated with increasing DMSO dose (p < 0.01; p < 0.05, respectively). Changes in SBP, DBP and HR were non-significant in control group. Conclusion: HC graft infusions cryopreserved with DMSO could cause statistically significant increases in SBP and DBP, without changes in HR. These changes were mostly transient and asymptomatic, not requiring therapeutic intervention. However, they might cause complications, especially in patients with preexisting cardiovascular disease, who should be monitored closely during HC transplantation.
format Article
author Horacek, J.M.
Jebavy, L.
Jakl, M.
Zak, P.
Mericka, P.
Maly, J.
author_facet Horacek, J.M.
Jebavy, L.
Jakl, M.
Zak, P.
Mericka, P.
Maly, J.
author_sort Horacek, J.M.
title Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide
title_short Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide
title_full Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide
title_fullStr Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide
title_full_unstemmed Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide
title_sort cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2009
topic_facet Short communications
url http://dspace.nbuv.gov.ua/handle/123456789/135722
citation_txt Cardiovascular changes associated with infusion of hematopoietic cell grafts in oncohematological patients — impact of cryopreservation with dimethylsulfoxide / J.M. Horacek, L. Jebavy, M. Jakl, P. Zak, P. Mericka, J. Maly // Experimental Oncology. — 2009. — Т. 31, № 2. — С. 121–122. — Бібліогр.: 15 назв. — англ.
series Experimental Oncology
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fulltext Experimental Oncology 31, 121–122, 2009 (June) 121 Dimethylsulfoxide (DMSO) is a chemical com- pound with a formula (CH3)2SO. DMSO has been used as a solvent in biological studies and as a vehicle for drug therapy for a long time [1, 2]. Since 1990, DMSO has been the most frequently used substance for cryopreservation of hematopoietic cell (HC) grafts [3–5]. The cryopreservation solution usually contains 10% DMSO and 2–4% albumin or autologous plasma. The grade of toxicity experienced by patients when cryopreserved HC grafts are infused is related to the amount of DMSO present in the HC concentrates. Recently, some institutions have started using 5% DMSO as cryoprotectant for the autologous HC grafts [6, 7]. The maximum recommended daily dose of DMSO is 1 g/kg of the recipient body weight due to dose-dependent side effects. The most common side effects of DMSO include nausea, vomiting, diarrhea, rashes, bronchospasm, headache and cardiovascular changes [8–10]. DMSO may lead to changes in blood pressure (BP) and heart rate (HR). In most studies, increase in BP and decrease in HR were found [2, 11, 12]. However, decrease in BP or increase in HR or no changes in BP and HR were reported in several stu- dies and the results are inconsistent [9, 13]. Thus, the European Group for Blood and Marrow Transplantation (EBMT) has recently launched a multicenter study on monitoring of side effect of DMSO including cardiovas- cular changes (so called “DMSO Toxicity Study”). The results of the study have not been published yet. The aim of our study was to monitor BP and HR du- ring HC graft infusions and to assess the effect of DMSO cryopreservation on these parameters in patients trans- planted for a hematological disease in our transplant center (Department of Medicine II, Clinical Hematology, University Hospital Hradec Kralove, Czech Republic). We evaluated 153 HC graft infusions in 153 con- secutive hematological patients. The patients con- sisted of 80 males and 73 females with the mean age of 49.1 ± 12.6 years. Forty-two patients were treated for arterial hypertension and were well compensated before HC transplantation. Cryopreservation with DMSO was used in 133 (86.9%) grafts, 20 (13.1%) grafts were infused directly without cryopreservation (control group). One hundred and fifteen (75.2%) grafts were autologous and 38 (24.8%) allogeneic (from that 18 matched unrelated donor transplants). The most frequent diagnoses were multiple myeloma (55 patients), non-Hodgkin’s lymphoma (35 patients) and acute myeloid leukemia (29 patients). Systolic blood pressure (SBP), diastolic blood pres- sure (DBP) and heart rate (HR) were measured imme- diately before and after HC graft infusion. Changes (ei- ther increase or decrease) in SBP or DBP by more than CARDIOVASCULAR CHANGES ASSOCIATED WITH INFUSION OF HEMATOPOIETIC CELL GRAFTS IN ONCOHEMATOLOGICAL PATIENTS — IMPACT OF CRYOPRESERVATION WITH DIMETHYLSULFOXIDE J.M. Horacek1, 2, *, L. Jebavy1, 2, M. Jakl2, P. Zak1, P. Mericka3, J. Maly1 1Department of Medicine II — Clinical Hematology, Faculty of Medicine, University Hospital and Charles University, Hradec Kralove 500 05, Czech Republic 2Department of Internal Medicine, Faculty of Military Health Sciences, University of Defence, Hradec Kralove 500 01, Czech Republic 3Tissue Bank, Faculty of Medicine, University Hospital and Charles University, Hradec Kralove 500 05, Czech Republic Aim: Dimethylsulfoxide (DMSO) is the most frequently used agent for hematopoietic cell (HC) graft cryopreservation. This study aimed to monitor blood pressure and heart rate (HR) during HC graft infusion and assess the impact of cryopreservation with DMSO. Methods: 153 HC graft infusions in 153 consecutive hematological patients (mean age 49.1 ± 12.6 years; 80 males) were evaluated. Cryopreservation with DMSO was used in 133 grafts (DMSO group). Twenty grafts were infused directly without cryo- preservation (control group). Systolic blood pressure (SBP), diastolic blood pressure (DBP) and HR were measured immediately before and after HC graft infusion. Results: SBP and DBP increased significantly after graft infusions cryopreserved with DMSO (p < 0.0001 for SBP; p < 0.01 for DBP). Increases (> 10 mmHg) in SBP were seen in 42 (31.6%) patients; in DBP in 31 (23.3%) patients. Changes in HR were non-significant in DMSO group. Increases in BP and HR correlated with increasing DMSO dose (p < 0.01; p < 0.05, respectively). Changes in SBP, DBP and HR were non-significant in control group. Conclusion: HC graft infusions cryopreserved with DMSO could cause statistically significant increases in SBP and DBP, without changes in HR. These changes were mostly transient and asymptomatic, not requiring therapeutic intervention. However, they might cause complications, especially in patients with preexisting cardiovascular disease, who should be monitored closely during HC transplantation. Key Words: dimethylsulfoxide, cryopreservation, transplantation, blood pressure, heart rate. Received: May 5, 2009. *Correspondence: E-mail: jan.hor@post.cz Abbreviations used: BP – blood pressure, DBP – diastolic blood pressure, DMSO – dimethylsulfoxide, HC – hematopoietic cell(s), SBP – systolic blood pressure, HR – heart rate. Exp Oncol 2009 31, 2, 121–122 122 Experimental Oncology 31, 121–122, 2009 (June) 10 mmHg or changes in HR by more than 10 beats/min were considered significant in our study. Statistical analysis was performed with the “Sta- tistica for Windows, Version 5.0” program. Paired two tailed t-tests and McNemar tests were used. The va- lues are expressed as mean ± standard deviation (SD). Probability values p < 0.05 and lower were considered statistically significant. The results are shown in Table 1 and Table 2. SBP and DBP increased significantly just after graft infu- sions cryopreserved with DMSO. Increase in SBP by more than 10 mmHg was seen in 42 (31.6%) patients, in DBP in 31 (23.3%) patients. Moreover, the increase in BP and HR correlated with the increasing DMSO dose — changes were more pronounced in patients with the total DMSO dose above 0.8 g/kg of recipient body weight (p < 0.01, p < 0.05 respectively). In the control group without DMSO cryopreservation, the changes in SBP, DBP and HR were not significant. Changes in SBP, DBP and HR were not significantly different in patients treated for arterial hypertension in comparison with the other patients. Table 1. Changes in blood pressure and heart rate during hematopoietic cell graft infusion with dimethylsulfoxide (n = 133) Parameters Before HCT After HCT p SBP (mmHg) 122.3 ± 17.9 127.7 ± 18.1 < 0.0001 DBP (mmHg) 70.9 ± 12.3 74.1 ± 12.6 < 0.01 HR (/min) 81.5 ± 13.6 81.8 ± 14.2 NS In Table 1 and Table 2: HCT – hematopoietic cell transplantation. Table 2. Changes in blood pressure and heart rate during hematopoietic cell graft infusion without dimethylsulfoxide (n = 20) Parameters Before HCT After HCT p SBP (mmHg) 136.3 ± 17.6 138.4 ± 15.6 NS DBP (mmHg) 78.1 ± 9.5 76.9 ± 11.3 NS HR (/min) 81.6 ± 23.0 81.1 ± 21.8 NS Our results on 153 consecutive hematological pa- tients show that only HC graft infusions cryopreserved with DMSO caused statistically significant increases in SBP and DBP. In our study, significant increases (by more than 10 mmHg) in SBP were found in 31.6% patients, in DBP in 23.3% patients. Changes in HR were not statistically significant. These changes were mostly transient and asymptomatic and did not require therapeutic intervention. However, they might cause complications, especially in patients with preexisting cardiovascular disease (amyloidosis with cardiac in- volvement, chemotherapy-induced cardiomyopathy, coronary artery disease, cardiac arrhythmia, not adequately compensated arterial hypertension prior to HC transplantation, etc.). The patients at risk for cardiovascular complications should be monitored closely during cryopreserved HC graft infusion, e.g. continuous monitoring of ECG and BP. To reduce the side effects of cryopreservation agent DMSO, the amount of infused DMSO could be decreased by centrifugation right before the HC graft infusion [14]. The drawback of this procedure is a sig- nificant loss of HC (according to our experience up to 30%) which may result in delayed engraftment. Ano- ther possibility is to fractionate the application of HC graft in more consecutive days and thereby reduce the total daily DMSO dose and toxicity [15]. To conclude, HC graft infusions cryopreserved with DMSO could cause statistically significant increases in SBP and DBP, without changes in HR. Patients with preexisting cardiovascular disease should by moni- tored closely during HC transplantation. Alternatively, the amount of DMSO could be depleted before HC graft infusions. ACKNOWLEDGMENTS The work was supported by research projects MO 0FVZ 0000503 (Czech Ministry of Defence) and MZO 00179906 (Czech Ministry of Health). REFERENCES David NA. 1. The pharmacology of dimethyl sulfoxide. Annu Rev Pharmacol 1972; 12: 353–74. Santos NC, Figueira-Coelho J, Martins-Silva J, Sal-2. danha C. Multidisciplinary utilization of dimethyl sulfoxide: pharmacological, cellular, and molecular aspects. Biochem Pharmacol 2003; 65: 1035–41. Rowley SD. 3. 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Donmez A, Tombuloglu M, Gungor A, 10. et al. Clinical side effects during peripheral blood progenitor cell infusion. Transfus Apher Sci 2007; 36: 95–101. Davis JM, Rowley SD, Braine HG, 11. et al. Clinical toxicity of cryopreserved bone marrow graft infusion. Blood 1990; 75: 781–6. Keung YK, Lau S, Elkayam U, 12. et al. Cardiac arrhyth- mia after infusion of cryopreserved stem cells. Bone Marrow Transplant 1994; 14: 363–7. López-Jiménez J, Cerveró C, Muñoz A, 13. et al. Car- diovascular toxicities related to the infusion of cryopreserved grafts: results of a controlled study. Bone Marrow Transplant 1994; 13: 789–93. Syme R, Bewick M, Stewart D, 14. et al. The role of deple- tion of dimethyl sulfoxide before autografting: on hematologic recovery, side effects, and toxicity. Biol Blood Marrow Trans- plant 2004; 10: 135–41. Martino M, Morabito F, Messina G, 15. et al. Frac- tionated infusions of cryopreserved stem cells may prevent DMSO-induced major cardiac complications in graft reci- pients. Haematologica 1996; 81: 59–61. Copyright © Experimental Oncology, 2009