Clinical toxicity of cryopreserved bone marrow graft infusion

Janice Davis Sproul, Scott D. Rowley, Hayden G. Braine, Steven Piantadosi, George W. Santos

Research output: Contribution to journalArticle

Abstract

We prospectively evaluated infusion-related toxicities in 82 recipients of autologous bone marrow grafts. The grafts were cryopreserved in 10% dimethylsulfoxide and stored in liquid nitrogen. All grafts were concentrated and buffy-coat cells were collected. Forty-seven grafts were treated ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 100 μg/mL; 26 grafts were further processed using densitygradient separation and treated with 4-HC at 60 μg/mL. Nine buffy-coat concentrates were frozen without drug treatment. Before infusion, patients were medicated with mannitol, hydrocortisone, and diphenhydramine. Grafts were rapidly thawed and immediately infused without further manipulation. During the infusions, 33 (70%) recipients of treated buffy-coat, 5 (56%) recipients of untreated buffy-coat, and 6 (23%) recipients of density-gradient separated grafts experienced varying symptoms including nausea, abdominal cramping, and flushing. Forced vital capacities for 83% of the recipients of treated buffy-coat concentrates decreased after the graft infusion; six of these patients complained of dyspnea and one patient experienced an acute episode of respiratory decompensation. Decreased heart rates were observed in 98% of the recipients of treated buffy-coat cells with asymptomatic bradycardia occurring in 45%. Forty-five patients (96%) in this group experienced transient hypertension, with 18 (38%) requiring additional medications within 6 hours after the infusion for control of blood pressure. Similar cardiovascular changes were observed in the recipients of untreated buffy-coat concentrates. One recipient of an untreated buffy-coat concentrate had 2° heart block after the graft infusion. Twenty-three (88%) recipients of density-gradient separated grafts had decreased heart rates and 21 (81 %) had increased blood pressure. However, the degrees of change were less than those experienced by the recipients of treated buffy-coat cells (P <.01). Forced vital capacities were not affected by the infusion of the densitygradient separated grafts. No renal failure or obvious hemolytic episodes occurred for any patient group. Minor to moderate toxicities were associated with cryopreserved graft infusions. Recipients of buffy-coat separated grafts, both treated and untreated, experienced more complications than the recipients of density-gradient separated grafts. These toxicities may relate to the volumes of cryoprotectant and cell lysis products infused, which were less for the more highly purified density-gradient separated grafts.

Original languageEnglish (US)
Pages (from-to)781-786
Number of pages6
JournalBlood
Volume75
Issue number3
StatePublished - Feb 1 1990

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Grafts
Toxicity
Bone
Bone Marrow
Transplants
perfosfamide
Glycocalyx
Vital Capacity
Blood pressure
Heart Rate
Blood Pressure
Drug therapy
Diphenhydramine
Heart Block
Mannitol
Liquid nitrogen
Bradycardia
Dimethyl Sulfoxide
Cell Size
Dyspnea

ASJC Scopus subject areas

  • Hematology

Cite this

Davis Sproul, J., Rowley, S. D., Braine, H. G., Piantadosi, S., & Santos, G. W. (1990). Clinical toxicity of cryopreserved bone marrow graft infusion. Blood, 75(3), 781-786.

Clinical toxicity of cryopreserved bone marrow graft infusion. / Davis Sproul, Janice; Rowley, Scott D.; Braine, Hayden G.; Piantadosi, Steven; Santos, George W.

In: Blood, Vol. 75, No. 3, 01.02.1990, p. 781-786.

Research output: Contribution to journalArticle

Davis Sproul, J, Rowley, SD, Braine, HG, Piantadosi, S & Santos, GW 1990, 'Clinical toxicity of cryopreserved bone marrow graft infusion', Blood, vol. 75, no. 3, pp. 781-786.
Davis Sproul J, Rowley SD, Braine HG, Piantadosi S, Santos GW. Clinical toxicity of cryopreserved bone marrow graft infusion. Blood. 1990 Feb 1;75(3):781-786.
Davis Sproul, Janice ; Rowley, Scott D. ; Braine, Hayden G. ; Piantadosi, Steven ; Santos, George W. / Clinical toxicity of cryopreserved bone marrow graft infusion. In: Blood. 1990 ; Vol. 75, No. 3. pp. 781-786.
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abstract = "We prospectively evaluated infusion-related toxicities in 82 recipients of autologous bone marrow grafts. The grafts were cryopreserved in 10{\%} dimethylsulfoxide and stored in liquid nitrogen. All grafts were concentrated and buffy-coat cells were collected. Forty-seven grafts were treated ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 100 μg/mL; 26 grafts were further processed using densitygradient separation and treated with 4-HC at 60 μg/mL. Nine buffy-coat concentrates were frozen without drug treatment. Before infusion, patients were medicated with mannitol, hydrocortisone, and diphenhydramine. Grafts were rapidly thawed and immediately infused without further manipulation. During the infusions, 33 (70{\%}) recipients of treated buffy-coat, 5 (56{\%}) recipients of untreated buffy-coat, and 6 (23{\%}) recipients of density-gradient separated grafts experienced varying symptoms including nausea, abdominal cramping, and flushing. Forced vital capacities for 83{\%} of the recipients of treated buffy-coat concentrates decreased after the graft infusion; six of these patients complained of dyspnea and one patient experienced an acute episode of respiratory decompensation. Decreased heart rates were observed in 98{\%} of the recipients of treated buffy-coat cells with asymptomatic bradycardia occurring in 45{\%}. Forty-five patients (96{\%}) in this group experienced transient hypertension, with 18 (38{\%}) requiring additional medications within 6 hours after the infusion for control of blood pressure. Similar cardiovascular changes were observed in the recipients of untreated buffy-coat concentrates. One recipient of an untreated buffy-coat concentrate had 2° heart block after the graft infusion. Twenty-three (88{\%}) recipients of density-gradient separated grafts had decreased heart rates and 21 (81 {\%}) had increased blood pressure. However, the degrees of change were less than those experienced by the recipients of treated buffy-coat cells (P <.01). Forced vital capacities were not affected by the infusion of the densitygradient separated grafts. No renal failure or obvious hemolytic episodes occurred for any patient group. Minor to moderate toxicities were associated with cryopreserved graft infusions. Recipients of buffy-coat separated grafts, both treated and untreated, experienced more complications than the recipients of density-gradient separated grafts. These toxicities may relate to the volumes of cryoprotectant and cell lysis products infused, which were less for the more highly purified density-gradient separated grafts.",
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N2 - We prospectively evaluated infusion-related toxicities in 82 recipients of autologous bone marrow grafts. The grafts were cryopreserved in 10% dimethylsulfoxide and stored in liquid nitrogen. All grafts were concentrated and buffy-coat cells were collected. Forty-seven grafts were treated ex vivo with 4-hydroperoxycyclophosphamide (4-HC) at 100 μg/mL; 26 grafts were further processed using densitygradient separation and treated with 4-HC at 60 μg/mL. Nine buffy-coat concentrates were frozen without drug treatment. Before infusion, patients were medicated with mannitol, hydrocortisone, and diphenhydramine. Grafts were rapidly thawed and immediately infused without further manipulation. During the infusions, 33 (70%) recipients of treated buffy-coat, 5 (56%) recipients of untreated buffy-coat, and 6 (23%) recipients of density-gradient separated grafts experienced varying symptoms including nausea, abdominal cramping, and flushing. Forced vital capacities for 83% of the recipients of treated buffy-coat concentrates decreased after the graft infusion; six of these patients complained of dyspnea and one patient experienced an acute episode of respiratory decompensation. Decreased heart rates were observed in 98% of the recipients of treated buffy-coat cells with asymptomatic bradycardia occurring in 45%. Forty-five patients (96%) in this group experienced transient hypertension, with 18 (38%) requiring additional medications within 6 hours after the infusion for control of blood pressure. Similar cardiovascular changes were observed in the recipients of untreated buffy-coat concentrates. One recipient of an untreated buffy-coat concentrate had 2° heart block after the graft infusion. Twenty-three (88%) recipients of density-gradient separated grafts had decreased heart rates and 21 (81 %) had increased blood pressure. However, the degrees of change were less than those experienced by the recipients of treated buffy-coat cells (P <.01). Forced vital capacities were not affected by the infusion of the densitygradient separated grafts. No renal failure or obvious hemolytic episodes occurred for any patient group. Minor to moderate toxicities were associated with cryopreserved graft infusions. Recipients of buffy-coat separated grafts, both treated and untreated, experienced more complications than the recipients of density-gradient separated grafts. These toxicities may relate to the volumes of cryoprotectant and cell lysis products infused, which were less for the more highly purified density-gradient separated grafts.

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