Evaluation of Toxicity From Stem Cell Transplant
| Status: | Completed |
|---|---|
| Conditions: | Hematology |
| Therapuetic Areas: | Hematology |
| Healthy: | No |
| Age Range: | 10 - 80 |
| Updated: | 1/13/2019 |
| Start Date: | February 29, 2008 |
| End Date: | December 7, 2015 |
Evaluation of Systemic Toxicity Associated With Allogeneic Peripheral Blood Stem Cell Infusion
This study will try to determine what causes toxic side effects of stem cell transplantation,
such as increased blood pressure, increased heart rate, decreased kidney function and
abnormal heart rhythms. Stem cells are used to treat various diseases, including cancer,
aplastic anemia and sickle cell disease. The cells may be given fresh to the patient or they
may be preserved first with a chemical called DMSO and frozen for later use. Some stem cell
transplant procedures include infusion of red blood cells along with the stem cells. This
study will examine whether side effects of stem cell transplants are associated with the DMSO
preservative in frozen cells or with hemoglobin (a protein released from defrosted red blood
cells) or neither of these factors.
Healthy volunteers and patients scheduled to receive a stem cell transplant may be eligible
for this study. Candidates must be between 10 and 80 years of age.
Transplant patients will undergo a stem cell transplant. The cells are infused through a
catheter placed in a vein for the procedure. Depending on the patient s requirements, the
infusion may or may not include red blood cells and may or may not contain DMSO. Healthy
volunteers undergo a 4-hour saline infusion. The saline (water mixed with salt) is infused
through a catheter (plastic tube) placed in a vein in the arm. In addition, all participants
have the following tests and procedures:
- Heart monitoring: Healthy volunteers wear a portable heart monitor, attached to the
chest using four stickers, for 24 hours starting the morning of the infusion. Transplant
patients wear the same device for 48 hours, starting the morning before the infusion.
- Blood draws and urine collections before, during, just after and the morning after the
infusion of saline or stem cells.
- Heart ultrasound before, during or just after and the morning after the infusion.
- Peripheral artery tonometry: A small cup is placed on one finger of each hand to measure
blood flow in the finger. A blood pressure cuff is inflated around the lower arm and
tight pressure is maintained for about 5 minutes.
such as increased blood pressure, increased heart rate, decreased kidney function and
abnormal heart rhythms. Stem cells are used to treat various diseases, including cancer,
aplastic anemia and sickle cell disease. The cells may be given fresh to the patient or they
may be preserved first with a chemical called DMSO and frozen for later use. Some stem cell
transplant procedures include infusion of red blood cells along with the stem cells. This
study will examine whether side effects of stem cell transplants are associated with the DMSO
preservative in frozen cells or with hemoglobin (a protein released from defrosted red blood
cells) or neither of these factors.
Healthy volunteers and patients scheduled to receive a stem cell transplant may be eligible
for this study. Candidates must be between 10 and 80 years of age.
Transplant patients will undergo a stem cell transplant. The cells are infused through a
catheter placed in a vein for the procedure. Depending on the patient s requirements, the
infusion may or may not include red blood cells and may or may not contain DMSO. Healthy
volunteers undergo a 4-hour saline infusion. The saline (water mixed with salt) is infused
through a catheter (plastic tube) placed in a vein in the arm. In addition, all participants
have the following tests and procedures:
- Heart monitoring: Healthy volunteers wear a portable heart monitor, attached to the
chest using four stickers, for 24 hours starting the morning of the infusion. Transplant
patients wear the same device for 48 hours, starting the morning before the infusion.
- Blood draws and urine collections before, during, just after and the morning after the
infusion of saline or stem cells.
- Heart ultrasound before, during or just after and the morning after the infusion.
- Peripheral artery tonometry: A small cup is placed on one finger of each hand to measure
blood flow in the finger. A blood pressure cuff is inflated around the lower arm and
tight pressure is maintained for about 5 minutes.
Allogeneic and autologous bone marrow transplantation is currently the only curative option
for many patients with life-threatening hematologic illnesses and malignancies. Peripheral
blood stem cell (PBSC) infusion has been associated with systemic toxicities including
arrhythmias, hypertension, and organ dysfunction. It has been thought that the preservative
dimethyl sulfoxide (DMSO) that is frequently used to store frozen PBSCs may be the etiology
of the adverse effects that occur during the infusion. However, we hypothesize that the red
blood cells that rupture upon thawing infused with the graft release free hemoglobin which
scavenges nitric oxide. This can lead to systemic vasoconstriction and organ dysfunction. In
this protocol, we will monitor subjects who are undergoing PBSC transplantation with either
fresh grafts that lack DMSO or frozen whole grafts. We will also evaluate patients who
receive purified stem cell grafts, which will contain negligible red blood cells and
associated free hemoglobin. We will then measure the frequency of infusion-related systemic
toxicity and organ dysfunction between the groups.
for many patients with life-threatening hematologic illnesses and malignancies. Peripheral
blood stem cell (PBSC) infusion has been associated with systemic toxicities including
arrhythmias, hypertension, and organ dysfunction. It has been thought that the preservative
dimethyl sulfoxide (DMSO) that is frequently used to store frozen PBSCs may be the etiology
of the adverse effects that occur during the infusion. However, we hypothesize that the red
blood cells that rupture upon thawing infused with the graft release free hemoglobin which
scavenges nitric oxide. This can lead to systemic vasoconstriction and organ dysfunction. In
this protocol, we will monitor subjects who are undergoing PBSC transplantation with either
fresh grafts that lack DMSO or frozen whole grafts. We will also evaluate patients who
receive purified stem cell grafts, which will contain negligible red blood cells and
associated free hemoglobin. We will then measure the frequency of infusion-related systemic
toxicity and organ dysfunction between the groups.
- INCLUSION CRITERIA HEALTHY VOLUNTEERS:
Ages 10 to 80
Normal renal function: creatinine less than 1.5 mg/dL in subjects greater than or equal to
18 years of age, less than or equal to 1.0 mg/dL in subjects 13 to 17 years of age, less
than or equal to 0.7 in subjects 10 to 12 years of age, and proteinuria less than 1+
Normal liver function: bilirubin less than 1.5 mg/dL and transaminases within normal limits
Normal pulmonary arterial pressure by transthoracic echocardiogram (tricuspid regurgitant
velocity less than 2.5 m/s)
Ability to comprehend and willing to sign an informed consent/assent
INCLUSION CRITERIA ALL OTHERS:
Ages 10-80
Otherwise as stated on the subject s primary protocol
EXCLUSION CRITERIA HEALTHY VOLUNTEERS:
History of clinically significant cardiac or pulmonary disease
EXCLUSION CRITERIA ALL OTHERS:
Patients receiving nitrate antihypertensive medications
Clinically unstable patients in which transfer to the intensive care unit is being
considered
Otherwise as stated on the subject s primary protocol
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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