Evaluation of Toxicity From Stem Cell Transplant
Condition: Organ Dysfunction; Hemolysis
MeSH terms: Hemolysis
Study type: Observational

Summary: 
      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.
    

Detailed description: 
      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.
    

Time perspective: Prospective
Keywords: Nitric Oxide; Hemolysis; Plasma Hemoglobin; Dimethyl Sulfoxide; Organ Dysfuntion; Healthy Volunteer; HV