I thought I would start this posting with a broad overview of a typical bone marrow transplant.


Bone marrow transplantations (BMT) is a medical procedure used to treat diseases once thought incurable such as leukemia.  In patients with leukemia, the stem cells in the bone marrow malfunctions, producing an excessive number of defective or immature blood cells or low blood cell counts.  The immature or defective blood cellls interfere with the productions of normal blood cells, accumulate in the bloodstream and may invade other tissue.

A transplant can increase the likelihood of a cure or at least prolong the period of disease-free survival for many patients.  In a bone marrow transplant, the patient's diseased bone marrow is destroyed and healthy marrow is infused into the patient's blood-stream.  In a successful transplant, the new bone marrow migrates to the cavities of the large bones, engrafts and begins producing normal blood cells.  A successful transplant requires the patient be healthy enough to undergo the rigors of the transplant procedure.  

A patient will first undergo several days of chemotherapy and/or radiation which destroys bone marrow and cancerous cellls and makes room for the new bone marrow.  This is callled the conditioning or preparative regimen.  Prior to conditioning, a small flexible tube called a central venous line will be inserted into a large vein in the patient's chest just above the heart.  This tube enables the medical staff to administer drugs and blood products to the patient painlessly, and to withdraw the hundreds of blood samples required during the course of treatment without inserting needles into the patient's arms or hands.

The dosage of chemotherapy and/or radiation given to patients during conditioning is much stronger than dosages administered to patients with the same disease who are not undergoing a BMT.  Patients may become weak, irritable and nauseous.  

A day or two following the chemotherapy and/or radiation treatment, the transplant will occur.  The bone marrow is infused into the patient intravenously in much the same way that any blood product is given.  The transplant is not a surgical procedure.  It takes place in the patient's room, not an operating room.  Patients are checked frequently for signs of fever, chills, hives and chest pains while the bone marrow is being infused.  When the transplant is completed, the days and weeks of waiting begin.  

The two to four weeks immediately following transplant are the most critical.  The high-dose chemotherapy and/or radiation given to the patient during conditioning will have destroyed the patient's bone marrow, crippling the body's "immune" or defense system.  As the patient waits for the transplanted bone marrow to migrate to the cavities of the large bones, set up housekeeping or "engraft," and begin producing normal blood cells, he or she will be very susceptible to infection and excessive bleeding.  Multiple antibiotics and blood transfusions will be administered to the patient to help prevent and fight infection.  Transfusions of platelets will be given to prevent bleeding.  Allergenic patients will receive additional medications to prevent and control graft-versus-host disease (GVHD).

Extraordinary precautions will be taken to minimise the patient's exposure to viruses and bacteria. Blood samples will be taken daily to determine whether or not engraftment has occurred and to monitor organ function.  When the transplanted bone marrow finally engrafts and begins producing normal blood cells, the patient will gradually be taken off the antibiotics, and blood and platelet transfusions will generally no longer be required.  Once the bone marrow is producing a sufficient number of healthy red blood cells, white blood cells and platelets, the patient will be discharged from the hospital, provided  no other complications have developed.  BMT patients typically spend four to eight weeks in the hospital.

After being discharged from the hospital, a patient cintinues recovery at home (or a lodging near the transplant center if the patient is from out of town) for two to four months.  Patients usually cannot return to full-time work or school for up to six months after the transplant.  Though patients will be well enough to leave the hospital, their recovery will be far from over.  For the first several weeks the patient may be too weak to do much more than sleep, sit up, and walk a bit around the house.  Frequent visits to the hospital or associated clinic will be required to monitor the patient's progress, and to administer any medications and/or blood products needed.  It can take six months or more from the day of transplant before a patient is ready to fully resume normal activities.

During this period, the patient's white blood cell counts are often too low to provide normal protection against the viruses and bacteria encountered in everyday life.  Contact with the general public is therfore restricted.  Crowded movie theaters, grocery stores, department stores, etc. are places recovering BMT patients avoid during their recuperation.  Often patients will wear protective masks when venturing outside the home.  

A patients will return to the hospital or clinic as an outpatient several times a week for monitoring, Blood transfusions, and administration of other drugs as needed.  Eventually, the patient becomes strong enough to resume a normal routine and to look forward to a productive, healthy life.  It can take as long as a year for the new bone marrow to function normally.  Patients are closely monitored during this time to identify any infections or complicatons that may develop.


The above timeframe is what Ryan along with his caregivers were anticipating.  Unfortunately, Ryan's bone marrow transplant did not follow the standard outline.  Ryan was initially admitted to the Texas Children's Bone Marrow transplant program on March 23, 2012, 148 days and over 5 months ago.  Since his inital admittance, Ryan has been released to go home on several occasions only to be readmitted within days.  Since Ryan's inital admittance in March, he has only spent 24 DAYS at home.  Not the typical 4 to 8 weeks we had been told.

Ryan's bone marrow transplant was successful in the fact that he is 100 percent "engrafted" and has had no issues with GVHD.  GVHD is when the donor's bone marrow is not a good genetic match and the patient's body will perceive it as a foreign material and will attack and destroy the new marrow which can be life- threatening.

So why is Ryan still in the hospital for over 5 months past his transplant?
  • Cytomegalovirus Viremia (CMV) and Adenovirus,
  • BK Virus with hemorrhagis cystitis,
  • Urinary retention that is secondary to the hemorrhagic cystitis,
  • Fungal infections,
  • Dysuria, and
  • Worsening hematuria
Cytomegalovirus Viremia (CMV) and Adenovirus

Cytomegalovirus (CMV) is a virus that can cause serious infections in patients with suppressed immune systms.  It usually affects the lungs and can cause a very serious pneumonia, but it can also affect the intestinal tract, the liver and the eyes.  Approximately 2/3 of normal people harbor this virus in their body.  In healthy people CMV rarely causes any problems because the immune system can keep it under control.

Adenovirus is a virus that just causes symptoms of a common cold normally but which can cause serious life-threatening infections in patients who have weak immune systems.  It usually affects the lungs and can cause a very serious pneumonia, but it can affect the gut, the liver, the pancreas and the eyes.

We have been treating Ryan with Antiviral medications to keep these virus under control, but unfortunately Ryan is also fighting the BK virus with severe hemorrhagic cystitis which is making it very difficult for his body to fight all of these complications at once.

In order to help Ryan and his immune system, he will be participating in a specail study where T cells have been grown in a special way to help treat these viruses.

Since these specially trained T cell (called CTLs) take 2-3 months to make the cells, we will be using another donor who matches as closely as possible to Ryan and if the CTLs last in his body, they will attack both of these viruses and help eliminate some of the energy Ryan's body is using to help fight the BK virus.

BK Virus with hemorrhagic Cystitis (HC)

The association of the BK virus infection with hemorrhagic cystitis in BMT receipients is a common complicaton following high-dose chemotherapy and a BMT.  The BK virus is a common virus that most of us are carriers of, but it remains dormant and asymptomatic for people with healthy immune systems.  Generally, only when the immune system is compromised does it cause a problem, such as a an organ transplant.

Hemorrhagic cystitis (HC) is a cause of morbidity and occasional mortality in patients undergoing bone marrow transplantation.  The manifestations vary from microscopic hematuria to severe bladder hemorrhage leading to clot retention and renal failure.  In Ryan's case, he is experiencing severe bladder hemorrhage and clot retention.  Ryan is currently being treated with blood and platelet transfusions to replace the blood lost through the bladder hemorrhage, continuous bladder irrigation (CBI), and cystoscopy.

In the past two months, Ryan has developed blood closts in his bladder that were the size of a large grapefruit.  In order to remove these clots, it took two Urology doctors, 28 catheters, and over 9 hours of manual irrigation to remove just half of the blood clot so that we could start the CBI which would break down the rest of the remaining clot.  I know most of you are thing, "Hopefully Ryan was not awake during this," but unfortunately he was.  In addition, Ryan's clots were so big and and hard, the doctors had to get an adult size catheter from Saint Luke's Hospital in order to complete the procedure.  The alternative was surgery.

Ryan has improved with intravesical and intravenous cidofovir and he continues to have occasional blood clots but for the most part he is asymptomatic.  The current plan is to remove the catheter in the next two to three weeks after discontinuing the CBI.

Are hope is that the CTLs Ryan will be receiving for the CMV and adenovirus will help significantly with his BK virus.  However, if his continues to struggle, a new study is being developed to genetically modify T cells specific to the BK virus.  We are hoping that this study will be available in September and Ryan will be one of the first participants of the study.