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Kinder, Gentler Procedure Gives Superior Results For Stem Cell Transplants

Date:
December 29, 2004
Source:
Washington University School Of Medicine
Summary:
An improved stem cell transplant regimen that is well-tolerated and has a high success rate has been developed by researchers at Washington University School of Medicine in St. Louis. The procedure holds promise for treatment of blood and bone marrow disorders, immune dysfunction and certain metabolic disorders.

St. Louis, Dec. 13, 2004 -- An improved stem cell transplant regimen that is well-tolerated and has a high success rate has been developed by researchers at Washington University School of Medicine in St. Louis. The procedure holds promise for treatment of blood and bone marrow disorders, immune dysfunction and certain metabolic disorders.

Designed for transplants that replace a patient's bone marrow with stem cells from donor marrow, peripheral blood or umbilical cord blood, the procedure allows early recovery of immune function, nearly eliminates transplant rejection, and decreases the incidence and severity of "graft vs. host disease," a common complication in transplants.

Termed a "reduced-intensity" protocol, in pediatric patients it may minimize damage to sensitive growing tissues like the brain and reproductive organs.

The pilot study of the procedure is reported in the journal Bone Marrow Transplantation. It is available through advance online publication on Dec. 13 and will appear in a future print issue.

The regimen was administered to 11 pediatric and 5 adult patients at St. Louis Children's and Barnes-Jewish hospitals and the Children's Hospital of New Orleans who had non-malignant bone marrow or metabolic disorders such as sickle cell anemia, thalassemia or Hurler's syndrome. Symptoms and disease parameters stabilized or improved in all patients that underwent successful transplants.

In a successful stem cell transplant, the donor stem cells become permanently established, or engrafted, in the patient's bone marrow and continually produce healthy blood cells. To prevent the host immune system from destroying the foreign stem cells, physicians administer a pretransplant immune suppressing treatment.

"We wanted an approach that would effectively knock out the patient's immune system to let the transplanted cells engraft, but then allow immune function to recover quickly," says study leader Shalini Shenoy, M.D., assistant professor of pediatrics and faculty member of the Siteman Cancer Center.

A key innovation in this study changes the timing of administering a powerful pretransplant conditioning drug. The drug, Campath-1H, targets and destroys several vital immune system components. Previous studies used Campath-1H in higher doses and gave the drug at transplant time. With such dosing, Campath stayed in the body for up to 56 days after the transplant.

"We give a short, three-day, lower-dose treatment of Campath, three weeks in advance of transplant," Shenoy says. "As a result, we ensure that Campath levels are lower by the time of transplant to help establish donor cells and allow early recovery of immune function."

With standard transplant protocols, immune function may not fully recover for a year or more, and during this time, the patient is highly susceptible to life-threatening infections. In this study, the patients' immune function showed significant recovery by six months, and no major infections were encountered after this period.

Fourteen of the 16 patients had successful bone marrow engraftment of the donor stem cells and only one experienced late graft rejection, an unusually high rate of success according to Shenoy. Furthermore, the grafts took hold quickly. Donor stem cells had established in the bone marrow completely at one month, contrasting with other reduced-intensity protocols where donor engraftment is gradual and often takes many months.

The protocol also reduced the incidence and severity of graft vs. host disease, which occurs when transplanted immune cells attack various cells in the body. For the majority of patients who experienced graft vs. host disease, the symptoms were limited to the skin and were controlled with treatments that were later successfully withdrawn.

To minimize damage to still-growing tissues such as the brain and reproductive organs in pediatric patients, the protocol uses smaller doses of standard conditioning chemotherapeutic agents.

"In the past, physicians had to accept the potential for brain damage or sterility in pediatric patients treated with chemotherapy," Shenoy says. "We're trying to provide treatments that protect developing tissues. We've had our first pregnancy and normal delivery in one of our stem cell transplant patients, so we think the protocol offers some hope."

Next, Shenoy plans to evaluate whether changing parameters and further reducing chemotherapy doses would enhance the protocol's effectiveness. She will also conduct studies targeted at sickle cell anemia and chronic myelogenous leukemia to explore the potential for successful transplants in children with these disorders.

###

Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ, Mohanakumar T, Rao A, Hayashi RJ. A novel reduced intensity stem cell transplant regimen for non-malignant disorders. Bone Marrow Transplantation, upcoming issue.

Funding from St. Louis Children's Hospital Foundation supported this research.

Washington University School of Medicine's full-time and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.


Story Source:

The above story is based on materials provided by Washington University School Of Medicine. Note: Materials may be edited for content and length.


Cite This Page:

Washington University School Of Medicine. "Kinder, Gentler Procedure Gives Superior Results For Stem Cell Transplants." ScienceDaily. ScienceDaily, 29 December 2004. <www.sciencedaily.com/releases/2004/12/041220004843.htm>.
Washington University School Of Medicine. (2004, December 29). Kinder, Gentler Procedure Gives Superior Results For Stem Cell Transplants. ScienceDaily. Retrieved September 15, 2014 from www.sciencedaily.com/releases/2004/12/041220004843.htm
Washington University School Of Medicine. "Kinder, Gentler Procedure Gives Superior Results For Stem Cell Transplants." ScienceDaily. www.sciencedaily.com/releases/2004/12/041220004843.htm (accessed September 15, 2014).

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