Kinder Procedure Gives Improved Stem Cell Results

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Kinder, Gentler Procedure Gives Superior Results For Stem Cell

Transplants

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 -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.

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Shenoy S, Grossman WJ, DiPersio J, Yu LC, D, YJ,

Mohanakumar T, Rao A, Hayashi RJ. A novel reduced intensity stem cell

transplant regimen for non-malignant disorders. Bone Marrow

Transplantation, upcoming issue.