Stem cell transplant without radiation or chemotherapy pre-treatment shows promise

December 7, 2014, Dana-Farber Cancer Institute

Researchers at Dana-Farber/Boston Children's Cancer and Blood Disorders Center report promising outcomes from a clinical trial with patients with a rare form of bone marrow failure who received a hematopoietic stem cell transplant (HSCT) after pre-treatment with immunosuppressive drugs only. This is the first trial reporting successful transplant in dyskeratosis congenita (DC) patients without the use of any radiation or conventional cytotoxic chemotherapy beforehand.

The trial's data were presented by study authors Leslie Lehmann, MD, and Suneet Agarwal, MD, PhD, of Dana-Farber/Boston Children's, at the 56th annual meeting of the American Society of Hematology (abstract #2941). The data suggest that this immunosuppression-only approach could benefit patients with DC—and, perhaps, other syndromes—who are at high risk of poor transplant outcomes because they cannot tolerate the toxicity of conventional or even reduced-intensity conditioning.

All four participants in the study are alive and well between 10 and 27 months after transplant. None remain dependent on transfusions to maintain blood counts, nor did any experience significant unexpected toxicities or infections during or after transplantation. Were it not for this new regimen, one patient would have been ineligible for transplant due to severe DC-related lung disease.

Conventional transplant conditioning employs radiation and/or high-dose cytotoxic drugs (also known as alkylators) to destroy the bone marrow and blood and ; it also causes widespread cellular damage throughout the body. The process prepares the patient's body to accept the donated , reducing the risk of rejection and providing a hospitable environment for the new cells to engraft, thrive and produce new blood and immune cells.

In DC and other bone marrow failure syndromes, however, the disease itself already weakens or destroys the patient's bone marrow, raising the question of whether a less toxic approach could effectively condition patients for transplant.

"These data show that it is possible to achieve engraftment within the context of DC using immunosuppression-only conditioning. This experience begs the question of whether we can think more broadly about this approach's applicability for other conditions, something I think is worth considering," Agarwal said.

"Bone marrow failure syndromes are problems of blood and immune cell production," he added. "In theory, then, in some of these conditions it should be possible for healthy donated stem cells to outcompete native cells, without exposing patients to the toxic effects of radiation or alkylating agents."

Eighty percent of patients with DC develop bone marrow failure before reaching age 30. The genetic defects underlying the disease prevent cells from maintaining their telomeres, the caps at the ends of chromosomes that gradually shorten as cells divide and a person ages. As a result, DC patients' age prematurely and do not divide well. While an HSCT can cure the resulting failure, outcomes are often poor, likely because of the toxicity associated with conventional conditioning.

The cellular defects in DC created an opportunity for Agarwal and his collaborators to attempt immunosuppression-only pre-transplant conditioning. Tamping down a patient's immune system, they theorized, would give donor stem cells and their progeny a chance to outcompete the patient's existing with a minimal risk of rejection. At the same time, avoiding radiation and alkylators—which cause widespread cellular damage throughout the body—should reduce the risk of long-term HSCT-related complications, such as organ failure and cancer.

Explore further: Disease decoded: Gene mutation may lead to development of new cancer drugs

Related Stories

Disease decoded: Gene mutation may lead to development of new cancer drugs

September 30, 2014
The discovery of a gene mutation that causes a rare premature aging disease could lead to the development of drugs that block the rapid, unstoppable cell division that makes cancer so deadly.

Bone marrow transplantation shows potential for treating adults with sickle cell disease

July 1, 2014
Use of a lower intensity bone marrow transplantation method showed promising results among 30 patients (16-65 years of age) with severe sickle cell disease, according to a study in the July 2 issue of JAMA.

Drug regimen enough to control immune disease after some bone marrow transplants

October 8, 2014
Johns Hopkins and other cancer researchers report that a very short course of a chemotherapy drug, called cyclophosphamide, not only can prevent a life-threatening immune response in some bone marrow transplant recipients, ...

Rare cause of anemia in newborns often overlooked, research suggests

December 7, 2013
Some babies diagnosed with and treated for a bone marrow failure disorder, called Diamond Blackfan Anemia, may actually be affected by a very rare anemia syndrome that has a different disease course and treatment, say scientists ...

No survival advantage with peripheral blood stem cells versus bone marrow

October 19, 2012
(Medical Xpress)—Claudio Anasetti, M.D., chair of the Department of Blood & Marrow Transplant at Moffitt Cancer Center, and colleagues from 47 research sites in the Blood and Marrow Transplant Clinical Trials Network conducted ...

Immune cells found to prevent bone marrow transplant rejection

June 27, 2014
(Medical Xpress)—Cornell researchers have identified a type of immune system cell that prevents a patient's body from attacking donor cells after a bone marrow transplant, a condition called graft-versus-host disease (GVHD).

Recommended for you

Breakthrough article on mechanistic features of microRNA targeting and activity

March 23, 2018
Giovanna Brancati and Helge Grosshans from the FMI have described target specialization of miRNAs of the let-7 family. They identified target site features that determine specificity, and revealed that specificity can be ...

Boosting enzyme may help improve blood flow, fitness in elderly

March 22, 2018
As people age, their blood-vessel density and blood flow decrease, which is why it's harder to maintain muscle mass after 40 and endurance in the later decades, even with exercise. This vascular decline is also one of the ...

Scientists pinpoint cause of vascular aging in mice

March 22, 2018
We are as old as our arteries, the adage goes, so could reversing the aging of blood vessels hold the key to restoring youthful vitality?

Sulfur amino acid restriction diet triggers new blood vessel formation in mice

March 22, 2018
Putting mice on a diet containing low amounts of the essential amino acid methionine triggered the formation of new blood vessels in skeletal muscle, according to a new study from Harvard T.H. Chan School of Public Health. ...

Cold can activate body's 'good' fat at a cellular level, study finds

March 21, 2018
Lower temperatures can activate the body's 'good' fat formation at a cellular level, a new study led by academics at The University of Nottingham has found.

Gradual release of immunotherapy at site of tumor surgery prevents tumors from returning

March 21, 2018
A new study by Dana-Farber Cancer Institute scientists suggests it may be possible to prevent tumors from recurring and to eradicate metastatic growths by implanting a gel containing immunotherapy during surgical removal ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.