Stem Cell Transplant without Radiation or Chemotherapy Pre-treatment Shows Promise for Rare Bone Marrow Failure
December 08, 2014
transplant success in a rare bone marrow failure syndrome, following
conditioning with immunosuppressive drugs alone
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.
trial's data were presented by study authors Leslie Lehmann, MD, and Suneet Agarwal, MD,
of Dana-Farber/Boston Children's, at the 56th annual meeting of the
American Society of Hematology in San Francisco (abstract #2941). The data
suggest that this immunosuppression-only approach could benefit patients with
DC—and, perhaps, other bone marrow failure syndromes—who are at high risk of
poor transplant outcomes because they cannot tolerate the toxicity of
conventional or even reduced-intensity conditioning.
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
transplant conditioning employs radiation and/or high-dose cytotoxic drugs
(also known as alkylators) to destroy the bone marrow and blood and immune
cells; it also causes widespread cellular damage throughout the body. The
process prepares the patient’s body to accept the donated stem cells, reducing
the risk of rejection and providing a hospitable environment for the new cells
to engraft, thrive and produce new blood and immune cells.
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.
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.
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
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' hematopoietic stem cells age
prematurely and do not divide well. While an HSCT can cure the resulting bone
marrow failure, outcomes are often poor, likely because of the toxicity
associated with conventional conditioning.
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 cells 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.