The mutations were found in about 30% of 401 patients with
non-Hodgkin lymphoma (NHL) whose blood was sampled at the time they
received autologous transplants, the scientists reported at the 58th
annual meeting of the American Society of Hematology in San Diego. Patients older than 60 were more likely to carry the
mutations, which occurred in several different genes, and were acquired,
‘A significant percentage of lymphoma patients undergoing transplants with their own blood stem cells carry acquired genetic mutations that increase their risks of developing second hematologic cancers.’
Transplant recipients who were mutation carriers had a higher risk -
14.4% versus 4.4% - of developing a second blood cancer
over the next 10 years compared with those lacking the mutation. The
second cancers were acute myeloid leukemia (AML) and myelodysplastic
Carriers of the mutations were also less likely to survive for 10
years (30.6% versus 60.9%) than individuals lacking the
mutations. The greater mortality in mutation carriers wasn't only due to
second cancers, but was also the result of other conditions such as
heart attacks and strokes, for reasons the scientists say aren't yet
The most commonly mutated gene in the transplant patients was PPM1D,
which plays a key role in cells' DNA damage repair toolkit.
The mutations cause an abnormal condition called CHIP (clonal
hematopoiesis of indeterminate potential), an age-related phenomenon
that occurs in 10 to 15% of patients over age 65. In clonal
hematopoiesis, some blood-forming stem cells acquire mutations and spawn
clones - subpopulations of identical cells that expand because they
have gained a competitive advantage over normal stem cells. Individuals
with CHIP don't have symptoms or obvious abnormalities in their blood
counts, but researchers are studying whether CHIP in some cases might
represent the earliest seeds of blood cancers.
The new study is the first to systematically look at how CHIP
influences outcomes in patients undergoing autologous stem cell
transplants, according to the report, whose first author is Christopher
J. Gibson of Dana-Farber. The senior author is Benjamin L. Ebert of Dana-Farber/Brigham and Women's Cancer Center.
Gibson noted that 30% of the patients with CHIP had more than
one mutation, and those patients had even greater odds of developing
second cancers and their overall survival was worse than individuals
having only one mutation.
The CHIP mutations may be caused by a combination of aging and prior
treatment with chemotherapy for their disease, and could also be
related to the lymphoma itself, Gibson said.
The authors said the study findings may have clinical implications.
"They suggest the need to specifically study the connection between CHIP
and lymphoma more deeply, which could be accomplished by assessing CHIP
in patients with newly diagnosed lymphoma prior to the administration
of any chemotherapy or mobilizing agents," they wrote. "They also
suggest the need to consider alternative therapeutic approaches" for
lymphoma patients who have a high risk of developing second cancers and
are being considered for autologous stem cell transplants.