CLINICAL NEWS
Eighteen patients received unrelated donor grafts (15
matched and 3 single-allele mismatched).
Primary myeloid engraftment was achieved in 19
of 20 patients (95%) at a median of 22 days post-HCT
(range 1-35 days). The single patient who had primary
graft failure was observed to have DC-related liver
disease and hypersplenism, the researchers noted. A
splenectomy was performed at 47 days post-HCT, which
“promptly revealed donor myeloid engraftment,” they
wrote.
Of the remaining 19 patients, 16 had sustained my-
eloid engraftment at a median post-
HCT follow-up of 21 months (range
= 1-74 months).
Removing the
“necessary
evils” of DNA-
alkylating
agents and
radiation
could enable
transplant
in high-risk
patients.
Three patients experienced second-
ary graft failure, two of whom had early
graft rejection but underwent success-
ful repeat HCT using higher-intensity
regimens. The third patient maintained
high donor chimerism after primary
engraftment but developed severe
neutropenia in the setting of multiple
viral reactivations and died of a fungal
infection 90 days post-HCT. Another
patient died as a result of DC-related
gastrointestinal complications at 19
months post-HCT.
Although it is difficult to compare
the post-HCT outcomes observed
in this single-arm trial with other
approaches, Dr. Agarwal said that the
mortality rates at 100 days post-HCT
and overall survival “appear to be
superior to other regimens.” Also,
“engraftment appears to be non-
inferior, despite the complete omis-
sion of alkylators and radiation.”
Four patients developed chronic
GVHD, classified as limited (involving
only localized skin and/or liver) in
three patients and extensive (gen-
eralized skin or limited disease plus
involvement of other organs) in one
patient. These patients were treated
successfully with limited courses of
topical or oral steroids, and “none
of the 16 patients who engrafted
ASHClinicalNews.org
durably under the protocol regimen had acute GVHD,
despite the fact that 90 percent had unrelated donors,”
Dr. Agarwal added.
“Long-term follow-up will be important to assess
whether avoiding the damaging effects of radiation and
alkylating agents slowed the progression or prevented
other life-threatening problems, such as cancer and lung
and liver disease, to which these patients are predis-
posed,” he concluded.
He also noted that because this protocol was limited
to HCT recipients with related or unrelated donors,
human leukocyte antigen 7/8 or 8/8 matches, and bone
marrow grafts, “we need to develop the best approach
for patients who don’t have such donors and for patients
with myelodysplastic syndromes/acute myeloid leuke-
mia due to an underlying telomere disease.”
The authors report no relevant conflicts of interest.
REFERENCE
Agarwal S, Myers KC, Antin JH, et al. Hematopoietic cell transplantation without radiation or DNA
alkylating agents in bone marrow failure with short telomeres. Abstract LBA2. Presented at the
Transplantation & Cellular Therapy Meetings of ASBMT and CIBMTR, February 24, 2019; Houston, TX.