CLINICAL NEWS
On Location Advances in Transplantation
Alemtuzumab Plus
Myeloablative
Conditioning Reduces
Post-Transplant
GVHD Risk
For younger patients with sickle cell disease (SCD) who
are eligible for a hematopoietic cell transplantation
(HCT), adding alemtuzumab lowered the risk of graft-
versus-host disease (GVHD), without increasing the
risk of graft rejection, according to results from a single-
center study presented at the 2019 Transplantation &
Cellular Therapy Meeting.
“Alemtuzumab is associated with low rates of GVHD,
but also severe immune suppression,” lead author and
presenter Tami John, MD, from Baylor College of
Medicine and Texas Children’s Hospital, told ASH
Clinical News.
To explore the use of myeloablative chemotherapy
with alemtuzumab to prevent GVHD and promote
durable engraftment, the authors retrospectively reviewed
outcomes for 38 patients who underwent HCT with
a matched related donor at Texas Children’s Hospital
between 2003 and 2017. Participants underwent trans-
plant at a median age of 8.6 years (range = 2.9-18.4 years).
Three patients had a non-sibling donor and 35 had a
sibling donor; bone marrow grafts served as the stem cell
source for all patients.
All patients received myeloablative conditioning with
intravenous busulfan every six hours for four days (with
a target area under the curve of 800-1,200 μM/min) and
cyclophosphamide 50 mg/kg daily for four days.
GVHD prophylaxis included methotrexate, a calci-
neurin inhibitor, and alemtuzumab (administered daily in
3-4 doses starting at 5 days prior to HCT). Alemtuzumab
was administered according to patient weight (5-15 kg =
3 mg; 15-30 kg = 5 mg; >30 kg = 10 mg).
Donor chimerism was evaluated periodically via
fluorescence in situ hybridization in patients’ peripheral
blood. Persistent mixed donor chimerism was defined
as the presence of recipient cells on two consecutive
evaluations, without return to full donor chimerism at
last follow-up.
All patients achieved neutrophil engraftment at a
median of 19 days post-HCT (range = 13-24 days). No
patient experienced graft rejection or recurrence of
SCD-related symptoms.
The incidence of persistent mixed donor chimerism
was high, at 60.5 percent, Dr. John reported, although
chimerism stabilized at greater than 50 percent donor
cells in most patients. At last follow-up, the median chi-
merism among all patients was 94 percent donor cells
(range = 24-100%).
“Only two patients had persistent severe mixed do-
nor chimerism (<50% donor cells),” she added. One of
these patients had mixed donor chimerism of less than
25 percent; how-
ever, mixed donor
chimerism stabilized
at 24 percent donor
cells at two years
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28
ASH Clinical News
Attendees browse the posters at the 2019 TCT Meeting.
GVHD had a matched father as a donor, as opposed to a
sibling donor, she noted.
At a median follow-up of 2.9 years (range = 90-4,627
days), the overall survival rate was 94.7 percent. Two
patient deaths occurred during study follow-up, both
of which were attributed to transplant-related compli-
cations; one death occurred within 100 days of HCT
due to disseminated Mycobacterium tuberculosis and
the other occurred 318 days after HCT due to hemo-
phagocytic syndrome. No deaths were attributed to
viral-associated infection, “which typically is a signifi-
cant concern with alemtuzumab,” Dr. John added. Most
patients had viral reactivations, but only three had viral
disease (adenovirus), and most responded to standard
antiviral therapy.
Although the researchers concluded that the
alemtuzumab plus myeloablative conditioning regimen
“may be a promising approach” for patients with SCD
who can tolerate myeloablative chemotherapy, Dr. John
noted that the findings of the study are limited by its
small sample size and the single-center design. Longer
follow-up also is necessary to determine the long-term
stability of the grafts.
Future research could focus on optimal dosing of
alemtuzumab to improve rates of mixed donor chime-
rism. “With new data regarding alemtuzumab pharma-
cokinetic targeting, we could potentially tailor dosing
based on pharmacokinetic data, though our data show
that weight-based dosing of alemtuzumab near the
time of HCT prevents GVHD very effectively in this
group,” she concluded.
The authors report no relevant conflicts of interest. ●
REFERENCE
John T, Yassine K, Naik S, et al. Myeloablative conditioning with alemtuzumab in matched related
donor hematopoietic cell transplant for sickle cell disease prevents graft-versus-host disease
without compromising engraftment. Abstract #49. Presented at the Transplantation & Cellular
Therapy Meetings of ASBMT and CIBMTR, February 22, 2019; Houston, TX.
April 2019