MEETING NEWS
was able to undergo a second alloHCT. For patients in group
B, overall survival after T-cell infusion ranged from four to 21
months, the authors observed.
To determine any correlation between response and in vivo
expansion of the infused leukemia-specific T-cell clones, the
investigators monitored circulating T-cell clones with T-cell
receptor deep sequencing. Compared with nonresponders,
patients who responded to treatment had demonstrated greater
expansion of product-derived clones.
“T cells targeted against multiple leukemia-associated
antigens directed to PRAME, WT1, NYESO1, and Survivin can
be safely administered to patients with AML/MDS, in whom
long-term and produce sustained responses can subsequently be
detected,” Dr. Lulla concluded.
The results of the trial are limited by the small patient popu-
lation, and Dr. Lulla noted that the investigators are now analyz-
ing these data to determine the effects of antigen spreading, “as
well as to elucidate mechanisms of antigen escape.”
The authors report relationships with Marker Therapeutics,
which sponsored this trial.
REFERENCE
Lulla P, Naik S, Tzannou I, et al. Administering leukemia-directed donor lymphocytes
to patients with AML or MDS to prevent or treat post-allogeneic HSCT relapse.
Abstract #11. Presented at the Transplantation & Cellular Therapy Meetings of
ASBMT and CIBMTR, February 20, 2019; Houston, TX.
Prognostic Significance of
Post-Transplant MRD Varies
Based on Conditioning
Regimen in ALL
Assessment of measurable residual disease (MRD) prior to
allogeneic hematopoietic cell transplantation (alloHCT) is
an established important prognostic factor in patients with
acute lymphocytic leukemia (ALL). According to results from
a retrospective study, the presence of MRD after alloHCT also
has prognostic value, and the significance of MRD differs
depending on the type of conditioning regimen.
Jiri Pavlu, MD, from Imperial College at Hammersmith
Hospital in London, presented the findings at the 2019 Trans-
plantation & Cellular Therapy (TCT) Meetings of ASBMT and
CIBMTR.
“In this large study, we confirmed that patients who are
MRD-negative prior to alloHCT achieve superior outcomes,”
Dr. Pavlu reported. “This was particularly apparent if total-
body irradiation conditioning was used.”
The researchers conducted this retrospective multicenter
20
Focus on Myeloid Malignancies
study to explore whether the prevalence of post-alloHCT
MRD differed when a patient underwent conditioning with
total-body irradiation versus chemotherapy. They analyzed
outcomes from 2,780 patients (median age = 38 years; range =
18-72 years) who underwent a first alloHCT in complete re-
mission between 2000 and 2017. All participants had alloHCT
with a sibling or unrelated 9/10 or 10/10 human leukocyte
antigen (HLA)-matched donor.
Before alloHCT, 1,816 patients (65.3%) had no detectable
disease (MRD-negativity) and 964 patients (34.7%) were
MRD-positive. Most patients (n=2,122; 76%) underwent con-
ditioning with total-body irradiation.
In the entire cohort, the authors observed that MRD-positive
status pre-alloHCT was an independent predictor for poorer
survival and higher risk of relapse (p values not reported):
• hazard ratio (HR) for overall survival (OS): 1.19 (95% CI
1.02-1.39)
• HR for leukemia-free survival (LFS): 1.26 (95% CI 1.1-
1.44)
• HR for relapse incidence (RI): 1.51 (95% CI 1.26-1.8)
When the researchers examined the relationship between
MRD and conditioning regimen, they found that, in the
total-body irradiation cohort, MRD-positivity before alloHCT
was associated with lower OS and LFS, but higher RI:
• HR for OS: 1.26 (95% CI 1.05-1.51)
• HR for LFS: 1.3 (95% CI 1.1-1.53)
• HR for RI: 1.53 (95% CI 1.23-1.9)
In the chemotherapy-based conditioning cohort, however, only
the risk of relapse was higher among MRD-positive patients
(HR=1.58; 95% 1.13-2.21).
“Total-body irradiation–based conditioning was associated
with improved OS, LFS, and RI in both MRD-negative and
MRD-positive patients,” the authors concluded. Based on these
findings, they wrote that “all patients with ALL, irrespective
of MRD status [before alloHCT], benefit from total-body
irradiation–based conditioning in the myeloablative setting.” ●
The authors report no relevant conflicts of interest.
REFERENCE
Pavlu J, Labopin M, Niittyyuopio R, et al. The role of measurable residual disease
(MRD) at time of allogeneic hematopoietic cell transplantation in adults with acute
lymphoblastic leukemia transplanted after myeloablative conditioning: a study on
behalf of the Acute Leukemia Working Party of the European Society for Blood and
Marrow Transplantation. Abstract #7. Presented at the Transplantation & Cellular
Therapy Meetings of ASBMT and CIBMTR, February 20, 2019; Houston, TX.