bone marrow transplant (BMT) significantly
reduced relapse rates and
increased event-free survival (EFS)
rates, but not overall survival, in
adults with Philadelphia chromosome
(Ph)-negative acute lymphoblastic
leukemia (ALL) in first complete
Jacob M. Rowe, MD, of Rambam
Medical Center, Haifa, Israel, reported
the intent-to-treat analysis at the
43rd Annual Meeting of the American
Society of Hematology (abstract
2009) on behalf of researchers in an
ongoing joint Medical Research
Council/Eastern Cooperative Oncology
Group study (E2993).
All patients in this protocol receive
two phases of standard induction
chemotherapy. If the regimen
produces a complete response, patients
are assigned to allogeneic BMT
if they have an HLA-matched sibling
donor and are age 50 or under.
Other complete remission patients
are randomized to either standard
for 21/2 years or autologous BMT.
All patients receive identical intensification
with high-dose methotrexate
prior to undergoing their
assigned or randomized therapy.
Over 1,200 patients have been
registered, 93% of whom achieved a
complete remission. The median age
is 30 years (range, 14 to 60 years).
The induction death rate is 5%.
Dr. Rowe's presentation was
Allogeneic BMT Ups
5-Year EFS in Ph-Negative ALL
based on 173 Ph-negative patients
assigned to allogeneic BMT and 264
Ph-negative patients who were randomized.
Standard risk was defined
as Ph-negative, age over 35 years,
time to complete remission longer
than 4 weeks, and white blood cell
count below 30,000/μL for B lineage
disease and below 100,000/μL
for T lineage disease.
Overall survival was 44% at 5
years and 35% at 7 years in the Phnegative
patients. "We have over 100
patients already out past 5 years,"
Dr. Rowe said.
The 5-year event-free survival was
54% in the Ph-negative patients who
had allogeneic BMT vs 34% for all
randomized Ph-negative patients (P
= .04). The 5-year overall survival
was 54% vs 43%, respectively (P =
.4), and the 5-year relapse rate was
23% vs 61% (P = .001), illustrating
what Dr. Rowe described as "a very
potent graft-vs-leukemia effect for
leukemia patients in first remission."
Analysis by Risk Group
The most impressive differences
were for standard-risk patients (see
Table). In this group, event-free survival
was 67% with allogeneic BMT
vs 44% for the randomized patients;
overall survival was 69% vs 50%,
respectively; and the relapse rate was
15% vs 51%, respectively.
"For each risk subgroup, the allogeneic
group appears to do better
than the randomized cohort, but
these are small numbers," Dr. Rowe
said. In the best subgroup, overall
survival was 80% for allogeneic BMT
for B lineage, standard-risk patients
vs 58% for similar patients in the
"Even though we are dealing with
relatively small numbers, this is notable
because there has been a persistent
objection to submitting standard-
risk patients, particular
T-lineage patients, to transplant, because
they do well with standard
therapy," he said. "We agree that
they do well, with a 60% overall survival
in the literature, but they appear
to do even better with allogeneic
He concluded that allogeneic BMT
"can provide a potent antileukemia effect
to all adult patients with ALL in first
complete remission. Despite increased
early toxicity and a transplant-related
mortality of 21%, allogeneic BMT provides
favorable long-term results."
Overall Survival an Issue
The lack of significant difference
in overall survival associated with
allogeneic BMT for the patients as a
whole sparked considerable discussion.
One attendee said that since
overall survival was not changed for
the group as a whole, "why should I
recommend this very toxic procedure
to a patient?"
Dr. Rowe said that the reason was
the greater chance of a cure at 5 years.
He attributed the lack of significance
in overall survival to study statisticians'
use of log-rank tests, which he
said "may not be the most appropriate,
as this is an ongoing study."
The study continues to accrue patients,
predominantly to complete accrual
to answer the "autologous
transplant vs chemotherapy question"
in the randomized arm, Dr.