Cano, Pedro

Champlin, Richard E.

Chan, Kawah

Cooper, Laurence

Couriel, Daniel

de Lima, Marcos

Fernandez-Vina, Marcelo

Giralt, Sergio

Hosing, Chitra

Kebriae, Partow

Khouri, Issa

Komanduri, Krishna V.

McMannis, John

Patah, Poliana A.

Petropoulos, Demetrios

Rondon, Gabriela

Saliba, Rima

Shpall, Elizabeth J.

Worth, Laura

Elsevier - Publisher Connector 

Symposium Abstracts
1
ANALYSIS OF RISK FACTORS IN ADULTS TRANSPLANTED WITH UCB
FOR TREATMENT OF HEMATOLOGIC MALIGNANCY
Guillermo F. Sanz, Susana Cantero, Luis Larrea, Dolores Planelles,
Ignacio Lorenzo, Luis Benlloch, Leonor Senent, Pau Montesinos, Jose
Cervera, Guillermo Martin, Jesus Martinez, Isidro Jarque, Javier de la
Rubia, and Miguel A. Sanz Department of Hematology, Hospital Uni-
versitario La Fe, Valencia, Spain
Risk factors analyses are urgently required for determining which
variables should guide the selection of the best UCB unit for
transplantation in adults. This study evaluated prognostic factors of
outcome in 92 adults with hematologic malignancy undergoing
single-unit UCBT in a single institution. Conditioning consisted
of thiotepa, busulfan, cyclophosphamide or ﬂudarabine, and anti-
thymocyte globulin (ATG). Median age and weight were 31 yr and
71 kg. Degree of HLA was 6/6 in 5, 5/6 in 33, and 4/6 in 54 cases.
The median number of nucleated and CD34 cells infused was
2.1  10E7/kg and 1  10E5/kg respectively. The cumulative
incidence of myeloid engraftment, grade III-IV acute GVHD, and
non-relapse mortality (NRM) at 100 days was 90%, 18%, and 25%
respectively. The cumulative incidence of relapse and the proba-
bility of disease-free survival (DFS) at 3 years were 21% and 39%
(median follow-up, 26 months). Multivariate analyses showed that
the absolute number of CD34 cells in the UCB unit was the most
important predictor of myeloid and platelet engraftment. The use
of rabbit ATG was related to faster platelet engraftment and lower
incidence of acute GVHD. The development of grade II-IV acute
GVHD was associated with slower platelet engraftment and
greater NRM. Older patients had a greater NRM whereas condi-
tioning with thiotepa, ﬂudarabine, intravenous busulfan as a single
daily dose, and rabbit ATG and higher numbers of CD3 cells
infused were associated with a lower NRM. Relapse risk was lower
for patients with chronic myelogenous leukemia and those trans-
planted in early stage. The only variable independently associated
with DFS was the stage of the disease at transplant. The number of
nucleated cells and HLA mismatches did not impact any outcome.
These results show that the current criteria for selecting the best
unit for UCBT in adults need to be modiﬁed.
2
DONOR-RECIPIENT HOST-VERSUS-GRAFT HUMAN LEUKOCYTE ANTI-
GEN MISMATCHES AND OUTCOME OF CORD BLOOD TRANSPLANTS
Marcos de Lima, Poliana A. Patah, Rima Saliba, Daniel Couriel,
Kawah Chan, Laura Worth, Sergio Giralt, Partow Kebriae, Issa
Khouri, Laurence Cooper, Marcelo Fernandez-Vina, Pedro Cano, Dem-
etrios Petropoulos, John McMannis, Chitra Hosing, Gabriela Rondon,
Krishna V. Komanduri, Richard E. Champlin and Elizabeth J. Shpall
Department of Stem Cell Transplantation and Cell Therapy, University
of Texas MD Anderson Cancer Center, Houston, TX, USA
The inﬂuence of HLA mismatches on outcomes of cord blood
transplants (CBT) is yet to be fully understood. We hypothesized
that donor-recipient mismatches in the host-versus-graft (HVG)
and graft-versus-host (GVH) direction impact engraftment, non-
relapse mortality (NRM) and survival after CBT, and addressed
the question studying CBT performed in our institution. We also
analyzed the possible contribution of HVG and GVH mismatches,
and graft-versus-graft mismatches in predicting which CB unit
would prevail after double CB transplants. We studied 91 patients.
Diagnoses were high-risk hematologic malignancies (n85; 93%)
or non-malignant disorders (n6; 7%). Conditioning was myeloa-
blative (n86; 95%), while patients not eligible for high-dose
therapy received reduced-intensity (n5; 5%) regimens. ATG was
part of the preparative regimen in 45 cases (49%). Graft-versus-
host disease (GVHD) prophylaxis was tacrolimus with (n83;
91%) or without methotrexate (n6; 6%), and cyclosporine and
MMF (n2; 2%). Grafts were single (n70; 77%) or double
(n21; 23%) CB units. Nine patients received ex-vivo expanded
grafts. For patients receiving a double CBT, the engrafted unit was
used as the reference for this analysis. HLA-A, B (intermediate
resolution) and DRB1 typing (high-resolution) was available for all
donor-recipient pairs. Median age was 18 years (range, 1-57); 46
(51%) were younger than 18 years old and 50 patients (55%) were
males. The patients were heavily pre-treated with 18 (20%) having
received prior autologous transplants. Disease status at CBT was
complete remission (CR; n43; 47%) and active disease (n48;
53%). Median number of infused total nucleated cells (TNC) was
3.45x10E7/kg (0.81-23.6). Numbers of mismatches in the HVG
direction were as follows: zero (n11), 1 (n37), 2 (n36), 3
(n6), and 4 (n1). Numbers of mismatches in the GVH direction
were as follows: zero (n8), 1 (n35), 2 (n41), and 3 (n7). 78
patients engrafted neutrophils (86%) at a median of 22 days (4-60).
65 patients engrafted platelets (71%) at a median of 42 days
(0-133). 13 patients (14%) failed to engraft. Grade II–IV and
III–IV acute GVHD rates were 49% and 8%, respectively, and
chronic GVHD incidence was 33%. 35 patients are alive with a
median follow-up of 25 months. 2-year actuarial survival is 21%.
100-day and 1-year NRM is 22% (14-32) and 37% (28-49). One-
year NRM was 21% (CI: 6-74) for patients that received grafts
without HVG HLA mismatches, while it was 33% (CI: 20-54) for
those with one mismatch, 47% (CI: 33-67) for those with two
mismatches, and 33% (CI: 11-100) for those with three mis-
matches (PNS). The proportion of patients that engrafted was
100% for the group without HVG mismatches, while it was 89%,
85% and 83%, respectively for patients with one, two or three
mismatches. The decreasing 2-year survival and worse NRM as-
sociated with increasing number of HVG mismatches was limited
to the group of patients younger than 18 years. There was no
difference in the proportion of patients in CR, or in the distribu-
tion of infused TNC/Kg across the HVG mismatch subgroups.
There was no correlation between mismatches in the GVH direc-
tion and NRM or 2-year survival. In addition, the number and
direction of HLA mismatches among CB units and recipient did
not predict which unit would prevail after double CB transplants.
We conclude that HVG mismatches may inﬂuence outcomes of
CBT.
3
UNRELATED DONOR HEMATOPOIETIC STEM CELL TRANSPLANTATION
(HSCT) IN CHILDREN WITH ACUTE LEUKEMIA: RISKS AND BENEFITS
OF UMBILICAL CORD BLOOD (UCB) VERSUS ALLELE-MATCHED BONE
MARROW (BM)
Mary Eapen, MD, MS Center for International Blood and Marrow
Transplant Research (CIBMTR), Medical College of Wisconsin, Mil-
waukee, WI
Though UCB has proven to be an acceptable alternative to BM
for transplantation, it is unknown how UCB mismatched at HLA
0-2 loci compares to HLA matched BM. Therefore, we compared
transplant results observed in 503 recipients of UCB with those in
116 recipients of allele-matched (at HLA A, B, C, DRB1) BM. Of
UCB recipients, 35 were matched at HLA A, B (antigen-level) and
DRB1 (allele-level), 201 were mismatched at 1-locus and 267 were
mismatched at 2-loci. Compared to recipients of allele matched
BM, UCB recipients were younger, non-Caucasian, more likely to
have advanced disease at HSCT, less likely to receive radiation and
somewhat more likely to receive cyclosporine. As previously ob-
served, probability of neutrophil recovery (500/ul) at day 42
depended on graft type, HLA disparity and cell dose: 97% with
BM; 85% with HLA matched UCB; 79% with 1-2 locus mis-
matched UCB/high cell dose (0.3  108/kg) and 64% 1-2 locus
mismatched UCB/low cell dose (0.3  108/kg). Compared to
allele-matched BM, risks of grade 2-4 graft-versus-host disease
(GVHD) was lower with HLA matched CB (RR 0.45, p0.04) and
similar after 1 or 2 loci HLA mismatched UCB. Risks of chronic
1393


2: Donor-Recipient Host-Versus-Graft Human Leukocyte Antigen Mismatches and Outcome of Cord Blood Transplants 

de Lima, Marcos

Patah, Poliana A

Saliba, Rima

Couriel, Daniel

Chan, Kawah

Worth, Laura

Giralt, Sergio

Kebriae, Partow

Khouri, Issa

Cooper, Laurence

Fernandez-Vina, Marcelo

Cano, Pedro

Petropoulos, Demetrios

McMannis, John

Hosing, Chitra

Rondon, Gabriela

Komanduri, Krishna V

Champlin, Richard E

Shpall, Elizabeth J

University of Miami: Scholarship Miami

Biology of Blood and Marrow Transplantation

2: Donor-Recipient Host-Versus-Graft Human Leukocyte Antigen Mismatches and Outcome of Cord Blood Transplants

file:///data/core-remote/dit/data/elsevier/pdf/572/aHR0cDovL2FwaS5lbHNldmllci5jb20vY29udGVudC9hcnRpY2xlL3BpaS9zMTA4Mzg3OTEwNzAwMzg5OA==.pdf

2: Donor-Recipient Host-Versus-Graft Human Leukocyte Antigen Mismatches and Outcome of Cord Blood Transplants

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