Brunstein, C.G.

Majhail, N.S.

Oran, B.

Sandhu, K.S.

Shanley, R.

Wagner, J.E.

Warlick, E.D.

Weisdorf, D.J.

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Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Older Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes: Comparable Outcomes With Unrelated Umbilical Cord Blood and HLA-Identical Sibling Donors 

Oral Presentations S15512
REDUCED INTENSITY ALLOGENEIC HEMATOPOIETIC CELL TRANSPLAN-
TATION IN OLDER PATIENTS WITH ACUTE MYELOID LEUKEMIA AND
MYELODYSPLASTIC SYNDROMES: COMPARABLE OUTCOMES WITH
UNRELATED UMBILICAL CORD BLOOD AND HLA-IDENTICAL SIBLING
DONORS
Majhail, N.S., Brunstein, C.G., Warlick, E.D., Oran, B., Shanley, R.,
Sandhu, K.S., Wagner, J.E., Weisdorf, D.J. University of Minnesota,
Minneapolis, MN
Reduced-intensity conditioning (RIC) regimens allow allogeneic
hematopoietic cell transplantation (HCT) in older patients with ac-
ceptable risks of treatment related mortality (TRM). Umbilical cord
blood (UCB) has increased access to HCT for patients who do not
have HLA-matched sibling donors (MSD). In this single institution
study, we prospectively collected data on 98 consecutive patients
(UCB5 60, MSD 5 38) aged $ 55 years who received a RIC HCT
for acute myeloid leukemia (AML) or myelodysplastic syndromes
(MDS) between 2001 and 2009. All patients received HCT using
RIC regimen because of their older age. All patients received cyclo-
phosphamide, fludarabine and 200 cGy total body irradiation as
conditioning and cyclosporine and mycophenolate mofetil as prophy-
laxis against graft-versus-host-disease (GVHD) (Brunstein et al, Blood
2007). Median age at HCT for UCB recipients was 61 (range, 55-70)
years and forMSDrecipientswas 63 (range,56-70) years.Therewasno
difference in transplant year, CMV status, cytogenetic risk, disease sta-
tus andHCT-comorbidity index (HCT-CI) scores betweenUCB and
MSD cohorts. AmongUCB recipients, 95% receivedHCTusing two
UCB units and 88% received 4/6 or 5/6 HLAmatched units; the me-
dian cryopreserved nucleated cell dose was 3.6  107 NC/kg. Overall
survival at 3-years after HCTwas 31% (95%CI, 19-44) for UCB and
37% (19-55) forMSDrecipients (P5 0.21).The 2-year cumulative in-
cidence of relapse was 47% and 34% (P 5 0.19) and TRM was 25%
and 25% (P 5 0.82), respectively. The cumulative incidence of acute
GVHD (grades 2-4) for UCB and MSD recipients was 45% and
38% (P5 0.19) and that for chronic GVHD at 2-years was 33% and
61% (P 5 0.04), respectively. In multivariate analyses, donor source
had no impact on overall survival, leukemia free survival, relapse or
TRM (Table). In conclusion, RIC HCT using UCB is an acceptable
alternative for older patients without a suitable MSD.
Table 1. Multivariate analysis of donor source and outcomes of
RIC HCTusing UCB and MSD in patients $55 years
UCB, N560Outcomes*
MSD, N538
(referent)(relative risk
[95% CI]) P-valueOverall survival 1.0 1.3 (0.8-2.3) 0.34
Leukemia free survival 1.0 1.2 (0.7-2.1) 0.44
Relapse 1.0 0.7 (0.3-1.3) 0.23
TRM 1.0 1.2 (0.6-2.7) 0.61*Adjusted for disease status and HCT-CI score13
EFFECTS OF MINOR HISTOCOMPATIBILITY ANTIGEN MISMATCHES ON
CLINICAL OUTCOME AFTER UNRELATED HEMATOPOIETIC STEM CELL
TRANSPLANTATION (HSCT) IN 320 RECIPIENTS AND THEIR UNRELATED
DONORS – A MULTIVARIATE ANALYSIS
Recker, K., Fuerst, D., Schrezenmeier, H., Mytilineos, J. Institute
for Clinical Transfusion Medicine and Immunogenetics (IKT), Ulm,
Germany
Introduction:MinorHistocompatibility Antigens (mHag) are poly-
morphic peptides arising from Single Nucleotide Polymorphisms
(SNP) in cytosolic proteins. When presented by class I or II MHC
molecules, mHag can induce cellular immune responses such as
transplant rejection, graft-versus-host-disease (GvHD) and the cura-
tive graft-versus-leukaemia-effect (GvL) after HSCT in individuals
lacking the same allelic variant.
Materials and Methods: We determined the allelic dimorphisms of
themHagHA-1,HA-2,HA-3,HA-8,HB-1, ACC-1, ACC-2,PANE-
1 andUGT2B17 aswell as SNP’s in the cell adhesionmoleculesCD31andCD62LbyPCR-SSP typing (mHagCTS-PCR-SSPMinitrayKit,
CTS Heidelberg) in 320 HSCT patients and their unrelated donors.
Overall survival, grades II-IV acute GvHD (aGvHD), treatment re-
lated mortality (TRM) and relapse/disease recurrence were correlated
with the mHag matching grade. We included several relevant covari-
ates in cox regressionmodel for overall survival analysis aswell as com-
peting risk analysis for the other outcomes.
Results: In theHLA-B44-positivegroup (n577), patientswith a sin-
gle ACC-2 GvH Mismatch had an increased overall survival (p 5
0,04, HR:2,44, CI:1,06-5,62), due to a lower TRM rate (p 5 0,03,
HR:0,34, CI:0,13-0,87). The same finding (overall survival: p 5
0,003, HR:2,4, CI:1,34-4,36, TRM: p 5 0,03, HR:0,45, CI: 0,22-
0,92) was detected for patients with CD62L Codon 206 Mismatch
in the HLA-A3 superfamily group (n 5 140). Mismatches in mHag
HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, PANE-1, UGT2B17
andCD31were not significantly associatedwith any of the endpoints.
Discussion: After correction for multiple testing, only CD62L
Codon 206 GvH Mismatch remained as a significant factor posi-
tively influencing the overall survival rate in mismatched donor re-
cipient pairs (p 5 0,04). This observation could not be attributed
to any secondary outcome factor such reduced risk for TRM (p 5
0,09) or disease recurrence (p5 0,93). Based on this analysis, we con-
clude that mHag mismatches at HA-1, HA-2, HA-3, HA-8, HB-1,
ACC-1, ACC-2, PANE-1, UGT2B17 and CD31 have no important
effect on the clinical outcomes after unrelated HSCT. In contrast,
mismatches on the adhesion molecule CD62L are significantly asso-
ciated with a higher overall survival.14
RISK SCORE PREDICTS OUTCOME OF SECOND ALLOGENEIC HEMATO-
POIETIC STEM CELL TRANSPLANTATION
Rezvani, K., Marin, D., Goldman, J.M., Kanfer, E., MacDonald, D.,
Dazzi, F., Milojkovic, D., Rahemtulla, A., Sargeant, J., Apperley, J.,
Szydlo, R. Hammersmith Hospital, London
Increasing numbers of second allogeneic hematopoietic stem cell
transplantation (allo-SCT) are being performed for patients who
have previously undergone and failed an allogeneic or autologous
stem cell transplant. We investigated whether the European Group
for Blood and Marrow Transplantation (EBMT) risk score, previ-
ously established for chronicmyeloid leukemia, could be used to pre-
dict outcome after second allo-SCT.We analyzed prognostic factors
in 124 consecutive patients who underwent second transplants using
allogeneic donors at our institution between 10/1985 and 02/2010.
Patients with either a first autologous (N 5 64) or first allogeneic
(N5 60) SCT were included. Age of patient, disease stage, time in-
terval from diagnosis to transplant, donor type, and donor-recipient
gender combination were used to establish a score from 0 to 7 points,
from which 3 groups were identified. The survival probability at 5
years decreased from 51.7% (95% Confidence interval [CI] 33-
70%) for risk scores 0-3 (low, n 5 25), to 29.3% (95% CI, 17%-
47%) for risk score 4 (medium, n 5 40), and only 10.4% (95%CI,
4%-24%) for risk scores 5-7 (high, n557).Other factors investigated
in univariate analysis included previous transplant type, myeloabla-
tive conditioning (Y/N), and interval between first and second SCT
(median 20 months). In multivariate analysis, two factors were found
to be important. An increased risk of deathwas associatedwith: a high
risk score (RelativeRisk 2.89, p50.001)when comparedwith the low
risk group and with a shorter interval between 1st and 2nd SCT (\
20months), RR 1.55, p 5 0.05. Given that relapse after transplant
can be a lethal situation and that select patients can remain alive
and disease-free after second allogeneic transplant, a recent evi-
dence-based guideline published by the American Society of Hema-
tology has given the use of second allogeneic transplant after relapse
a recommendation score of 1B.Wepropose that the fivewell-defined
pre-transplant patient and donor characteristics that make up the
EBMT risk score give an excellent risk estimate of outcome for sec-
ond allogeneic HSCT. Taking into account both the interval be-
tween first and second SCT’s and the risk score, can provide an
accurate estimate of outcome and help in the selection of patient
who are most likely to benefit from a second transplant.


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Reduced Intensity Allogeneic Hematopoietic Cell Transplantation in Older Patients With Acute Myeloid Leukemia and Myelodysplastic Syndromes: Comparable Outcomes With Unrelated Umbilical Cord Blood and HLA-Identical Sibling Donors

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