12th Congress of the European Hematology ... - Haematologica

12 th Congress of the European Hematology Association
0950
HIGH DOSE CHEMOTHERAPY AND AUTOLOGOUS STEM CELL TRANSPLANT
IN ADOLESCENT PATIENTS WITH RELAPSED OR REFRACTORY HODGKINS LYMPHOMA:
CLINICAL OUT COME AND IMPACT OF PROGNOSTIC FACTORS IN 53 PATIENTS
S. Akhtar, A. El Weshi, M. Rahal, M. Abdelsalam, H. Al Husseini,
I. Janabi, I. Maghfoor
King Faisal Specialist Hospital &Res Ctr, RIYADH, Saudi Arabia
Background . High dose chemotherapy and autologous stem cell transplantation
(HDC ASCT) is well-accepted therapy for most patients with
hodgkin’s lymphoma (HL) who have persistent disease or relapse after
multi-agent chemotherapy / combination treatment. Literature is limited
in adolescent patients in this setting. Aims. To review clinical outcome
and prognostic factors for over all survival (OS) and event free survival
(EFS) in adolescent patients with recurrent and/or primary refractory
HL (PR-HL) after HDC ASCT. Methods. From 1996 to May 2006, 113
consecutive patients with HL had HDC ASCT, 53 of these were
between the ages of 14-21 years. Impact of various prognostic factors
(Table 1) prior to the initiation of salvage chemotherapy on EFS and OS
was evaluated using multivariate regression analysis. Primary refractory
HL (PR-HL) is defined as patients who failed induction chemotherapy
i.e. only partial response (PR), no response , stable disease (SD), progressive
disease (PD) or relapsing within 3 months. Patients with progressive
disease on salvage chemotherapy were not eligible for HDC
ASCT. BEAM was used as HDC. Results. 26 male (49%), 27 female
(51%), Median age at diagnosis 15 years ( 6 to 20) and at ASCT 16.6
years (14 to 21). Prior to salvage chemotherapy, stages I:II:III:IV were
4:18:9:22, bulky disease (≥8 cm) in 15 (28%), involvement of mediastinum
in 35 (66%), spleen in 10 (19%) and extranodal involvement in
23 (43%) patients. Relapsed disease in 23 (43%) and PR-HL in 30 (57%)
in patient. 37 patients (70%) had tissue confirmation at relapse/progression.
ESHAP as first line salvage in 47 patients (89%); median cycles
administered were 3. Disease evaluation post ASCT showed overall
response in 44 patients (83%); total CR / CRu 40 patients (75%), PR 6
(11%), NR/SD 2 (4%), PD 8 (15%) patients. 24 out of 39 patients (61%)
with no CR prior to ASCT achieved CR after HDC ASCT. 13 (32%) out
of 40 patients in CR post ASCT relapsed. Median followup: 53 months
from diagnosis and 28 months from ASCT. EFS is 49%; 29 (55%) remain
in CR, 8 (15%) are alive with disease and 16 (30%) died of disease. Prognostic
factors for EFS and OS are shown in the Table 1, only B symptom
at relapse was a significant negative factor for OS (p=0.031). EFS was
71% and 34% respectively in relapsed and refractory disease (p=0.049).
Conclusions. In this group of adolescent patients with 57% PR-HL,
ESHAP + BEAM combination resulted in 83% response rate with 75%
CR rate. Despite this high responsiveness, almost quarter of these
patients with CR have relapsed. At a median follow up of 28 months,
EFS is only 49%. Negative prognostic factor was B symptom at relapse
for OS (p= 0.031) and refractory disease for EFS (p=0049). Better treatment
strategies are needed for this group of patients.
Table 1. Impact of various prognostic factors on EFS on OS.
* P value significan
354 | haematologica/the hematology journal | 2007; 92(s1)
0951
DELETERIOUS EFFECTS OF KIR LIGAND INCOMPATIBILITY ON CLINICAL OUTCOMES
IN HAPLOIDENTICAL HEMATOPOIETIC STEM CELL TRANSPLANTATION WITHOUT
IN VITRO T CELL DEPLETION
X.-J. Huang, X.-Y. Zhao, K.-Y. Liu, D.-H. Liu, L.-P. Xu
Peking University Institute of Hematolog, BEIJING, China
Backgrounds. KIR ligand incompatibility in graft versus host direction
is associated with natural killer (NK) cell alloreactivity. The effect of this
incompatibility on outcomes of haploidentical or mismatched unrelated
hematopoitic stem cell transplantation (HSCT) remains controversial.
In recent years, we have successfully established a novel conditioning
protocol that includes antithymocyte globulin followed by haploidentical
hematopoietic stem cell transplantation without in vitro T cell depletion,
and we have found that this protocol can achieve outcomes comparable
to those obtained with HLA-matched transplantation. Aims.
Because of inconsistent NK cell-mediated alloreactivity in haploidentical
or mismatched unrelated HSCT, we analyzed the relationship of the
KIR ligand mismatch with clinical outcomes in our cohort of 116
patients. Methods. This analysis included 116 recipients of haploidentical
donor HSCT. Cases were divided into those with (n=30) and those
without KIR ligand incompatibility (n=86), as described by Ruggeri et al.,
based on known KIR ligands (HLA-C alleles with Asn77-Lys80; HLA-C
alleles with Ser77-Asn80; and HLA-Bw4 alleles). Results. Multivariate
analysis showed that both KIR ligand mismatch (HR 2.484, CI 1.241-
4.973, p= 0.01) and high dose T cell categorization (>1.48×108/kg) (HR
4.099, CI 1.899-8.849, p= -0.0003) were independent risk factors for
aGVHD. There was a higher cumulative incidence of aGVHD in patients
with KIR ligand mismatch compared to those patients without KIR ligand
mismatch (p=0.013), or in patients in the high T cell group compared
to those in the low T cell group (p=0.001). Meanwhile, KIR ligand
mismatch significantly increased the incidence of aGVHD in the high T
cell group (p=0.039), but had little effect in the low T cell group (p=-
0.213). We found a significant and striking difference in the cumulative
incidence of aGVHD between the patients with KIR ligand mismatch in
the high T cell group and those without KIR ligand mismatch in the low
T cell group (p