denotes an abstract that is clinically relevant.
denotes that this is a recommended PHD Trainee Session.
denotes that this is a ticketed session.Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Clinical Allogeneic Transplantation: Results: Matched Related, Unrelated, and Alternative Donor Allograft Outcomes for Myeloid and Lymphoid Malignancies
Methods: Included are 917 adult (>18) lymphoma pts who underwent allogeneic HCT between 2008 and 2013. All pts received non-myeloablative or reduced-intensity conditioning regimens. The study cohort was divided into 3 groups; haploidentical (n=185), MUD without (w/o) antithymocyte globulin (ATG; n=491) and MUD with (w/) ATG (n=291). The primary end-point was overall survival (OS). Secondary endpoints included cumulative incidence (Cum-Inc) of acute GVHD, chronic GVHD, non-relapse mortality (NRM), relapse/progression (rel/prog) and progression-free survival (PFS). The study had an 83% power to detect an 11% difference in OS.
Results:The baseline characteristics are shown in Table 1. Pts in the haploidentical group received conditioning with Flu/CY/2Gy TBI and PT-Cy + CNI and mycophenolate as GVHD prophylaxis, while the two MUD cohorts received fludarabine-based (+ an alkylator or 2GyTBI) conditioning and CNI-based GVHD prophylaxis. Graft source was bone marrow in 93% of the haploidentical pts and peripheral blood in 94% and 91% of MUD w/o ATG and MUD w/ ATG pts, respectively.
The 28-day neutrophil recovery and platelet recovery were 94%, 97%, 97% (p=0.32) and 63%, 89%, 84% (p<0.001) in the haploidentical, MUD w/o ATG and MUD w/ ATG groups respectively. Cum-Inc of grade II-IV acute GVHD at day100 and chronic GVHD at 1 year was 27%, 40% and 49% (p=0.07) and 13%, 51% and 33% (p<0.001) in the haploidentical, MUD w/o ATG and MUD w/ ATG groups, respectively. On multivariate analysis (MVA) higher risk of chronic GVHD was seen in MUD w/o ATG (RR=5.85, 95%CI 3.96–8.64; p<0.0001) and MUD w/ ATG (RR=3.64, 95%CI 2.37–5.59; p<0.0001) groups relative to the haploidentical cohort. The 3 year NRM was 17%, 22% and 26% in the haploidentical, MUD w/o ATG and MUD w/ ATG groups (p=0.08), respectively. On MVA a trend towards higher NRM was noted in MUD w/ ATG cohort, RR 1.54 (95%CI 0.98 – 2.41, p=0.06), relative to the haploidentical group. Among the haploidentical, MUD w/o ATG and MUD w/ ATG cohorts the 3 year Cum-Inc of rel/prog was 36% vs. 28% vs. 36%, PFS was 47% vs. 49% vs. 38% and OS was 60%, 62% and 50% (Figure), respectively. MVA demonstrated no significant difference between the three groups in terms of rel/prog (p=0.27) and PFS (p=0.07). Compared to the haploidentical group, the two MUD groups did not have a significantly different mortality risk (inverse of OS; p>0.05), but compared to MUD w/ ATG, the MUD w/o ATG pts had a reduced mortality risk (RR=0.67; p=0.001). We tested for a transplant center effect on survival and found none.
Conclusion: With lower-intensity conditioning regimens the early (up to 3 years) survival outcomes are comparable between conventional MUD transplants (w/ or w/o ATG) and haploidentical HCT with PT-Cy approach. Chronic GVHD was significantly lower with haploidentical HCT. Prospective, randomized confirmation of these findings is necessary before wide spread adoption of haploidentical HCT over MUD transplants in lymphomas.
Table 1. |
Haploidentical N=185 (%) |
MUD w/o ATG N=491 (%) |
MUD w/ ATG N=241 (%) |
p-value |
Age @ HCT, median (range) |
55 (18-75) |
55 (19-74) |
55 (20-73) |
0.13 |
Male sex |
118 (64) |
301 (61) |
163 (68) |
0.25 |
White race |
149 (81) |
469 (96) |
227 (94) |
<0.001 |
KPS ≥ 90 |
145 (78) |
311 (63) |
153 (63) |
<0.001 |
HCT-CI≥3 |
55 (30) |
175 (36) |
88 (37) |
<0.001 |
Histology NHL Hodgkin |
139 (75) 46 (25) |
386 (79) 105 (21) |
193 (80) 48 (20) |
<0.001 |
Months from diagnosis to HCT, median (range) |
31 (<1-255) |
34 (<1-342) |
32 (4-460) |
0.19 |
High LDH @ HCT |
16 (31) |
31 (33) |
11 (27) |
<0.001 |
BM +ve @ HCT |
6 (12) |
5 (5) |
2 (5) |
0.35 |
Extranodal disease @ HCT |
18 (35) |
20 (21) |
6 (15) |
0.11 |
Prior lines of therapy, median (range) |
3 (1-7) |
3 (1-12) |
3 (1-8) |
0.41 |
Remission @ HCT CR PR Refractory Untreated / missing |
72 (39) 99 (54) 10 (5) 4 (2) |
215 (44) 215 (44) 55 (11) 6 (1) |
100 (41) 96 (40) 40 (17) |
0.02 |
Disease Risk Index Low Intermediate High |
45 (24) 126 (68) 13 (7) |
199 (41) 263 (49) 48 (10) |
75 (31) 129 (54) 37 (15) |
<0.001 |
Median follow-up, months (range) |
36 (5-73) |
35 (4-74) |
35 (<1-75) |
Disclosures: Armand: Infinity: Consultancy , Research Funding ; Merck: Consultancy , Research Funding ; BMS: Research Funding ; Sequenta, Inc.: Research Funding . Smith: Celgene: Consultancy ; Pharmacyclics: Consultancy . Sureda: Seattle Genetics Inc.: Research Funding ; Takeda: Consultancy , Honoraria , Speakers Bureau .
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