1. Haploidentical Transplantation with Post-transplant Cyclophosphamide and Melphalan-based Conditioning– A retrospective Analysis of the First 100 Patients Treated at MD Anderson Cancer Center
Piyanuch Kongtim, Ravi Pingali, Antonio M. Jimenez, Roberto Ferro, Gabriela Rondon, Julianne Chen, Oran Betul, Aimee Hammerstrom, Lindsey Lombardi, Partow Kebriaei, Martin Korbling, Uday R. Popat, Simrit Parmar, Dean A  Lee, Laurence Cooper, Katayoun Rezvani, Issa Khouri, Elizabeth J. Shpall, Richard E. Champlin, Stefan O. Ciurea
Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX

2. Background
Haploidentical stem cell transplantation (haploSCT) is a treatment option in patients with hematologic malignancies who have no HLA-matched donor. However, it has been limited by the high rates of graft rejection and GVHD.
Introduction of high dose cyclophosphamide in the early post-transplant period has significantly improved the outcomes of patients undergoing haploSCT1,2.
1.       Luznik L. Blood. 2001;98:3456
2.       Ciurea SO. Biol Blood Marrow Transplant. 2012;18:1835

3. Background
Here we report results of the first 100 patients treated with haploSCT at our institution.

4. Patients and Methods
We retrospectively analyzed the outcomes of 100 patients who underwent haploSCT for various hematologic malignancies between September 2009 to July 2012 at the university of Texas MD Anderson Cancer Center.
Diseases were: AML/MDS 54 (33 had high-risk cytogenetics), lymphoma/CLL 17 (12 not in remission at transplant), ALL 12 (11 beyond first remission), CML 12 (all progressed to accelerated/blast phase), other 5 pts.

5. Patients and Methods
The conditioning regimen included melphalan ( mg/m2), fludarabine (160 mg/m2) +/- thiotepa (5-10 mg/kg).
GVHD prophylaxis consisted of cyclophosphamide 50 mg/kg on day +3 and +4, tacrolimus and mycophenolate.

6. Patient and transplant characteristics
Number
Median age (year)
45 (IQR 19-67)
Gender female/male
46/54
Diagnosis
AML/MDS
Lymphoma/CLL
ALL
CML
MPN
Aplastic anemia
Myeloma 54 17 12 2 1
Disease status at transplant CR
Not in CR 58 42
Cytogenetic risk (N=66)
Good
Intermediate
High 4 29 33
Prior AlloSCT 11
Prior ASCT
RIC
SC sources
Marrow
Peripheral blood 96

7. Results
The median follow-up of 55 survivors was 18 months (range 2-48 months).
Ninety-six patients engrafted with time to ANC engraftment of 18 days (range days).
Delayed engraftment was seen in 2 patients.
Of 96, 89 patients achieved full donor chimerism.
At day +30 post SCT, 90 and 4 patients achieved CR and PR respectively.

8. Transplant outcomes according to diseases
All patients (N=100)
Myeloid malignancies in CR (N=40)
Lymphoid malignancies (N=17)
ALL
(N=12)
3-year PFS
43.3
56.5
62.3
44.4
1-year TRM
24.1
11.8
25.9
33.3
1-year CI of relapse
23.3
30.1
24.4
aGVHD grade 2-4 30 25
35.3 50
aGVHD grade 3-4 10
41.7
cGVHD 15
12.5
cGVHD (extensive) 8
5.9
8.3
Presented by:

9. A B C D
Progression free survival of the whole cohort (A), myeloid malignancies in CR (B), lymphoid malignancies (C) and ALL (D)

10. A B C D
Overall survival (A), progression free survival (B), cumulative incidence of relapse (C) and treatment related mortality (D) of myeloid malignancies according to disease status prior to haploSCT

11. Transplant outcomes according to first and second SCT
1ST SCT (N=89)
Second SCT
(N=11)
1st CR
Others
P value
3-year PFS
62.3
36.4
0.131
32.7
1-year TRM
19.9 28
0.402 10
1-year CI of relapse 21
34.2
0.236
61.8
aGVHD grade 2-4 25
32.8
0.620
27.3
aGVHD grade 3-4
14.3
8.2
0.454
9.1
cGVHD 12
22.9
0.354
cGVHD (extensive)
3.6
9.8
0.426
Presented by:

12. Univariate analyses for PFS
Variables HR
95%CI
P value
Age
1.12
0.432
Sex
1.14
0.326
CR prior to SCT
0.77
0.042
RIC
0.97
0.873
aGVHD grade 3/4
2.21
0.044
cGVHD extenxive
1.29
0.618
Second SCT
1.78
1.158
Presented by:

13. Results
In multivariate analysis, factors associated with worse PFS were lack of remission at SCT (HR 1.73, 95%CI , p=0.04) and the development of aGVHD grade 3-4 (HR 2.6, 95%CI , p=0.033).

14. Conclusions
HaploSCT with melphalan-based conditioning and PTCy is well tolerated with low TRM and outcomes comparable with matched transplantation.
Prospective studies comparing HaploSCT with matched transplants are needed.