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

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

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

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.

Patients and Methods The conditioning regimen included melphalan (100-140 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.

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

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 11-43 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.

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:

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

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

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:

Univariate analyses for PFS Variables HR 95%CI P value Age 1.12 0.84-1.48 0.432 Sex 1.14 0.87-1.51 0.326 CR prior to SCT 0.77 0.58-0.92 0.042 RIC 0.97 0.72-1.30 0.873 aGVHD grade 3/4 2.21 1.02-4.98 0.044 cGVHD extenxive 1.29 0.46-3.60 0.618 Second SCT 1.78 0.79-4.00 1.158 Presented by:

Results In multivariate analysis, factors associated with worse PFS were lack of remission at SCT (HR 1.73, 95%CI 1.02-3.03, p=0.04) and the development of aGVHD grade 3-4 (HR 2.6, 95%CI 1.08-6.26, p=0.033).

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.