209 Chimerism, Immune Reconstitution and Outcome after Allogeneic Myeloablative and Reduced Intensity Unrelated and Haploidentical PBSC Transplantation Using Post-Transplant Cyclophosphamide

Track: Poster Abstracts
Wednesday, February 11, 2015, 6:45 PM-7:45 PM
Grand Hall CD (Manchester Grand Hyatt)
Ayman Saad, MD, , Bone Marrow Transplant and Cellular Therapy, University of Alabama at Birmingham - UAB, Birmingham, AL
Racquel Innis-Shelton, MD , Medicine, University of Alabama at Birmingham, Birmingham, AL
Donna Salzman, MD , Bone Marrow Transplantation and Cell Therapy Program, The University of Alabama at Birmingham, Birmingham, AL
Luciano J. Costa, MD, PhD , University of Alabama at Birmingham, Birmingham, AL
Antonio di Stasi, MD , Stem Cell Transplantation and Cellular Therapy, University of Alabama at Birmingham, Birmingham, AL
Ravikumar Paluri, MD , Medicine, University of Alabama at Birmingham, Birmingham, AL
Melissa Gazi , Bone marrow transplant, University of Alabama at Birmingham, Birmingham, AL
Lisa Williams, RN , Bone Marrow Transplantation and Cellular Therapy, University of Alabama / Birmingham, Birmingham, AL
John Townsend , Histocompatibility Laboratory, University of Alabama at Birmingham, BIrmingham, AL
Vera Hauptfeld , Histocompatibility Laboratory, University of Alabama at Birmingham, Birmingham, AL
Lawrence Lamb, PhD , Medicine, University of Alabama at Birmingham, Birmingham, AL
Shin Mineishi, MD , Bone Marrow Transplantation Program, University of Alabama at Birmingham, Birmingham, AL
Presentation recording not available for download or distribution as requested by the presenting author.
BACKGROUND: Post-transplant cyclophosphamide (PTCy) is increasingly used as a GVHD prophylaxis after alternative donor hematopoietic cell transplant (HCT). We sought to characterize outcomes, chimerism and immune reconstitution (IR) after PTCy following myeloablative/reduced intensity (MA/RIC) peripheral blood stem cell (PBSC) HCT and compare these to matched related donor HCT (MRD). 

METHODS: We identified 107 patients who received MA/RIC T-cell replete allogeneic PBSC HCT between July 2012 and July 2014 at our center. A total of 39 patients underwent MRD without PTCy and 68 patients received PTCy after HLA matched unrelated donor (MUD), mismatched unrelated donor (mMUD), or haploidentical (haplo) HCT. The preparative regimens were fludarabine(FLU)/busulfan (BU), FLU/TBI 10-12 Gy or CY/TBI 12 Gy. The GVHD prophylaxis was PTCy 50 mg/m2 on day +3 (days +3 and +4 for haplo), tacrolimus on day +5 to +100 and MMF on day +5 to day +35. After transplant, peripheral blood short tandem repeat donor chimerism of CD3 and CD15 cells and flow cytometry IR panel were done on days +30, +60, +100 +180, +270 and 1 year.   

RESULTS:  The PTCy group (n =68) were MUD, mMUD, and haplo (n=44, 12, and 12). Patients had hematological malignancies except 1 SAA and 1 porphyria. Median age was 50 years (range). The median follow up of alive patients was 10 months. All patients engrafted except one haplo patient (salvaged with repeat haplo from a different donor). Absolute neutrophil count and platelet recovery occurred after a median of 12 and 13 days respectively. Rates of acute GVHD (grades II-IV) and extensive chronic GVHD were 8% and 8% in haplo vs 18% and 18% in MUD/mMUD. One-year relapse was 8% in haplo vs 30% in MUD/mMUD. One-year non-relapse mortality (NRM) was 17% and 25% in haplo and MUD/mMUD. There was no difference in disease-free survival (DFS) [55% vs 50%] and overall survival (OS) [73% vs 62%] between haplo and MUD/mMUD. 

We compared these 2 groups with the MRD HCT (n: 39) that did not receive PTCy. DFS, OS and NRM were similar among the 3 groups. On day +30, CD15 donor chimerism was 100% in the 3 groups. Day +30 CD3 donor chimerism was higher in haplo vs MRD and MUD (P=0.004). Day +60 chimerism did not differ among the 3 groups. T cell count normalized by day +90 (MRD); +180 (MUD/mMUD); and +270 (haplo) with faster recovery on day +30 in the MRD group (p = 0.006). Robust CD4 recovery was noted in the haplo group on day +180. NK cell recovery was similar in all groups, but tended to be higher on day +270 in haplo.

CONCLUSION: PTCy with MA/RIC PBSC transplant is feasible with favorable outcome. PTCy does not compromise donor chimerism. Lower relapse among haplo patients may be attributed to early donor chimerism. T cell recovery after PTCy was delayed but did not impact NRM or survival.

Disclosures:
R. Innis-Shelton, Millenium, Advisory Board: Advisory Board

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