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486 Haploidentical Transplantation Using High Dose Post-Transplant Cyclophosphamide for Patients with Aplastic Anemia : The European Group for Blood and Marrow Transplantation Experience

Program: Oral and Poster Abstracts
Type: Oral
Session: 732. Clinical Allogeneic Transplantation: Results: Advances in Haploidentical and Mismatched Transplantation
Hematology Disease Topics & Pathways:
Biological, Therapies, transplantation, stem cells
Sunday, December 2, 2018: 5:45 PM
Seaport Ballroom A (Manchester Grand Hyatt San Diego)

Pedro H Prata, MD1, Boris Afanasyev2*, Dirk-Jan Eikema3*, Frans Smiers4*, Cora Knol3*, Jose L. Diez-Martin, MD, PhD5, Vanderson G. Rocha, MD, PhD6*, Yener Koc7, Xavier Poire, MD8*, Nathalie Fegueux9*, Nicolaus Kröger, MD10*, Wolfgang Holter, MD11*, Adrian Bloor, MA MB BChir PhD FCRP FRCPath12*, Charlotte Jubert, MD13*, Amal Al-Seraihy, MD14*, Arnold Ganser, MD15, Herve Tilly, MD16, Pietro Pioltelli, MD17*, José A. Pérez-Simón, MD, PhD18, Aloysius YL Ho, MBBS, FRCP, FRCPath19, Mahmoud Aljurf20, Nigel H. Russell21, Hélène Labussière-Wallet22*, Tessa Kerre, MD23*, Carlo Dufour, MD24 and Regis Peffault De Latour25*

1Department of Hematology and Transplantation, Hôpital Saint Louis, Colombes, France
2Hematology and Transplantology Department, Pavlov First Saint Petersburg State Medical University, Saint-Petersburg, Russian Federation
3EBMT Registry Office, Leiden, Netherlands
4Department of Pediatric Hematology, University Medical Center Leiden, Leiden, Netherlands
5Department of Hematology, Hospital G U Gregorio Marañon, Madrid, Spain
6Churchill Hospital, NHS, Oxford, GBR
7Medical Park Hospitals, Stem Cell Transplant Unit, Antalya, TUR
8Section of Hematology, Cliniques Universitaires Saint-Luc, Brussels, Belgium
9Department of Hematology, CHU Lapeyronie, Montpellier, France
10Department of Stem Cell Transplantation, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
11St.Anna Children's Hospital, Vienna, AUT
12Haematology and Transplant Unit, The Christie NHS Foundation Trust, Manchester, United Kingdom
13Hemato Pediatrics, CHU Bordeaux, Bordeaux Cedex, France
14King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia
15Department of Hematology, Hemostasis, Oncology and Stem Cell Transplantation, Hannover Medical School, Hannover, Germany
16Hematology Department, Henri Becquerel Cancer Centre, Rouen, France
17Ospedale San Gerardo, Clinica Ematologica dell`Universita Milano-Biocca, Monza, MB, Italy
18Instituto de Biomedicina de Sevilla (IBiS), UGC-Hematología, Hospital Universitario Virgen del Rocío/ CSIC/ CIBERONC, Universidad de Sevilla, Sevilla, Spain
19Singapore General Hospital, Singapore, SGP
20Oncology Center, King Faisal Specialist Hosp. & Rsrch. Ctr., Riyadh, Saudi Arabia
21Nottingham University Hospital, Nottingham, United Kingdom
22Service Hematologie, Centre Hospitalier Lyon Sud, Lyon, France
23Ghent University Hospital, Gent, BEL
24Hematology Unit, Giannina Gaslini Children Hospital, Genova, Italy
25Department of Hematology and Transplantation, Hôpital Saint Louis, Paris, France

The outcome of patients with severe aplastic anemia (SAA) has greatly improved in recent years but is still poor for patients who failed or relapsed after immunosuppressive therapy (IST) and don’t have a matched donor. Recent use of eltrombopag shows blood count improvements in 40% of cases, but most patients refractory to immunosuppressive therapy, are also unresponsive to eltrombopag. In this situation, hematopoietic stem cell transplantation (HSCT) using alternative donor sources (mismatched unrelated donors, cord blood, and haploidentical family donors) may be curative but are also associated with a high risk of morbidity and mortality. Moreover, ethnic minorities have limited access to an alternative donor, especially in the adult population. Haploidentical transplantation using post-transplant cyclophosphamide (Haplo-PTCy) has been shown to facilitate engraftment and shows GvHD rates comparable to those of matched sibling HSCT in hematologic malignancies. However, few papers have been published on Haplo-PTCy in the context of aplastic anemia.

We conducted a retrospective analysis of 36 patients (72% male), who received an haplo-PTCy for aplastic anemia in 22 EBMT centers from June 2010 to March 2017. Haplo-PTCy was the first transplantation for 81% patients (second, 11%; third, 8%). The non-myeloablative preparatory regimen included anti-thymocyte globulin in 33% of patients and low dose TBI in 58% of patients. Donors were father (n=12, 35%), mother (n=12, 35%), brother (n=5, 15%), sister (n=3, 9%), cousin (n=1, 3%) and daughter (n=1, 3%). The stem cell source was mainly bone marrow (55%). All patients received cyclophosphamide 50mg/kg/day IV on days +3, and +4 post-transplant and 75% received tacrolimus or cyclosporine plus mycophenolic acid. The primary endpoint was the probability of OS. Secondary study endpoints included probability of neutrophil recovery (ANC 500/ μL for at least 3 consecutive days), platelet recovery (platelets 20 000/ μL for at least 3 consecutive days, and 7 days after the last transfusion), cumulative incidences of acute and chronic GVHD and relapse-free survival without Grade III-IV acute GvHD and without extensive chronic (GRFS).

Thirty-two patients were diagnosed with moderate (7%), severe (52%) or very severe idiopathic aplastic anemia (41%), while 4 patients were transplanted for congenital aplastic anemia (3 Fanconi Anemia and 1 Diamond Blackfan). The median age was 19.4 years (range 2.5-45.4 years; 58% adults). Median disease duration before haplo-PTCy was 11.3 months (1.9-201.2). Thirty patients (83%) received pretreatment (77% anti-thymocyte globulin plus cyclosporine, 12% eltrombopag, and 1 patient (3%) received androgens). Cumulative incidence (CI) of neutrophil recovery at day 60 was 78% (64-91) with a median time of 21 days (18-26). Cumulative incidence (CI) of platelet recovery at day 60 was 60% (44-76) with a median time of 31 days (22-185). The CI of grade II-IV acute GvHD was 26% (12-41%) (grade II 19% (7-32%), grade III 6% (0-13%) and no grade IV). CI of chronic GvHD was 17% (5-30) at 1 year (6% (0-13%) extensive) and a CI of 22% (7-37) at 2 years (only limited, there was no new case of extensive cGvHD after one year). With a median follow-up of 24.6 months (15.9 – 38.2), the estimated probability of overall survival (OS) was 78% (64-91) at 1 year and 74% (60-89) at 2 years. Of note, among the 4 patients with inherited disorders, 2 died [1 infection (Diamond Blackfan) and 1 aGvHD (Fanconi Anemia)] and 2 are alive at month 12 and month 15 of follow-up, respectively. Nine patients died during the study. The main cause of death was infection (n=6, 67%). Finally, the GRFS (alive, full donor chimerism, without previous grade III-IV GvHD and without extensive cGvHD) was 58% (41-75) at 2 years.

In conclusion, with a median follow-up of 2 years, Haplo-PTCy leads to 74% overall survival in 36 patients with aplastic anemia, with almost 60% of the patients being free from GvHD complication. In a population with no other therapeutic options, our data suggests haplo-PTCY is a feasible option. However, prospective well-designed trials are urgently needed before the inclusion of Haplo-PTCy in the treatment strategy of aplastic anemia.

Disclosures: Bloor: Janssen: Research Funding; AbbVie: Research Funding. Ganser: Novartis: Membership on an entity's Board of Directors or advisory committees. Tilly: Celgene: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria; Astra-Zeneca: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees. Russell: Pfizer: Consultancy, Honoraria, Speakers Bureau; Jazz Pharma: Speakers Bureau; Daiichi Sankyo: Consultancy. Kerre: Celyad: Consultancy; BMS: Consultancy; Celgene: Consultancy, Research Funding. Peffault De Latour: Novartis: Consultancy, Honoraria, Research Funding; Pfizer Inc.: Consultancy, Honoraria, Research Funding; Amgen Inc.: Research Funding; Alexion Pharmaceuticals, Inc.: Consultancy, Honoraria, Research Funding.

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