POST-TRANSPLANT CYCLOPHOSPHAMIDE AND SIROLIMUS IN HAPLOIDENTICAL TRANSPLANT WITH PBSC GRAFTS: RESULTS IN 151 PATIENTS
Author(s): ,
Margherita Silani
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Raffaella Greco
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Serena Albanese
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Francesca Lorentino
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Maria Teresa Lupo Stanghellini
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Fabio Giglio
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Daniela Clerici
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Lorenzo Lazzari
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Francesca Serio
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Simona Piemontese
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Magda Marcatti
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Sara Mastaglio
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Andrea Assanelli
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Consuelo Corti
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Massimo Bernardi
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Jacopo Peccatori
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
Fabio Ciceri
Affiliations:
IRCCS San Raffaele Scientific Institute,Milan,Italy
EHA Library. Silani M. Jun 14, 2019; 266550; PF751
Margherita Silani
Margherita Silani
Contributions
Abstract

Abstract: PF751

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background

The use of haploidentical hematopoietic stem cell transplantation (HSCT) with post- transplant cyclophosphamide (PT-Cy) and calcineurin inhibitors (CNI) as graft-versus-host disease (GVHD) prophylaxis is rapidly increasing.

Aims

Herein we describe long-term outcomes of haploidentical HSCT from PBSC grafts, using intensified myeloablative conditioning, and GVHD prophylaxis with PT-Cy and sirolimus.

Methods

From 2012 to 2017, 151 adult patients received haploidentical HSCT for high-risk hematological malignancies, mainly acute myeloid leukemia (n=92). Disease risk index (DRI; Armand et al) was low-intermediate in 52, high in 64 and very high in 35 patients. At HSCT, 58% of patients were not in CR; 25% of patients received a previous allogeneic HSCT.

Conditioning was myeloablative in 123 and reduced-intensity in 28 patients. It was based on treosulfan-fludarabine, and 116 patients receive a regimen intensified by a 2nd alkylating agent (melphalan or thiotepa). The majority of patients (n=148) received unmanipulated PBSCs.

All pts received PT-Cy (50 mg/kg/day) on days 3 and 4. Sirolimus was given from day 5, and withdrawn 3 months after HSCT. Mycophenolate mofetil (MMF) was initiated on day 5, and withdrawn on day 30.

All patients were treated according to current institutional programs upon written informed consent for transplant procedures and for the use of medical records for research.

Results

Median follow up was 26 months (3-68). Median PBSC graft CD34+ and CD3+ cell doses were respectively 6x10^6/Kg (range, 5-8) and 2x10^8/Kg (range, 0.8-4.8). The majority of patients reached the neutrophil (86%) and platelet (77%) engraftment within 30 and 90 days after HSCT, respectively.

Post-HSCT recovery of lymphocyte subsets was broad and fast, reaching more than 100/ml CD3+ T cells within a median of 33 days (20-799). Clinically relevant CMV and HHV-6 infections occurred in 63 and 60 patients, respectively. Invasive fungal diseases were reported in 14 cases.

The cumulative incidence of grades II-IV and III-IV acute GVHD at 100 days was 35% and 20%, respectively. The cumulative incidence of chronic GVHD was 42% at 3 years; we observed severe chronic GVHD only in 16% of pts.

The cumulative incidences of relapse and non-relapse mortality (NRM) were respectively 35% and 27% at 3 years.

Three-year overall survival (OS) was 44% and progression free survival (PFS) 38%.  The composite end point of GVHD-free/relapse-free survival (GRFS) was 24% at 3 years.

Multivariate analysis confirmed the effect of DRI on transplant outcomes, with worse PFS in high and very high compared to low-intermediate DRI population.

Conclusion

Extended follow-up in 151 high-risk patients confirms that Sirolimus and PT-Cy association as GvHD prophylaxis is feasible in haploidentical HSCT based on unmanipulated PBSC graft; DRI is still a major issue for transplant long-term outcome.

Session topic: 22. Stem cell transplantation - Clinical

Keyword(s): Cyclophosphamide, Haploidentical stem cell transplantation, Peripheral blood stem cell transplant

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