Alessandro, Busca

Boccadoro, Mario

Bruno, Benedetto

Chiara, Dellacasa

Elona, Saraci

Federica, Ferrando

Giaccone, Luisa

Maffini, Enrico

Paola, Omed&#232

Roberta, Pulito

English

Institutional Research Information System University of Turin

EBMT 2015 - Physicians Abstract (including Data and QualityManagement)Topic area: General TopicsTopic: 01. Cell therapy / Cellular TherapyEBMT15-ABS-1713HLA-haploidentical allografting with high-dose post-transplant cyclophosphamide: clinical outcomes and immune-reconstitution.Alessandro Busca* 1, Enrico Maffini1, Federica  Ferrando1, Chiara Dellacasa1, Roberta Pulito1, Elona Saraci1, LuisaGiaccone1, Mario Boccadoro1, Paola Omedè1, Benedetto Bruno11Division of Hematology, Department of Molecular Biotechnology and Health Sciences, University of Torino, A.O.U. Cittàdella Salute e della Scienza di Torino, Torino, ItalyPreferred Method of Presentation: Oral or Poster PresentationIntroduction: HLA-haploidentical allografting is a potential cure in patients (pts) without a HLA-identical donorMaterials (or patients) and methods: Between April 2010 and November 2014, 41 pts (median age 50, r 21-71 years)with hematologic malignancies (33 acute leukemias; n=2 CML; n=6 lymphomas) were transplanted from a HLA-haploidentical donor. Fifty% had advanced disease at the time of transplant. Eight pts had received a previous allograft.Conditioning was either reduced-intensity (11 pts) with fludarabine (30 mg/m2/day for 5 days), cyclophosphamide (Cy)(14.5 mg/Kg/day for 2 days) and single dose 2 Gy TBI, or myeloablative (29 pts) with thiotepa (TT) (5 mg/Kg/day for 2days), fludarabine (50 mg/m2/day for 3 days) and i.v. Busulphan (Bu) (3.2 mg/Kg/day for 3 days) or thiotepa-fludarabine-melphalan (140 mg/m2/day) (1 patient), followed by T-cell replete bone marrow (34 pts) or peripheral blood stem cells (7pts). Post-transplant immunosuppression consisted of Cy, 50 mg/Kg/day on days +3 and +4, followed by mycophenolatemofetil and FK-506. G-CSF was administered from day +5 until engraftment. In 22 (54%) pts, T-cell reconstitution andthymic activity were studied for the first 2 years post-transplant. T-cells subsets in both the CD4+ and CD8+ T cellcompartments were evaluated by flow-cytometry: naïve (CD45RO - and CD27 +); central memory (CD45RO + CD27 +);effector memory (CD45RO - CD27 -); and revertant (CD45RA + CD45RO +). Thymic function through T-cell receptorrearrangement excision circles (TRECs) was measured by RT quantitative PCR on DNA extracted from peripheralmononuclear cells and from sorted CD4+ and CD8+ T cells. Here we present preliminary data on thymic output andnaïve CD4+ T cell recoveryResults: Neutrophil recovery occurred at a median of 17 days.  Incidence of acute grade II-IV and III-IV GVHD was28,2% and 7,6%. Blood stream infections were documented in 13 pts (7 gram+ bacteria; 6  gram- bacteria). Six hadprobable invasive fungal infection, in 2 cases after prophylaxis with micafungin and in 4 with azoles. CMV reactivationoccurred in 21 and EBV reactivation, successfully treated with rituximab, in 1. At a median follow-up of 501 days (r 18-1278 days), 19 pts (67%) are alive, 11 (58%) in complete remission. Median OS and DFS at 2 years were 46% and 34%.Overall, 14 pts (34%) died of relapse and 8 pts (19%) of transplant  related mortality (TRM). The probability of TRM was16% at 100 days and 26% at 1 year. (CD4+CD27+CD45RA+) Naïve T cells decreased from a median of 23.92/ul at day28 to 1.8/ul at day 90, then gradually increased to 3.8/ul, 3.9/ul, 8.7/ul at 6, 12 and 18 months, respectively. MedianTREC copies/100 ng DNA from sorted CD4+ cells decreased from 14.5 (r 0-202.2) pre-transplant to 4.4 (r 0-49.2) at day90, than increased to  9.5 (r 0-134.2), 24.8 (r 2.7-83), 41.5 (r 5.5-102.2) and 47.41 (r 31.5-584.3) at 6, 12, 18 and 24months,  respectively. In healthy donors, median TREC copies/100 ng DNA was 74.5 in sorted CD4+cellsConclusion: Feasibility of HLA-haploidentical transplantation with high-dose post-transplant Cy in heavily pretreated ptswas confirmed. Thymic activity and immune recovery of naïve CD4+ T cells were slow and less robust when comparedwith transplants from HLA identical donors. Longer follow-up on a larger series of pts is needed to evaluate long-termoutcomes and correlate clinical issues with immunological dataDisclosure of Interest: None DeclaredKeywords: cyclophosphamide, haploidentical hematolopoietic stem cell transplantation, immune reconstitution, thymus

HLA-haploidentical allografting with high-dose post-transplant cyclophosphamide: clinical outcomes and immunereconstitution.

https://iris.unito.it/bitstream/2318/1507515/1/EBMT15-ABS-1713-preview-11_MANDATO%20IO.pdf

HLA-haploidentical allografting with high-dose post-transplant cyclophosphamide: clinical outcomes and immunereconstitution.

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