Implementation of An Alternative Donor Option Is Prerequisite for a Good Intention-to-Treat (ITT) In Patients In Need of Allogeneic Transplantation: Analysis of 410 Patients
Authors: Lupo-Stanghellini Maria Teresa , Forno Barbara , Marcatti Magda , Bitetti Cinzia , Coppola Milena , Assanelli Andrea , Greco Raffaella , Lunghi Francesca , Tassara Michela , Guggiari Elena , Carrabba Matteo , Matteazzi Francesca , Camba Lionello , Clerici Daniela , Malato Simona , Marktel Sarah , Bonini Chiara , Bordignon Claudio , Corti Consuelo , Bernardi Massimo , Peccatori Jacopo , Ciceri Fabio 
Published: October 2019

Abstract
Abstract 2382

Background.
Allogeneic transplantation of haemopoietic stem cells (allo-SCT) from an HLA- matched related (MRD) or unrelated donor (MUD) is a curative option for patients (pts) with high-risk haematological disease (HRHD). In the absence of a MRD or MUD, pts have been offered investigational transplant strategies such as umbilical cord blood (UCB) or family haploidentical SCT (haplo-SCT). In our Institution, all patients with HRHD are typed at entry; if a suitable MRD donor is missing a MUD search is promptly activated through the Bone Marrow Donors Worldwide Registry (BMDW). Our policy is to offer an haplo-SCT to adult pts lacking an MRD or MUD in order to adequately treat HRHD in the ideal appropriate time according to clinical indications for allo-SCT. This policy is based on our ongoing protocols for primary disease.

Methods.
Here we report the intention-to-treat (ITT) analysis of alternative donor transplantation at our Institution. Data were obtained from Institutional database; all HRHD patients were included in analysis.

Results.
Between Jan-2004 and July-2010, 410 pts (100% of the following ITT analysis; median age 48y, range 15–76, 91 pts over-60y; male 264) received indication to allo-SCT according to EBMT recommendations. The majority of pts presented with a diagnosis of acute leukaemia (15% lymphoblastic, 45% myeloid), while 12% presented with non Hodgkin lymphoma, 8% myelodysplastic syndrome, 6% Hodgkin disease, 5% multiple myeloma, 2% chronic myeloid leukaemia, 2% chronic lymphocytic leukaemia, 2% severe aplastic anaemia, 1% primary myelofibrosis, 2% others.
Eighty-nine pts (22%) received a transplant from a MRD; 190 pts (46%) activated an MUD search in the BMDW registry; 84 pts (20% of total pts, 44% of MUD searching) received a MUD transplant; 42 pts (10%-21%) received an haplo-SCT due to lacking of a suitable MUD in the appropriate timing according to disease status, or absence of suitable criteria to engage a MUD donor; 11 pts (3%-6%) received a UCB if lacking a suitable haplo donor. Overall, 149 pts received an haplo-SCT (36%): 42 after BMDW research, 107 up-front. Twenty-one pts died before receiving a transplant (5%), 37 (9%) are still searching for a suitable donor and an eligible donor is under final evaluation for 19 pts (5%).
One-hundred-fifty pts underwent transplant in complete remission (CR), 12 in early phase, 9 in very-good-partial remission (VGPR), 7 in partial response (PR), while 155 were in progression of disease (PD). The median time from diagnosis to transplant was 165 days, the median time from MUD search to transplant 103 days (range 28–824 days).
The overall survival (OS) analysis in intention to treat is 51% at 1 year, 39% at 3y; the 1y and the 3y OS for pts transplanted in CR/early phase/VGPR are 74% and 57% respectively, for the pts transplanted in PR/PD 29% and 21% (p<0.0001). Interestingly, the OS according to donor source (MRD vs MUD vs haplo-SCT) is comparable (p = ns) in pts transplanted in CR/early phase/VGPR.
At last evaluation 149 pts are alive, with a median follow-up of 802,5 days (range 2–2315); 93/149 received transplant in CR, 10 in early phase, 6 in VGPR, 3 in PR, 37 in PD. Twenty out of 149 experienced disease relapse and were rescue with salvage treatment and adoptive immunotherapy in 15 cases, while 5 pts received a second transplant from a different donor. Up to 155 pts transplanted in PD, 37 (24%) are alive with a median follow-up of 499 days, of these 22 pts received a haplo-SCT, 8 MUD, 6 MRD, 1 UCB. The median follow-up for pts dead is of 118 days (range 2–2315), the cause of death were disease relapse (53,26%), graft-versus-host-disease (8,7%), infection (31,5%), multi organ failure (3,8%), cardiovascular disease (1,09%), haemorrhage (1,63%).

Conclusion.
In ITT analysis, 81% of overall pts candidate received an allo-SCT (59% from an alternative donor, 22% from a MRD) and the outcome achieved for pts transplanted in CR is comparable within the three major donor source (MRD – MUD – haplo-SCT).
This result confirm the need to offer to every candidate pts a transplant option in the appropriate time, but also support the use of alternative donors, particularly haplo-SCT, in absence of an available MRD or MUD. The highly committed policy performed in the alternative-SCT setting and the implementation of an alternative donor option are essential prerequisite to obtain these results, offering to every candidate pts a concrete opportunity of treatment.

Disclosures:
Bordignon: Molmed: Employment.