Haploidentical Allogeneic Hemopoietic Stem Cell Transplant for High Risk Myelodysplastic Syndrome
Authors: Raiola Anna Maria , Aquino Sara , Beltrami Germana , Bregante Stefania , Cruciani Fabio , Di Grazia Carmen , Dominietto Alida , Ghiso Anna , Gualandi Francesca , Ibatici Adalberto , Lamparelli Teresa , Marani Carlo , van Lint Maria Teresa , Varaldo Riccardo , Bacigalupo Andrea , Angelucci Emanuele 
Published: October 2019

Abstract

Introduction
Allogeneic hematoopoietic stem cell transplantation (HSCT) is the only today available curative treatment for Myelodysplastic Syndrome (MDS) patients. Wide approach to transplant has been hampered by HLA compatible donors availability, advanced diseases, donor and patients advanced age.
In the recent years improvement of haploidentical HSCT has offered to many patients the opportunity to undergo this curative approach.
The Genova transplant team included haplo HSCT for MDS in his standard operative procedure since 2011. Therefore this unselected consecutive patients cohort offers the possibility to verify feasibility of haplo HSCT in MDS patients.
Patients and Methods.
Form August 2011 since March 2016 thirty (30) consecutive patients were transplanted from an haploidentical donor in our center. All of them were lacking an HLA identical family donor and an 8/8 matched unrelated donor. Table 1 reports patients and disease characteristics.
All donors were haploidentical family member. Conditioning regimen was myeloablative for 10 patients and reduced intensity for 20 patients as previously reports (Raiola et al Biol Blood Marrow Transplant. 2013; 1:117-22). Patients received a median of 3.1 x10e8 /kg (range 1.1 -6) un-manipulated marrow derived nucleated cells. Graft versus host disease (GvHD) prophylaxis consisted in post transplant cyclophosphamide 50 mg/kg , on day+3 and +5 , cyclosporine (from day 0) , and micophenolate (from day +1).
Data are expressed and median with a range unless indicated. Disease free survival and GvHD rate are calculated with the methods of Kaplan and Meier.
Results
Hematologic recovery was complete in 28 (93%) patients. The median times to neutrophil (>500/μL) and platelet recovery (>20,000/μL) was 18 days (range, 14-24 days) and 25 days (range, 12 - 51 days), respectively. Two patients had autologous recovery and were successfully re-transplanted with the same protocol. The incidence of acute GVHD grade II-IV was 15%. No early death was registered. Two patients died, in complete remission of MDS, at 389 (chronic GVHD + sepsis) and 1123 (interstitial pneumonitis) days after transplant, respectively.
Seven patients relapsed at median time from transplant of 188 days (range 139 - 560 days). All relapsed patients subsequently died by disease progression.
The incidence of chronic GVHD was 20% (6 patients, severe in 5). At the time of this report of the 21 surviving patients (all in remission by MDS) two are under chronic GvHD treatment.
With a median follow up of 20.5 months (range 4 - 54) the 3 years probability disease free survival is 69% (95%, CI 51-87).
Discussion
Haploidentical transplant, together with conventional donor approach, offers the majority of patients the possibility to undergo HSCT. The data here presented demonstrated feasibility of the procedure in advanced disease patients even by an haploidentical donor. In our knowledge no similar results are achievable by today available or experimental medical therapy. HSCT transplantation, even from haploidentical donor, should be offered to all MDS patients presenting with this indication. Disease relapse is the most important cause of transplant failure.

Disclosures
Angelucci: Novartis oncology, celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.