The Impact of Age in Allogeneic Stem Cell Transplantation with Thiotepa Busulfan and Fludarabine (TBF) for Myelofibrosis : A Retrospective Analysis

Allogeneic hematopoietic stem-cell transplantation (HSCT) currently remains the only curative therapy for intermediate or high risk disease.myelofibrosis (MF). We are reporting 56 patients (pts) who underwent an allogeneic HSCT in our Centre between 2016 and 2020, and assessed factors predictive of outcome.

The median age was 59 years (36-72). Most patients (72%) were JAK2+ and had int2-high DIPSS (92%). The conditioning regimen consisted of thiotepa, busulfan , fludarabine (TBF). All pts received thiotepa 10 mg/kg and fludarabine 150 mg/m^2. The dose of busulfan was adjusted considering the age and the comorbidity score. One pt received 3 days of busulfan (total dose 9.6 mg/kg); 47 received 2 days (total dose 6.4 mg/kg) and 8 received one day of busulfan iv (3.2 mg/kg). Donor was an identical sibling in 13 pt, haploidentical in 18, matched unrelated donor (UD) in 18 and a mismatchedUD in 7. Thus we had 31 HLA matched and 25 HLA mismatched grafts. Fortytwo patients received post-transplant cyclophosphamide (PTCy)-based GVHD (Graft versus host disease ) prophylaxis with cyclosporine and mycophenolate mofetil , and 14 patients received a standard GvHD prophylaxis (CSA+MTX+ATG).

The 2 year survival (OS) was 73 % and disease free survival (DFS) was 66 % and the cumulative incidence (CI) of TRM was 23% and of relapse 11%.

The incidence of acute GvHD grade II-IV was 22% in HLA matched and 50% in HLA mismatched pts (p=0.022), grade III-IV was 6% and 25% respectively (p=0.042) . The incidence of moderate-severe chronic GvHD was 25% in HLA matched and 36% in HLA mismatched grafts (p=0.36). HLA had a major impact on survival : 85% vs 49% survival for matched vs mismatched patients (p=0.01). Patients age >60 years had a major impact on outcome, with a 2 year survival of 51% vs 88% in patients over (n=24) or under 60 years of age (n=32) (p=0.007; the DFS was 46 % and 80% respectively and the CI of TRM was 42% vs 9% (p=0.003).

As to the total dose of busulfan, we found 26% TRM in patients receiving busulfan for 2 days (total doe 6.4 mg/kg) (n=47) and 0% in older patients receiving 1 day only (total dose 3.2 mg/kg) (n=8) ; relapse rate was 10% and 20% respectively.

In multivariate cox analysis including age, spleen size ,DIPSS score, number of transfusion received and donor type, only HLA matching influenced the incidence of acute GvHD; transfusion burden and age plays a role in NRM and OS; DIPSS predicts relapse .

In conclusion: older patients with MF have a high NRM and need to be prepared with a milder conditioning regimen.