Outcome Depend On Age But Not Comorbidity Score, In Patients treated With Fludarabine and Busulfan (FB4) As Conditioning Regimen In Allogeneic Stem Cell Transplantation
Authors: Nunez Javier , Bermudez Arancha , Yanez Lucrecia , Martin Guillermo , Insunza Andres , Richard Carlos , Gaisan Carmen Montes , Conde Eulogio 
Published: October 2019

Introduction
The best conditioning regimen in allogeneic stem cell transplantation (SCT) for myeloid malignancies is unknown. In the last decade, conditioning regimens based on busulfan (BU) and fludarabine (FLU) have shown a good security profile with low early toxicity and mortality but long term follow up is needed to confirm the efficacy in the disease control.

Objective
To analyze retrospectively the efficacy (overall survival OS, progression free survival PFS) of the conditioning regimen with FLU (40mgr/m2/4 days) and BU (3,2 mgr/kg once daily/4 days) in adult patients with myeloid neoplasms after SCT. Outcome was assessed considering age, comorbidity, disease, and donor.
Patients and transplant characteristics
Between 2006 and 2012, 90 patients (40 males, 50 females) underwent SCT conditioned with FB4 in our center. The median age of patients was 50 (24-74) years and 34 patients (37%) were older than 55 years. The diagnoses were 65 AML (11 secondary AML and 19 with adverse cytogenetic), 19 MDS (11 with IPSS high/intermediate 2) and 6 MPD (3 CML, 3 myelofibrosis). At time of SCT, 52 patients (80%) with AML were in first CR. High risk disease (secondary AML or with adverse cytogenetic and MDS with high/intermediate IPSS) were considered in 41 patients (45%). The HCT comorbidity index (Sorror) was low, intermediate or high in 20 (22%), 31 (34%) and 39 (43%) patients, respectively. Donor type was matched related in 42 patients (47%), matched unrelated in 30 patients (33%) and mismatched unrelated in 18 patients (20%). Stem cell source were bone marrow in 81 cases (90%). GvHD prophylaxis was done with calcineurin inhibitor associated with short course of methotrexatre or mycophenolate in all patients and Thymoglobulin was administered in 8 patients (9%).

Results
All patients but one engrafted. The median time to recovery >500 ANC/uL and >50000 platelets/uL was 16 days (range, 9-28) and 16 days (range, 11-455) respectively. Donor complete chimerism was achieved during first or second month in 90% cases. The incidence of acute GVHD grade II-IV and III-IV was 45% and 12% respectively. Chronic GvHD was diagnosed in 60 patients (68%) (26 mild, 18 moderate and 16 severe) and 22 patients (36%) had pulmonary affectation. Transplant related mortality at 100 days and 1 year was 5.5% and 15%. With a median follow up of 26 months (IQL 12-45), the estimated overall survival (OS) was 64% and progression free survival (PFS) was 61%. To be more than 55 years at time of SCT had a negative impact on survival (estimated OS at 40 months: 42% vs 75%, p=0.005). Neither HCT comorbidity index nor disease type had a significant influence on estimated OS at 40 months (70%, 62% and 58% in low, intermediate and high risk) and (64% in AML and 51% in MDS) respectively. However considering the group of high risk disease had worse OS (53% vs 78%, p=0.07). Although there was no significant difference, the OS in mismatched unrelated SCT was worse than matched unrelated and related SCT (40%, 63 % and 71%).

Conclusion
Conditioning regimen with fludarabine and busulfan (FB4) offers a good effectiveness in patients with myeloid neoplasms and allow the use of myeloablative regimen in patients with high risk disease and significant comorbidities. Only the age at time of SCT had a statically significant impact on overall survival.

Disclosures:
No relevant conflicts of interest to declare.