Age and Disease Status Are Important Risk Factors for Outcome after Reduced Intensity Conditioning (RIC) Umbilical Cord Blood Transplantation (UCBT) in Adults

UCBT in adult patients with hematological malignancies has significantly increased over the last 5 years. In addition, the introduction of RIC regimens can allow a decreased incidence of TRM. Thus, the use of UCBT after a RIC regimen can represent an attractive treatment modality for those high risk patients who lack a suitable HLA-matched donor. The aim of this analysis was to assess the outcome of 35 patients who received RIC UCBT in a single centre between 2005 and 2008. All 35 patients had high risk hematological malignancies (AML, n=19; ALL, n=9; NHL, n=5; CML, n=1; and Hodgkin disease, n=1). 27 patients (77%) were in CR (CR1, n=18; CR2, n=8; CR3, n=1), whereas 8 had a more advanced disease (PR, n=2; refractory, n=6) at time of UCBT. Of note, 12 patients (34%) have already received and failed prior autologous transplantation. The median age and weight was 44 (range, 17–62) years and 63 (range, 44–125) kg with 13 patients (37%) older than 50 years (range 51–62). The RIC regimen included Fludarabine 200 mg/m², Cyclophosphamide 50 mg/kg and low dose TBI (2 Gy). All patients received CSA and MMF for GVHD prophylaxis. 13 patients (37%) received a single CB unit, whereas 22 (63%) received 2 CB units in order to achieve a minimum required cryopreserved cell dose of 3.0×10e7 TNC/kg. For the entire group, the median cryopreserved and infused cell doses were 4.8×10e7 TNC/Kg (range, 3.3–7.0) and 3.7×10e7/Kg (range, 1.9–5.5) respectively. 94% of the patients received 1–2 HLA mismatched grafts. Neutrophil engraftment (ANC>500/μL) occurred in 33 patients (94%) at a median of 20 (range, 6–45) days and a sustained platelets recovery (>50000/μL) was observed in 25 patients (71%) at a median of 36 (range, 23–136) days after UCBT. Hematological recovery was comparable between single and double CB unit recipients. Primary and secondary graft failure occurred in 4 and 1 patients respectively (AML, n=2; ALL, n=1; CML, n=1; NHL, n=1). Two out of these 5 patients underwent and failed a second UCBT. The overall incidence of grade II–IV acute GVHD was 54% (95%CI, 41–77%; 7 grade II, 10 grade III and 2 grade IV). 19 patients were evaluable for chronic GVHD for an overall incidence of 37% (8 limited and 5 extensive cases). 20 patients (57%; 95%CI, 42–76 %) with experienced at least one episode of a “serious” or “life-threatening” infectious complication (virus other than CMV reactivation, n=11; bacteria, n=10; fungal, n=4) at a median time of 74 (range, 0–595) days after UBCT, requiring long-term hospitalization, and of whom 8 patients were in grade III–IV acute GVHD. 7 patients (20%) experienced severe interstitial pneumonia, with 4 patients (11%) developing ARDS. Most importantly, 5 patients (14%) also required transfer to ICU. With a median follow-up of 468 (range, 105–1170) days, 10 patients (28%) had relapsed or progessed with this being significantly lower in those patients transplanted in CR (P=0.01), but without a significant difference between single and double CB recipients. 14 patients have died (infection, n=5; GVHD, n=3; relapse, n=6; TRM=23%). The KM estimate of OS and DFS was 61% (95%CI, 42–75%) and 52% (95%CI, 34–67%) at 2 years respectively for the entire population. On univariate analysis younger age at transplant and disease status in CR were the only factors associated with significantly better outcome. Although our patients population is small, we conclude that RIC UCBT is an efficient therapy for high risk hematological malignancies. Age and the disease status at transplant are crucial for patients outcome and further efforts are needed to define risk factor specific transplant procedures. Infectious complications and GVHD are still a matter of concern warranting better strategies to provide optimal prophylactic approaches.