Dynamics of Recovery in Double Umbilical Cord Blood Transplantation With an ex-vivo Mesenchymal Cell Expanded Unit: Faster Recovery With Engraftment of the Expanded Unit

Double cord blood transplantation (CBT) with ex-vivo expansion aims at overcoming the delayed engraftment frequently observed after CBT. Thirty-one patients received myeloablative therapy with melphalan, fludarabine, thiotepa and ATG followed by double CBT for treatment of hematologic malignancies. One of the 2 units was expanded (exp) ex-vivo in a co-culture with either third party haploidentical family member marrow derived mesecnchyal stem cells (N = 8) or off-the-shelf mesenchymal progenitor cells from Angioblast (N = 23). Both CB units were matched in at least 4/6 HLA antigens with the patient, and contained a minimum of 1x107 TNC/Kg per unit. The majority of patients (pts) received CBT for treatment of acute leukemia including AML / MDS (64%) and ALL (19%), and 42% were in remission at CBT. Median age was 36 years (range 2.8-62). The non-exp unit was matched with the pt in 6/6 HLA antigens in 3%, 5/6 in 26% and 4/6 in 71% of cases; the corresponding distribution for the exp unit was 6%, 29%, 64%. Engraftment was documented in 29 evaluable pts at a median of 15 (range 9 to 42) days for neutrophils and 40 (range 18 to 62) days for platelets. Day 30 chimerism showed evidence of engraftment of the non-exp unit only in 15 (52%) pts, and of both units in 13 (45%) pts, including 9 and 4 in whom the non-exp and the exp unit dominated, respectively. Chimerism was undetermined in 1 pt. Comparison of the rate of recovery in pts who had (N = 13) and those who did not have (N = 15) evidence of engraftment of the exp unit showed that neutrophils and platelet recovery was faster when the exp unit engrafted (median of 15 vs. 19 days for neutrophils; and 38 vs. 40 days for platelet). This difference did not reach statistical significance however. The median numbers of TNC and CD34+ cells infused/Kg were significantly higher in the engrafted exp than in the non-engrafted exp unit (p < 0.05). Sixteen pts were diagnosed with grade II-IV aGVHD including 12 within 100 days post CBT. GVHD was severe (grade III-IV) in 5 pts. On univariate analysis, there was a trend for a higher 6 month rate of grade II-IV aGVHD when the exp unit engrafted (cumulative incidence (CI) 65% vs 49%, P = 0.2); when the non-exp unit was only 4/6 HLA matched with the pt (CI 65% vs 25%), p = 0.2; and when CMV serostatus was reactive in both the recipient and in the non-exp unit (CI 77% vs 35%, p = 0.1). The investigation of CB expansion is warranted in a larger study population and accrual to our study continues.