Engraftment Kinetics After Transplantation of Double Units of Umbilical Cord Blood From Unrelated Donors in Adolescents and Adults with Hematologic Malignancies.

To evaluate the clinical therapeutic effects and the early engraftment kinetics of the transplantation of double partially-human leukocyte antigen (HLA)-matched umbilical cord blood (UCB) units in patients with hematologic malignancies from November 2005 to March 2009.

Twenty-one adults and adolescents (median age 21 years [range 10-40 years]; median weight 57 kg [range 31-76 kg]; 16 males and 5 females) with hematologic malignancies were given transplants of double UCB units. Diagnoses included 7 ALL patients, 7 AML, 5 CML, 1 Mix-AL, and 1MDS. 17 (81%) of the patients were refractory to chemotherapy and considered at high risk. All patients received myeloablative conditioning, which included Flu/Cy/TBI for 16 patients, and Bu/CY2±ATG±Ara-C for 5 patients. Graft versus host disease (GVHD) prophylaxis was CSA+MMF. The analytic method used was based on the quantitative amplification of informative polymorphic short tandem repeat (STR) regions in the recipient and donor using polymerase chain reaction (PCR), which detect engraftment and chimerism dynamically.

The median nucleated cell dose was 4.93×10⁷ nucleated cell [NC]/kg range:3.26-7.70×10⁷ NC/kg. Eighteen patients (86%) achieved hematopoietic recovery after the double UCB transplantation. The median number of days required to reach an ANC > 0.5×10⁹/L was 20 days (14–35 days), and platelet> 20×10⁹/L was 34.5 days (25 - 49 days). One patient's engraftment was derived from both donors, which were 6/6 HLA matched the recipient's, for six months until her death. The other 17 patients achieved sustained hematopoietic engraftment that was derived from a single dominant donor based on STR-PCR results. The median infused cell dose of the engrafted units was 2.34×10⁷ NC /Kg (ranging from 1.87 to 4.45 ×10⁷NC/kg), and 3.225×10⁷CD3+/Kg (ranging from 0.51 to 13.92×10⁷ CD3+/kg). This compared with 2.17×10⁷ NC/Kg (range: 0.96 - 3.98×10⁷ NC/kg) and 1.71×10⁷CD3+/Kg (range: 0.40 - 10.65×10⁷ CD3+/kg) in the nonsustained unit. The difference in cell doses was not significant(P=0.718 AP=0.073. By STR-PCR, the donor DNA can be detected as early as post-transplantational day 7. Seventeen patients who achieved dominant engraftment had full donor chimera (FDC) at post-transplantational day 14, and this was highly consistency with chimerisms at post-transplantational days 21 and 30. If no unit reached FDC at post-transplantational day 14, the graft would be rejected. Therefore, the result at post-transplantational day 14 could indicate the last chimerism (Kappa =1). Complications: 1) Three patients had UCB graft rejections at early period; two were adolescent ALL, one was MDS-RCMD. Depending on long-term transfusion, they all achieved long-term hematopoiesis recovery after a secondary haploidentical stem cell transplantation at post-DUCBT 33-38 day. 2) Eight/eighteen patients(44.4%)had grade±-IIacute GVHD, 2 in accessible 13 patients developed local (non-extensive) cGVHD. 3) Three patients relapsed (1 was CNSL, and 1 relapsed on cellular level and re-achieved FDC after treatment with imatinib and benzene). 4) All patients had a median follow-up of 12 months (ranging 5 months to 43 months). The one-year disease-free survival rate was 66.64%, with 6 patients died. The one hundred-day transplantation-related mortality was 14.3%; 4 died of invasive fungal infection, 1 died of body exhaustion, and 1 died of serious hepatitis.

1) Double-unit UCB can overcome the shortage of cell dose in one-unit UCB, and was proved to be a safe, effective, and promising alternative treatment option with good engraftment potential. 2) The total nucleated cells and CD3 cell dose were not associated with the UCB unit that would predominate. 3) The STR -PCR and capillary electrophoresis techniques can accurately evaluate grafting at an early time after UCBT. Detecting the chimerism at 14 days after UCBT can provide the information on graft implantation. 4) The relapse rate was 14.3% in 18 CB-engrafted patients with high-risk and refractory disease conditions, which suggests that UCBT has a fairly good graft versus leukemia effect.

No relevant conflicts of interest to declare.