A Novel Therapy Of HLA-Mismatched Sibling Donor Combined With Third-Party Single Cord Blood Cell Transplantation In Patients With Hematologic MalignanciesFimproved Outcome Compared To Conventional Transplantation

In the absence of a HLA-matched sibling donor, a HLA-mismatched sibling donor can be considered an alternative for allogeneic stem cell transplantation (SCT), although its application is associated with theincreased risk of severe acute graft-versus- host-disease (aGVHD ), prolonged length of hospital stay, and poor overall survival(OS). To overcome these drawbacks, HLA-mismatched sibling donor cell combined with a third party single cord blood cell transplantation, known as dual SCT, has been shown to reduce the incidence of aGVHD and related early morbidity and mortality. The objective of this study was to investigate the clinical effect of HLA-mismatched sibling transplantation combined with third-party single cord blood cell infusion in patients with hematologic disorders, and compare that to a cohort of patients who underwent single conventional HLA-mismatched sibling transplants in our center in the same time period.

From September 2003 to April 2013, 169 patients with malignant hematological diseases received HLA sibling mismatched hematopoietic stem cell transplantation in our hospital. Groups A included 98 patients who received HLA-mismatched donor cell combined with third-party single cord blood cell. For the single cord blood cell, we selected HLA low resolution 4/6 consistency with the highest cell count (TNC>1× 107/Kg). Donor umbilical cord blood was infused on d -1 before transplantation. Group B included 71 patients who received HLA-mismatched sibling donor cell alone. We analyzed the differences between the two groups for hematopoietic reconstitution,complications,treatment outcome and prognostic factors.

In groupA: neutrophil reconstruction duration was 13.64 ± 2.981 d, platelet reconstruction duration was 18.68 ± 11.041 d, which have no significant difference (P > 0.05) compared to group B. Recurrence rate were 26.20% and 22.14% respectively and with no statistical difference in the two groups (P > 0.05). However, the incidence of aGVHD in the single HLA-mismatched donor transplant group (group B) was significantly higher than that of combined transplant group (group A) (31% vs17.3%, P < 0.05). In the combined transplant group (group A) , 2-year OS, DFS and treatment related mortality( TRM) were 66.7%, 61.8% and 13.5%, respectively. These results were significantly better than that of the single HLA-mismatched donor transplant group (OS 36.3%, DFS 33.5% and TRM 55.9% , P < 0.05).

Compared to the conventional HLA-mismatched sibling donor stem cell transplant, the novel therapy of HLA-mismatched sibling donor stem cell combined with third-party single cord blood cell transplantation in patients with malignant hematological diseases demonstrated superior clinical outcomes in reducing the incidence of aGVHD and improving OS and DFS. These preliminary but promising results warrant further investigation

No relevant conflicts of interest to declare.