Xingbing Wang

Pre-engraftment syndrome after unrelated donor umbilical cord blood transplantation in patients with hematologic malignancies.

Pre‐engraftment syndrome (PES) after umbilical cord blood transplantation (CBT) remains poorly characterized, and the prognosis and appropriate management are unclear. Therefore, we retrospectively analyzed the incidence, risk factors, manifestations, and clinical outcomes of PES in CBT recipients, who had been treated for hematologic malignancies at our transplantation center. PES was defined as unexplained fever higher than 38.3°C that is not associated with documented infection and unresponsive to antimicrobial manipulations and/or unexplained erythematous skin rash occurring prior to neutrophil engraftment. A total of 81 patients (median 18 yr, range 3–48) received either myeloablative (n = 72) or non‐myeloablative (n = 9) conditioning. Neutrophil engraftment was achieved in 69 of the 81 cases [86.2%, 95% confidence interval (CI) = 78.9–94.1%], and the median time to more than 0.5 × 109/L ANC was 19 d (range, 12–39). Fifty‐one patients (63.0%) developed PES at a median of 7 d (range 3–15) post‐transplant: 46 patients had both rash and unexplained fever; one patient had unexplained fever alone; and four patients had rash only. Forty‐seven patients (92.2%) received IV methylprednisolone (MP) at a median dose of 1 mg/kg (range 0.4–3). All patients treated with MP responded as evidenced by fever resolution combined with resolution of rash. All patients with PES had high serum levels of C‐reactive protein (CRP), which were significantly reduced after effective steroid treatment. Univariate analysis identified myeloablative conditioning and younger age as significant risk factors for developing PES. Cumulative incidence of grade II–IV acute graft‐versus‐host disease (aGVHD) in the PES+ and PES− groups was 51.5% (95% CI = 38.0–70.0%) and 17.0% (95% CI = 6.9–41.7%), respectively. In a multivariate analysis, we found significantly increased risk of grade II–IV aGVHD among PES patients (P = 0.041). However, PES was not associated with sustained donor engraftment, the day to neutrophil recovery, chronic graft‐versus‐host disease, transplant‐related mortality at day 180, and overall survival. Despite of the inherent limitations of this small retrospective study, PES seemed to be common after CBT and associated with high incidence of aGVHD.

CD123 redirected multiple virus-specific T cells for acute myeloid leukemia

Hematopoietic stem cell transplantation (HSCT) has been increasingly used as a curative treatment for acute myeloid leukemia (AML). However, relapse rates after HSCT in complete remission (CR) are reported between 30% and 70%. In addition, numerous studies suggested that secondary viral infection from a variety of viruses including Epstein-Barr virus (EBV), adenovirus (Adv), and cytomegalovirus (CMV) are among the most common causes of death post-HSCT. Currently, chimeric antigen receptor (CAR)-based T cells have been developed to treat AML in clinical studies, while virus-specific cytotoxic T cells (VST) have been proven to be able to effectively prevent or treat viral infection after HSCT. Thus it would be desirable to develop T cells with the ability of simultaneously targeting AML relapse and viral infection. In this article, we now describe the generation of VST cells that are engineered to express CAR for a specific AML cell-surface antigen CD123 (CD123-CAR-VST). Using Dendritic cells (DCs) pulsed with EBV, Adv, and CMV peptides as sources of viral antigens, we generated VST from A2 donor peripheral mononuclear cells (PBMC). VST were then transduced with retroviral vector encoding CD123-CAR to generate CD123-CAR-VST. We demonstrated that CD123-CAR-VST recognized EBV, Adv, and CMV epitopes and had HLA-restricted virus-specific cytotoxic effector function against EBV target. In addition, CD123-CAR-VST retained the specificity against CD123-positive AML cell lines such as MOLM13 and THP-1 in vitro. Thus our results suggested that CD123-CAR-VST might be a valuable candidate to simultaneously prevent or treat relapse and viral infection in AML HSCT recipients.

Successful second transplantation with non-myeloablative conditioning using haploidentical donors for young patients after graft failure following double umbilical cord cell transplantation.

Liu H, Wang X, Geng L, Tang B, Tong J, Yao W, Wang Z, Sun Z. Successful second transplantation with non‐myeloablative conditioning using haploidentical donors for young patients after graft failure following double umbilical cord cell transplantation.
Pediatr Transplantation 2010: 14:465–470.

Primary research on unrelated double umbilical cord blood transplantation and implantation kinetics

Abstract Objective This study sought to examine implantation and implantation kinetics in double umbilical cord blood transplantation (DUCBT). Methods Twenty-nine patients who underwent a two-unit unrelated donor cord blood transplantation were included in this study. After transplantation, hematopoietic chimerism of the peripheral blood was evaluated based on the results of short tandem repeat polymerase chain reaction. Using these results, we were able to judge whether the transplanted cells implanted, determine which donors cells implanted, and further examine the kinetics of implantation in DUCBT. The numbers of total nucleated cells (TNCs), CD34+ cells, colony forming units (CFUs), colony forming unit-granulocytes and macrophages (CFU-GMs), and CD3+ cells were compared between the dominant units and the non-dominant units in an attempt to understand the discipline and implantation kinetics of DUCBT. Results Neither the TNC counts nor the counts of CD34+ cells, CFU, CFU-GM, or CD3+ cells were significantly different between the dominant units and the non-dominant units (P values of 0.584, 0.322, 0.842, 0.534, and 0.082, respectively). Conclusions We were able to determine the engraftment status at 14 days after DUCBT, although the implantation kinetics of DUCBT remain uncharacterized and require further research.

European Group for Blood and Marrow Transplantation Risk Score Predicts the Outcome of Patients with Acute Leukemia Receiving Single Umbilical Cord Blood Transplantation

The European Group for Blood and Marrow Transplantation (EBMT) risk score has been implemented as an important tool to predict patient outcomes after allogeneic hematopoietic stem cell transplantation. However, to our knowledge, this score has never been applied in cases of single umbilical cord blood transplantation (sUCBT). We retrospectively analyzed 207 consecutive patients with acute leukemia who received sUCBT at our center between February 2011 and December 2015. The probabilities of 3-year overall survival (OS) and leukemia-free survival (LFS) of the entire cohort were 65.0% and 59.8%, respectively, whereas the cumulative incidences of 3-year nonrelapse mortality (NRM) and relapse rate were 19.5% and 20.3%, respectively. In the univariate analysis, a higher EBMT risk score was associated with worse OS and LFS and higher NRM and relapse rate, ranging from 81.7%, 75.9%, 7.3%, and 15.3%, respectively, for patients with a score of 1 to 43.8%, 44.3%, 31.7%, and 23.9%, respectively, for patients with scores of 4 to 6. Hazard ratios of OS, LFS, and NRM all steadily increased for each additional score point. Importantly, the prognostic value of the EBMT risk score on OS, LFS, NRM, and relapse was maintained in the multivariate analysis. Moreover, considering the univariate analysis results of donor-recipient gender and mismatched allele-level HLA-A, -B, -C, and -DRB1 loci on patient outcomes and the fairly strong interaction between time from diagnosis to sUCBT and disease status, we developed a modified sUCBT-EBMT risk score by using degrees of 8-allele HLA match instead of donor type, donor-recipient gender combination, and time from diagnosis to sUCBT, and found that the modified score could also be used as a predictor for patient outcomes after sUCBT. The EBMT risk score is a good predictor of outcomes of patients with leukemia after sUCBT. The modified sUCBT-EBMT risk score can also be used as a pretransplant risk assessment, but this metric still requires further evaluation with a larger cohort.