Lujia Dong

Adoptive transfer of cytomegalovirus/Epstein-Barr virus-specific immune effector cells for therapeutic and preventive/preemptive treatment of pediatric allogeneic cell transplant recipients.

This report describes a safe and effective therapy through adoptive transfer of donor cytomegalovirus (CMV)/Epstein-Barr virus (EBV) immune effector cells. The patients, from 3 to 10 years of age, suffering from hematologic diseases received haploidentical transplantation. All 3 patients developed varying levels of viremia from days 13 to 31 and 2 patients developed CMV-interstitial pneumonitis or interstitial inflammation after transplantation. Tapering down the dose of immunosuppressives together with intensive antivirus therapy and escalated infusions of donor-derived CMV/EBV immune effector cells effectively controlled virus-related diseases. All 3 patients survived and remained CMV/EBV-free 14-16 months after transplantation.

Surveillance of Active Human Herpesvirus 6 Infection in Chinese Patients after Hematopoietic Stem Cell Transplantation with 3 Different Methods

Human herpesvirus 6 (HHV-6) reactivation was studied in 72 consecutive allogeneic hematopoietic stem cell transplant (HSCT) recipients and 53 “healthy” donors. The feasibilities of real-time quantitative polymerase chain reaction (RQ-PCR), nested-PCR, and antigenemia assays in the assessment of HHV-6 reactivation were also evaluated. HHV-6 DNA was detected in 62.5% and 48.6% of post-HSCT patients with the nested-PCR assay and RQ-PCR analysis, respectively, and HHV-6B was identified as the predominant variant. The incidence of HHV-6 infection peaked from the second to the seventh week, whereas the HHV-6B DNA loads peaked from the second to the third week. Compared with RQ-PCR analysis, the sensitivity and specificity of the nested-PCR assay were 100% and 88%, respectively, with positive and negative predictive values of 60% and 99%, respectively. For the HHV-6 antigenemia assay, the sensitivity and specificity were 89% and 97%, respectively, and the positive and negative predictive values were both 94%. Conditioning with antithymocyte globulin in HLA-mismatched or unrelated HSCT increased the possibility of HHV-6B reactivation after HSCT (hazard ratio, 5.92; 95% confidence interval, 1.99-17.59; P = .001). In conclusion, HHV-6B reactivation is commonly encountered after HSCT. Of the 3 methods we adopted for HHV-6 detection, both RQ-PCR analysis and the antigenemia assay could be seen as essential tests for predicting HHV-6 reactivation.

Haploidentical hematopoietic stem cell transplantation for a case with X-linked chronic granulomatous disease.

CGD is a rare primary immunodeficiency with high mortality rates when treated conventionally, especially for the X‐chromosome‐linked form. HSCT is the only curative therapy for CGD; however, haploidentical transplantation in CGD is rare. Here, we report a case of X‐linked CGD treated successfully by haploidentical HSCT. The patient showed a positive result with full donor chimerism, good quality of life, and the absence of recurrent infectious diseases at follow‐up (68 months). Thus, haploidentical HSCT may serve as an acceptable treatment approach for patients who have CGD, but no HLA‐matched related or unrelated donor.

195. Allogeneic CD19-CART Therapy to the Rescue of a Pediatric Patient with Relapsed and Refractory Acute B Lymphoblastic Leukemia

Acute B lymphoblastic leukemia (B-ALL) is a common hematological malignancy in children. Using a fourth generation, safety-switch inserted, chimeric antigen receptor (4SCAR) technology, we have treated more than 200 patients with B-ALL in China, with an overall complete remission rate of more than 80% (ASH 2015). Here we report the case of a 7-year-old girl with a high load of refractory B-ALL, who was heavily pretreated with chemotherapy but relapsed with >80 leukemic blasts in her bone marrow. The patient received CD19-4SCAR T cells generated from her mothers peripheral blood T cells (allo-4SCAR19) for three times at total of 0.76 x106 CART/kg on day 0, 4, and 7, followed by an infusion of autologous 4SCAR19 (auto-4SCAR19) at total of 0.16 x106 CART/kg on day 56, which was derived from the patients own T cells after her immune recovery. Complete remission was achieved as revealed by bone marrow examination on day 77. Graft versus host disease signs were not observed throughout the days following the infusions, and the syndrome of suspected cytokine storm was generally mild. The only adverse responses were intermittent fever and skin rashes following allo-4SCAR19 infusions which lasted for about 20 days. The outcome of this case suggests that allo-4SCAR19 may be a safe approach in treating B-ALL patients who could not provide their own T cells for CART engineering, and allo-4SCAR19 combined with auto-4SCAR19 is a novel strategy that may rescue chemo-refractory, high-risk and highly immune suppressed leukemia patients.