The Outcome of Allogeneic Hematopoietic Stem Cell Transplantation From Different Donors in Recipients With Mucopolysaccharidosis.

There is limited information regarding hematopoietic stem cell transplantation (HSCT) for mucopolysaccharidosis (MPS) IV and VI. This study examined the full donor chimerism, specific lysosomal enzyme levels, and the survival of different MPS children after HSCT from various donor sources and compared the prognosis. A total of 42 children with MPS underwent HSCT, 9 cases were type I, 14 were type II, 15 were type IV, and 4 were type VI. A total of 24 patients received peripheral blood stem cells (PBSC) and 18 patients received umbilical cord blood (UCB). Patients who received PBSC were conditioned with intravenous (IV) busulfan every 6 h for a total of 16 doses, IV cyclophosphamide (CY, 200 mg/kg), and antihuman thymocyte globulin (ATG, 10 mg/kg). While conditioning regimen of patients who received UCB was adjusted to ATG (preposed, pre-) + busulfan + fludarabine + Cy, which includes IV ATG (pre-, 6 mg/kg), IV busulfan every 6 h for a total of 16 doses, IV fludarabine (200 mg/m2) and CY (200 mg/kg). Also, 95.2% (40 of 42) of patients achieved full donor chimerism, and all patients' specific lysosomal enzyme levels reached normal. The estimated overall survival (OS) at 1 year was 92.9%. There was no significant difference in 1-year OS between patients who received PBSC transplantation and those who received UCB grafts (87.5% vs. 100%, p = 0.0247). The incidence of acute and chronic GVHD did not differ between them. The incidences of pneumonia in PBSC recipients and UCB recipients were 45.8 and 33.3%, respectively, but there few patients suffering from respiratory failure (4.2 and 5.6%, respectively) due to pneumonia. The incidence of cytomegaloviremia was also high in both groups, 58.3 and 44.4% respectively, However, no patient developed CMV disease. All deaths (3 of 42) occurred in patients receiving PBSC grafts, and there was no death in patients receiving UCB grafts. There was no death after transplantation in patients with MPS IV and VI. In addition, respiratory and nervous system functions were improved, whereas valvular heart disease was improved in some patients but progressed in more patients after transplantation. In summary, HSCT is a good therapeutic option for MPS, not only for patients with MPS I or II but also for those with MPS IV or VI. The specific lysosomal enzyme levels can be completely restored to normal, which is the basis for patients to resolve a broad range of clinical outcomes. Moreover, UCB with suitable HLA (HLA-match above 7/10 and 4/6) is a suitable donor source for MPS. Patients who underwent UCB transplantation using the conditioning regimen ATG (pre-) + busulfan + fludarabine + Cy can achieve a higher proportion of full donor chimerism and survival with less severe complications. HSCT can improve organs function in patients with MPS, but it is still worth exploring.

Hematopoietic stem cell transplantation for thalassemia major using HLA fully-matched and mismatched donor grafts.

BACKGROUND: Until now, allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only effective method to cure Thalassemia major. However, it has not been determined whether similar results can be obtained with the same conditioning regimen for both fully-matched and mismatched donors grafts. We hypothesized that using modified NF-08-TM conditioning regimen could achieve similar results for both fully and mismatched donors grafts. METHODS: This retrospective cohort study included patients with ß-thalassemia major who underwent HSCT with modified NF-08-TM conditioning regimen at Guangzhou Women and Children's Medical Centre between January 2013 and January 2019. RESULTS: Among the 257 patients (172 males) included in this study, 3 had two transplantations. Totally 193 and 67 had fully-matched and mismatched donors were examined, respectively. The median follow-up was 29 months; 6-year overall survival (OS), thalassemia-free survival (TFS), graft rejection (GR) and transplantation-related mortality (TRM) were 92.08%, 90.89%, 1.24% and 8.01%, respectively. Multivariate analysis showed that human leukocyte antigen (HLA) compatibility between patient and donor was not independently associated with OS, TFS, GR or TRM. Mismatched donor graft transplantation for ß-thalassemia major is associated with similar survival outcomes and incidences of complications (except for acute GVHD) to fully-matched donor graft transplantation based on modified NF-08-TM conditioning regimen. CONCLUSIONS: In conclusion, based on the modified NF-08-TM regimen, certain mismatched donor transplantations for thalassemia major patients could achieve similar results as fully-matched donor transplantations.

Enterovirus 71 VP1 promotes mouse Schwann cell autophagy via ER stress­mediated PMP22 upregulation.

Enterovirus 71 (EV71) accounts for the majority of hand, foot and mouth disease­related deaths due to fatal neurological complications. EV71 structural viral protein 1 (VP1) promotes viral replication by inducing autophagy in neuron cells, but the effect of VP1 on myelin cells is unclear. The present study aimed to investigate the role and mechanism of VP1 in autophagy of mouse Schwann cells. An EV71 VP1­expressing vector (pEGFP­C3­VP1) was generated and transfected into mouse Schwann cells. Transmission electron microscopy and western blot analysis for microtubule­associated protein 1 light chain 3 α (LC3) II (an autophagy marker) were used to assess autophagy. Reverse transcription­quantitative PCR and immunofluorescence were performed to determine the expression of peripheral myelin protein 22 (PMP22). Small interfering RNA against PMP22 was used to investigate the role of PMP22 in mouse Schwann cell autophagy. Salubrinal [a selective endoplasmic reticulum (ER) stress inhibitor] was used to determine whether PMP22 expression was affected by ER stress. The present results indicated that VP1 promoted mouse Schwann cell autophagy. Overexpression of VP1 upregulated PMP22. PMP22 deficiency downregulated LC3II and thus inhibited autophagy. Furthermore, PMP22 expression was significantly suppressed by salubrinal. In conclusion, VP1 promoted mouse Schwann cell autophagy through upregulation of ER stress­mediated PMP22 expression. Therefore, the VP1/ER stress/PMP22 autophagy axis may be a potential therapeutic target for EV71 infection­induced fatal neuronal damage.

[Expression of two subtype molecules of CD133 in childhood with B linage acute lymphoblastic leukemia and its clinical significance].

This study was to explore the expression of two subtype molecules of CD133 and its relationship with clinical prognostic factors in childhood with B linage acute lymphoblastic leukemia (B-ALL) at initial diagnosis and the 33rd day of induction chemotherapy. Expression of CD133-1 and CD133-2 in 48 cases of B-ALL and 25 cases at initial diagnosis and the 33rd day of treatment was detected by flow cytometry. Minimal residual disease (MRD) of B-ALL at 33rd day was evaluated by flow cytometry. The results indicated that the expression of CD133-1 was positive in 18 cases (37.5%), and expression of CD133-2 in 30 cases (62.5%) was positive from 48 cases with newly diagnosed ALL (P < 0.05). At 33rd day of treatment, expression of CD133-1 in 2 cases (8.0%) from 25 cases was positive, and expression of CD133-2 in 23 cases (92.0%) was positive (P < 0.05). After induction chemotherapy in B-ALL, the expression of CD133-1 decreased significantly, but still higher than that in the normal control group. Compared to expression of CD133-1, expression of CD133-2 decreased slowly. It is concluded that there is no relations among expression of CD133 and sex, age, white blood cell count, percentage of bone marrow blast cells, FAB subtype, cytogenetics, leukemia fusion gene, risk stratification and complete remission rate in childhood B-ALL. The positive expression rates and levels of CD133-2 are higher than those of CD133-1 in B-ALL. There is no statistical correlation between expression of CD133 and CD34 in B-ALL. The expression of CD133-2 is significantly related to the level of MRD.

[Analysis of clinical features and prognostic significance of childhood T-lineage acute lymphoblastic leukemia].

This study was aimed to explore the clinical features and prognosis outcome of childhood T-cell acute lymphoblastic leukemia (T-ALL). The clinical data of 38 cases of newly diagnosed T-ALL from Jan 2005 to Aug 2010 were analyzed retrospectively, and 78 cases of B-ALL with intermediate and high risk were collected as control group, then the sensitive rate of patients to prednisone pretreatment, complete remission (CR) rate at day 33 after induction chemotherapy, relapse rate and 3-year event-free survival (EFS) were compared between T-ALL and B-ALL children. The results showed that no significant statistic difference were found in distribution of age, infiltration of liver, spleen and lymph nodes as well as central nervous system disease, chromosome abnormality, expression level of fusion gene and so on between T-ALL and B-ALL groups (p > 0.05), but there were significant differences in sex and number of cases with WBC count ≥ 50 × 10(9)/L between them (p < 0.05). The sensitive rate of T-ALL and B-ALL patients to prednisone pretreatment was 51.9% and 89.3% respectively (p < 0.05). The ratio failed to achieve CR at day 33 after induction chemotherapy was 15.4% and 8.1% in the two groups (p > 0.05). The relapse rate of T-ALL and B-ALL cases was 30.8% (8/26) and 14.9% (11/74) respectively (p > 0.05). The time from CR to relapse was (9.78 ± 3.48) month and (21.28 ± 14.32) month (p < 0.05). The 3 year EFS of T-ALL cases with intermediate and high risk was (37.5 ± 17.1)% and (22.2 ± 9.8)%, while 3 year EFS of B-ALL cases was (66.7 ± 7)% and (51.7 ± 9.3)% respectively (p < 0.05) according to Kaplan-Meier survival curve. It is concluded that as compared with B-ALL cases, the male ratio and initial WBC count are higher, moreover the early response to prednisone pretreatment and 3 year EFS are poor in T-ALL cases, the prognosis outcome is poor also.