Comparison of hematopoietic stem cell transplantation and repeated intensified immunosuppressive therapy as second-line treatment for relapsed/refractory severe aplastic anemia.

The optimal treatment for patients with severe aplastic anemia (SAA) who fail an initial course of antithymocyte globulin (ATG) plus cyclosporine has not yet been established. We compared the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) (n = 36) with repeated immunosuppressive therapy (IST) (n = 33) for relapsed/refractory SAA between 2007 and 2022. In the IST group, patients were retreated with ATG (n = 16) or high-dose cyclophosphamide (n = 17). The overall response rate was 57.6% at 6 months and 60.6% at 12 months. In the allo-HSCT group, patients received a transplant from a matched sibling donor (n = 6), matched unrelated donor (n = 7), or haploidentical donor (n = 23). All patients achieved neutrophil engraftment, and there were no cases of primary graft failure. The cumulative incidences (CIs) of grades II-IV and III-IV acute graft-versus-host disease (GVHD) were 36.1% ± 0.7% and 13.9% ± 0.3% at day +100, respectively. The 4-year CI of chronic GVHD (cGVHD) was 36.2% ± 0.7%, with moderate to severe cGVHD at 14.9% ± 0.4%. Compared with IST, HSCT recipients showed much higher hematologic recovery rate at 3, 6, and 12 months (63.9%, 83.3%, and 86.1%, respectively, p < 0.001). The estimated 4-year overall survival (OS) (79.8% ± 6.8% vs. 80.0% ± 7.3%, p = 0.957) was similar; however, the failure-free survival (FFS) was significantly better in the HSCT group (79.8% ± 6.8% vs. 56.6% ± 8.8%, p = 0.049). Of note, children in the HSCT cohort were all alive without treatment failures, exhibiting superior OS (100% vs. 50.0% ± 17.7%, p = 0.004) and FFS (100% vs. 50.0% ± 17.7%, p = 0.004) than children in the IST cohort. Subgroup analysis revealed that younger patients (age ≤ 35 years), especially children, and those with refractory SAA benefited more from HSCT. Therefore, for these patients, salvage HSCT may be more preferable than a second course of IST.

Addition of ruxolitinib to standard graft-versus-host disease prophylaxis for allogeneic stem cell transplantation in aplastic anemia patients.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers rapid hematopoietic and immune reconstitution for aplastic anemia (AA). As a non-malignant disorder, attenuation of GVHD remains a clinical priority in AA patients. Our study sought to investigate the safety and efficacy of the prophylactic use of ruxolitinib in allogeneic HSCT. A total of 35 AA patients were retrospectively consecutively treated with allo-HSCT whereby ruxolitinib was added to the standard GVHD prophylaxis regimen (rux group). The addition of peri-transplant ruxolitinib did not impact the engraftment and graft function, while better recovery of CD4+ Tregs in the rux group was observed. Interestingly, the rux group demonstrated significantly lower incidence of bacterial/fungal infections (17.14% vs 45.71%). Compared to the control group, the rux group exhibited significantly lower incidence of moderate to severe aGVHD (17.1% vs 48.6%) with a trend toward lower severe aGVHD (8.6% vs 20%) and cGVHD (26.2 vs 38.3). The rux group also demonstrated a trend toward higher GVHD and failure-free survival (GFFS: 85.7% vs 68.6%) and lower TRM (2.9% vs 14.3%). Addition of ruxolitinib to standard GVHD prophylaxis regimen, thus, represents a safe and highly efficient method for the attenuation of GVHD with better outcome of allo-HSCT.

Post-HSCT Maintenance Treatment Using Entrectinib for an AML Patient Accompanied with ETV6::NTRK3: A Case Report.

The neurotrophic receptor tyrosine kinase (NTRK) gene fusions occur in a large number of solid tumors and tropomyosin receptor kinase (TRK) inhibitors exhibit attractive antitumor activity. However, the occurrence of NTRK fusions is rare in hematological malignancies, and just a few cases or pre-clinical researches have been reported. This case report presents a refractory acute myeloid leukemia (AML) patient, accompanied with ETV6::NTRK3, was failed by traditional chemotherapy, then entered long-term remission after hematopoietic stem cell transplantation (HSCT) and maintenance therapy with entrectinib. It was the first successful use of the TRK inhibitor in an AML patient after HSCT.

Ruxolitinib as an Effective and Steroid-Sparing First-Line Treatment in Newly Diagnosed BOS Patients After Hematopoietic Stem Cell Transplantation.

Bronchiolitis obliterans syndrome (BOS) is a life-threatening pulmonary complication of chronic graft-versus-host disease (cGVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). In this study, we retrospectively identified seven patients newly diagnosed with BOS post HSCT and analyzed the outcomes in those patients treated with ruxolitinib as a first-line treatment. All seven patients achieved symptom responses within 2 weeks after ruxolitinib administration. Three months after treatment, five patients (71.43%) achieved a CR, and two (28.57%) achieved a PR. The overall response rate (ORR) was 100%. In addition, the steroid therapy was determined within 2 months after ruxolitinib treatment, indicating ruxolitinib as a steroid-sparing agent. We also found that ruxolitinib was well-tolerated and safe in treating newly diagnosed BOS. According to our results, ruxolitinib would be a promising and safe option in newly diagnosed BOS post HSCT.

Data analysis of PD-1 antibody in the treatment of melanoma patients.

Data presented in this article are supplementary materials to the research article entitled "IGFBP2 regulates PD-L1 expression by activating the EGFR-STAT3 signaling pathway in malignant melanoma". Data for melanoma patients who did not receive anti-PD-1 treatment were obtained from Tianjin Medical University Cancer Institute & Hospital from February 1981 to May 2013. Kaplan-Meier was used for survival analysis. RNA sequencing data from 28 melanoma patients receiving anti-PD-1 therapy were download from GEO database (GSE78220). Cluster analysis of RNA expression was performed using R (package pheatmap). The difference of PD-L1 expression was analysed by the Boxplot (R ggplot2 package). Differences between each group were analyzed by Fisher exact test. Information of 13 melanoma patients who had failed prior chemotherapy and treated in the Tianjin Medical University Cancer Institute & Hospital between July 2015 and December 2018 was collected. The response was captured by Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1).

IGFBP2 regulates PD-L1 expression by activating the EGFR-STAT3 signaling pathway in malignant melanoma.

Immunotherapy targeting the PD-1/PD-L1 receptor has achieved great success in melanoma patients. Although many studies have addressed the underlying mechanisms involved in the blockade of PD-1/PD-L1 and the consequent modulation of the immune system, the mechanisms of PD-L1 upregulation and reliable biomarkers to predict the efficacy of anti-PD-1/PD-L1 therapy remain unknown. The present study demonstrates the correlation between IGFBP2 and PD-L1, revealing a novel immune-associated tumor function of IGFBP2 in facilitating nuclear accumulation of EGFR and activation of the EGFR/STAT3/PD-L1 signaling pathway in melanoma cells. Our results also suggest that combined IGFBP2 and PD-L1 expression has the potential to predict the efficacy of anti-PD-1 treatment for malignant melanoma; because the combination of high IGFBP2 and PD-L1 expression characterizes melanoma patients with worse overall survival and is associated with a better immune ecosystem. These characteristics have been confirmed by both in vitro and in vivo data. Consequently, IGFBP2 regulates PD-L1 expression by activating the EGFR-STAT3 signaling pathway and its function as a PD-L1 regulator might suggest novel therapeutic approach for melanoma.

Clinical characteristics and prognostic indicators for metastatic melanoma: data from 446 patients in north China.

Melanoma is an extremely rare tumor in Asia. This retrospective study aimed to identify the clinical characteristics and prognostic factors of metastatic melanoma patients at Tianjin Medical University Cancer Hospital over the last 30 years. Survival analysis was performed with Kaplan-Meier, log-rank test, and multivariate Cox regression method using SPSS 19.0 software. The 1-, 2-, and 5-year survival rates of metastatic melanoma patients were 52, 32, and 16 %, respectively. Median overall survival (OS) was 13.5 months, median progression-free survival (PFS) 9.0 months, and median disease-free survival 20.3 months. Furthermore, patients with a single metastatic site achieved better OS and PFS than those with two or more metastatic lesions (OS 21.6 vs. 8.9 months, P < 0.001; PFS 11.3 vs. 7.1 months, P < 0.001). Survival times of patients with visceral metastases were the shortest (OS 8.5 months; PFS 7.5 months). Specifically, patients with primary mucosal lesions had a worse OS (9.7 months) and PFS (6.8 months) than those with acral (19.2 and 15.6 months, respectively) or non-acral primary lesions (11.8 and 11.1 months, respectively). The treatment of advanced melanoma was unitary, and prognoses of patients with metastatic melanoma in China were poor. Visceral metastasis, multiple metastatic sites, and primary mucosal lesions were significant predictors of survival of patients with metastatic melanoma. Those with primary mucosal lesions had significantly worse survivals than those with primary cutaneous lesions. More active involvement in clinical studies and more feedback on various treatment options are required.

Advances in targeted therapy for unresectable melanoma: new drugs and combinations.

Melanoma is the most deadly cutaneous cancer primarily derived from melanocytes with a poor prognosis in advanced stage. The therapy regimen for early stage melanoma patients is surgical resection with adjuvant IFN-alpha-2b therapy. For metastatic lesions, standard chemotherapy such as dacarbazine (DTIC) has not achieved a satisfying response rate. Therefore, new approaches to manage this deadly disease are highly expected to enhance the cure rate and to extend clinical benefits to patients with unresectable melanoma. Fortunately, the targeted therapeutic drugs and immunotherapy such as vemurafenib, dabrafenib, ipilimumab, and trametinib have shown their special advantage in the treatment of advanced melanoma. This article is to overview the advances in targeted therapy for unresectable melanoma patients.

Novel anti-melanoma treatment: focus on immunotherapy.

Melanoma is an intractable cancer that is aggressive, lethal, and metastatic. The prognosis of advanced melanoma is very poor because it is insensitive to chemotherapy and radiotherapy. The incidence of melanoma has been ascending stably for years worldwide, accompanied by increasing mortality. New approaches to managing this deadly disease are much anticipated to enhance the cure rate and to extend clinical benefits to patients with metastatic melanoma. Due to its high degree of immunogenicity, melanoma could be a good target for immunotherapy, which has been developed for decades and has achieved certain progress. This article provides an overview of immunotherapy for melanoma.

Advances in targeted therapy for osteosarcoma.

Osteosarcoma is an aggressive cancer in skeletal system with unknown molecular mechanisms of etiology and pathogenesis, therefore it remains a challenge for current therapeutic strategies to effectively treat osteosarcoma. The aim of this review is to give an overview of the molecular and mechanistic changes identified in recent years which might be new targets for the treatment of osteosarcoma. These molecules play important roles in different biological and pathological programs of osteosarcoma, including the altered oncogenes and tumor suppressor genes, molecules involved in tumor cell migration and invasion, angiogenesis, apoptosis and proliferation, miRNAs, and molecules involved in osteoclast function and multidrug resistance. Further research on these molecules in osteosarcoma will provide new insights into the target therapy for osteosarcoma.

The role of mesenchymal stem/progenitor cells in sarcoma: update and dispute.

Sarcoma is the collective name for a relatively rare, yet heterogeneous group of cancers, most probably derived from mesenchymal tissues. There are currently over 50 sarcoma subtypes described underscoring the clinical and biologic diversity of this group of malignant cancers. This wide lineage range might suggest that sarcomas originate from either many committed different cell types or from a multipotent cell. Mesenchymal stem/progenitor cells (MSCs) are able to differentiate into many cell types and these multipotent cells have been isolated from several adult human tumors, making them available for research as well as potential beneficial therapeutical agents. Recent accomplishments in the field have broadened our knowledge of MSCs in relation to sarcoma origin and sarcoma treatment in therapeutic settings. However, numerous concerns and disputes have been raised about whether they are the putative originating cells of sarcoma and their questionable role in sarcomagenesis and progression. We summarize the update and dispute about MSC investigations in sarcomas including the definition, cell origin hypothesis, functional and descriptive assays, roles in sarcomagenesis and targeted therapy, with the purpose to give a comprehensive view of the role of MSCs in sarcomas.