Xinchuan Chen

Although post-transplant cyclophosphamide (PTCy) is widely used to prevent graft-versus-host disease (GVHD), its protective effect remains inadequate in patients undergoing myeloablative haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). We retrospectively evaluated the efficacy of PTCy combined with either pre-transplant or post-transplant antithymocyte globulin (ATG) for GVHD prevention in 114 haplo-PBSCT recipients. The PTCy+FTATG group (n = 74) received ATG at a total dose of 5 mg/kg on days −3 to −1, together with PTCy at 25 mg/kg on days +3 and +4. The PTCy+PTATG group (n = 40) received PTCy at 50 mg/kg on days +3 and +4, followed by ATG at 2.5 mg/kg on day +8. Both univariate and multivariate analyses showed that PTCy+FTATG prophylaxis significantly lowered the risk of grade II–IV acute GVHD (9.5% vs 27.5% [HR 0.24; 95% CI: 0.10–0.59; P = 0.002]) and grade III–IV acute GVHD (5.4% vs 17.5% [HR 0.19; 95% CI: 0.07–0.54; P = 0.002]). The 2-year cumulative incidence of chronic GVHD was 16.7% in the PTCy+FTATG group and 27.5% in the PTCy+PTATG group ( P = 0.15). At 2 years, overall survival (OS), progression-free survival (PFS), and graft-versus-host disease-free relapse-free survival (GRFS) were 87.8% vs 72.5% ( P = 0.04), 82.2% vs 65.0% ( P = 0.03), and 78.1% vs 55.0% ( P = 0.005), respectively. These results suggest that half-dose PTCy combined with low-dose pre-transplant ATG may be a promising strategy for GVHD prophylaxis.

Caplan syndrome is a rare disorder characterized by the coexistence of pneumoconiosis and rheumatoid arthritis (RA), primarily observed in individuals with silica or coal dust exposure. Data on disease behavior in the context of incomplete or irregular immunosuppressive therapy remain limited. This case report describes a 56-year-old man with a history of mixed dust exposure and smoking who presented with recurrent fever, chest pain, and polyarthralgia. Despite being diagnosed and treated for pulmonary tuberculosis and cryptococcosis, his respiratory and articular symptoms persisted. Serological tests revealed persistently elevated rheumatoid factor (RF) and anticitrullinated peptide antibody (ACPA), while a lung biopsy demonstrated chronic inflammation with carbon deposition, confirming Caplan syndrome. Retrospective analysis indicated that elevations of RF and ACPA preceded observable radiological and pathological changes. Notably, inflammatory markers continued to rise significantly even after infections were controlled and despite only episodic glucocorticoid use. This case highlights the importance of early serological monitoring and comprehensive management in high-risk patients and underscores that, rather than being viewed merely as complications, infections in autoimmune contexts should be recognized as potential triggers and aggravators of immune dysregulation, warranting heightened vigilance in both diagnosis and management.

Chronic graft-versus-host disease (cGVHD)-related serositis is rare, and primarily presents as polyserous effusions. The low incidence and differential diagnosis impose significant challenges to the prompt diagnosis and the effective treatment of the disease. Here we report the diagnosis and treatment of a 57-year-old woman who experienced recurrent steroid-refractory cGVHD-related serositis after allogeneic hematopoietic stem cell transplantation (allo-HSCT). We thus added baricitinib, a specific JAK1/2 inhibitor, into the treatment regimen for the recurrent disease. The patient’s clinical symptoms and effusions were effectively relieved. Currently, no recurrence of serositis and significant adverse events were observed. The utilization of baricitinib might emerge as a novel promising therapeutic option for the treatment of steroid-refractory GVHD following allo-HSCT.

Progressive multifocal leukoencephalopathy (PML) is characterized by demyelination in the central nervous system. It is caused by infection with human polyomavirus 2 and has a poor prognosis. Therapeutic strategies involve restoring immune function and/or discontinuing immunosuppressive treatment. Immune checkpoint inhibitors such as those targeting programmed death receptor-1 (PD-1) can alleviate PML by restoring T cell function. There are no case reports on the use of the PD-1 inhibitor, Sintilimab, for treating PML. Here, we report a case of successful treatment of PML with sintilimab following allogeneic hematopoietic stem cell transplantation. A 35-year-old woman with high-risk acute myeloid leukemia underwent allogeneic hematopoietic stem cell transplantation after induced remission and developed PML 12 months after transplantation. She received five courses of 100 mg every 4 weeks with monitoring by magnetic resonance imaging (MRI) and viral load in the cerebrospinal fluid, showing clinical improvement, resolution of neurological symptoms, and reduced viral load. MRI showed initial exacerbation of lesions but significant improvement after five courses of treatment. No graft-versus-host disease occurred, but manageable immune reconstitution inflammatory syndrome was observed. Sintilimab, a PD-1 inhibitor, might be used to treat PML in patients with hematologic malignancies undergoing allo-HSCT, which needs further investigation.

Post-transplant cyclophosphamide (PTCy) and anti-thymocyte globulin (ATG) are mainstay prophylactic treatment options for graft-versus-host disease (GVHD), widely used in haploidentical stem cell transplantation. Due to a lack of prospective studies, a number of retrospective comparisons have yielded different conclusions as to which prophylaxis regimen is superior. We performed a meta-analysis of these studies to get more informed and comprehensive decisions from clinicians. Nine studies were eligible, and a total of 1674 patients were included. The combined hazard ratio (HR), relative risk (RR), and weighted mean difference (WMD) results demonstrated that, compared with ATG, PTCy demonstrated better overall survival (OS) (HR 0.7, 95% CI 0.51–0.97), leukemia-free survival (LFS) (HR 0.66, 95% CI 0.53–0.81), and GVHD-free/relapse-free survival (GRFS) (HR 0.79, 95% CI 0.65–0.97); faster lymphocyte reconstitution, lower risk of relapse (HR 0.69, 95% CI 0.53–0.9) and fungal infection (RR 0.23, 95% CI 0.07–0.79). However, neutrophil engraftment was delayed in the PTCy regimen group (WMD 3.29, 95% CI 2.49–4.10). No statistically significant differences were observed in the time to platelet engraftment, bacterial infection, or viral infection, including cytomegalovirus, polyomaviruses BK/JC and Epstein-Barr virus. Nor was any statistically significant difference observed in the incidences of II-IV acute-GVHD (aGVHD) (HR 0.81, 95% CI 0.62–1.05), III–IV aGVHD (HR 0.67, 95% CI 0.22–2.19) or severe chronic-GVHD (cGVHD) (RR 1.22, 95% CI 0.51–2.88), or non-relapse mortality (NRM) outcomes (HR 0.67, 95% CI 0.4–1.11). Therefore, in haploidentical transplantation, PTCy accelerates lymphocyte reconstitution, significantly reduces the risk of recurrence and fungal infection, and improves the OS, LFS and GRFS, compared with ATG, with no significant difference in the efficacy of preventing acute or severe cGVHD, or the risk of bacterial or viral infection.

Myelofibrosis (MF) is a myeloproliferative neoplasm (MPN) with a poor prognosis, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment with curative potential. Ruxolitinib, a JAK1/2 inhibitor, has shown promising results in improving patients’ symptoms, overall survival, and quality of life, and can be used as a bridging therapy to HSCT that increases the proportion of transplantable patients. However, the effect of this and similar drugs on HSCT outcomes is unknown, and the reports on their efficacy and safety in the peri-transplantation period vary widely in the published literature. This paper reviews clinical data related to the use of JAK inhibitors in the peri-implantation phase of hematopoietic stem cell transplantation for primary myelofibrosis and discusses their efficacy and safety.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for many malignant hematological diseases. Mesenchymal stem cells (MSCs) are nonhematopoietic stem cells with strong self-renewal ability and multidirectional differentiation potential. They have the characteristics of hematopoietic support, immune regulation, tissue repair and regeneration, and homing. Recent studies have shown that HSCT combined with MSC infusion can promote the implantation of hematopoietic stem cells and enhance the reconstruction of hematopoietic function. Researchers have also found that MSCs have good preventive and therapeutic effects on acute and chronic graft-versus-host disease (GVHD), but there is still a lack of validation in large-sample randomized controlled trials. When using MSCs clinically, it is necessary to consider their dose, source, application time, application frequency and other relevant factors, but the specific impact of the above factors on the efficacy of MSCs still needs further clinical trial research. This review introduces the clinical roles of MSCs and summarizes the most recent progress concerning the use of MSCs in the field of HSCT, providing references for the later application of the combination of MSCs and HSCT in hematological diseases.

Background: Hereditary hyperferritinaemia cataract syndrome (HHCS) is an autosomal dominant disease characterized by high serum ferritin levels and juvenile bilateral cataracts. It is often caused by mutations in the Iron Response Element (IRE) of the ferritin L-subunit (FTL) gene. Most of the mutations are point mutations located in the upper stem and the conserved hexanucleotide of the hairpin structure of IRE, only a few mutations are deletions. Case presentation: Here we report a 73-year-old woman who presented to clinic with persistently elevated serum ferritin and family history of juvenile bilateral cataracts in four generations. DNA sequencing analyses identified a heterozygous c.-167C>T mutation in the 5’ untranslated region (UTR) of the FTL gene. Her daughter and granddaughter were also confirmed to have the same genetic mutation.Conclusion: HHCS should be considered in the differential diagnosis of hyperferritinemia, especially in the presence of normal serum iron concentration and transferrin saturation. For patients with unexplained hyperferritinemia and bilateral cataracts who have experienced early vision loss, the establishment of genetic counseling is essential to diagnose other family members who are at risk in time, so as to avoid unnecessary liver biopsy and venesection.

Objectives: Hereditary hyperferritinaemia cataract syndrome (HHCS) is an autosomal dominant disease characterized by high serum ferritin levels and juvenile bilateral cataracts. It is often caused by mutations in the iron response element (IRE) of the ferritin L-subunit (FTL) gene. Here, we report a 73-year-old woman who presented to clinic with persistently elevated serum ferritin and family history of juvenile bilateral cataracts in four generations. Methods: Exome sequencing was used to identify the mutation of the FTL gene. Moreover, Sanger sequencing was performed to validate the mutation in the proband. We also reviewed the FLT gene mutations in published HHCS cases to provide experience for accurate diagnosis of similar patients. Results: A heterozygous mutation at position +33 (c.-167C > T, chr19:49468598) of the FTL gene was identified in the patient. Discussion: HHCS should be considered in the differential diagnosis of hyperferritinemia, especially in the presence of normal serum iron concentration and transferrin saturation. Conclusion: For patients with unexplained hyperferritinemia and bilateral cataracts who have experienced early vision loss, the establishment of genetic counseling is essential to diagnose other family members who are at risk in time. Abbreviations: FTL: ferritin L-subunit; HHCS: hereditary hyperferritinaemia cataract syndrome; IDT: integrated DNA technologies; IRE: iron response element; IRP: iron regulatory proteins; MRI: magnetic resonance imaging; SNV: single nucleotide variant; UTR: untranslated region