ABSTRACT
HLA-haploidentical hematopoietic stem cell transplantation (HSCT) may be an option for severe aplastic anemia (SAA) patients. However, to date, no large-sample studies have been performed to determine which types of SAA patients are suitable for HLA-haploidentical HSCT. We retrospectively studied 189 consecutive patients with SAA who underwent HLA-identical or HLA-haploidentical HSCT at seven transplant centers in China. Propensity score matching (PSM) was applied in this study to reduce the influence of potential confounders. The 5-year overall survival (OS) rate was 72.0% in the HLA-haploidentical group and 76.5% in the HLA-identical group. The median time to achieve engraftment and the incidence of acute GVHD/chronic GVHD were not significantly different between the two groups. In the subgroup analysis, the outcome of patients older than 40 years in the HLA-haploidentical group was significantly poorer than that of patients younger than 40 years in the same group and that of patients older than 40 years in the HLA-identical group. Based on the above results, we suggest that HLA-haploidentical relative HSCT should be considered as a valid alternative option for patients younger than 40 years with SAA for whom no matched sibling donor is available.
Subject(s)
Anemia, Aplastic/therapy , Graft vs Host Disease/diagnosis , HLA Antigens/immunology , Hematopoietic Stem Cell Transplantation/methods , Acute Disease , Adolescent , Adult , Anemia, Aplastic/immunology , Anemia, Aplastic/mortality , Anemia, Aplastic/pathology , Child , Child, Preschool , China , Chronic Disease , Female , Gene Expression , Graft vs Host Disease/immunology , Graft vs Host Disease/mortality , Graft vs Host Disease/pathology , HLA Antigens/genetics , Histocompatibility Testing , Humans , Male , Middle Aged , Propensity Score , Retrospective Studies , Sample Size , Severity of Illness Index , Survival Analysis , Tissue Donors/classification , Transplantation, HaploidenticalABSTRACT
BACKGROUND: Gap junctional intercellular communication (GJIC) is typically decreased in malignant tumors. Gap junction is not presented between hematopoietic cells but occurred in bone marrow stromal cells (BMSCs). Connexin 43 (Cx43) is the major gap junction (GJ) protein; our previous study revealed that Cx43 expression and GJIC were decreased in acute leukemic BMSCs. All-trans retinoic acid (ATRA) increases GJIC in a variety of cancer cells and has been used to treat acute promyelocytic leukemia, but the effects of ATRA on leukemic BMSCs is unknown. In this study, we evaluated the potential effects of ATRA on cell cycle, proliferation, and apoptosis of leukemic BMSCs. Effects of ATRA on Cx43 expression and GJIC were also examined. METHODS: Human BMSCs obtained from 25 patients with primary acute leukemia, and 10 normal healthy donors were cultured. Effects of ATRA on cell cycle, cell proliferation, and apoptosis were examined with or without co-treatment with amphotericin-B. Cx43 expression was examined at both the mRNA and protein expression levels. GJIC was examined by using a dye transfer assay and measuring the rate of fluorescence recovery after photobleaching (FRAP). RESULTS: ATRA arrested the cell cycle progression, inhibited cell growth, and increased apoptosis in leukemic BMSCs. Both Cx43 expression and GJIC function were increased by ATRA treatment. Most of the observed effects mediated by ATRA were abolished by amphotericin-B pretreatment. CONCLUSIONS: ATRA arrests cell cycle progression in leukemic BMSCs, likely due to upregulating Cx43 expression and enhancing GJIC function.
Subject(s)
Cell Communication/drug effects , Cell Cycle Checkpoints/drug effects , Connexin 43/genetics , Gap Junctions/drug effects , Mesenchymal Stem Cells/drug effects , Tretinoin/pharmacology , Acute Disease , Adult , Amphotericin B/pharmacology , Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Apoptosis/genetics , Blotting, Western , Cell Communication/genetics , Cell Cycle Checkpoints/genetics , Cell Proliferation/drug effects , Cell Proliferation/genetics , Cells, Cultured , Connexin 43/metabolism , Female , Fluorescence Recovery After Photobleaching , Gap Junctions/metabolism , Gene Expression/drug effects , Humans , Leukemia, Myeloid/genetics , Leukemia, Myeloid/metabolism , Leukemia, Myeloid/pathology , Male , Mesenchymal Stem Cells/metabolism , Microscopy, Confocal , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Mantle cell lymphoma (MCL) is a set of heterogeneous non-Hodgkin lymphoma characterized by involvement of lymph nodes, spleen, bone marrow and blood. Under conventional treatment, survival time is 4 to 5 years with short remission period and there is still no standard treatment for MCL. In general, a close observation period called "watchful waiting" is used in elderly patients with low-risk slow clinical progress. And intensive chemotherapy including high-dose of cytarabine ± autologous hematopoietic stem cell transplantation (auto-HSCT) is recommended for younger and fit patients. Allogenic stem cell transplantation (allo-SCT) and drugs targeting the cell metabolic pathway, such as bortezomib (NF-κB inhibitor) and lenalidomide (anti-angiogenesis drug), are considerable treatments for relapsed/refractory patients. Clinical trials and less intensive chemotherapy such as R-CHOP (rituximab with cyclophosphamide, hydroxydaunomycin, oncovin and prednisone) and R-bendamustine should be considered for elderly MCL patients who are at intermediate/high risk. Recent clinical trials with ibrutinib (Bruton's Tyrosine Kinase inhibitor) and temsirolimus (mTOR inhibitor) have shown excellent efficacies in the treatment of MCL. This review will introduce the present status and major therapeutic progress in the treatment of MCL over recent years in order to provide a cutting edge to look into promising clinical progress of MCL.
