Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

Objectives:To investigate the physical growth status of pediatric patients with transfusion-dependent thalassemia (TDT) and analyze the effects of treatment-related and socioeconomic factors on physical growth.Methods:Based on the specialized thalassemia database from gene therapy clinical research at the Institute of Hematology & Hospital of Blood Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, we collected data on height and weight development, family economic status, and medical records of 338 pediatric patients with TDT from October 2023 to May 2024. The length/height-for-age and body mass index (BMI) -for-age were classified based on the Growth Standard for Children under 7 Years of Age, Standard for Height Level Classification among Children and Adolescents Aged 7-18 Years, and Dietary Guidelines for Chinese Residents. Logistic regression analysis was conducted to assess the effects of family economic status and disease-related treatment on length/height-for-age and BMI-for-age.Results:Among the 338 patients, 118 were children and 220 were adolescents (192 males and 146 females), with a median age of 12 years (range: 0.8-18) and a median diagnosis duration of 10.3 years (range: 0.5-17.9). Subtypes included α-thalassemia [21 cases (6.2%) ], β-thalassemia [288 cases (85.2%) ], and combined αβ-thalassemia[29 cases (8.6%) ]. The monthly household income of patients was concentrated in 3 000-5 000 yuan (39.9%) and 5 001-10 000 yuan (34.9%), whereas 67.2% of the families had monthly medical expenses of <3 000 yuan. Of the patients, 75.5% received their first transfusion before 1 year of age. The proportions of children and adolescents with pretransfusion hemoglobin (HGB) of ≤70 g/L were 4.2% and 6.4%, respectively. Adolescents demonstrated significantly higher rates of transfusion frequency of <4 weeks/session, monthly red blood cell infusion of >2 U, serum ferritin (SF) of ≥5 000 μg/L, iron chelation therapy, and splenectomy compared with children (all P<0.05). Of the 338 patients, 26.0%, 22.8%, and 8.9% demonstrated stunted growth, underweight, and concurrent stunted growth with underweight, respectively. No significant difference was observed in the stunted growth rates between children (22.9%) and adolescents (27.7%) ( P=0.402). However, the underweight rate in adolescents (26.8%) was significantly higher than that in children (15.3%) ( P=0.023). The multivariate analysis determined the following risk factors for stunted growth: monthly household income of <10 000 yuan (5 001-10 000 yuan: OR=5.49, 95% CI: 1.48-35.76; 3 000-5 000 yuan: OR=6.87, 95% CI: 1.88-44.60; <3 000 yuan: OR=9.29, 95% CI: 2.20-64.77), pretransfusion HGB of ≤70 g/L ( OR=3.25, 95% CI: 1.07-10.18), and SF of ≥5 000 μg/L ( OR = 3.04, 95% CI: 1.20-7.70). Longer diagnostic duration was associated with underweight ( OR=1.10, 95% CI: 1.01-1.20) . Conclusions:Children and adolescents with TDT with pretransfusion SF of ≥5 000 μg/L, HGB of ≤70 g/L, low monthly household income, or longer diagnosis duration were significantly more likely to experience delayed physical growth.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

OBJECTIVE: To explore the genetic basis of a Chinese pedigree affected with Dyggve-Melchior-Clausen syndrome. METHODS: Whole exome sequencing and Sanger sequencing were carried out to detect potential pathogenic variants associated with the syndrome. The function of candidate variant was verified by Western blotting. RESULTS: A novel homozygous variant, c.1222delG of the DYM gene was detected in the two affected siblings, for which both parents were heterozygous carriers. The variant has caused replacement of Asp by Met at amino acid 408 and generate a premature stop codon p.Asp408Metfs*10. Western blotting confirmed that the variant can result in degradation of the mutant DYM protein, suggesting that it is a loss of function variant. CONCLUSION The homozygous c.1222delG frameshift variant of the DYM probably underlay the Dyggve-Melchior-Clausen syndrome in the two affected siblings. Above findings has enabled clinical diagnosis and genetic counseling for the family.
China ; Dwarfism/genetics* ; Humans ; Intellectual Disability ; Osteochondrodysplasias/genetics* ; Pedigree

Objective:To explore the diagnostic process and outcomes of patients with aplastic anemia (AA) who received outpatient treatment in a real-world setting.Methods:The diagnostic processes, treatment regimens, and outcomes of 176 patients with AA treated in outpatient centers from January 2018 to December 2019 were reviewed.Results:The median interval from the onset of symptoms to the first visit was 7 (5-120) months. Complaints during the first visit included bleeding (52.3% ) , anemia (51.7% ) , and infection (6.8% ) . For diagnosis, 168 patients (95.5% ) underwent bone marrow aspiration; however, only 22 of them (17.1% ) consented aspiration in multiple sites (sternum) . The completion rate of bone marrow biopsy was 85.1% (143/168) ; flow immunophenotype and karyotype analyses were performed on 59.5% (100/168) and 58.9% (99/168) of AA patients, respectively, and the culture of clonal forming units by bone marrow mononuclear cells was performed on 26.8% (45/168) of AA patients. The most preferred regimen was cyclosporine combined with androgen and levamisole (43.8% , 77 patients) , followed by cyclosporine combined with androgen (25.6% , 45 patients) . Cyclosporine alone was administered in 24 patients (13.6% ) and androgen alone in 16 patients (9.1% ) . Furthermore, 14 patients (7.9% ) did not consent to any drugs or only chose traditional Chinese medicine. The patients were divided according to the frequencies of follow-up: regular follow-up group (≥4 times/year, n=130) and irregular group (<4 times/year, n=46) . The former had a higher 6-month remission rate (52.5% vs 28.0% , P=0.005) , a greater high-quality remission rate in 12 months (40.7% vs 16.7% , P=0.027) , and a lower relapse rate in 24 months (4.4% vs 36.4% , P=0.001) . Conclusion:In real-world settings, bone marrow aspiration in multiple sites should be addressed in outpatient treatment for AA diagnostic work-up, including PNH clone screening, flow immunophenotype, chromosome karyotype analysis, and culture of clonal forming units. Patients with AA who follow regular visits were more likely to achieve high-quality remission and a lower relapse rate. Visits at least four times per year are recommended for AA patients undergoing outpatient treatment.