Study of clinical manifestations and outcomes of 14 newborns with primary immunodeficiency disease / 中国小儿急救医学

Objective:To explore the clinical manifestations, genetic disorder, prognosis of 14 neonates with primary immunodeficiency disease(PID).Methods:A total of 14 newborns with PID admitted to Department of Neonatology at Beijing Children′s Hospital from January 2017 to December 2019 were enrolled for retrospective analysis, focusing on their clinical manifestation, peripheral blood cell examnations, gene mutation, and outcomes after hemotopoietic stem cell transplantation(HSCT).Results:The average gestational age of the newborn was (38.6±1.2) weeks, the birth weight was (3 265±325)g, and the median diagnosis time was 57.5 days.Fourteen newborns with PID were diagnosed by whole exome sequencing as chronic granuloma (6/14), DiGeogre syndrome (3/14), Wiskott-Aldrich syndrome (2/14), severe combined immunodeficiency (2/14) and selective IgA deficiency (1/14). Regarding the clinical manifestations, fever, pneumounia and colitis accounted for 7/14, the decrease of T lymphocytes in peripheral blood accounted for 6/14, and the decrease of B lymphocytes accounted for 5/14.The absolute value of eosinophils increased (>500 cells/mm 3) accounted for 12/14, of which moderately increased (1 500 to 5 000 cells/mm 3) accounted for 5/12, and the absolute value of monocytes increased (median>1.5×10 9/L) accounted for 7/14.Follow-up children received HSCT accounted for 7/14, and the median time of receiving transplantation was 330 days after birth.By the time of follow-up, the primary disease resolved after HSCT accounted for 5/7, and the survival rate was 85.7%.Among them, two children with chronic granulomatosis were diagnosed with inflammatory bowel disease before transplantation, and the primary disease improved after HSCT.Three-quarters of the deaths had inflammatory bowel disease-like manifestations and died of infectious shock. Conclusion:The clinical manifestations of children with PID during the neonatal period are not specific.The manifestations of colitis need more attention.Some of the newborns with PID will evolve into inflammatory bowel disease or have inflammatory bowel disease-like manifestations or even die of it.HSCT is a fundamental treatment for the primary disease.

Clinical manifestation and outcome of 21 newborns with human inborn error of immunity / 中国小儿急救医学

Objective:To explore the clinical characteristics and prognosis of children with inborn error of immunity (IEI) onset in the neonatal period.Methods:The clinical data of 21 cases of IEI neonates admitted to the Neonatal Center of Beijing Children′s Hospital were collected, and their clinical manifestations, peripheral blood test characteristics, genetic diagnosis, and primary disease during hospitalization were collected.The prognosis follow-up results were summarized and analyzed.Results:Twenty-one children with IEI were finally diagnosed by whole exome sequencing, including 15 cases of primary immunodeficiency(including 6 cases of chronic granulomatous disease, 3 cases of DiGeogre syndrome, 2 cases of Wiskott-Aldrich syndrome, 2 cases of severe combined immunodeficiency disease, 1 case of selective IgA deficiency, and 1 case of ectodermal dysplasia with immunodeficiency), 5 cases of infantile inflammatory bowel disease, and 1 case of familial haemophagocytic lymphohistiocytosis.Clinical manifestations of sepsis and colitis were the most common(accounting for 12/21), and 16/21 of the children had an increase in the absolute value of eosinophils(>0.5×10 9/L). Children received hematopoietic stem cell transplantation accounted for 7/21, and the median time of receiving transplantation was 11 months after birth.By the time of follow-up, the primary disease remission after hematopoietic stem cell transplantation accounted for 5/7.Among them, 2 cases were diagnosed with CGD associated inflammatory bowel disease before transplantation, and the primary disease resolved after hematopoietic stem cell transplantation.Of the 14 children who did not receive hematopoietic stem cell transplantation, 10 children died.Five of the 11 deaths were treated with systematic steroid before diagnosised. Conclusion:The clinical manifestations of IEI in the neonatal period are not specific.Sepsis and colitis are the most common manifestations.Most of the cases have elevated eosinophils in the peripheral blood.Systematic streoid therapy needs to be cautious, and timely evaluation for hematopoietic stem cells transplantation is an effective option to resolution.

Efficacy observation of hemocoagulase for the treatment of severe hemorrhagic cystitis following allogeneic hematopoietic stem cell transplantation / 白血病·淋巴瘤

Objective To investigate the clinical efficacy of hemocoagulase for severe hemorrhagic cystitis (HC) following allogeneic hemotopoietic stem cell transplantation (HSCT). Methods Twenty patients undergoing allogeneic HSCT developed severe HC with an onset time of 14 to 70 days, all patients received the treatment of hemocoagulase (1 U ivgtt q12 h × 5 d). The urine speciments reserved before and after hemocoagulase were examined by naked eye and microscope to evaluate the efficacy. Results Twenty patients received the treatment of hemocoagulase. The HC was cured in 18 patients, improved in 1 patient and uncontrolled in 1 patient. For the patients with response, macroscopic hematuria disappeared at a median of 28 days (4-127 days) after the treatment. All procedures were tolerated well and no severe adverse effect was observed. Conclusion Hemocoagulase seems to be a safe and effective drug for severe HC following HSCT.

Correlation between CD34+ cell and immature granulocyte in donor's peripheral blood by rhG-CSF / 白血病·淋巴瘤

Objective To investigate the correlation between immature granulocyte and CD34+ cells, mononuclear cells (MNC) in donor's peripheral blood by recombinant human granulocyte colony-stimulating factor (rhG-CSF). Methods The stem cell were mobilized by rhG-CSF 7.25-10 μg·kg-1·d-1 from 122 allo-PBSCT donors. Before and after mobilization, to test CD34+ cells of peripheral blood stem cell graft and number of MNC, immature granulocyte, CD34+ cell per patient' weight were calculated. Results White blood cell count and immature granulocyte gradually increased, and reached the peak on the frith day. There was a good relationship between increased immature granulocytes and increased CD34+ cells. The patients all achieved completed donor engraftment and achieved hematopoietic recovery. The chromosome, blood type and HLA type were transformed to be donor's type. Ph1 changed to be negative in CML patients. Conclusion rhG-CSF (7.25～10 μg·kg-1·d-1) had a good effect to mobilize PBSC. There was a good relationship between in-creased immature granulocytes and increased CD34+ cells after mobilization by rhG-CSF. The number of immature granulocytes can reflect indirectly the count of stem/progenitor, so the MNC and immature granulo-cytes can become a threshold of dosage standard.

Nonmyeloablative allogeneic peripheral blood stem cell transplantation for chronic leukemia:a report of seven cases / 中华器官移植杂志

Objective To summarize the experimence of nonmyeloablative allogeneic peripheral blood cell transplantation in the treatment of chronic leukemia. Methods Seven patients, including 6 cases of chronic myeloid leukemia (in chronic phase), one of chronic lymphoid leukemia (in third stage), with HLA-identical siblings donor received allogeneic peripheral blood stem cell transplantation after a nonmyeloablative conditioning. Results All of them were engrafted with donor cells (4 with full of donor cells grafted, 3 with mixed chimerism) and recovered hematopoiesis (WBC recovered to more than 0.5 ?10 9/L during postoperative 9 day to 21 day and platelet recovered to more than 30?10 9/L during postoperative 11 day to 28 day). One of them developed a GVHD of degree IV. One of them developed aGVHD of degree I. Conclusion This procedure is much safe, effective and of less complications than the myeloablative condioning regimens and may represent another new approach in the management of patients with chronic leukemia.

Analysis of the infectious complications following nonmyeloablative allogeneic peripheral blood stem cell transplantation / 中华器官移植杂志

Objective To investigate the infectious complications after nonmyeloablative allogeneic peripheral blood stem cell transplantation (NASCT). Methods Ten patients with leukemia received NASCT from HLA-identical or 1-3 antigen mismatched sibling donors with conditioning regimens of Flu/Cy+BU+ALG. Five patients were acute leukemia (AL) and all of them is in complete remission (CR1). Cyclosporine in combination with methotrexate was administered for GVHD prophylaxis. Results WBC recovered to more than 0.5 ?10 9/L during postoperative 10 day to 38 day and platelet recovered to more than 20?10 9/L during postoperative 8 day to 16 day. Bacterial infections occurred in 3 patients (30 %) and cytomegalovirus (CMV) infections in 2 patients (20 %). Varicella zoster virus (VZV) infections occurred in one patient (10 %). No fungal infections were documented. No patients died as a result of infection . Conclusion NASCT is a safe and effective therapeutic method for leukemia. It reduces acute GVHD,regimen-related toxicity and early neutropenia associated with traditional allo-HSCT.