Systemic sclerosis with portal hypertensive ascites responded to corticosteroid treatment / 中华医学杂志(英文版)

We describe a case of systemic sclerosis (SSc) complicated with portal hypertensive ascites which did not improve with diuretics and ascitic drainage. When corticosteroid added, her ascites diminished dramatically. Though portal hypertension can be imputed to other causes, such as polycystic liver in this case, it can occur in limited SSc with positive anti-centromere antibody and respond to corticosteroid treatment.

Changes of lymphocyte subsets in autologous hemopoietic stem cell transplantation for severe/refractory autoimmune disease / 中国医学科学院学报

<p><b>OBJECTIVE</b>To investigate the dynamic changes of lymphocyte subsets before and after autologous hemopoietic stem cell transplantation (HSCT) in severe/refractory autoimmune disease (AID) and study the post-transplantation immunological reconstitution in AID.</p><p><b>METHODS</b>Thirteen patients with severe/refractory AID who registered for HSCT from April 2003 to April 2005 in Peking Union Medical College Hospital, including 8 patients with systemic lupus erythematosus, 4 patients with rheumatoid arthritis, and 1 patient with primary Sjögren's syndrome (pSS) were enrolled in this study. Blood samples were collected before/after mobilization, before conditioning, and 2 weeks, 1 month, 3 months, 6 months, 12 months, and 18 months post-transplantation. Lymphocyte subsets were tested by flow cytometry as follows: T cell (CD3 +), B cell (CD19 +), natural killer (CD3-CD16 + CD56 +), Th (CD3 + CD4 +), Tc (CD3 + CD8 +), naïve T (CD4 + CD45RA), memory T (CD4 + CD45RO), and CD4/CD8 ratio.</p><p><b>RESULTS</b>Lymphocyte subsets for SLE patients were severely abnormal compared to normal or RA patients (both P < 0.01). B cell reconstituted to normal level within 18 months, meanwhile NK and T cell remained low. The repopulations of Th and naive T cell were delayed, which caused the up-side-down of CD4/CD8 ratio and low level of naYve T cell percentage for a relatively long time.</p><p><b>CONCLUSIONS</b>Lymphocyte subsets abnormality in SLE patients are more severe than in RA patients. Although most autoimmune T/B cell in the grafts and patients can be effectively removed after transplantation, nonmyeloablative conditioning may be a risk for the relapse of AID. The long-term inhibition of CD4 + T cell may be related with the relief of AID after transplantation.</p>

Peripheral blood CD34+ cell mobilization in 42 patients with severe autoimmune disease / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the feasibility and safety of peripheral CD34+ cell mobilization in patients with severe autoimmune disease.</p><p><b>METHODS</b>Forty-two patients underwent a total of 46 mobilizations by the regimen of cyclophosphamide 2-3 g/m2+ recombinant human granulocyte colony stimulating factor (rhG-CSF) 5 microg x kg(-1) x d(-1). The positive selection of CD34+ cell was performed through the CliniMACS.</p><p><b>RESULTS</b>In 8.1 +/- 2. 3 days after administration of cyclophosphamide, the peripheral white blood cell and mononuclear cell (MNC) decreased to the lowest level. In 3.7 +/- 1.6 days after injection of rhG-CSF, the peripheral absolute MNC and CD34+ cell counts were 0.95 x 10(9)/L and 0.035 x 10(9)/L, respectively. After 2.4 +/- 0.6 times of leukapheresis, there gained 4.46 x 10(8)/kg of MNC and 5.26 x 10(6)/kg of CD34+, respectively. After mobilization, the underlying diseases were ameliorated more or less. In systemic lupus erythematosus (SLE) patients, SLE Disease Activity Index (SLEDAI) decreased from a median of 17 to 3 (P < 0.01). In rheumatic arthritis patients, an American College of Rheumatology criteria for 20% (ACR20) response was achieved in all five patients. Totally, 17.4% of patients whose absolute neutrophil count < 0.5 x 10(9)/L suffered infection, and 31.0% of patients had bone pain after the injection of rhG-CSF. Two patients suffered severe complications, one with acute renal failure and recovered by hemodialysis, the other died of thrombotic thrombocytopenic purpura. Failed mobilization occurred in three patients.</p><p><b>CONCLUSIONS</b>Sufficient CD34+ cells can be mobilized by low dose of cyclophosphamide and rhG-CSF. CD34+ cell mobilization for treatment of severe autoimmune disease not only is appropriate in both effectiveness and safety but ameliorates disease also.</p>

A pilot trial for severe, refractory systemic autoimmune disease with stem cell transplantation / 中国医学科学杂志(英文版)

<p><b>OBJECTIVE</b>To evaluate the feasibility, efficacy, and safety of high dose immunosuppressive therapy (HDIT) and autologous hemopoietic stem cell transplantation (HSCT) with CD34+ cell selection in patients with severe, refractory autoimmune diseases.</p><p><b>METHODS</b>Twenty-six patients with persistent systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), primary Sjögren's syndrome (pSS), or systemic sclerosis (SSc) who had been treated unsuccessfully with conventional treatment were enrolled in the trial in Peking Union Medical College Hospital from September 1999 to June 2004. The patients received HDIT with 200 mg/kg cyclophosphamide followed by an infusion of autologous stem cells that were CD34 selected. Disease activity, adverse effect, hemopoietic and immune reconstitution, and time to recurrence of disease were monitored.</p><p><b>RESULTS</b>Overall treatment related mortality was 7.7% (2/26) with 1 patient died of cytomegalovirus infection and another of severe pneumonia. Relapse occurred in 3 SLE patients (17.6%) in 37, 26, and 19 months posttransplantation respectively, and 1 RA patient in 15 months posttransplantation. SLE Disease Activity Index (SLEDAI) scores of SLE survivors decreased significantly (P < 0.01). RA patients recorded a drop of Disease Activity Score 28 (DAS 28). The pSS patient remained symptoms free up to now, more than 50 months after the transplantation.</p><p><b>CONCLUSION</b>HSCT can be performed relative safely in patients with severe autoimmune disease. Short-term effect of HSCT is promising. However treatment related mortality and relapse were observed in a subset of patients.</p>

Treatment of severe primary Sjgren syndrome with peripheral blood stem cell transplantation / 中华风湿病学杂志

Objective To investigate the feasibility,efficacy and safety of high dose chemotherapy (HDC)and autologous peripheral blood stem cell transplantation(PBSCT)with CD34~+ cell selection in patients with severe primary Sjgren's syndrome(pSS).Methods Three patients with persistent and severe pSS de- spite of glucocorticoid and immunosuppressive treatment were enrolled from 1999.All patients underwent high dose chemotherapy and peripheral blood stem cell infusion with CD34~+ cell selection.Autologous hematopoietic stem cells were mobilized with 2～3 g/m~2 CTX(total dosage,infused in two days)and 5?g/kg granulocyte colony stimulating factor(G-CSF),enriched with CD34~+ cell selection by CliniMACS,and reinfused after con- ditioning with 200 mg/kg CTX and 90 mg/kg swine antithymocyte globulin or 200 mg/kg CTX and total body irradiation of 4 Gy.Results One patient got complete remission after 2 times of mobilization,so no condi- tioning and transplantation were given.Other 2 patients completed the mobilization and leukapheresis proce dures successfully,and proceeded to receive conditioning and transplantation.All patients had rapid hematopoi- etic reconstitution.Three patients were followed up for 48 months,60 months and 18 months,respectively.All patients were free from abnormal activity of B lymphocytes.The titer of antibody decreased and anti-SSB anti- bodies of 2 patients turned to negative.Aggregation of focal lymphocytes in labial gland disappeared in 1 pa- tient after PBSCT.Improvement of pulmonary dysfunction and reversibility of interstitial pulmonary fibrosis fol- lowing hematopoietic stem cell transplantation were observed in 2 patients.Conclusion The abnormal activity of B lymphocytes in pSS patients can be controlled successfully with PBSCT.High close chemotherapy followed by peripheral blood stem cell transplantation with CD34~+ cell selection is feasible and safe.