Xiaodan Luo

Nephrotic syndrome after allogeneic hematopoietic stem cell transplantation: etiology and pathogenesis

In this study we investigated the etiology and pathogenesis of nephrotic syndrome (NS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in 257 patients with hematopoietic malignancies who survived more than 2 months post allo-HSCT. Associations of NS with the conditioning regimen, graft versus host disease (GVHD), and other variables were analyzed. Pathologic features of the kidney, regulatory T cells (Tregs), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were studied. NS was identified in 9 patients. The number of Tregs at day+30, 60, 90, and 180 was lower in NS patients than non-NS patients (P=0.001, 0.001, 0.007, 0.003). Serum levels of IFN-γ and TNF-α were higher in NS patients (P=0.032, 0.001, respectively). NS post allo-HSCT was associated with the occurrence of chronic GVHD (P=0.02). NS post-HSCT is an immune disorder that may involve immune complex deposition, Th1 cytokines, and Tregs.

Epstein-Barr virus-associated pneumonia in patients with post-transplant lymphoproliferative disease after hematopoietic stem cell transplantation

Q.‐F. Liu, Z.‐P. Fan, X.‐D. Luo, J. Sun, Y. Zhang, Y.‐Q. Ding. Epstein–Barr virus‐associated pneumonia in patients with post‐transplant lymphoproliferative disease after hematopoietic stem cell transplantation.
Transpl Infect Dis 2010: 12: 284–291. All rights reserved.

Association between acute graft versus host disease and lung injury after allogeneic haematopoietic stem cell transplantation

Abstract Objective: To investigate the characteristics of chest high-resolution computed tomography (HRCT) and pathogenesis of acute graft versus host disease (acute GVHD)-induced lung injury after allogeneic haematopoietic stem cell transplantation (allo-HSCT). Methods: A study of 47 patients with acute GVHD of grades II–IV describes the clinical manifestations and characteristics of chest HRCT of acute GVHD-induced lung injury. Detection of serum interferon γ (IFNγ) and tumour necrosis factor α (TNFα) were performed before the treatment for acute GVHD. Transbronchial biopsy was performed in four patients whose chest HRCT did not recover completely after treatment for acute GVHD. Pulmonary function was measured in patients who survived more than 6 months in every 3 months. Results: Chest HRCT scans were performed in 47 cases and 20 cases showed abnormal in which 17 cases were suspected of acute GVHD-induced lung injury. In 17 patients with acute GVHD-induced lung injury, HRCT revealed diffused interstitial infiltrate in five cases, diffused interstitial and alveolar infiltrate in seven cases, diffused interstitial and segmental lobar alveolar infiltrate in five cases accompanied by bilateral pleural effusion and hydropericardium in nine patients. There was no statistical significance between the levels of serum IFNγ and TNFα in cases with and without lung injury, but the levels of serum IFNγ and TNFα in patients were significantly higher than the healthy group (IFNγ: p=0·000, TNFα: p=0·000). The histopathology of the lung tissue was characterized by disorganization, epithelial cell damage, interstitial fibroplasias and interstitial T lymphocyte or macrophage infiltrate. Forty-seven cases all attained the treatment for acute GVHD, and the total effective rate and the rate of completely remission (CR) were 74·47 and 55·32%, respectively. The total effective rate and the rate of CR in the treatment for acute GVHD-induced lung injury were 94·12 and 58·82%, respectively. The effective rate of treatment for acute GVHD-induced lung injury positively correlated with that for acute GVHD (r=0·771, p=0·001). Three cases in nine cases with lung injury and three cases in 15 cases without lung injury who survived more than 6 months developed late-onset non-infectious lung injury. Eleven patients of 24 patients who survived more than 6 months had abnormal pulmonary function, including seven patients in nine patients with acute GVHD-induced lung injury and four patients in 15 patients without acute GVHD-induced lung injury. There was no difference in the incidence of late-onset non-infectious lung injury, but significance in the incidence of abnormal pulmonary function between cases with and without lung injury (p=0·033, cross-tabs). Conclusions: These results suggested that the lung might be one of the target organs of acute GVHD and participation of T lymphocyte, macrophage and cytokines such as IFNγ and TNFα might play a role in the pathogenesis of acute GVHD-induced lung injury. Acute GVHD-induced lung injury may progress to late-onset non-infectious lung injury.

Idiopathic pneumonia syndrome in mice after allogeneic bone marrow transplantation: association between idiopathic pneumonia syndrome and acute graft-versus-host disease ☆

OBJECTIVE To explore the association between idiopathic pneumonia syndrome (IPS) and acute graft-versus-host disease (aGVHD) in allogeneic hematopoietic stem cell transplantation. METHODS Established acute GVHD model of C57BL/6-->BALB/c mice. Chest computed tomography (CT) scans were dynamically performed in recipient mice after transplant. Lung histopathology and cytokine levels (including TNF-alpha and IFN-gamma) were examined in three experimental groups: mice receiving simple irradiation, syngeneic transplants, and allogeneic transplants. RESULTS All allogeneic transplant mice developed aGVHD. On CT, most aGVHD mice had bilateral diffuse lung infiltrates, while syngeneic transplant mice had normal lungs. On histopathology, aGVHD mice had acute pneumonitis. On immunohistochemistry, the infiltrates were mainly CD4+ T cells during aGVHD onset, but CD8+ T cells predominated during aGVHD progression. Lung TNF-alpha and IFN-gamma levels were higher in the three experimental groups than in normal controls on days +3 and +7 post-transplant. On day +7, TNF-alpha levels were higher in allogeneic than in syngeneic transplant mice; IFN-gamma levels were not different. On days +12 and +16, TNF-alpha levels were higher but IFN-gamma levels were lower in allogeneic mice than in syngeneic transplant mice. CONCLUSIONS The underlying cause of IPS is aGVHD. T cells and TNF-alpha may play a role in the pathogenesis of aGVHD-induced IPS. IPS progression may be associated with decreasing lung IFN-gamma levels.