Hematopoietic Stem Cell Transplantation

Abstract

Hematopoietic stem cell transplantation (HCT), formerly known as bone marrow transplantation, is an integral part of treatment for many hematological malignancies. HCT is associated with several complications and comorbidities with differential effects on a wide spectrum of organs and tissues. We present an update on HCT-associated complications such as graft versus host disease (GVHD) and infection, with focus on the surgical pathology of the gastrointestinal (GI) tract, liver, and lung. Although the grading system for GI tract acute GVHD was proposed 40 years ago, recent studies have shed light on minimal histologic criteria for diagnosis of GVHD, as well as its differential diagnosis, including histologic effects of various medications. GI dysfunction in autologous transplant recipients is increasingly appreciated and patients are often biopsied. Acute liver injury in HCT is often due to sinusoidal obstruction syndrome (previously known as venoocclusive disease), or acute GVHD. Liver dysfunction at later time posttransplantation may be associated with acute or chronic GVHD, iron overload, or other causes of hepatitis. Lung injury in HCT is multifactorial, and it remains crucially important to diagnose and treat pulmonary infections. The pulmonary biopsy yields clinically unsuspected diagnoses in the majority of cases and its utilization is likely to increase. The pathology of the skin and kidney in HCT patients are detailed in accompanying articles.

Narrow-Band Ultraviolet B Phototherapy Ameliorates Acute Graft-Versus-Host Disease of the Intestine by Expansion of Regulatory T Cells

“…Interstitial and alveolar pneumonitis, perivascular lymphocytic inflammation, and lymphocytic bronchiolitis were observed in the “TBI/BMT” group ( Fig 3A ). These findings were compatible with the clinically defined “idiopathic pneumonia syndrome (IPS)”, encompassing widespread alveolar injury in the absence of infection, cardiac dysfunction, renal failure, and iatrogenic fluid overload, and affecting 5% to 25% of allo-HSCT recipients [ 29 – 31 ]. By the semi-quantitative scoring system of IPS [ 26 ], it was clearly demonstrated that NB-UVB irradiation ameliorated IPS with statistical significance (p = 0.0019), as shown in Fig 3B .…”

“…IPS is widespread alveolar injury in the absence of infection, cardiac dysfunction, renal failure, and iatrogenic fluid overload, and affects 5% to 25% of allo-HSCT recipients [ 29 – 31 ]. The mortality rate of IPS in allo-HSCT recipients ranges from 60 to 80% overall, and is greater than 95% among patients requiring mechanical ventilation [ 31 ].…”

Inhibition of 5-lipoxygenase alleviates graft-versus-host disease

“…Because leukotrienes may cause significant lung dysfunction ( Cingi et al, 2015 ; Qian et al, 2015 ; Sekioka et al, 2015 ; Ee et al, 2016 ; Shigematsu et al, 2016 ) and the lung is a target organ of GVHD (Ferrara, 2009; Haddad, 2013 ; Xu et al, 2013 ; Kambham et al, 2014 ), we evaluated the effect of treatment with zileuton, CP-105,696, and montelukast in the pulmonary injury that follows GVHD. We observed that there was significant pulmonary injury at the onset of mortality caused by the induction of GVHD (Fig.…”

“…Pulmonary complications are responsible for ∼70% of morbidity and 30% of mortality after GVHD ( Yousef et al, 2013 ). In humans, the disease tends to be more often chronic and characterized primarily by an obliterating bronchiolitis ( Haddad, 2013 ; Xu et al, 2013 ; Yousef et al, 2013 ; Kambham et al, 2014 ). Regardless, we observed that pulmonary injury in our system was acute at onset and occurred at significant levels during the onset of lethality.…”

Plasma vascular non-inflammatory molecule 3 is associated with gastrointestinal acute graft-versus-host disease in mice

“…A diagnosis of GI aGVHD is traditionally based on clinical manifestations and endoscopic biopsy [ 3 ]. Manifestations of GI aGVHD is characterized by watery diarrhea, nausea, anorexia and abdominal cramps, but these non-specific symptoms may mimic infection [ 3 , 4 ]. Digestive endoscopy is often restrained by poor general patient health after HSCT, and crypt apoptosis in a mucosal biopsy is not specific for GI aGVHD.…”