Immune Phenomena in Myeloid Neoplasms: An "Egg or Chicken" Question.

Immune phenomena are increasingly reported in myeloid neoplasms, and include autoimmune cytopenias/diseases and immunodeficiency, either preceding or complicating acute myeloid leukemia, myelodysplastic syndromes (MDS), chronic myeloproliferative neoplasms, and bone marrow failure (BMF) syndromes. Autoimmunity and immunodeficiency are the two faces of a dysregulated immune tolerance and surveillance and may result, along with contributing environmental and genetic factors, in an increased incidence of both tumors and infections. The latter may fuel both autoimmunity and immune activation, triggering a vicious circle among infections, tumors and autoimmune phenomena. Additionally, alterations of the microbiota and of mesenchymal stem cells (MSCs) pinpoint to the importance of a permissive or hostile microenvironment for tumor growth. Finally, several therapies of myeloid neoplasms are aimed at increasing host immunity against the tumor, but at the price of increased autoimmune phenomena. In this review we will examine the epidemiological association of myeloid neoplasms with autoimmune diseases and immunodeficiencies, and the pivotal role of autoimmunity in the pathogenesis of MDS and BMF syndromes, including the paroxysmal nocturnal hemoglobinuria conundrum. Furthermore, we will briefly examine autoimmune complications following therapy of myeloid neoplasms, as well as the role of MSCs and microbiota in these settings.

Biomimetic 3D in vitro model of biofilm triggered osteomyelitis for investigating hematopoiesis during bone marrow infections.

In this work, we define the requirements for a human cell-based osteomyelitis model which overcomes the limitations of state of the art animal models. Osteomyelitis is a severe and difficult to treat infection of the bone that develops rapidly, making it difficult to study in humans. We have developed a 3D in vitro model of the bone marrow, comprising a macroporous material, human hematopoietic stem and progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). Inclusion of biofilms grown on an implant into the model system allowed us to study the effects of postoperative osteomyelitis-inducing bacteria on the bone marrow. The bacteria influenced the myeloid differentiation of HSPCs as well as MSC cytokine expression and the MSC ability to support HSPC maintenance. In conclusion, we provide a new 3D in vitro model which meets all the requirements for investigating the impact of osteomyelitis. STATEMENT OF SIGNIFICANCE: Implant-associated osteomyelitis is a persistent bacterial infection of the bone which occurs in many implant patients and can result in functional impairments or even entire loss of the extremity. Nevertheless, surprisingly little is known on the triangle interaction between implant material, bacterial biofilm and affected bone tissue. Closing this gap of knowledge would be crucial for the fundamental understanding of the disease and the development of novel treatment strategies. For this purpose, we developed the first biomaterial-based system that is able to mimic implant-associated osteomyelitis outside of the body, thus, opening the avenue to study this fatal disease in the laboratory.

A Rare Case of Disseminated Tuberculosis of the Bone Marrow in Systemic Lupus Erythematosus: Case Report.

Patients with systemic lupus erythematosus (SLE) are susceptible to tuberculosis (TB), especially in endemic areas such as China. The variable and nonspecific clinical features of disseminated TB often leads to an erroneous or misdiagnosis. When a patient presents with TB of the bone marrow, the clinical condition is more perplexing and the prognosis is typically poor. Till now, there is no case report after apatinib came in the market.Here, we report a case of TB of the bone marrow accompanied with SLE. The patient exhibited remarkable features, including widespread lesions in the lungs, spinal vertebrae, sacrum, and ilium that were found to be consistent with TB of the bone marrow after histopathological examination.This case highlights the importance of clinical suspicion for TB during the follow-up of SLE patients, especially in endemic areas. An aggressive diagnostic biopsy should be performed in suspected TB patients as early as possible.

Bacteremia and Bone Marrow Infection Caused by Moraxella Atlantae in an Elderly Patient with Pneumonia.

The clinical manifestations of Moraxella Atlantae infection were rarely described. Here we reported an elderly pneumonia patient with Moraxella Atlantae infection and the detailed clinical manifestations were firstly described. A bacterial automatic identification system in combination with phenotypic methods can be routinely used to identify this pathogen. If possible, 16S rDNA gene sequencing is also an alternative and effective method.

Disseminated cryptococcosis in an apparently immunocompetent patient presenting with primary intraventricular haemorrhage.

Disseminated cryptococcosis is uncommon and almost always occurs in HIV-infected patients. However, cryptococcosis can also be found in patients of organ transplantation, in those on disease modifying agents for rheumatological conditions and in patients with underlying immunodeficiency. Cryptococcal infection may occur in an immunocompetent patient, but the pathogenic strain is usually Cryptococcus gattii, and not C. neoformans. However, disseminated disease, especially cerebral involvement in the form of primary intraventricular haemorrhage, is exceedingly rare. We report a case of disseminated cryptococcosis with cutaneous, cerebral and bone marrow involvement in an HIV-negative, apparently immunocompetent patient. Although the patient did not have the usual immunocompromising diseases, there were clinical signs possibly indicating a weakened immune system. This report highlights the need for awareness of disseminated cryptococcosis among patients with no apparent immunocompromising conditions.

Cutaneous and bone marrow histoplasmosis after 18 years of renal allograft transplant.

The frequency of histoplasmosis among solid organ transplant (SOT) recipients appears to be low where there are only a few case series, mostly among renal and liver transplant recipients. Herein we report a case of a 44-year-old woman who underwent a living-related renal transplant 18 years prior to evaluation, developed a nodule after followed by ulceration upon her posterior right leg and a second one upon her left leg 3 months and 2 months before her hospitalisation, respectively. The biopsy of lesion revealed the presence of Histoplasma spp. Bone marrow aspiration was performed and also revealed the same organism. She had initially received itraconazole without improvement of lesions, while a new lesion appeared on her left arm. Healing of all lesions could be observed after 40 days of liposomal amphotericin B when she was submitted to skin grafts on the legs and a surgical treatment on the arms, and the myelosuppression improved simultaneously. Histoplasmosis seems to be very uncommon among patients who underwent to organ solid transplantation. Most cases occur within 12-18 months after transplantation, although unusual cases have been presented many years post-transplant. There are cases reported in the literature, occurring from 84 days to 18 years after organ transplantation, but without cutaneous involvement. Our patient developed lesions on limbs and myelosuppression after 18 years of chronic immunosuppression medication. This case suggests that besides cutaneous histoplasmosis is an uncommon infection following iatrogenic immunosuppression and even rarer over a long period after the transplantation. Clinicians who care SOT recipient patients must bear in mind histoplasmosis infection as differential diagnosis in any case of cutaneous injury with prolonged fever and try to use as many tools as possible to make the diagnosis, once this disease presents a good prognosis if it is diagnosed and treated promptly.

Mycobacterial bone marrow infections at a medical centre in Taiwan, 2001-2009.

Mycobacterial bone marrow (BM) infection is the most common diagnosis established by BM examinations for fever of unknown origin. In this study, clinical features and outcomes of patients who fulfilled the criteria for BM infection due to Mycobacterium tuberculosis (MTB) and non-tuberculous mycobacteria (NTM) at a medical centre in Taiwan from 2001 to 2009 were investigated. The BM histopathological findings were also analysed. A total of 24 patients (16 men, eight women) with mycobacterial BM infections were found. Of these, nine (38%) were positive for human immunodeficiency virus (HIV) and six (25%) had no pre-existing immunocompromised conditions. MTB isolates were obtained from 11 (46%) patients and NTM species were isolated from 10 (42%) patients, including M. avium complex (MAC, n = 7) and M. kansasii (n = 3). Patients with MTB infections were significantly older than those with NTM infections (60·5 vs. 47·7 years, P = 0·043) and were less likely to have a positive BM culture (45% vs. 100%, P = 0·012). The 90-day survival rates for MTB and NTM BM infections were 68% and 60%, respectively (P = 0·61). In addition, the presence of BM granulomas was significantly more common in patients with MTB BM infections than in those with NTM infections (82% vs. 30%, P = 0·030). In Taiwan, the importance of NTM was not inferior to MTB and besides MAC, M. kansasii might be an important pathogen in non-HIV-infected patients. The presence of BM granulomas and caseation provides valuable information regarding early treatment pending culture results.

Pancytopenia due to lepromatous involvement of the bone marrow: successful treatment with multidrug therapy.

Leprosy is a chronic infectious disease with a wide spectrum of signs and symptoms depending on the ability of the host's immune system to resist the infection. The disease is frequently associated with sensory loss in skin lesions and damage in peripheral nerve trunks leading to nerve function impairment. In lepromatous leprosy, the immune system offers no protection against the multiplying bacilli and this results in heavy infiltration of the internal organs. We report a case of florid lepromatous leprosy with bone marrow suppression due to the disease, presenting with anemia, leukocytopenia and thrombocytopenia. The hematological abnormalities were fully reversed by mutidrug therapy for leprosy. We suggest that infiltration of the bone marrow by Mycobacterium leprae can cause pancytopenia, which can be cured by treatment of the leprosy alone.

[Q fever: bone marrow characteristic granuloma]. / Fièvre Q : localisation médullaire d'un granulome caractéristique.

Q fever is a worldwise zoonosis, caused by an obligate intracellular bacterium, Coxiella burnetii. In humans, acute disease, when symptomatic, can manifest by a flu-like illness, pneumonia or hepatitis. Patients with predisposing conditions can evolve with chronic disease, which major clinical presentation is endocarditis with negative routine blood cultures. Histological studies of Q fever based on infected organs biopsies (liver and bone marrow) have demonstrated a distinctive type of granuloma, typically appearing as a "doughnut" granuloma, characterized by a central clean space surrounded by inflammatory cells and rimmed with an eosinophilic fibrinoid material. We describe a 37-year-old man, admitted to hospital for persistent fever. Bone marrow biopsy showed the characteristic "doughnut" granuloma, suggesting a Q fever. Diagnosis was then confirmed by serological tests for C. burnetii.

Bone marrow infection with Mycobacterium fortuitum in a diabetic patient.

Incidence and prevalence of Mycobacterium fortuitum infection vary greatly by location and death is very rare except in disseminated disease in immunocompromised individuals. We present what we believe is the first case of bone marrow infection with Mycobacterium fortuitum in an HIV negative patient. Bone marrow examination revealed presence of numerous acid fast bacilli which were confirmed as Mycobacterium fortuitum on culture and by molecular analysis. Patient was managed successfully with amikacin and ciprofloxacin.

Clinicohaematological profile of infections in bone marrow - single centre experience in North Himalayan region of India.

The bone marrow examination in cases of infections may be non-specific but certain reactive changes may raise high index of suspicion of infections. The present study from a tertiary centre in the North Himalayan region of India describes the clinicohaematological profile and the changes associated with infections in the marrow. The study included all the cases of infections in which bone marrow examination was done during the period between January 2006 and July 2010. Leishmaniasis was the most common infection observed and most of the patients presented with fever along with anaemia and pancytopenia. Bone marrow examination showed predominantly transient myelodysplasia, plasmacytosis, and hemophagocytosis along with associated fibrosis and necrosis. Another important feature observed was accumulation of mature plasma cells around capillaries along with increased iron stores in the marrow. Thus, these features are important indicators of infections and should lead to their vigilant search in the patient.