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1.  The relationship between inflammation and new bone formation in patients with ankylosing spondylitis 
Arthritis Research & Therapy  2008;10(5):R104.
Introduction
Spinal inflammation as detected by magnetic resonance imaging and new bone formation as identified by conventional radiographs are characteristic of ankylosing spondylitis. Whether and how spondylitis and syndesmophyte formation are linked are unclear. Our objective was to investigate whether and how spinal inflammation are associated with new bone formation in ankylosing spondylitis.
Methods
Spinal magnetic resonance images and conventional radiographs from 39 ankylosing spondylitis patients treated with anti-tumour necrosis factor (anti-TNF) agents at baseline and after 2 years were analysed for syndesmophyte formation at vertebral edges with or without inflammatory lesions at baseline.
Results
Overall, 922 vertebral edges at the cervical and lumbar spine were analysed. At baseline, the proportion of vertebral edges with and without inflammation (magnetic resonance imaging) that showed structural changes (conventional radiographs) was similar (in total, 16.6% of all vertebral edges in 71.4% of patients). From the perspective of syndesmophyte formation (n = 26, 2.9%) after 2 years, there were more vertebral edges without (62%) than with (38%) inflammation at baseline (P = 0.03). From the perspective of spinal inflammation at baseline (n = 153 vertebral edges), more syndesmophytes developed at vertebral edges with (6.5%) than without (2.1%) inflammation (P = 0.002, odds ratio 3.3, 95% confidence interval 1.5 to 7.4). Inflammation persisted in 31% of the initially inflamed vertebral edges (n = 132), and new lesions developed in 8% of the vertebral edges without inflammation at baseline (n = 410). From the perspective of spinal inflammation after 2 years (n = 72 vertebral edges), 5.6% of the vertebral edges showed syndesmophyte development in contrast to 1.9% of the vertebral edges with new syndesmophytes without inflammation (P = 0.06).
Conclusions
These findings obtained in patients treated with anti-TNF agents suggest linkage and some dissociation of inflammation and new bone formation in ankylosing spondylitis. Although syndesmophytes were also found to develop at sites where no inflammation had been seen by magnetic resonance imaging at baseline, it was more likely that syndesmophytes developed in inflamed vertebral edges. More effective suppression of spinal inflammation may be required to inhibit structural damage in ankylosing spondylitis.
doi:10.1186/ar2496
PMCID: PMC2592781  PMID: 18761747
2.  Lateral pharyngeal wall myeloid sarcoma as a relapse of acute biphenotypic leukemia: a case report and review of the literature 
Introduction
Myeloid sarcoma is a rare extramedullary malignant tumor composed of immature myeloid cells. The tumor can affect any part of the body. Involvement of the oral cavity and nasopharynx has been reported in 50 cases. We report a case describing myeloid sarcoma affecting the lateral pharyngeal wall.
Case presentation
A 31-year-old Arabian man who had acute biphenotypic leukemia treated with chemoradiation and allogeneic stem cell transplant was referred to our department with sore throat and a mass lesion in his lateral pharyngeal wall after failed antibiotic therapy. Biopsy of his lesion revealed myeloid sarcoma. He was referred to the Department of Hematology-Oncology for further evaluation that showed no other lesions.
The patient was diagnosed with isolated extramedullary myeloid sarcoma of his lateral pharyngeal wall as a relapse of acute biphenotypic leukemia and managed with chemoradiation.
Conclusions
Myeloid sarcoma of the pharynx is a rarely encountered malignancy in the practice of otolaryngology-head and neck surgery. It can develop de novo, but may also represent relapse of leukemia. Thus, it should be considered in the differential diagnosis of any pharyngeal lesions in patients with leukemia.
doi:10.1186/1752-1947-7-292
PMCID: PMC3880180  PMID: 24377982
Acute biphenotypic leukemia; Extramedullary tumor; Lateral pharyngeal wall; Myeloid sarcoma
3.  Iatrogenic fractures in ankylosing spondylitis—a report of two cases 
European Spine Journal  2005;15(1):100-104.
Study design: Two cases of intraoperative, iatrogenic cervical spine fractures in patients with ankylosing spondylitis are reported. Objective: To describe the uncommon complication of iatrogenic cervical spine fractures occurring during spine surgery in patients with ankylosing spondylitis. Summary of background data: To our knowledge, this is the first report on this rare complication. Methods: A 39-year-old patient (1) with ankylosing spondylitis was operated on for cervical stenosis due to C1/2 anterolisthesis. Fifteen hours postoperatively, he developed acute quadriplegia. MRI revealed a fracture/dislocation of C6 on C7 and compression of the spinal cord at this level. Revision was performed with decompression and instrumentation from the occiput to T3. A 55-year-old patient (2) with ankylosing spondylitis and thoracic hyperkyphosis underwent a correction procedure consisting of costotransversectomy, anterior cage implantation at T8/9, and posterior instrumentation from T4 to L1. Halo traction was temporarily applied for correction. At the end of the operation, with the patient still under anesthesia, increased mobility of the cervical spine was noticed. Emergent MRI revealed a fracture of the anterior structures of C6/7. Posterior instrumentation from C5 to T1 was then performed. Results: Quadriplegia persisted in patient 1 until his death secondary to further complications. Patient 2 was mobilized without any neurologic deficits. The fracture healed in good alignment. Conclusions: Iatrogenic fractures of the cervical spine during surgery in ankylosing spondylitis patients are a rare but potentially severe complication. Early diagnosis and therapy are necessary before dislocation, cord compression, and subsequent neurologic impairment occur.
doi:10.1007/s00586-005-0973-8
PMCID: PMC3454562  PMID: 16032433
Ankylosing spondylitis; Iatrogenic fracture; Cervical spine fracture
4.  Prolonged Survival of a Refractory Acute Myeloid Leukemia Patient after a Third Hematopoietic Stem Cell Transplantation with Umbilical Cord Blood following a Second Relapse 
Case Reports in Hematology  2014;2014:918708.
Although hematopoietic stem cell transplantation (HSCT) has been considered to be the only way for potential cure of relapsed acute myeloid leukemia (AML), there has been no report on a third HSCT in patients with multiple relapsed AML. Here, we report a case of 53-year-old female who received a successful third allogeneic HSCT after relapse of AML following a second allogeneic HSCT. She was treated with a toxicity reduced conditioning regimen and received direct intrabone cord blood transplantation (CBT) using a single unit of 5/6 HLA-matched cord blood as a graft source. Graft-versus-host disease prophylaxis was performed with a single agent of tacrolimus to increase graft-versus-leukemia effect. She is in remission for 8 months since the direct intrabone CBT. This report highlights not only the importance of individually adjusted approach but also the need for further investigation on the role of HSCT as a treatment modality in patients with refractory or multiple relapsed AML.
doi:10.1155/2014/918708
PMCID: PMC3934324  PMID: 24660078
5.  Improved precision of syndesmophyte measurement for the evaluation of ankylosing spondylitis using CT: a phantom and patient study 
Physics in medicine and biology  2012;57(14):4683-4704.
Ankylosing spondylitis is a disease characterized by abnormal bone formation (syndesmophyte) at the margins of intervertebral disk spaces. Syndesmophyte growth is currently typically monitored by visual inspection of radiographs. The limitations inherent to the modality (2D projection of a 3D object) and rater (qualitative human judgment) may compromise sensitivity. With newly available treatments, more precise measures of syndesmophytes are needed to determine if treatment can slow rates of syndesmophyte growth. We previously presented a computer algorithm measuring syndesmophyte volumes and heights in the 3D space of CT scans. In this study we present improvements to the original algorithm and evaluate the gain in precision as applied to an anthropomorphic vertebral phantom and patients. Each patient was scanned twice in one day, thus providing two syndesmophyte volume and height measures. The difference between those two measures (ideally zero) determines our algorithm’s precision. The technical improvements to the algorithm decreased the mean volume difference (standard deviation) between scans from 3.01% (2.83%) to 1.31% (0.95%) and the mean height difference between scans from 3.16% (2.99%) to 1.56% (1.13%). The high precision of the improved algorithm holds promise for application to longitudinal clinical studies.
doi:10.1088/0031-9155/57/14/4683
PMCID: PMC3427026  PMID: 22750760
6.  Progression of radiographic damage in patients with ankylosing spondylitis: defining the central role of syndesmophytes 
Annals of the Rheumatic Diseases  2007;66(7):910-915.
Background
Structural changes such as erosions, syndesmophytes and ankylosis are characteristic of ankylosing spondylitis (AS). These can be quantified by the modified Stokes Anklylosing Spondylitis Spinal Score (mSASSS). It is unknown which radiographic feature is most relevant for the assessment of change and the prediction of future damage in AS.
Objectives
To analyse radiographic progression in AS by using different assessments to define the most important changes.
Methods
Spinal radiographs of 116 patients with AS were scored by the mSASSS at baseline (BL) and after 2 years. Radiographic progression was assessed by differentiating (1) any change; (2) progression to syndesmophytes/ankylosis (definite change); and (3) changes exceeding the smallest detectable change (SDC) as predefined. A growth angle of 45° was used to differentiate syndesmophytes from spondylophytes.
Results
Some radiographic progression after 2 years was detected in 42% of patients, novel syndesmophytes in 31% of patients, and, using the SDC (calculated at 2 mSASSS units) as cut‐off, progression was seen in 28% of patients. Thus, in 74% of the patients changes were because of syndesmophytes and/or ankylosis. Using the predefined cut‐off, only 12% of all syndesmophytes were spondylophytes. Patients with such changes were of older age. Definite radiographic progression was found in 44% of the patients with syndesmophytes/ankylosis at BL (n = 57) versus 19% (p = 0.03) of the patients without such changes (n = 59).
Conclusions
Syndesmophytes and ankylosis are the most relevant structural changes in AS, and also in the mSASSS. Development of just one syndesmophyte within 2 years indicates progression of structural changes in AS; this is relevant for clinical practice. Syndesmophytes are the best predictors of radiographic progression.
doi:10.1136/ard.2006.066415
PMCID: PMC1955120  PMID: 17329306
7.  Prevalence of vertebral compression fractures due to osteoporosis in ankylosing spondylitis. 
BMJ : British Medical Journal  1990;300(6724):563-565.
OBJECTIVE--To determine the prevalence of vertebral compression fractures due to osteoporosis in patients with ankylosing spondylitis. DESIGN--Prospective study of 111 consecutive patients; patients with vertebral compression fractures were entered into a case-control study. SETTING--Outpatient clinic at the centre for rheumatic diseases, Glasgow. PATIENTS--111 Consecutive patients with ankylosing spondylitis. Patients with compression fractures were matched for age and sex with two controls selected from the rest of the group. Patients with biconcave vertebral fractures were also studied. MAIN OUTCOME MEASURES--Assessments of spinal deformity and mobility and analysis of lateral radiographs of spines for presence of syndesmophytes. RESULTS--Fifteen patients with compression fractures and five with biconcave fractures were studied. Compared with the controls the patients with compression fractures had increased formation of syndesmophytes in the lumbar spine, whereas those with biconcave fractures had increased formation throughout the spine. Patients with compression fractures also had a greater degree of spinal deformity (distance from wall to tragus 24.5 cm v 12.7 cm in controls), less spinal mobility (20 v 45.6 degrees of flexion), and reduced chest expansion (2 cm v 3cm). CONCLUSION--Vertebral compression fractures due to osteoporosis are a common but frequently unrecognised complication of ankylosing spondylitis and may contribute to the pathogenesis of spinal deformity and back pain.
Images
PMCID: PMC1662343  PMID: 2108749
8.  Long-term persistence of nonpathogenic clonal chromosome abnormalities in donor hematopoietic cells following allogenic stem cell transplantation 
Cancer genetics and cytogenetics  2009;190(2):125-130.
We describe two unrelated patients who exhibited multiple chromosomal abnormalities in donor cells after allogeneic peripheral blood stem cell transplantation (PBSCT). The patients were diagnosed with chronic myeloid leukemia and chronic lymphocytic leukemia, respectively, and both underwent non-myeloablative conditioning with cyclophosphamide and fludarabine followed by PBSCT from their HLA-matched opposite-sex siblings. Post-transplant bone marrow cytogenetics showed full engraftment, and the early post-transplant studies demonstrated only normal donor metaphases. Subsequent studies of both patients, however, revealed a population of metaphase cells with abnormal, but apparently balanced, karyotypes. Chromosome studies performed on peripheral blood cells collected from both donors after transplantation were normal. Both patients remained in clinical remission during follow-up of up almost 6 years, despite the persistence of the abnormal clones. Chromosomal abnormalities in residual recipient cells after bone marrow or PBSCT are not unusual. In contrast, only rare reports of chromosome abnormalities in donor cells exist, all of which have been associated with post-bone marrow transplant myelodysplastic syndrome or acute leukemias. Ours is the first report of persistent clonal non-pathogenic chromosome aberrations in cells of donor origin.
doi:10.1016/j.cancergencyto.2009.01.001
PMCID: PMC2764294  PMID: 19380032
9.  Symptomatic improvement in function and disease activity in a patient with ankylosing spondylitis utilizing a course of chiropractic therapy: a prospective case study 
Background
There is limited outcome measure support for chiropractic manipulative therapy in the management of ankylosing spondylitis. An improvement in specific indices for both function and disease activity during chiropractic therapy for ankylosing spondylitis has not previously been reported.
Objective
To measure changes in function and disease activity in a patient with ankylosing spondylitis during a course of chiropractic therapy. The clinical management of ankylosing spondylitis, including chiropractic manipulative therapy and the implications of this case study are discussed.
Clinical Features
A 34-year-old male with a 10 year diagnosis of ankylosing spondylitis sought chiropractic treatment for spinal pain and stiffness. His advanced radiographic signs included an increased atlantodental interspace and cervical vertebral ankylosis.
Intervention and outcome
The Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), finger-tip-to-floor distance and chest expansion were assessed during an 18 week course of chiropractic spinal manipulation and mobilization therapy. There was a 90% improvement in the disease activity index and an 85% improvement in the functional index from the pre-treatment baseline, as measured by the BASDAI and BASFI respectively. Spinal flexibility and chest expansion also improved.
Conclusion
To the authors knowledge this is the first study to incorporate ankylosing spondylitis specific indices, for both disease activity and function, to objectively support the use of chiropractic manipulative therapy in the management of ankylosing spondylitis. More intensive research is suggested.
PMCID: PMC1840019  PMID: 17549197
ankylosing spondylitis; chiropractic; manipulation; Bath Ankylosing Spondylitis Functional Index (BASFI); Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)
10.  Precision of Syndesmophyte Volume Measurement for Ankylosing Spondylitis: a Phantom Study Using High Resolution CT 
Ankylosing Spondylitis is a disease characterized by abnormal bone structures (syndesmophytes) growing at intervertebral disk spaces (IDS). The growth of syndesmophytes is typically monitored by visual inspection of radiographs. The limitations inherent to the modality (2D projection of a 3D object) and rater (qualitative human judgment) entail a possibly important loss in sensitivity. We previously presented a method designed to overcome both limitations: a computer algorithm that quantitatively measures syndesmophytes in the 3D space of a high-resolution computed tomography scan. To establish the method's usefulness for longitudinal studies, it is necessary to assess its precision (repeatability) which can be affected by the limitations of both the algorithm itself and the imaging modality. To this end, an anthropomorphic vertebral phantom with syndesmophytes in 4 IDSs was manufactured. It was scanned 22 times with varying positions and resolutions. The syndesmophyte volumes extracted by our algorithm have an average coefficient of variation of 1.6% per IDS and 0.85% for the total.
doi:10.1109/IEMBS.2009.5335439
PMCID: PMC2952880  PMID: 19965231
11.  Gynecologic complication of chronic graft-versus-host disease: Vaginal obstruction 
Obstetrics & Gynecology Science  2013;56(4):277-280.
Allogenic peripheral blood stem cell transplantation (Allo-PBSCT) is being used to treat hematological malignancies with increasing frequency. Graft-versus-host disease (GvHD) is a complex complication of PBSCT. A 43-year-old woman came to the gynecology clinic for amenorrhea. She had been diagnosed with acute myeloid leukemia 2 years earlier and treated with induction and consolidation chemotherapy. After developing complete remission, she underwent Allo-PBSCT. When she started chemotherapy, her menstrual cycle completely disappeared. Fourteen months after menopausal hormone replacement therapy, it was discovered that her upper vaginal canal was completely obstructed. The lower vagina had an atrophic appearance. We report a rare case of partial vaginal obstruction as a complication of chronic GvHD and review the literature. We expect that this case report provides an opportunity to remind clinician of the gynecologic complications of GvHD.
doi:10.5468/ogs.2013.56.4.277
PMCID: PMC3784143  PMID: 24328016
Graft vs host disease; Hematocolpos; Peripheral blood stem cell transplantation; Vagina
12.  Isolated central nervous system relapse of chronic myeloid leukemia after allogeneic hematopoietic stem cell transplantation 
BMC Blood Disorders  2012;12:9.
Background
This case report highlights the relevance of quantifying the BCR-ABL gene in cerebrospinal fluid of patients with suspected relapse of chronic myeloid leukemia in the central nervous system.
Case presentation
We report on a female patient with isolated central nervous system relapse of chronic myeloid leukemia (CML) during peripheral remission after allogeneic hematopoietic stem cell transplantation. The patient showed a progressive cognitive decline as the main symptom. MRI revealed a hydrocephalus and an increase in cell count in the cerebrospinal fluid (CSF) with around 50% immature blasts in the differential count. A highly elevated BCR-ABL/ ABL ratio was detected in the CSF, whilst the ratio for peripheral blood and bone marrow was not altered. On treatment of the malresorptive hydrocephalus with shunt surgery, the patient showed an initial cognitive improvement, followed by a secondary deterioration. At this time, the cranial MRI showed leukemic infiltration of lateral ventricles walls. Hence, intrathecal administration of cytarabine, methotrexate, and dexamethasone was initiated, which caused a significant decrease of cells in the CSF. Soon after, the patient demonstrated significant cognitive improvement with a good participation in daily activities. At a later time point, after the patient had lost the major molecular response of CML, therapy with dasatinib was initiated. In a further follow-up, the patient was neurologically and hematologically stable.
Conclusions
In patients with treated CML, the rare case of an isolated CNS blast crisis has to be taken into account if neurological symptoms evolve. The analysis of BCR-ABL in the CSF is a further option for the reliable detection of primary isolated relapse of CML in these patients.
doi:10.1186/1471-2326-12-9
PMCID: PMC3469402  PMID: 22871019
Chronic myeloid leukemia; CNS relapse; BCR-ABL
13.  Disease flare of ankylosing spondylitis presenting as reactive arthritis with seropositivity: a case report 
Introduction
Concurrent rheumatoid factor seropositivity is occasionally detected in ankylosing spondylitis and often causes confusion in clinical routine. Overlap between various seronegative arthritides is a known but uncommon association. Differentiation of spondyloarthropathy from rheumatoid arthritis is important, since the natural history, complications, treatments and prognosis of the two diseases differ significantly.
Case presentation
Here, we report the case of a 47-year-old Sri Lankan man who had a long history of intermittent joint pains worsening following a recent episode of self-resolving non-bloody diarrhea. Subsequently, he developed a skin rash suggestive of keratoderma blenorrhagica and circinate balanitis. He had classical radiological evidence of ankylosing spondylosis (previously undiagnosed) associated with human leukocyte antigen B27 antigen, but was positive for rheumatoid factor.
Conclusions
A disease flare of ankylosing spondylitis prompted by a minor diarrheal illness showing well documented features of reactive arthritis is remarkable. The prognostic implications of seropositivity in spondyloarthritis are discussed.
doi:10.1186/1752-1947-6-60
PMCID: PMC3295684  PMID: 22333429
14.  Unrelated Hematopoietic Stem Cell Transplantation for Children with Acute Leukemia: Experience at a Single Institution 
Journal of Korean Medical Science  2009;24(5):904-909.
We evaluate the outcomes in children with acute leukemia who received allogeneic hematopoietic stem cell transplantation (HCT) using unrelated donor. Fifty-six children in complete remission (CR) received HCT from unrelated donors between 2000 and 2007. Thirty-five had acute myeloid leukemia, and 21 had acute lymphoid leukemia. Stem cell sources included bone marrow in 38, peripheral blood in 4, and cord blood (CB) in 14. Four patients died before engraftment and 52 engrafted. Twenty patients developed grade II-IV acute graft-versus-host disease (GVHD) and 8 developed extensive chronic GVHD. With median follow-up of 39.1 months, event free survival and overall survival were 60.4% and 67.5%, respectively, at 5 yr. Events included relapse in 10 and treatment-related mortality (TRM) in 10. The causes of TRM included sepsis in 4, GVHD in 4 (1 acute GVHD and 3 chronic GVHD), veno-occlusive disease in 1 and fulminant hepatitis in 1. Patients transplanted with CB had event free survival of 57.1%, comparable to 63.2% for those transplanted with other than CB. In conclusion, HCT with unrelated donors is effective treatment modality for children with acute leukemia. In children with acute leukemia candidate for HCT but lack suitable sibling donor, unrelated HCT may be a possible treatment option at the adequate time of their disease.
doi:10.3346/jkms.2009.24.5.904
PMCID: PMC2752776  PMID: 19794991
Child; Acute Leukemia; Allogeneic Hematopoietic Stem Cell Transplantation; Unrelated Donor
15.  Stem cell transplant: An experience from eastern India 
Background:
Hematopoietic stem cell transplant using human leukocyte antigen (HLA)-matched sibling or unrelated bone marrow, or related or unrelated cord blood has been performed successfully to treat patients with different types of hematological malignancies, genetic disorders and hereditary immune deficiencies. Since 1983, stem cell transplantation has been carried out in different institutes of India. But, till then, no transplantation was performed in eastern India.
Materials and Methods:
Our present study is reporting for the first time stem cell transplantation in eastern India. From August 2000 to June 2011 (with a 3-year gap for up-gradation), we have performed a total of 22 transplants. Thirteen patients (M:F:9:4) with indications of aplastic anemia, thalassaemia, acute myeloid leukemia and chronic myeloid leukemia underwent allogenic transplant, whereas autologous transplant was performed for nine patients (M:F:2:1) of multiple myeloma, Hodgkin's and non-Hodgkin's lymphoma and neuroblastoma. The median age of the patients was 19.6 years, with a range of 5 years 8 months to 52 years. Fourteen patients received myeloablative conditioning regime whereas eight patients received immunosuppressive and less myeloablative protocol. Sources of stem cells in case of allogenic transplant are bone marrow and related or unrelated umbilical cord blood and in case of autologous transplant, these are peripheral blood stem cells or self-bone marrow. Standard prophylactic medication was followed prior to transplants.
Results:
A disease-free survival of 68.18% and overall survival of 86.3% were seen at the median follow-up period of 4.6 years. Common post-transplant complications were mucositis, infection, venoocclusive disease, graft versus host disease, hemorrhagic cystitis, etc.
Conclusion:
The use of cord blood as a source of stem cells has been proved inferior as compared with the bone marrow stem cell source in cases of thalassaemia in our institute and thus is not recommended for thalassaemia. But, it has been proved to be a very useful and effective stem cell source (both related and unrelated cord blood) in cases of aplastic anemia and other immunological disorders.
doi:10.4103/0971-5851.107078
PMCID: PMC3618641  PMID: 23580820
Aplastic anemia; bone marrow transplantation; cord blood transplantation; eastern Indian data; stem cell transplantation; thalassaemia
16.  Dengue hemorrhagic fever in a peripheral blood stem cell transplant recipient: the first case report 
Dengue infection, a mosquito-borne infectious disease in tropical and subtropical areas, has recently become an emerging global disease. The clinical course of dengue infection may be unfavorable in immunocompromised patients. In this report, we present a 16-year old female patient with acute myeloid leukemia who received allogeneic peripheral blood stem cell transplant five months prior to presentation. She was hospitalized at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, due to fever, headache, and myalgia for one day. During hospitalization, she developed capillary leakage syndrome and progressive thrombocytopenia. A diagnosis of dengue hemorrhagic fever was made and confirmed by positive dengue serology and polymerase chain reaction testing. She made a full recovery 14 days after hospitalization. Our case possibly acquired dengue virus from infected mosquitoes while visiting her relatives four days before her present illness. In conclusion, this is the first reported case of dengue hemorrhagic fever in a peripheral blood stem cell transplant recipient. In addition, we review all previous reports of dengue infection in organ transplant recipients.
doi:10.4081/idr.2009.e3
PMCID: PMC3892570  PMID: 24470881
dengue; dengue hemorrhagic fever; stem cell transplantation; bone marrow transplantation.
17.  Functional unresponsiveness and replicative senescence of myeloid leukemia antigen-specific CD8+ T cells after allogeneic stem cell transplantation 
Purpose
The therapeutic effect of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with myeloid malignancies has been attributed in part to a graft-versus-leukemia effect that is dependent on donor T lymphocytes. CD8+ T cell responses to MHC class I restricted tumor epitopes, not just allogeneic antigens, may help mediate anti-leukemia effects after HSCT, but the specificity and function of such cells are not completely understood.
Experimental Design
We examined the diversity, phenotype, and functional potential of leukemia-associated antigen-specific CD8+ T cells in patients with myeloid leukemia following allogeneic HSCT. Screening for antigen-specific T cells was accomplished with a peptide/MHC tetramer library.
Results
Patients with AML or CML in remission following HSCT exhibited significant numbers of peripheral blood CD8+ T cells that recognized varying combinations of epitopes derived from leukemia-associated antigens. However, these cells failed to proliferate, release cytokines, or degranulate in response to antigen-specific stimuli. As early as two months after HSCT, CD8+ T cells from patients were predominantly CD28neg CD57+ and had relatively short telomeres, consistent with cellular senescence.
Conclusions
Circulating leukemia-specific CD8+ T cells are prominent in myeloid leukemia patients after HSCT, but such cells are largely functionally unresponsive, most likely due to replicative senescence. These findings carry important implications for the understanding of the graft-versus-leukemia effect and for the rationale design of immunotherapeutic strategies for patients with myeloid leukemias.
doi:10.1158/1078-0432.CCR-08-3332
PMCID: PMC2722844  PMID: 19602548
18.  The prevalence of moderate to severe radiographic sacroiliitis and the correlation with health status in elderly Swedish men – The MrOS study 
Background
Ankylosing Spondylitis (AS) is a chronic inflammatory disease with onset in young adults, but little is known about the prevalence in older age groups. Furthermore, there is very limited information of health status of elderly patients with AS. Our objective was to estimate the prevalence of moderate to severe radiographic sacroiliitis in elderly men and its impact on health.
Methods
A cross-sectional, population-based survey, that included 1005 men aged 69-81 years old, with the primary aim to study risk factors for osteoporosis (MrOS), was used. X-rays of the pelvis and spine were done for the whole population and then examined by two readers. The prevalences of grade 3-4 sacroiliitis, syndesmophytes and spondylophytes were ascertained. Using a self-administered questionnaire, information was obtained on physical activity (PASE), functional status (IADL items), health related quality of life - QoL (SF-12) and back pain (pain question, Quebec Pain Disability Scale items).
Results
Fourteen cases with grade 3-4 sacroiliitis were identified, corresponding to a prevalence of 1.4% (95%CI: 0.7-2.4). Eight of the patients with sacroiliitis had both AS-typical and degenerative changes in the spine, 4 had only degenerative changes and 2 had only AS-related changes. There were no statistically significant differences between those with and without radiographic sacroiliitis regarding demographics, anthropometric measures, smoking status or health status, reflected by measures on physical activity, functional status, health related QoL and back pain.
Conclusions
The prevalence of moderate to severe radiographic sacroiliitis was estimated to be 1.4% among elderly men in Sweden. Self-reported health was only slightly different in those with sacroiliitis, suggesting that the relative impact of AS is modest in this age group.
doi:10.1186/1471-2474-14-352
PMCID: PMC3878735  PMID: 24330533
19.  Cauda equina syndrome as a rare manifestation of leukemia relapse during postallograft period. 
Here we report a 41-year-old woman with the diagnosis of acute myeloid leukemia. While being followed on remission after allogeneic peripheral blood stem cell transplantation, she developed systemic and central nervous system (CNS) relapse. CNS involvement presented first with meningeal irritation signs and then with cauda equina syndrome (CES). We define an interesting presentation of CES as abdominal pain and discuss the rare coexistence of the syndrome and leukemia under the light of the pertinent literature.
Images
PMCID: PMC2569274  PMID: 16749661
20.  Granulocytic Sarcoma by AML M4eo (inv16) after Allogeneic Stem Cell Transplantation without Bone Marrow Involvement 
Case Reports in Hematology  2011;2011:692982.
Granulocytic sarcoma (GS) represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML). We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT). The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.
doi:10.1155/2011/692982
PMCID: PMC3420739  PMID: 22937311
21.  Rare myeloid sarcoma/acute myeloid leukemia with adrenal mass after allogeneic mobilization peripheral blood stem cell transplantation 
Cancer Biology & Medicine  2013;10(4):232-235.
Myeloid sarcoma (MS) is a rare hematological neoplasm that develops either de novo or concurrently with acute myeloid leukemia (AML). This neoplasm can also be an initial manifestation of relapse in a previously treated AML that is in remission. A 44-year-old male patient was diagnosed with testis MS in a local hospital in August 2010. After one month, bone marrow biopsy and aspiration confirmed the diagnosis of AML. Allogeneic mobilization peripheral blood stem cell transplantation was performed, with the sister of the patient as donor, after complete remission (CR) was achieved by chemotherapy. Five months after treatment, an adrenal mass was detected by positron emission tomography-computed tomography (PET-CT). Radiotherapy was performed for the localized mass after a multidisciplinary team (MDT) discussion. The patient is still alive as of May 2013, with no evidence of recurrent MS or leukemia.
doi:10.7497/j.issn.2095-3941.2013.04.008
PMCID: PMC3860347  PMID: 24349834
Myeloid sarcoma (MS); acute myeloid leukemia (AML); allogeneic hematopoietic stem cell transplantation; multidisciplinary team (MDT)
22.  Do the radiological changes of classic ankylosing spondylitis differ from the changes found in the spondylitis associated with inflammatory bowel disease, psoriasis, and reactive arthritis? 
Annals of the Rheumatic Diseases  1998;57(3):135-140.
OBJECTIVE—In 1971 McEwen and colleagues suggested that the radiological changes of classic ankylosing spondylitis (AS), and the changes of the spondylitis associated with inflammatory bowel disease differ in several respects from the radiological features of psoriatic and reactive spondylitis. The findings of this study have never been confirmed. The aim of this study was to replicate the McEwen study comparing films blinded to diagnostic group.
METHODS—The study population comprised 91 patients with classic AS, 15 patients with regional enteritis, 16 patients with ulcerative colitis, five patients with sexually acquired reactive arthritis, two with post-dysenteric arthritis, and 34 with psoriatic arthritis. Blinded reading of spinal radiographs was undertaken, scoring for severity, symmetry, paravertebral ossification, size of syndesmophytes, ligamentous calcification, squaring, discitis, pseudo-fractures, zygoapophyseal joint involvement, and complete ankylosis.
RESULTS—Comparison of the four groups—classic, enteropathic, psoriatic, and reactive AS— showed differences with respect to symmetry of sacroiliitis, symmetry of lumbar spinal involvement, and frequency and size of syndesmophytes. Zygoapophyseal joint involvement was more frequent in the lumbar spine in classic and enteropathic spondylitis but no between group differences were found with respect to symphisitis, squaring, apophyseal joint involvement and ligamentous calcification in the lumbar spine, and other areas.
CONCLUSIONS—Some of the radiological differences described by McEwen et al, notably the asymmetry, the less severe changes, and the distinctive syndesmophytes in psoriasis, have been confirmed. A number of hypotheses are proposed to explain these differences including biomechanical, biochemical, and genetic factors.

 Keywords: psoriatic arthritis; ankylosing spondylitis; reactive arthritis; inflammatory bowel disease
PMCID: PMC1752543  PMID: 9640127
23.  Peripheral blood CD5-positive B lymphocytes (B-1a cells) after allogeneic stem cell transplantation for acute myeloid leukaemia in humans 
Blood Transfusion  2008;6(4):220-224.
Background
Only few data are available in literature regarding the reconstitution of B-1a cells after allogeneic bone marrow transplantation performed for haematological malignancies.
Methods
In this study we used flow cytometry to assess the reconstitution of the peripheral blood B-1a cell compartment after allogeneic peripheral blood stem cell transplantation. Cytometric analyses were performed over time on 11 consecutive patients undergoing allogeneic peripheral blood stem cell transplantation for acute myeloid leukaemia in our Haematology Unit and the results were compared with available data regarding B-1a cell reconstitution after allogeneic bone marrow stem cell transplantation.
Results
In spite of an earlier recovery of B-1a cells in the peripheral blood after allogeneic bone marrow transplantation, the reconstitution of this B-cell subset was similar, regardless of the source of stem cells employed.
Conclusions
Further studies are necessary in order to clarify the origin of B-1a cells in humans in health and illness.
doi:10.2450/2008.0010-08
PMCID: PMC2626909  PMID: 19112737
B-1a cells; reconstitution; stem cell transplantation
24.  Early response to adalimumab predicts long-term remission through 5 years of treatment in patients with ankylosing spondylitis 
Annals of the Rheumatic Diseases  2011;71(5):700-706.
Objectives
To describe the efficacy and safety through 5 years of adalimumab treatment in patients with ankylosing spondylitis (AS), and to identify predictors of remission.
Methods
Patients with active AS were followed up to 5 years during a 24-week randomised, controlled period, followed by an open-label extension. Disease activity and clinical improvement were evaluated by Assessment in Spondyloarthritis International Society (ASAS) responses, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Kaplan–Meier was used to identify patients with sustained ASAS partial remission (PR) or ASDAS inactive disease (ID) for three or more consecutive visits spanning ≥6 months. Logistic regression was used to identify factors associated with remission. Explanatory variables included baseline demographic and disease characteristics and week 12 responses.
Results
Of the 311 patients who received at least one dose of adalimumab, 202 (65%) completed the 5-year study. Among 125 patients who received 5 years of adalimumab, 70%, 77%, 51% and 61% achieved ASAS40, BASDAI 50, ASAS PR and ASDAS ID, respectively. Of 311 adalimumab-treated patients, 45% and 55% achieved sustained ASAS PR and ASDAS ID at any time during study participation. The strongest predictor of remission at years 1 and 5 and of sustained remission was achieving remission at 12 weeks of treatment; baseline characteristics showed weaker associations. Adverse events were comparable with previous reports on adalimumab safety.
Conclusions
In patients with active AS, the efficacy and safety of adalimumab were maintained through 5 years with about half of the patients experiencing sustained remission at any time during the study. Early achievement of remission was the best predictor of long-term and sustained remission.
doi:10.1136/annrheumdis-2011-200358
PMCID: PMC3329233  PMID: 22128084
25.  AA amyloidosis in the renal allograft: a report of two cases and review of the literature 
Clinical Kidney Journal  2012;5(2):146-149.
AA amyloidosis is a disorder characterized by the abnormal formation, accumulation and systemic deposition of fibrillary material that frequently involves the kidney. Recurrent AA amyloidosis in the renal allograft has been documented in patients with tuberculosis, familial Mediterranean fever, ankylosing spondylitis, chronic pyelonephritis and rheumatoid arthritis. De novo AA amyloidosis is rarely described. We report two cases of AA amyloidosis in the renal allograft. Our first case is a 47-year-old male with a history of ankylosing spondylitis who developed end-stage renal disease reportedly from tubulointerstitial nephritis from non-steroidal anti-inflammatory agent use. A biopsy was never performed. One year after transplantation, AA amyloidosis was identified in the femoral head and 8 years post-transplantation, AA amyloidosis was identified in the renal allograft. He was treated with colchicine and adalimumab and has stable renal function at 1 year-follow-up. Our second case is a 57-year-old male with a long history of intravenous drug use and hepatitis C infection who developed end-stage kidney disease due to AA amyloidosis. Our second patient's course was complicated by renal adenovirus, pulmonary aspergillosis and hepatitis C with AA amyloidosis subsequently being identified in the allograft 2.5 years post-transplantation. Renal allograft function remains stable 4-years post-transplantation. These reports describe clinical and pathologic features of two cases of AA amyloidosis presenting with proteinuria and focal involvement of the renal allograft.
doi:10.1093/ckj/sfs019
PMCID: PMC3341841  PMID: 22833808
AA amyloidosis; kidney transplant; post transplant

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