Post Bone Marrow Transplant Patients Research Articles

Gastric antral vascular ectasia, also known as watermelon stomach - diagnosis and treatment

Gastric antral vascular ectasia (GAVE), also referred to as watermelon stomach is a rare disease accounting for about 4% of non-variceal upper gastrointestinal bleeding. It can manifest as occult bleeding requiring transfusion or acute gastrointestinal bleeding. This condition often coexists with liver cirrhosis, autoimmune diseases, heart failure, in patients post-bone marrow transplantation, or kidney failure. It is crucial to differentiate GAVE from portal hypertensive gastropathy (PHG), because despite a similar clinical presentation, the treatment for these conditions is different.
 Endoscopic diagnosis is necessary and in some cases, it may require further investigation and histopathological examination of the biopsy. Treatment is administered to patients with bleeding symptoms. Currently, the most commonly used treatment method is endoscopic thermal ablation using argon plasma coagulation.
 The focus of this work is to present essential information regarding the clinical picture, diagnosis and treatment of watermelon stomach.

Designing food and meals for bone marrow transplant patients with compromised immunity

Immunocompromised post-bone marrow transplant patients must follow a restrictive diet after discharge to avoid microbiological risks in food. Despite the apparent health considerations, these restrictions can sometimes create confusion and apprehension during home meal preparation which has a negative impact on patients’ social dining experiences with families and friends and ultimately leads to adverse health effects such as appetite and weight loss. A user-friendly meal guidebook, specifically designed to fit patient’s needs, was developed to ensure a smooth transition from controlled hospital food to home-cooked meals without compromises in food safety and pleasure. With this guidebook, the objective of this uncommon collaboration between chefs and health professionals was to provide clear instructions to the patients on their diet and adapted recipes (six starters, eight main dishes and eight desserts) easy to do and share with the whole family. This design project represents a unique approach to addressing the food and nutrition needs of these transplant patients. Thus, this article presents an example of a multi-actor collaboration between health and culinary professionals who combined their expertise to help the patients feel less marginalized after their hospitalization and to support their recovery by providing adapted recipes that they can share with their family.

Amino acid mixture (enterade) as a new approach to reducing cancer therapy-induced gastrointestinal toxicity: A retrospective study.

e24107 Background: Gastrointestinal toxicity is a common side effect of cancer therapy. Pre-clinical studies using a proprietary mixture of amino acids, demonstrated a reduction in mucositis and gastrointestinal toxicity following irradiation via tightening of the mucosal barrier, increasing proliferation of crypt cells, increasing villous height and increasing absorption of fluid, electrolytes and nutrients. A novel 5-amino acid mixture “enterade” was previously evaluated in a Phase II clinical trial for anti-diarrheal effects in post bone marrow transplant patients at Dana Farber Cancer Institute (NCT02919670). Signs of anti-diarrheal efficacy were found in treatment-compliant patients.Enterade is currently being tested in two prospective Phase II studies (NCT03722511 and NCT04073017) in neuroendocrine tumor patients with quality of life limiting diarrhea. We conducted a pilot study to evaluate early antidiarrheal signals in oncologic treatment-induced diarrhea. Methods: An IRB-approved retrospective chart review was conducted at Markey Cancer Center between Sept 2019 and Dec 2019. Medical records were retrospectively reviewed for all solid tumor patients who received enterade for chemotherapy or immunotherapy-induced diarrhea. Patients were instructed to consume one 8-oz bottle of enterade twice a day for at least one week in addition to standard of care antidiarrheal medications. Results: A total of 46 patients were offered enterade. Antidiarrheal efficacy data was available on 17 patients. 11 were female and the mean age of the cohort was 64 years. Six out of 17 patients had a previous history of bowel resection. Four patients had immune checkpoint induced colitis. Three patients developed diarrhea from TKI use and rest were on cytotoxic chemotherapy at the time of the diarrheal episode. Eighty-eight percent (15/17) of patients reported a reduction in diarrhea frequency after consuming enterade. On average, patients noticed an improvement in diarrhea frequency after 3.6 days of enterade consumption, with 86% (13/15) of responders reporting at least 50% reduction in diarrhea frequency. Conclusions: Patient-reported diarrheal improvement after enterade consumption is consistent with pre-clinical data. Results suggest the amino acid mixture may alleviate symptoms of cancer therapy-induced gastrointestinal toxicity (i.e. diarrhea). A prospective clinical trial is warranted to substantiate the observed improvement in chemotherapy and immunotherapy induced diarrhea.

P790 Bi-ventricular dysfunction in patients after bone marrow transplant: the value of strain imaging

Abstract Background Cardiovascular events are a significant cause of morbidity and mortality in cancer survivors, particularly occurring at 5-10 years after their cancer therapy. Purpose To assess the utility of strain imaging by 2-dimensional (2D) speckle tracking echocardiography in detecting bi-ventricular dysfunction, as compared to traditional measures, in patients post bone marrow transplantation (BMT) with previous anthracycline (AC) therapy for haematological conditions. Methods 50 consecutive patients post BMT + AC, reviewed at a long-term survivor clinic, were compared to 50 age and gender matched controls. 48/50 patients received AC doses below the recommended cumulative lifetime thresholds set by the European Society of Medical Oncology. 2D left ventricular global longitudinal strain (LV GLS) and right ventricle free wall strain (RV FWS) were compared to conventional measures of bi-ventricular function. Results The mean LVEF (58 ± 6% vs 63 ± 6%) and RV fractional area change (FAC) (39 ± 5% vs 44 ± 5%), although reduced in the BMT + AC group vs controls, were within normal limits. LV GLS was reduced in BMT + AC patients as compared to controls (-17.8 ± 3.1% vs -20.5 ± 2.2%, p < 0.01) while RV FWS was also reduced (-23.2 ± 4.0% vs -27.9 ± 2.7%, p < 0.001). In BMT + AC patients with a preserved LVEF (LVEF > 53%), 28% (11/40) had reduced GLS (GLS < -17%) while 52% (24/46) of those with preserved FAC (FAC > 35%) had reduced FWS (FWS < -25%). Major adverse cardiac events (MACE) occurred in 9/50 patients in the BMT + AC group and none in the control group. 8/9 patients had normal biventricular function as assessed by traditional parameters (LVEF and RV FAC) but 5/9 patients had reduced LV GLS and/or RV FWS. Conclusions Subclinical bi-ventricular dysfunction is common in patients post BMT + AC therapy, and can be detected using strain analysis, despite preserved LV and RV systolic function using conventional measures. MACE occurred at a significantly higher rate in BMT patients exposed to AC. More than half of MACE events occurred in patients with reduced LV or RV strain, with preserved bi-ventricular function by traditional measures. LV GLS and RV FWS should be utilised for early identification of subclinical dysfunction in BMT patients.

The antidiarrheal efficacy of a proprietary amino acid mixture in neuroendocrine tumor (NET) patients.

218 Background: Gastroenteropancreatic neuroendocrine tumor (GEPNET) incidence has risen 6-fold over past 3 decades. North American Neuroendocrine Tumor Society estimates that over 100,000 GEPNET patients are currently living in the United States. One of the common quality of life limiting symptom seen in GEPNET patient is diarrhea. Diarrhea in these patients could be due to excessive serotonin production, secondary to post-operative short gut syndrome, steatorrhea from somatostatin analogs, bile acid colitis or intestinal bacterial overgrowth. A novel amino acid based oral rehydration solution (enterade) is currently being evaluated in a Phase II clinical trial for antidiarrheal effects in post bone marrow transplant patients (NCT02919670). We conducted a pilot study of enterade in neuroendocrine tumor (NET's) patients with quality of life limiting diarrhea. Methods: Medical records of all the NET patients given enterade to alleviate symptomatic diarrhea were evaluated. Patients were treated at Markey Cancer Center between May 2017-June 2018. Results: Total 69 NETs patients were treated with enterade. Enterade was administered as 8 Oz bottle BID for 1 a week. Antidiarrheal efficacy data was available on 41 patients at the time of abstract submission. 15 patients had small bowel NETs, 5 had bronchial NETs, 1 had colorectal NETs, 3 had NETs of unknown primary, 3 had gastric NETS, 3 had pancreatic NETs and one had high grade neuroendocrine carcinoma of the prostate. Data regarding primary site was unavailable in 10/41 patients. 21 patients had history of prior bowel resection either for primary neuroendocrine tumor resection or debulking. 25 patients were on somatostatin analogs at the time of initiation of enterade. 31 out of 41 patients reported some reduction in diarrhea frequency. 21 out of these 41 patients reported at least a 50% reduction in diarrhea frequency. Conclusions: 75.6% (31/41) neuroendocrine tumor patients reported improvement in diarrhea frequency with enterade. 51.2% (21/41) reported more than 50% reduction in diarrhea frequency. A prospective Phase II study of enterade in neuroendocrine tumor patients with quality of life limiting diarrhea is currently planned.

Posterior Reversible Encephalopathy Syndrome in Pediatric Oncology and Post Bone Marrow Transplant: Single Center Experience and Systematic Review

BackgroundPosterior reversible encephalopathy syndrome (PRES) is a clinical radiologic disease described initially over two decades ago. This usually reversible entity is becoming more recognized and reported due to the increased index of suspicion and subsequent early brain imaging. It is described in pediatric oncology and post bone marrow transplant (BMT) patients mainly as case reports and case series. The aim of this single institution retrospective study is to describe a cohort of pediatric patients with oncologic diseases and post BMT and incorporate them in a systematic review of the literature to evaluate for differences in risk factors for developing PRES in patients post BMT for oncologic diseases compared to those transplanted for a benign disorder.MethodsWe retrospectively analyzed 11 patients admitted to a single center in Saudi Arabia and conducted a systematic review of previously published case reports and case series from January 1996 to December 2016.ResultsA total of 61 case reports and series were evaluated, 42 papers met the inclusion criteria in addition to our 11 patients for a total of 124 patients of which 27 were post BMT. The post BMT patients were divided by the indication of BMT into malignant and benign groups (14 (53.8%) and 12 (46.2%), respectively). One patient had missing data on the indication of BMT and was excluded. PRES was more common in males 69 / 120 (57.5%) in general, however, more common in females 17 / 27 post BMT (63%, p 0.015). The median age of presentation was 9.5 years (range 1.4 to 16 years) and PRES occurred on a median day +42 post BMT (range +2 to +144 days), and seemed to occur earlier in patients with benign diseases compared to malignant (median day +24 and day +45 respectively, p 0.104).We studied immunosuppression, hypertension history, and acute elevation of blood pressure (BP) as risk factors for developing PRES. There were 25 patients on immunosuppression; 20 (80%) were on cyclosporine (CsA) and 5 (20%) on tacrolimus. There were only 10 patients post BMT with reported presence or absence of toxicity of immunosuppression, 8 in the benign group, of which 3 (37.5%) patients had toxic levels of CsA, and 2 in the malignant group both with reported elevated CsA levels while other reviews showed PRES occurred independent of CsA level. Four patients were resumed on the same immunosuppression after the resolution of PRES, 2 developed recurrences and both were from the malignant group. The presence of history of hypertension as a risk factor was more common in the post BMT group compared to the non BMT group (9 / 13 (69.2%), 14 of 62 (22.6%) respectively, p 0.001), particularly in patients of the malignant group compared to the benign, but not statistically significant (5 of 6 (83.3%), 4 of 7 (57.1%) respectively, p 0.308). Acute hypertension was noted in all the patients with malignant disease who reported the BP, however, was only in 9 / 12 (75%) patients with benign disease. We were not able to evaluate hypomagnesemia as a risk factor due to the deficiency in reporting electrolytes in the case series, possibly due to the diverse specialties describing the disease.MRI was the diagnostic modality of choice. In the post BMT group, 18 / 26 patients (69.2%) had involvement of areas other than the parietal and occipital lobe on imaging, most commonly the temporal lobe. All the patients resolved from the acute episode of PRES. MRI was repeated in 10 patients at a median of 4 weeks (range 0.4 to 44 weeks), 5 patients had complete resolution of the MRI findings and 5 showed improvement in findings, with no differences in the two groups.Recurrence of PRES occurred in 4 / 26 patients (15.4%). There were no differences in the recurrence in relation to the underlying cause of BMT, clinical presentation, or imaging. There were 9 deaths (34.6%), none were due to PRES nor related to recurrence.ConclusionOur review showed the risk of PRES post BMT increased in females, the presence of history of hypertension, and immunosuppressive therapy, particularly CsA, which is similar to the literature. The time of presentation of PRES and the weight of each risk factor appears to be different in relation to the cause of BMT, however, the study is limited by the small number and reporting bias. The risk factor differences may be better elicited in a large cohort study. DisclosuresNo relevant conflicts of interest to declare.

MOLECULAR DETECTION OF CYTOMEGALOVIRUS IN A SAMPLE OF IRAQI PATIENTS WITH ACUTE LEUKEMIA AND STEM CELL TRANSPLANTATION

Background: Acute leukemia and hematopoietic stem cell transplantation are risk factors for opportunistic infection and reactivation of many latent infection like cytomegalovirus. Objective: Detection and quantification of cytomegalovirus viremia in patients with acute leukemia after induction chemotherapy and post allogeneic stem cell transplantation patients. Methods: A prospective study enrolled 61 patients with acute leukemia. Forty-eight of them evaluated while induction chemotherapy (group I), while the other 13 within 1-year post bone marrow transplantation (BMT) (group II). In addition, 30 apparently healthy individuals were recruited as (control group), blood samples were collected from all groups. Viral DNA was extracted from 1 ml plasma samples, and then, cytomegalovirus DNA was detected and quantitatively assessed by Taqman quantitative real-time PCR. Results: Twelve (25%) out of 48 patients in group I, 2 (15.4%) out of the 13 patients in group II, and 2 (6.7%) out of 30 in the control group had positive cytomegalovirus viremia. The mean cytomegalovirus viremia was 5.192x102, 2.71x102 and 1.60x102 copies/ml for group I, group II and controls respectively, p=0.056. Conclusion: There is a relatively high prevalence of cytomegalovirus viremia in Iraqi patients with acute leukemia after chemotherapy and post BMT. Real-time PCR assay is helpful for early diagnosis of cytomegalovirus viremia in leukemic patients and used to monitor post BMT patients at risk for cytomegalovirus disease. Keywords: HCMV, acute leukemia, stem cell transplantation, real-time PCR Citation: Al-Toban HA, Al-Marsomy HD, Al-Obaidi AB, Al Tameemi WF, Mohammed MA, Al-Saeed RM, Al-Shemary IK. Molecular detection of cytomegalovirus in a sample of iraqi patients with acute leukemia and stem cell transplantation. Iraqi JMS. 2018; 16(3): 344-352. doi: 10.22578/IJMS.16.3.14

The assessment of testicular sperm extraction (TESE) and intracytoplasmic sperm injection (ICSI) in couples of post chemotherapy non-obstructive azoospermia (NOA)

Advances in chemotherapeutic treatments can achieve high remission rates in pediatric and adolescent patients with cancer, but cytotoxic chemotherapy may lead to irreversible spermatogenic dysfunction. In cancer survivors, the restoration of fertility and achievement of paternity have become important concerns, however, at diagnosis, patients with such serious diseases are often not concerned with reproductive issues. A retrospective study in a reproductive center. We evaluated sperm retrieval rate (SRR) of microdissection TESE (micro TESE), two pronuclei (2PN) oocyte rates, blastocyst development rates, good-quality blastocyst (Grade 3BB and above on day 5 by the Gardner scoring) rates, and clinical pregnancy rates per embryo transfer (ET) in 44 cases with post chemotherapy NOA patinets (including 8 patients with bone marrow transplantation (BMT)), 330 NOA cases with 46,XY without past history (unexplained NOA; not including after orchidopexy, Klinefelter syndrome, cryptozoospermia, mumps orchitis, etc), and 107 cases with obstructive azoospermia (OA) between September 2013 and April 2018. The cancer types included testicular cancer, colon cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, leukemia, neuroblastoma, and osteosarcoma. The age at micro TESE and chemotherapy was 33.9±5.4 and 17.3±10.4 years of age, respectively, and the wives age at ICSI was 33.7±3.9 years. SRR of micro TESE in post chemotherapy NOA (21/44=47.7%) was higher than unexplained NOA (92/330=27.9%) patients (P<0.01). In sperm retrieved post chemotherapy NOA, age at chemotherapy end was older (20.6±9.1 years) than failure group (14.2±10.8 years) (P<0.05). With respect to type of cancer, there was no predictor for SRR and no significant differences in the pregnancy and live birth rates. In 3 of 8 post BMT patients spermatozoa were successfully retrieved. Two of 3 patients even showed a 46,XX karyotype (transplantation from female donor). The 23 patients who failed to obtain sperm could not find any germ cells in their testicular samples in wet preparations and histopathological sections (Sertoli cell only syndrome). 2PN oocytes, blastocysts development, and good-quality blastocysts rates were 63.2%, 55.8%, and 61.9% in post chemotherapy NOA, 58.3%, 45.2%, and 37.8% in unexplained NOA, and 66.0%, 51.6%, and 42.8% in OA. Post chemotherapy NOA showed higher clinical pregnancy rates per ET (44.9%: 22/49) than unexplained NOA (26.2% : 37/141) (P<0.05). Fourteen children have been born and 4 patients are on going pregnancy in post chemotherapy NOA couples. Age at chemotherapy was important predictive factor for successful sperm recovery. Once sperm were obtained their reproductive performance was satisfactory. These findings provides hope for men of reproductive age who have not undergone sperm cryopreservation before chemotherapy.

Corneal fluorescein staining and ocular symptoms but not Schirmer test are useful as indicators of response to treatment in chronic ocular GVHD

PurposeTo evaluate long-term ocular surface clinical signs and symptoms response to therapy in patients with chronic ocular GVHD. MethodsRetrospective review and data modeling. We reviewed the records of post-bone marrow transplantation patients who were newly diagnosed with ocular GVHD and initiated therapy, and analyzed changes in symptoms (Ocular Surface Disease Index [OSDI]; Symptom Assessment in Dry Eye [SANDE]) and signs (corneal fluorescein staining [CFS]; Schirmer test). We used a LOESS technique to fit a model in function of data variations and obtain a predictive value of the scores progression over time. ResultsThe records of 123 patients who were followed-up for over 2 years (up to 62 months) were reviewed. The median baseline scores recorded were: OSDI 52 units, SANDE 62.2 units, CFS 2.0 Oxford units, and Schirmer 4 mm. After six months of follow up, scores improved for OSDI (−18.6 units, p = 0.007), SANDE (23.7 units, p = 0.01), and CFS (−0.7 Oxford units, p < 0.001). Data analysis showed that after a 2-year follow up the three parameters continued to improve: OSDI -13.67 units (27% reduction), SANDE -17.55 units (28%), CFS -1.1 units (54%), but Schirmer test scores progressively worsened −1.2 mm (22%). ConclusionIn patients with ocular GVHD symptoms and corneal fluorescein staining improved after initiation of treatment, meanwhile Schirmer scores declined progressively. This indicates that appropriate treatment in chronic ocular GVHD can lead to mid- and long-term improvements in symptoms and corneal epitheliopathy; however, sustained reduction in Schirmer test scores suggests chronic tear production impairment.

The antidiarrheal efficacy of a proprietary amino acid mixture in gastroenteropancreatic neuroendocrine patients.

509 Background: Based on SEER database, gastroenteropancreatic neuroendocrine tumor incidence has increased 6 fold from 1 in 100,000 cases to about 6 in 100,000 cases over past 3 decades. North American Neuroendocrine Tumor Society estimates that over 100,000 GEPNET patients are currently living in the United States. One of the common quality of life limiting symptom seen in GEPNET patient is diarrhea. Diarrhea in these patients could be due to excessive serotonin production, secondary to post-operative short gut syndrome, steatorrhea from somatostatin analogs, bile acid colitis or intestinal bacterial overgrowth. A novel amino acid based oral rehydration solution (Enterade) is currently being evaluated in a Phase II clinical trial for antidiarrheal effects in post bone marrow transplant patients (NCT02919670). We conducted a pilot study of Enterade in neuroendocrine tumor patients with quality of life limiting diarrhea to evaluate its antidiarrheal efficacy. Methods: Medical records of all the GEPNET patients treated with Enterade for symptomatic diarrhea were evaluated. Patients were treated at Markey cancer center between May 2017-August 2017. Results: Total 8 patients were treated with Enterade. Five were small bowel NETs and 3 were pancreatic NETs. Five patients had prior bowel resections for removal of primary tumor; 5 patients were on somatostatin analogs at the time of initiation of Enterade. Five (62%) patients reported improvement in diarrhea within 6 days of initiating Enterade. The responders had 50 % reduction in their stool output. Mean stools dropped from 6 per day to 3 per day in responders. Conclusions: These pilot data suggest that Enterade may be an effective option in diarrhea control in NET patients. A prospective Phase II study of Enterade in gastroenteropancreatic neuroendocrine tumor patients with quality of life limiting diarrhea is planned.

Pleuroparenchymal Fibroelastosis: Associations and Underlying Conditions

Pleuroparenchymal fibroelastosis (PPFE) is a clinicopathologic entity characterized by clinical presentation suggestive of a chronic idiopathic interstitial pneumonia, radiologic features of pleural and parenchymal involvement accentuated in the upper lobes, and a constellation of histologic findings including visceral pleural fibrosis and prominent fibroelastosis of the subpleural lung parenchyma. While the large majority of cases of PPFE have been considered idiopathic, development of PPFE in post-bone marrow transplant patients and in lung transplant recipients has recently been reported. Further, with the growing number of idiopathic PPFE cases reported in the literature, interesting patterns of association between PPFE and various clinical conditions – including prior treatment for malignancy, autoimmunity, recurrent infections, and vascular compromise/ischemia – are beginning to emerge. These associations, reviewed here, may offer clues into the pathogenesis of this rare condition. Keywords: Chronic lung allograft dysfunction, graft versus host disease, interstitial lung disease, pleuroparenchymal fibroelastosis, pulmonary fibrosis, pulmonary upper lobe fibrosis, restrictive allograft syndrome.

Intrahost genetic variability of human herpes virus‐8

Studies were conducted to determine whether HHV-8 hyperactivity could be the consequence of the propensity of the host to multiple HHV-8 infection. The aim of the present work was to investigate HHV-8 intrahost genetic variability. HHV-8 subgenomic DNA was amplified by PCR from patients infected with HIV, health care workers (HCW) and bone marrow transplant recipients (BMT), and from oral lesional tissues of AIDS-Kaposi's sarcoma (KS) patients. As controls, blood from HIV-negative health care workers, and the cell lines BC-1, BC-2, and BCP-1 were used. Clones derived from amplicons originating from DNA fragments in open reading frame (ORF) 26 and ORF K1 were isolated. For each ORF, intra-specimen nucleotide sequence differences were determined. The extent of HHV-8 variation in clones derived from blood of patients infected with HIV was significantly higher than in blood from health care workers or post-bone marrow transplantation patients or in AIDS-KS tissue. Among the clones derived from the latter three categories of specimens, sequence variations were not significant. It is concluded that HIV-infected individuals can have multiple of HHV-8, but AIDS-KS lesions are associated with infection by a single HHV-8 variant or a small group of related variants.

Expression of BLM mRNA in leukemia and its clinical significance

Objective To investigate the correlation between the expression level of BLM and its clinical significance in leukemia. Methods 125 bone marrow specimens of inpatients and outpatients with leukemia were collected in Anhui provincial hospital from January 2011 to December 2011.125 leukemia patients were diagnosed and classified into acute leukemia (AL, n=66) and chronic myelogenous leukemia (CML, n=59) by Morphologic and Immunologic criteria, 5 non-tumor individuals were included as control group.The BLM mRNA expressions were by reverse transcription-polymerase chain reaction(RT-PCR).The specimens were devided into groups according to the age, gender, leukemia type, peripheral blood leukocyte counts, hepatomegalia and(or) splenomegaly, fusion gene, chromosome karyotype, whether first visit and transplantation.The expression of BLM gene in each group and the correlation with above factors were retrospectively analysed.The statistical methods such as chi-square test, single factor variance analysis, t test and Pearson correlation test were mainly used. Results BLM mRNA was detected in leukemia. In bone marrow cells, the BLM gene expression was positive in 71 patients and negative in 54 patients.But none of 5 non-tumor bone marrow cells expressed BLM gene.The difference of BLM expression between patients and controls was statistically significant in two groups, i.e. peripheral blood leukocyte counts and fusion gene (χ2=14.730, 22.399; P<0.05), but there is no statistical significant differences in other groups.The expressions of BLM mRNA in leukemia patients who had been treated with chemotherapy were lower than those newly diagnosed (0.1788±0.1091 vs 0.3276±0.2016; P<0.05).Moreover, BLM mRNA level in post-bone marrow transplant patients was lower than those not treated (0.1271±0.1009 vs 0.2902±0.2034; P<0.05).Pearson correlation analysis showed that higher BLM mRNA expression positively correlated with fusion gene (r=0.357, P<0.01) and chromosome abnormality (r=0.279, P<0.05). Conclusion The BLM mRNA expression level of measurement can be used as judgment for leukemia patients disease severity and the index of prognosis, testing the level may provide a basis for clinical and curative effect judgment.（Chin J Lab Med，2012,35：1130-1134） Key words: Leukemia; RecQ helicases; Bone marrow cells; Reverse transcriptase polymerase chain reaction

Relationship between clinical sinusitis symptoms and sinus CT severity in pediatric post bone marrow transplant and immunocompetent patients

Since typical inflammatory responses may be diminished in children following bone marrow transplant (BMT), computed tomography (CT) imaging of the sinuses has been increasingly ordered to diagnose sinusitis in this group. The objective of this study was to determine the association between clinical sinusitis symptoms and sinus opacification on CT scans in post BMT versus immunocompetent children. Our sample was comprised of 64 post BMT and 86 immunocompetent children with sinus CT scans. CT sinus opacification was scored using the modified Lund-Mackay staging system. The relationship between clinical sinusitis symptoms (rhinorrhea, nasal congestion, cough, headache, and facial pain) and opacification was compared for the two groups. The severity of sinus opacification in the BMT group was significantly higher compared to the immunocompetent group. In combined patient groups the odds ratio (OR) for moderate/severe sinusitis was significantly elevated for rhinorrhea (OR = 3.00; 95% confidence interval [CI], 1.27-7.12), cough (OR = 2.80; 95% CI, 1.22-6.42), and having either rhinorrhea, nasal congestion, or cough (OR = 4.76; 95% CI, 1.71-13.24). While the immunocompetent group had a greater number of sinusitis symptoms compared to the post BMT group, both groups had a significant increase in the severity on CT with increasing number of symptoms. In post BMT patients, our data demonstrated higher odds of moderate/severe sinusitis on CT scans associated with rhinorrhea, cough or nasal congestion. These finding suggest that in post BMT children, detailed sinus history may still play a vital role in the diagnosis of sinusitis.

Supportive Care Assessment: Patient Preferences for Disclosure of Palliative Care Information

Objectives 1. Describe the interactions with hematologic malignancy (HM) clinicians enabling the integration of a palliative medicine consult service into the HM unit serving patients with acute leukemias, multiple myeloma, lymphomas, MDS, and post bone marrow transplant patients. 2. Identify outcomes including clinician satisfaction and improvement in patient symptom control, goals of care discussions, and hospice referral created by the collaboration with palliative medicine. I. Background. There is little published data on the utility of palliative care (PC) consultation in HM inpatients. II. Research Objectives. We hypothesized that integrating PC consultants in the HM team would improve symptom control, frequency of goals of care (GOC) discussions, and hospice referrals. III. Methods. We assessed the HM team’s understanding of PC, gave PC lectures, held IDT meetings and daily PC rounds. Satisfaction surveys were administered 18 months into the PC program. Patients reported symptom intensity daily. GOC discussions and hospice enrollment were documented. IV. Results. August 2006eApril 2009, 282 PC consults were performed on HM patients for pain control (70%), GOC (46%), or other refractory symptoms. 14/18 (78%) HM physicians and 18/ 35 (51%) HM nurses completed satisfaction surveys. Mean ratings for ease of referral, communication, useful symptom management recommendations, and help with end-of-life (EOL) discussions were 4.8e5 (out of 5) for physicians and 4.3e4.4 for nurses. Helpfulness in addressing physical symptoms, delirium, psychosocial issues, EOL decision-making, family distress, and home care planning was 4.4e5 among physicians, and 4e4.5 among nurses. HM physicians and nurses agreed PC was extremely important to the care of their patients (mean 4.9 and 4.8). Eighty percent ofpatients reported pain acceptable or very acceptable within 48 hours of consultation. Non-pain symptoms of constipation, N/V, and dyspnea were well controlled within 48e72 hours; depression, delirium, and anxiety were not. PC consultants documented the first inpatient GOC conversations in 129 patients, ~70% of whom subsequently had a DNR entered. Fifty-three of 119 patients who died (44.5 %) were referred to hospice programs. V. Conclusion. HM patients receive intense therapy that bears witness to frequent patient/family suffering that a PC team can ameliorate. EOL decision-making and hospice referral are markedly enhanced. VI. Implications for Research, Policy, or Practice. PC plays a vital role on an HM unit.

Multi-organ failure due to Mycobacterium tuberculosis and Aspergillus flavus infection after allogeneic bone marrow transplantation

Mycobacterium tuberculosis (MT) is a serious, but rare infectious complication after allogeneic bone marrow transplantation (BMT). We describe a case of fatal sepsis due to MT and Aspergillus flavus after allogeneic BMT for Aplastic Anemia. The diagnosis was made on bone marrow biopsy and asitic fluid culture. Broadspectrum antituberculous and Amphotericin B therapy was started immediately after diagnosis. The patient developed severe hypoxia and finally died of multi-organ failure. Rapid progression of mycobacterial infection as well as fungal infection should be considered in patients post BMT with unexplained fever, particularly in patients from endemic areas.

Fibroblasts of Recipient Origin Contribute to Bronchiolitis Obliterans in Human Lung Transplants

The participation of circulating precursor cells in the development of experimental pulmonary fibrosing lesions in mice has been recently demonstrated. This study analyzes whether circulating, bone marrow-derived, fibroblastic precursor cells contribute to the development of fibrosing lesions in human lungs, especially bronchiolitis obliterans. The occurrence of in situ microchimerism in bronchiolitis obliterans lesions of human lung allografts (n = 12) as well as of autologous lung tissue from patients post-bone marrow transplantation (n = 2) was analyzed using laser-assisted microdissection after immunohistochemical labeling of leukocytes followed by short tandem repeat-polymerase chain reaction-based genotyping. Combined immunofluorescence and fluorescence in situ hybridization for sex chromosomes was performed for independent confirmation in cases with appropriate sex mismatch (n = 2). The bronchiolitis obliterans lesions of all 12 lung transplant patients contained considerable numbers of recipient-derived fibroblasts (mean, 32%). The fibrosing pulmonary lesions of the two bone marrow-transplanted patients also displayed clear in situ microchimerism. The in situ detection methodology confirmed these results, although to a lower degree (6-16%). These data clearly demonstrate the involvement of circulating fibroblastic precursor cells in the development of human fibrosing lung lesions and provide evidence that these cells are most probably bone marrow derived. These results may open new venues regarding the prevention of fibrosis in lung transplants and potentially in other organs.

CD4+CD25high T regulatory cells in SCID patients post-bone marrow transplantation (BMT)

CD4+CD25high T regulatory cells in SCID patients post-bone marrow transplantation (BMT)

Bloodstream infection surveillance in a cancer centre: a prospective look at clinical microbiology aspects

A prospective clinical and microbiological surveillance study was conducted during a 26-month period to evaluate consecutive malignancy or post-bone marrow transplant patients with positive blood cultures. The study included 859 episodes of bloodstream infection (BSI) in 719 patients. There were 6.9 BSI episodes/1000 patient-days. Overall mortality was 25%. The median age of patients was 43 years, with 71% of episodes occurring in patients aged > 18 years. Patients with underlying haematology malignancies accounted for 38.2% of the episodes. An indwelling central vein catheter was present in 61% of episodes. BSI origin was unknown in 27% of episodes, associated with other sites in 49.6%, and catheter-related in 23.4%. There were 638 concomitant infection sites, of which the most common were pulmonary (28.4%), urinary tract (14.8%), and non-surgical skin or soft tissue (9.7%). In total, 1039 microorganisms were isolated within 48 h of the first blood culture, of which Gram-negative bacilli accounted for 56%. Among Klebsiella pneumoniae and Escherichia coli isolates, 37.8% and 8.9%, respectively, produced extended-spectrum beta-lactamases. High rates of ceftazidime resistance were detected among Acinetobacter spp. (40%) and Enterobacter spp. (51.2%). E. coli and K. pneumoniae were isolated frequently from haematology patients, and Enterobacter spp. from solid tumour patients. E. coli, K. pneumoniae and Pseudomonas aeruginosa were isolated more often from neutropenic than from non-neutropenic patients. Oxacillin resistance was detected in 18.7% of Staphylococcus aureus isolates. It was concluded that continuous multidisciplinary surveillance of BSI is warranted in this high-risk group of patients in order to develop strategies for antimicrobial resistance control and treatment of infectious complications.

The effect of extracorporeal photopheresis on intracellular cytokine expression in chronic cutaneous graft‐versus‐host disease

Cytokines derived from T helper (Th)1 lymphocytes are thought to be involved in the pathogenesis of graft-versus-host disease (GVHD) and extracorporeal photopheresis (ECP) has been reported to affect Th1/Th2 lymphocyte ratios. It may also influence the balance of cytotoxic Tcells (Tc1/Tc2). This study was formulated to assess the effect of ECP on the cytokine profiles of peripheral blood (PB) lymphocytes from patients with chronic GVHD. Nine patients were studied. Peripheral blood was sampled at baseline and between 3 and 4 months of therapy when clinical effects are demonstrable. Intracellular cytokine production was assessed in vitro by stimulating PB lymphocytes with phorbol-12-myristate 13-acetate (PMA), inhibiting cytokine release and staining with fluorescein-labelled monoclonal antibodies to interleukin (IL)-2, interferon gamma (IFN-gamma) and IL-4. Flow cytometry analysis gave the absolute number and the percentage of cells expressing a particular cytokine within each lymphocyte subset. Absolute counts of CD3, CD4, CD8, CD19 and CD16+ cells per microlitre were recorded before and after ECP. There was a small but non-significant reduction in all subsets after 3 months of ECP. The percentage of cells expressing IL-2 and IFN-gamma rose following ECP in both the CD4 and CD8 subsets. However, only the percentage of CD4 cells expressing IFN-gamma reached statistical significance (P = 0.02; 95% confidence interval, CI 0.6-15.6). There were no significant changes in the percentage of CD4 cells expressing IL-4. Our findings appear to be inconsistent with current theories regarding the pathogenesis of GVHD as increased production of Th1 or Tc1 cytokines might be expected to exacerbate GVHD. However, chronic GVHD is characterized by a relative deficiency of IL-2 and IFN-gamma producing cells compared with other patients post-bone marrow transplantation (BMT). This indicates that Th1 and Tc1 cytokines are depleted in chronic GVHD. Thus, by reducing disease activity, ECP could allow cytokine production by these cells to recover. This indicates that the therapeutic effect of ECP is mediated by a different mechanism, and that the changes observed in this study are epiphenomena.