90Y-ibritumomab Tiuxetan in B-cell Non-Hodgkin Lymphomas: Real-world Data From the United Arab Emirates.

Purpose: B-cell non-Hodgkin lymphomas (NHLs) are significant contributors to cancer-related mortality. In this single-arm, retrospective cohort study, we aimed to examine the outcomes of a radioimmunotherapeutic modality, 90Y-labeled ibritumomab tiuxetan (90YIT) in B-cell NHLs. Methods and Materials: We conducted this study based on data from the United Arab Emirates lymphoma registry. All patients with NHL subjected to 90YIT were eligible for inclusion. The country of research lacked a national autologous stem cell transplantation (ASCT) center, but many ASCT-eligible patients received 90YIT. We investigated overall survival (OS) and event-free survival (EFS), as well as safety outcomes. Results: Between 2004 and 2008, 54 of 111 patients with B-cell NHL received radioimmunotherapy. The therapy was applied as first-line treatment in 18 cases (33.3%) and second- or later-line treatment in 36 cases (66.7%). All patients were evaluable for response. The first-line group consisted mainly of follicular lymphoma cases, and 3 of 18 patients died (16.7%) during the follow-up (range, 22-67 months). Median OS was not reached. No progression occurred after treatment (median EFS, 36.5 months [Q1-Q3 range, 30.5-44 months]). The second- or later-line group consisted mainly of diffuse large B-cell lymphoma cases, and 3 of 36 patients died (8.3%) during the follow-up (range, 4-68 months). Median OS was not reached. One case of progression was registered (median EFS: 33 months [Q1-Q3 range, 30.5-44 months]). 90YIT had acceptable short- and long-term safety profiles. Conclusions: The findings suggest that patients with NHL may benefit from 90YIT as salvage treatment if ASCT is not available; however, this should be validated in randomized studies.

Use of simulation in teaching haematological aspects to undergraduate medical students improves student's knowledge related to the taught theoretical underpinnings.

BACKGROUND: Simulation is an educational method which has several modalities and applications. In the last few decades Simulation-Based Medical Education (SBME) has become a significant influence in medical education. Despite the recognized potential of simulation to be used widely in support of healthcare education, there are no studies focused on the role of simulation in teaching haematology. Moreover, the reaction level is the most commonly reported in medical education. This study evaluates, at two levels of Kirkpatrick's model, the effectiveness of incorporating SBME in teaching haematological aspects to medical students. METHODS: A total of 84 second year medical students from two cohorts received theoretical components of Haematopoietic and Immune System in 4 credits course, delivered using lecture approach. First cohort students (n = 49) participated in interactive learning tutorials to discuss clinical vignettes. Second cohort (n = 35) students participated in simulation sessions where the tutorial's clinical vignettes were developed to clinical simulation scenarios conducted in the simulation centre. The potential influence of the simulation in learning enhancement was evaluated using Kirkpatrick's Evaluation Framework. RESULTS: The students rated the simulation sessions highly and found them to be a valuable learning experience. The category performance summary, generated by the assessment platform, demonstrates improvement in the student's knowledge enhanced by the SBME. CONCLUSIONS: Adaptation of SBME in teaching haematological aspects is a feasible way to improve the student's knowledge related to the taught theoretical foundations. SBME has the potential to enhance the undergraduate medical curriculum and it is expected, in the near future, to be an increasingly recommended educational strategy to bridge the gap between theory and practice.

Addressing the room for improvement in management of acute promyelocytic leukemia.

Acute promyelocytic leukemia (APL) is highly curable. To achieve high cure rates, targeted therapy with retinoic acid (ATRA) must be started promptly at time of suspected diagnosis. Early death rates (EDRs, ≤30 days from diagnosis) differ markedly in patients treated on clinical trials compared to the general population. OBJECTIVES AND METHODS: We used the comprehensive Danish National Acute Leukemia Registry (DNLR) to investigate the incidence, treatment, EDR, and long-term clinical outcome in APL between 2000 and 2014. RESULTS: Twenty-two of 41 deaths occurring in 122 APL patients were EDs which were primarily caused by intracranial hemorrhage, disseminated intravascular coagulation (DIC), sepsis, and multiorgan failure. The overall EDR was 18.0%, whereas clinical trial participants had an EDR of 6.7%. Fifteen patients recruited to the NCRI AML17 APL trial from 2010 to 2013 were younger and had decreased mortality (HR 0.18, CI 0.04-0.86, P = 0.02) compared to contemporarily treated patients (n = 15) not recruited to a clinical trial. Performance status, leukemia origin, and Sanz-score were independent prognostic variables. CONCLUSIONS: The very low EDR for on-trial patients is not observed in the general cohort of APL patients. Diagnostic awareness emerges as the greatest clinical challenge in management of APL.

Re-induction chemotherapy using FLAG-mitoxantrone for adult patients with relapsed acute leukemia: a single-center experience from United Arab Emirates.

We studied the outcome of 47 adult patients with relapsed acute leukaemia (AML = 25 and ALL = 22) treated with FLAG-mitoxantrone regimen. Median time to relapse was 10.7 months (range 1.9-27.7). Complete remission (CR2) was 60.1% which was significantly more frequent in ALL compared to AML (P = 0.049). WBC count < 100 × 109/L at initial diagnosis and time to relapse > 1 year were significantly predictor for CR2 in AML (P = 0.005 for both). Induction death was significantly higher in ALL compared to AML (P = 0.039). Median follow-up was 4.0 months (0.9-119.8) for AML and 2.1 months (range 0.6-118.1) for ALL. Nine patients underwent allogeneic stem-cell transplantation (allo-SCT). Estimated overall survival (OS) at 12 and 18 months was 60.5 and 34.6%, respectively, for AML, and 39.9 and 29.9%, respectively, for ALL. For AML patients failure to achieve CR, WBC count at initial diagnosis > 5 × 109/L and poor cytogenetic risk group was significant predictors of poor OS (P = 0.010, P = 0.025, and P = 0.015, respectively). For ALL patients failure to achieve of CR, WBC count at relapse < 5 × 109/L (CR patients) and lack of any type of consolidation therapy were significant predictor of poor OS (P < 0.001, P = 0.008, P = 0.008, respectively).

Cytokine Syntheses by T-Cell Subsets From Chronic Myeloid Leukemia Patients: Relationship Between Pre-Treatment Levels and Response to Imatinib Therapy.

BACKGROUND: Although T-cell cytokine's role in the long-term control of chronic myeloid leukemia (CML) is well established, previous studies showed contradicting results regarding imatinib (IM) effect on the endogenous T-cell function by IM. The purpose of this study was to determine the relation between the endogenous T-cell function prior to therapy and the degree of response to IM therapy in CP CML. In addition, modulation of the endogenous T-cell function during IM therapy was studied. METHODS: We evaluated Th1 (gamma interferon (IFN-γ)), Th2 (interleukin (IL-4)) and tumor necrosis factor (TNF)-α cytokine synthesis by activated T-cell subsets in 20 patients with newly diagnosed CML in chronic phase (CP CML) using flow cytometry before and during IM therapy compared to patients with IM resistance (IM Res) and healthy donors. RESULTS: Patients with optimal response (CML OR) to IM demonstrated a lower pre-treatment Th1 cytokine compared to that of healthy donors, and a higher percentage of Th2 and TNF-α producing T cells compared to that of healthy donors, non-optimal responders (CML nOR) and those with IM Res. A shift from Th2 profile to Th1 profile and initial decline of TNF-α producing T cells was detected early during therapy in optimal responders which was coinciding with complete hematological remission with a significant increase in the percentages of CD4+ve/IFN-γ+ve cells (P = 0.01) and a significant drop of in CD8+ve/IL-4+ve T cells (P = 0.04). CONCLUSION: We believe that pre-treatment levels of IL-4 and/or TNF-α may have a role in identifying CP CML patients who may respond to IM therapy; however, further investigation is needed.

Characteristics features and factors influencing early death in Acute promyelocytic leukemia; Experience from United Arab Emirates (UAE).

Although acute promyelocytic leukemia (APL) is a curable hematologic malignancy, early death (ED) remains a significant cause of treatment failure especially in developing countries. In a retrospective data analysis of 67 adult APL patients diagnosed in United Arab Emirates we report an ED rate of 11.9% which is comparable to that reported from more developed countries. We identified the following parameters at presentation as significant predictor of increased ED: Age >40 years (P = 0.015), fever (P = 0.030), WBC count >20 × 109/L (P = 0.010), the breakpoints other than bcr1 (P = 0.043) and fibrinogen level <1.5 g/L (P = 0.025). Delay in ATRA administration beyond 24 h from admission and fibrinogen <150 mg/dL were also significant predictors of ED, but only among high-risk patients (P = 0.035 and P = 0.033, respectively). WBC count >10 × 109/L and expression of HLA-DR (P = 0.018) or CD2 (P = 0.017) were significant predictors for differentiation syndrome (DS) which was found to be a predictor of ED (P = 0.002). Reducing the APL related ED rate in centers with limited resources is feasible provided early initiation of ATRA administration and early correction of coagulopathy in high-risk patients in addition to prompt treatment of DS. To our knowledge this is the first report from the Arabian Gulf describing ED in APL.

Outcome of patients with acute lymphoblastic leukemia (ALL) following induction therapy with a modified (pulsed dexamethasone rather than continuous prednisone) UKALL XII/ECOG E2993 protocol at Tawam Hospital, United Arab Emirates (UAE).

This retrospective data analysis examined the outcome of 99 acute lymphoblastic leukemia (ALL) patients treated at Tawam Hospital between January 2000 and December 2009. Sixteen patients were treated before June 2002, and 83 patients were treated from June 2002. A modified form of UKALL XII/ECOG E2993 with pulsed dexamethasone in induction phase one (modified UKALL) was the main therapy from June 2002 (71/83). The median age was 28 years. Fifty-eight percent had pre-B ALL where 36 % of them were Philadelphia chromosome-positive (Ph+). Overall, complete remission (CR) rate was 86.7 % which was significantly inferior for patients with white blood cell count 30-100 × 109/l (p = 0.009), therapy before June 2002 (p = 0.02), pregnancy (p = 0.005), CNS leukemia (p = 0.028), and unknown karyotype (p = 0.004). With a median follow-up of 11.8 months (0.49-126 months), the estimated overall survival (OS) and event-free survival (EFS) at 3 years were 50.6 and 28.7 %, respectively. OS and EFS were significantly inferior for patients not in CR after induction, age >20 years, Ph+, unknown karyotype and therapy before June 2002. In addition, CR, OS and EFS were significantly superior (p = 0.004, p < 0.001 and p = 0.001, respectively) for therapy with our modified UKALL protocol compared to Tawam protocol (main therapy before June 2002). In conclusion, the outcome of treatment for ALL at our institute is encouraging with significant improvement in the outcome of older adolescents and young adults when using high-intensity chemotherapy. This suggests that such an approach is feasible in developing countries in spite of some limitations including lack of stem cell transplantation service.

Reasons for treating secondary AML as de novo AML.

In a Danish bi-regional registry-based study, we conducted an analysis of the incidence and clinical importance of secondary acute myeloid leukaemia (AML). In a total of 630 cases of AML, we found 157 (25%) cases of secondary AML. The secondary leukaemia arose from MDS (myelodysplastic syndrome) in 77 cases (49%), CMPD (chronic myeloproliferative disorder) in 43 cases (27%) and was therapy-related AML (t-AML) in 37 cases (24%). Median age at diagnosis of AML was 69 yr in secondary cases when compared to 66 yr in de novo cases (P = 0.006). In univariate analyses, secondary AML was associated with an inferior complete remission (CR) rate (P = 0.008) and poorer overall survival (OS, P = 0.003) whereas in complete remitters, disease-free survival (DFS) of secondary cases was equal to that of de novo cases. Interestingly, in all further analyses of CR-rates, OS and DFS, when correcting for the influence of age, cytogenetic abnormalities, performance status and leucocyte count (WBC), presence of secondary AML completely lost prognostic significance. We conclude that the presence of secondary AML does not per se convey an unfavourable prognosis and that patients with secondary AML should be offered the chance of benefiting from treatment according to current frontline AML protocols.

[Microsurgical varicocele operation: a retrospective statement of Danish results]. / Mikrokirurgisk varicoceleoperation: en retrospektiv opgørelse af danske resultater.

INTRODUCTION: Varicoceles are present in about 15% of the male population. The treatment is surgical and internationally there has been an increase in the use of a subinguinal microsurgical approach in which the veins of the spermatic cord are ligated. The purpose of this paper is to evaluate the results of the first microsurgical varicocelectomies performed in Denmark. MATERIAL AND METHODS: The medical records of boys and men who underwent microsurgical varicocelectomy between 1 February 1999 and 1 June 2007 at Rigshospitalet, Gentofte Hospital and Herlev Hospital, were reviewed. RESULTS: A total of 132 patients were included in the study. Ten recurrences (8%) and ten complications (8%) were found (one lesion of the vas deferens, six haematomas, two hydroceles and one patient with haematoma/infection). Following surgery, two patients underwent orchiectomy due to a lack of blood flow and sustained pain from the scrotum one year after the operation, respectively. When pain was the indication for surgery, resolution of this symptom was seen in 69 of 77 patients (90%). In one patient, the pain increased. After the implementation of a structured surgery schedule and after assigning the procedure to a single surgeon only, the number of recurrences and complications for the last 47 operated patients decreased to 0% and 4%, respectively. CONCLUSION: In trained hands microsurgical varicocelectomy was an effective method with few complications and recurrences.

A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever.

A high intermittent dose regimen (group A: 10 mg kg(-1) on day 1, 5 mg kg(-1) on days 3 and 6) was compared with standard dosing (group B: 3 mg kg(-1) per day for 14 days) of liposomal amphotericin B (LAB) for empirical treatment of persistent febrile neutropenia. A total cumulative dose of 1275 mg (group A) and 2800 mg (group B) was administered. Infusion-related adverse drug events, mainly rigors/chills, occurred more frequently with group A (11/45, 24 % infusions) than with group B (12/201, 6 % infusions) (P=0.002), which extended the mean infusion time by 20 min (P=0.001). Creatinine levels were similar in the two regimens: the A : B ratio of the area under the curve for creatinine (AUC(CREATININE)) for days 2-7 was 1.09 (P=0.27) and for days 2-14 was 1.05 (P=0.51). Rises in creatinine were mild (clinical toxicity criteria 1) in all patients with elevations. Hypokalaemia tended to be less severe in group A with a lower proportion of hypokalaemic days [57/143 (39 %) vs 80/137 (58 %), P=0.21], a higher AUC(POTASSIUM) (A : B ratio of 1.06, P=0.12), a lower proportion of patients with hypokalaemia at the end of study (10 vs 61 %, P=0.01) and fewer potassium-supplemented days [12/210 (6 %) vs 41/210 (19.5 %), P<0.1]. There were mildly elevated median levels of serum bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, which were similar for the two regimens and were usually associated with other co-existing co-morbid conditions. The AUC for these enzymes was also similar in the two groups. No patient had discontinuation of the study drug due to toxicity. Composite success was identical for each regimen (11/15 patients, 73 %). Three of the fifteen patients in group B and none in group A developed invasive fungal infections (IFIs). Beta-D-Glucan levels were similar in both groups for patients without an IFI [AUC(GLUCAN) of 362 and 683 (P=0.36) for groups A and B, respectively]. The rate of defervescence was similar for each regimen (P=0.75). This feasibility study suggests that a short intermittent high-dose course of 10/5/5 mg LAB kg(-1) on days 1, 3 and 6 may be as safe and effective as a standard 14 day course of 3 mg kg(-1) per day, with drug-acquisition cost savings and reduced drug exposure. A larger study is indicated for confirmation of this.

Acute leukemia among the adult population of United Arab Emirates: an epidemiological study.

There is no published data regarding adult acute leukemia (AL) in the United Arab Emirates (UAE). Our objectives were to determine the distribution and incidence of adult AL in UAE (nationals and non-nationals). This epidemiological survey recovered 263 adult patients with AL diagnosed between January 2000 and December 2006 with a median age of 34 years. Twenty-four percent were UAE nationals and 63% were males. Acute lymphoblastic leukemia (ALL) was more frequently diagnosed (32%) than in western countries. This clearly reflects the population structure of the UAE which consists of predominantly young males. There is a tendency for lower crude and age-specific incidence rates of AL, acute myeloid leukemia (AML) and ALL in the UAE when compared with those in western countries. We found a statistically significant higher incidence of AML among national females than in national males (p = 0.04). This is reflected in a significantly higher incidence of AL (p = 0.02) and AML (p = 0.02) among the females when compared with the males in the total population of the UAE. This result contradicts the generally known finding that AML and ALL are more common in males. The implication of cumulative risk factors to which females could be exposed, such as vitamin D deficiency as a result of sunlight deprivation and direct exposure to benzene and color enhancement chemicals in henna, could not be excluded and warrant further investigation.

Prospective evaluation of mannan and anti-mannan antibodies for diagnosis of invasive Candida infections in patients with neutropenic fever.

The diagnostic performance and usefulness of the Platelia antigen and antibody test (Bio-Rad) was investigated in a prospective study of haematological patients at risk for invasive Candida infections. Among 100 patients, 86 were eligible, of whom invasive candidiasis (IC) occurred in 12 (14%), according to the criteria of the European Organization for Research and Treatment of Cancer/Mycoses Study Group. These included candidaemia due to Candida albicans (one patient) or Candida tropicalis (four patients), and hepatosplenic candidiasis (seven patients). The comparator group of 74 patients included 50 with febrile neutropenia alone and 24 with mould infections. A strategy was developed to determine diagnostic cut-offs from receiver operating characteristic curves with maximal sensitivity and, given this sensitivity, maximal specificity, both being greater than 0. In this patient population, these values were 0.25 ng ml(-1) for mannan (M) and 2.6 arbitrary units ml(-1) for anti-mannan (AM), which are lower than those recommended by the manufacturer. All patients developed at least one positive diagnostic M or AM result during the 10 days of persistent febrile neutropenia (PFN). The optimal overall performance was found when two consecutive positive tests for both M and AM were used [sensitivity, specificity, positive predictive value and negative predictive value (NPV) (95 % confidence intervals) of 0.73 (0.39-0.94), 0.80 (0.69-0.89), 0.36 (0.17-0.59) and 0.95 (0.86-0.99), respectively]. There was a positive correlation of M with beta-D-glucan (r=0.28, P=0.01). The first positive M test was found up to a mean+/-sd of 8.8+/-8.5 (range 2-23) days prior to a clinical/mycological diagnosis of IC. Day-to-day variation in quantitative M levels was high. High-level AM responses were delayed until leucopenia resolved. The low specificities of the test performance may have been due to some of the comparator patients having subclinical Candida infections as evidenced by the high incidence of colonization among them (60% had a colonization index of >or=0.5). The high NPVs suggest that the tests may be particularly useful in excluding IC. It is feasible to explore the use of serial measurements of M and AM as part of a broader diagnostic strategy for selecting PFN patients to receive antifungal drug therapy.

Assessment of the clinical utility of serial beta-D-glucan concentrations in patients with persistent neutropenic fever.

The performance of the Fungitell assay was investigated in 100 patients with haematological malignancy undergoing chemotherapy who developed antibiotic-unresponsive neutropenic fever (AUNF). Serum beta-D-glucan (BG) concentrations were significantly elevated on the first day of AUNF and all subsequent alternate days to day 10 in 38 patients who developed an invasive fungal infection (IFI) compared to 42 patients remaining free of such infections. The mean and median values of BG were 171.9+/-29.6 and 95.8 pg ml(-1), respectively, for patients with IFI and 64.4+/-17.1 and 32.9 pg ml(-1) for patients with only AUNF (P<0.0001). The differences remained significant over the 10 days despite antifungal therapy. The occurrence of > or =2 sequential concentrations of > or =80 pg ml(-1) ('positive' test) was found to give the best overall option for diagnosis, with an accuracy of 81.3%, sensitivity of 86.8%, positive predictive value of 76.7% and negative predictive value of 86.5%. Of the patients with an IFI, 78% developed a positive test at or before the clinical diagnosis was made -- this occurred at a mean (range) of 1.25 (-14 to +14) days prior to the IFI diagnosis. By starting sampling of blood from the first day of neutropenia rather than from the first day of AUNF, 50% of the patients with subsequent IFI would have been identified 5 days earlier. Increasing sampling to daily from alternate-day frequency did not further improve this earlier timing of an IFI diagnosis. A greater proportion of patients with persistent high levels of BG without overt IFI had severe enterocyte damage or mucositis than those with lower levels of BG without IFI (P=0.002). If the results of the initial BG test had been acted on to change antifungal therapy, discontinuation would have been inappropriate in 30% of patients and would have delayed definitive antifungal therapy. Although the findings for the cohort of patients studied are very useful, there is inter-patient variability in the test's performance. An holistic diagnostic approach is therefore necessary to interpret the test results optimally. Future studies should address this in further detail as well as the impact of empirical antifungal drug use and patient outcome.

Modeling of in vitro drug activity and prediction of clinical outcome in acute myeloid leukemia.

The objectives of this study were to develop a population pharmacodynamic model describing the in vitro drug sensitivity of tumor cells and to relate in vitro parameters to clinical outcome. Cell samples from 179 patients with acute myelocytic leukemia were exposed to cytosine arabinoside and daunorubicin, and cytotoxicity was analyzed using the fluorometric microculture cytotoxicity assay. A sigmoid E(max)-model for daunorubicin and an E(max)-model for cytosine arabinoside described the data. The model predicted drug potency (EC(50)) adequately from 1 concentration measurement. A logistic regression on individual in vitro parameters of 46 patients treated with the daunorubicin plus cytosine arabinoside regimen showed that the probability of complete response was significantly (P < .05) related to the product of the E(max)/EC(50) ratio of the two drugs. The findings demonstrate the value of population pharmacodynamic modeling of in vitro drug sensitivity data and a significant relationship between the in vitro parameters and clinical outcome.

Urinary calculi following traumatic spinal cord injury.

OBJECTIVE: To investigate the time aspect of the development of renal and bladder calculi in individuals with traumatic spinal cord injury (SCI) and a possible relation between the development of calculi and the bladder-emptying method. MATERIAL AND METHODS: The study comprised a retrospective data collection from medical records and a questionnaire follow-up at least 10 years after the SCI. RESULTS: A total of 236 individuals with SCI (82% male, 18% female; 47% tetraplegic, 53% paraplegic) who were injured between 1956 and 1990 participated in the study and the response rate was 84.6%. The mean age at the time of follow-up was 50.5 years (range 28-84 years). The mean duration from the time of SCI was 24.1 years (range 10-45 years). During follow-up 47 participants (20%) had at least one episode of renal calculi and 32 (14%) had at least one episode of bladder calculi. The risk of first renal and bladder calculus was highest within the first 6 months post-injury. The cumulative proportion of calculi-free participants 45 years post-injury was 62% for renal calculi and 85% for bladder calculi. For participants who did not develop renal calculi within the first 2 years post-injury, the risk of having a renal calculus within the next 43 years was 34%. For bladder calculi the corresponding risk of having a bladder calculus within the next 43 years was 5%. No significant differences were found regarding the bladder-emptying method and either renal or bladder calculi, only a non-significant trend that more participants with bladder calculi used indwelling catheters. Participants with renal or bladder calculi were not statistically significantly different from the remainder of the study group regarding gender, para- or tetraplegia or Frankel classification. CONCLUSIONS: The risk of developing renal and bladder calculi was higher in the SCI population compared to the normal population. Bladder calculi primarily occur early post-injury and renal calculi appear both early post-injury and years later. Therefore, it is important to follow individuals with SCI regularly by means of urological investigations from the time of the injury until death.

Strongyloides hyper-infection causing life-threatening gastrointestinal bleeding.

A 55-year old male patient was diagnosed with strongy-loides hyper-infection with stool analysis and intestinal biopsy shortly after his chemotherapy for myeloma. He was commenced on albendazole anthelmintic therapy. After initiation of the treatment he suffered life-threatening gastrointestinal (GI) bleeding. Repeated endoscopies showed diffuse multi-focal intestinal bleeding. The patient required huge amounts of red blood cells and plasma transfusions and correction of haemostasis with recombinant activated factor VII. Abdominal aorto-angiography showed numerous micro-aneurysms ('berry aneurysms') in the superior and inferior mesenteric arteries' territories. While the biopsy taken prior to the treatment with albendazole did not show evidence of vasculitis, the biopsy taken after initiation of therapy revealed leukoclastic aggregations around the vessels. These findings suggest that, in addition to direct destruction of the mucosa, vasculitis could be an important additive factor causing the massive GI bleeding during the anthelmintic treatment. This might result from substances released by the worms that have been killed with anthelmintic therapy. Current guidelines advise steroids to be tapered and stopped in case of systematic parasitic infections as they might reduce immunity and precipitate parasitic hyper-infection. In our opinion, steroid therapy might be of value in the management of strongyloides hyper-infection related vasculitis, in addition to the anthelmintic treatment. Indeed, steroid therapy of vasculitis with other means of supportive care resulted in cessation of the bleeding and recovery of the patient.

An open study of the comparative efficacy and safety of caspofungin and liposomal amphotericin B in treating invasive fungal infections or febrile neutropenia in patients with haematological malignancy.

In a clinical non-trial setting, the efficacy and safety of caspofungin was compared with liposomal amphotericin B for the management of febrile neutropenia or invasive fungal infections in 73 episodes in patients with haematological malignancy. There were fewer episodes of drug toxicity with caspofungin than liposomal amphotericin B (58.3 vs 83.7 %, P=0.02). The favourable response rate for episodes of febrile neutropenia treated with caspofungin or liposomal amphotericin B was similar at 37.5 and 53.8 %, respectively, but more breakthrough fungal infections occurred with caspofungin than with liposomal amphotericin B (33.3 vs 0 %, P<0.05) in these patients who did not receive antifungal prophylaxis. None of four episodes of candidaemia or hepatosplenic candidiasis responded to caspofungin compared with three of four episodes treated with liposomal amphotericin B. Mortality was significantly higher with caspofungin treatment compared with liposomal amphotericin B (6/24 vs 2/49, P=0.01), mainly due to an excess of fungal infections (P=0.04). Caspofungin treatment was a significant independent predictor of mortality [odds ratio=7.6 (95 % confidence interval 1.2-45.5)] when sepsis severity, prolonged neutropenia and length of antifungal therapy were considered in a multiple logistic regression model. In clinical practice, there is a suggestion that caspofungin may not be as effective as liposomal amphotericin B in preventing breakthrough invasive fungal infections in febrile neutropenia or in preventing fungus-related deaths. Because of the potential biases in this observational study, these preliminary findings should be interpreted with caution and clarified with a larger cohort of patients.

Modulation of the systemic inflammatory response by recombinant human interleukin-11: a prospective randomized placebo controlled clinical study in patients with hematological malignancy.

The immunomodulatory activities of recombinant human interleukin-11 (rhIL-11) were investigated in a clinical trial among patients with hematological malignancy, randomized to either rhIL-11 or placebo throughout chemotherapy. Daily serum concentrations of sTNFRI, IL-6, IL-8, TNFalpha, and CRP were measured. Higher sTNFRI levels [mean pg/ml (95% CI)] were detected in patients receiving rhIL-11 compared to placebo [1749.7 (1626-1882.9) versus 1038.5 (953.3-1131.3)] respectively (P = 0.01) for all 898 observations and during febrile days [2327.6 (2142.6-2528.2) versus 1308.9 (1163-1473.2), P = 0.12] and during days without infection [1406.6 (1266.1-1563) versus 871.3 (774.9-979.6), P < 0.001]. A similar pattern in CRP concentrations was observed. Multivariate analysis indicated rhIL-11 was associated with elevated sTNFRI or CRP independent of infectious episodes and other factors. 7 patients (all receiving placebo) of 40 had elevated TNFalpha levels. IL-6 and IL-8 levels were not substantially affected by rhIL-11. Bacteremia, fungal infections, and fever of unknown origin (FUO) were reduced in rhIL-11-treated patients. Given the role of sTNFRI in dampening the deleterious effects of a hyperactive TNFalpha environment, rhIL-11-induced upregulation of sTNFRI shedding is a potentially important mechanism for modulating immune and inflammatory responses in humans.

High serum concentration of YKL-40 is associated with short survival in patients with acute myeloid leukemia.

PURPOSE: YKL-40 is secreted by cancer cells, macrophages, and neutrophils. It may be a growth or differentiation factor, play a role in angiogenesis, or protect against apoptosis. High serum YKL-40 is associated with poor prognosis in solid carcinomas. The aim was to examine serum YKL-40 in patients with acute myeloid leukemia (AML). EXPERIMENTAL DESIGN: YKL-40 was measured by ELISA in serum from 77 patients recently diagnosed with AML before and during the first month of chemotherapy. RESULTS: Forty (52%) of the AML patients had elevated serum YKL-40 (compared with age-matched healthy subjects) and their survival was shorter than in patients with normal serum YKL-40 (median, 128 days; interquartile range, 18-629 days versus 386 days; interquartile range, 180-901; P=0.018 Mann-Whitney test). Univariate analysis of serum YKL-40 (logarithmically transformed and treated as a continuous covariate) showed significant association with survival within the first month after start of chemotherapy [hazard ratio (HR), 1.7; 95% confidence interval (CI), 1.2-2.4; P=0.002], first 12 months (HR, 1.6; 95% CI, 1.2-2.0; P=0.0002), and overall survival (HR, 1.3; 95% CI, 1.1-1.6; P=0.003). Multivariate Cox analysis showed that serum YKL-40 was an independent prognostic variable for survival (first month: HR, 1.7; P=0.011; 12 months: HR, 1.6; P=0.0002; overall survival: HR, 1.4; P=0.002). High serum YKL-40 at start of chemotherapy was a risk factor for pneumonia within the first month, and serum YKL-40 increased (P=0.002) at time of pneumonia and was unchanged in patients without infections. CONCLUSIONS: Serum YKL-40 is a prognostic biomarker of survival in AML patients. Its role in AML and infections needs to be determined.