Didem Uzunaslan

Dendritic cell sarcoma: A pooled analysis including 462 cases with presentation of our case series

Dendritic cell tumors are extremely rare and current knowledge on these tumors is limited. The characteristics of three dendritic cell sarcoma subtypes and their optimal treatment approaches are not fully clarified. We aimed to make a systematic review of the literature and enrich the current data with five new cases. Pooled analysis of 462 reported cases revealed that the tumor had no age, gender or racial predilection. Our analysis suggests that the young age, advanced stage, intraabdominal involvement and unfavorable histological features (i.e. large tumor size, absence of lymphoplasmacytic infiltration, coagulative necrosis, high mitotic count) may predict poor prognosis. Subtypes of this tumor have different clinical behaviors with interdigitating dendritic cell sarcoma being the most aggressive form. In general, surgery is the most effective treatment modality and adjuvant radiotherapy has no significant effect on overall survival of patients. The role of chemotherapy for the management of advanced disease is controversial.

Expression of MMP-1, MMP-9 and TIMP-2 in prostate carcinoma and their influence on prognosis and survival

PurposeMatrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) participate in tumorigenesis, and their association with disease outcome is highly controversial. The present study investigates the influence of MMP-1, MMP-9 and TIMP-2 on different clinicopathologic variables and disease-free survival (DFS) of patients with prostate carcinoma.MethodsHundred and forty-five cases are included in the study, and levels of MMP/TIMP expressions are assessed in three tissue compartments (i.e., tumor, stroma and normal glands) with immunohistochemistry.ResultsMatrix metalloproteinase-1 expression in tumor cells was associated with lower Gleason scores, pretreatment prostate-specific antigen levels and lower incidence of vascular, perineural and extracapsular invasions. Moreover, MMP-9 positivity and TIMP-2 expression in normal glands were correlated with lower Gleason patterns and early stage at presentation. Expression of MMP in tumor cells and the presence of TIMP-2 in normal glands were associated with better DFS.ConclusionVariability of MMP/TIMP expressions from case to case makes it difficult to evaluate their impact on clinical outcome. However, these proteins might be new and promising targets for prostate cancer therapy in the future.

No appreciable decrease in fertility in Behçet’s syndrome

OBJECTIVES Behçets syndrome (BS) follows an active course during the childbearing years in both men and women. We formally surveyed the infertility rate and the effect of drugs and types of organ involvement on fertility in BS. METHODS We compared fertility among BS patients with and without major organ involvement with those with FMF, AS and healthy controls. A structured interview was performed and the medical records of the patients were reviewed to confirm the sites of involvement and drugs they used during their entire follow-up. RESULTS The number of female patients who were not able to ever conceive, who were not able to conceive before or after disease onset or who were able to conceive late or only with assisted reproductive technology was not increased among the BS group. The same was true for the male patients to successfully achieve a conception and/or father a child. The average number of children, miscarriages, terminations and ectopic pregnancies were similar among the groups. Infertility was more common in BS patients with major organ involvement who used cyclophosphamide (CYC) compared with those who did not (P = 0.009). CONCLUSION Infertility is not appreciably increased among BS patients attending a dedicated outpatient clinic. Major organ involvement does not increase the risk of infertility and CYC is the only drug that seems to compromise fertility in BS.

A 17-year experience with ALL-BFM protocol in acute lymphoblastic leukemia: prognostic predictors and interruptions during protocol.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and despite the intense combination chemotherapy, cure rates are less than 90%. Several prognostic parameters, including nonneoplastic hematologic cell counts during induction phase, are suggested to predict outcome in ALL. We analyzed 242 ALL patients treated in our center to investigate individual prognostic parameters and the impact of delays on disease outcome. Age at diagnosis, risk groups, extramedullary involvement, t(9;22), prednisone response, bone marrow response at days 15 and 33, day 15 platelet count, day 33 lymphocyte, monocyte, and platelet counts, treatment delay, sepsis, and omission of day 64 cyclophosphamide were valuable predictors of survival in univariate analysis. However only the age, CNS involvement, omission of cyclophosphamide, and total delay during treatment were associated with survival in multivariate analysis. Omission of second cyclophosphamide dose had no impact on survival of standard risk group patients, but adversely affected the long term survival of medium risk group (MRG) patients. The second dose might be given with the first dose on day 36 to MRG patients to prevent delays. Day 15 and 33 platelet counts are promising predictors of survival in low income countries where assessment of minimal residual disease is difficult, but this data needs further consolidation.

ANTINEUTROPHIL CYTOPLASMIC ANTIBODY-ASSOCIATED NEUTROPENIA IN A PATIENT WITH TYPE 1 DIABETES MELLITUS

Case report: Our case is a 37-year old male, who admitted to hospital several times with infections accompanying neutropenia. On his last admission, he had fever, chills, abdominal pain, nausea, vomiting and diarrhea. He had been treated with an insulin regimen for six years, but HbA1C level was 8.4%. Further investigation revealed high CRP (23 mg/L) and ESR (30 mm/h), positive RF (16.7; normal range 0-15) and C-ANCA levels. Whole body CT scan failed to identify a lesion and he received 15-day tazobactam antibiotherapy. Filgrastim (G-CSF) was given, but neutrophil counts did not respond and we switched to steroid therapy. Symptoms got better, neutrophil counts rised gradually and antibiotherapy was stopped. Due to the potential side effects of steroids and abnormal blood sugar levels, we started intravenous immunoglobulin (IVIG) therapy (400mg/kg/day-monthly) with moderate doses of prednisolone.

A2.7 Concomitant transverse myelitis and guillain-barre syndrome after adalimumab therapy in a case with ankylosing spondylitis

Background The introduction of TNF inhibitors into clinical practice has revolutionalised the treatment of most inflammatory diseases. However, these drugs are associated with various and potentially serious side effects. Despite being rare, demyelinating neuroinflammatory disordes including multiple sclerosis, optic neuritis, transverse myelitis, polyradiculoneuropathy, and Guillain-Barre Syndrome (GBS) have been reported after using anti-TNF drugs, particularly with infliximab. Adalimumab is a newer fully humanised monoclonal anti-TNF antibody and to date, transverse myelitis during the course of adalimumab treatment has never been reported. Herein, we describe a patient who received adalimumab for management of his ankylosing spondylitis (AS) and developed synchronous transverse myelitis and GBS after therapy. Case Report A 69-year old male with a 30-year history of AS, was admitted to neurology clinic with lower extremity weakness. Physical examination revealed bilateral 5/5 and 0/5 motor strengths in upper and lower extremities, respectively. He did not have sphincteric or sensorial deficits, cerebellar symptoms, or aphasia. He had received adalimumab treatment for 8 months (40 mg subcutaneously every 2 weeks) which controlled his refractory AS symptoms, but the patient had stopped taking the drug 3 months before the onset of his symptoms. MRI showed increased signal intensity at distal spinal cord which supported the diagnosis of myelitis. After one week course of pulse steroids, the patient responded well and gained full strength. One month later, he presented again with bilateral lower extremity weakness and falls, and physical examination showed full strength in upper extremity and muscle strength was 2/5 on right and 0/5 on left lower extremity. He had hypotonia and hyporeflexia on the right and areflexia on the left lower extremity. Repeated MRI scan showed regressed spinal lesion, lumbar puncture revealed elevated protein levels (107 mg/dL) and EMG was compatible with GBS. The patient received intravenous immunoglobulin and showed gradual improvement in lower extremity muscle strength. Conclusion Central and peripheral progressive demyelinating neuroinflammatory lesions might occur during anti-TNF treatment, with the latter being more common than central nervous system involvement. There are a few reports indicating an association between adalimumab and GBS in patients with rheumatoid arthritis, but synchronous occurence of transverse myelitis and GBS is so unusual, and both diseases responded well to standard measures.

FRI0364 Fertility in behçet’s syndrome: structured interview in a multidisciplinary center

Background Behçet’s Syndrome (BS) follows an active course during the child-bearing years in both men and women. Whether fertility is decreased among the BS patients due to the condition itself or to the frequently used medications like cyclophosphamide (CYC), azathioprine or colchicine is not clear. Objectives To determine the infertility rate, and the effect of drugs and types of organ involvement on fertility in BS patients. Methods We included BS patients with and without major organ involvement, familial Mediterranean fever (FMF), ankylosing spondylitis (AS) patients and healthy controls recruited from hospital staff. In order to show a 20% increase in infertility in BS with 0.05 alpha and 80% power, we calculated that each group should contain at least 125 individuals. Among patients who visited the clinic for routine controls, individuals with an even waiting list number were selected. A structured interview was performed by two physicians and medical records were reviewed. Infertility was defined as the inability to conceive after one year of unprotected intercourse. We compared the differences in the proportion of individuals who had never conceived in their lifetime, who had a successful conception but became infertile after disease onset, and individuals who conceived late or with assisted reproductive technology (ART), between BS and control groups. Finally infertility was separately assessed in a group of 62 patients who had used CYC and was compared to that observed among patients with major organ involvement who were CYC naïve. Multivariate logistic regression analysis was used to determine the association of infertility with involved organs and the drugs which were used. Results The numbers of subjects who were not able to ever conceive, who were not able to conceive only after disease onset, and who were able to conceive late or only with ART were not increased among patients with BS (Table). There were more FMF patients who conceived late or only with ART. Average number of children, miscarriages, terminations and ectopic pregnancies were not significantly different in patients with BS. The number of infants with reported congenital anomalies was not increased in BS patients and the most commonly reported anomalies were cardiovascular defects and cleft lip/palate. Univariate logistic regression showed an increased risk of infertility with CYC (OR 6.1, %95 CI 0.7-54.2), however this effect was not confirmed in multivariate analysis. This was attributed to a type II error caused by the low number of patients who had used CYC. Finally the infertility was higher among the separate group of 62 CYC users as compared to the patients with major organ disease who were CYC naive (7/20 vs 3/60 among those who atttempted to conceive, p=0.002) Conclusions Infertility rate is not appreciably increased among BS patients as compared to FMF patients, AS patients and healthy controls. Major organ involvement does not seem to affect this. CYC is the only drug which seems to decrease fertility in BS. Disclosure of Interest: None Declared