Natural killer (NK) cells can orchestrate effective antitumor immunity. The presence of tumor-infiltrating NK cells in diagnostic biopsies predicts pathologic complete response (pCR) to HER2-specific therapeutic antibodies in patients with primary breast cancer. Here, we analyzed whether diversity in circulating NK cells might influence tumor infiltration and HER2-specific therapeutic antibody efficacy. We found that numbers of circulating CD57 þ NK cells inversely correlated with pCR to HER2-specific antibody treatment in patients with primary breast cancer independently of age, traditional clinicopathologic factors, and CD16A 158F/V genotype. This association was uncoupled from the expression of other NK-cell receptors, the presence of adaptive NK cells, or changes in major T-cell subsets, reminiscent of cytomegalovirus-induced immunomodula-tion. NK-cell activation against trastuzumab-coated HER2 þ breast cancer cells was comparable in patients with high and low proportions of CD57 þ NK cells. However, circulating CD57 þ NK cells displayed decreased CXCR3 expression and CD16A-induced IL2-dependent proliferation in vitro. Presence of CD57 þ NK cells was reduced in breast tumorassociated infiltrates as compared with paired peripheral blood samples, suggesting deficient homing, proliferation, and/or survival of NK cells in the tumor niche. Indeed, numbers of circulating CD57 þ were inversely related to tumor-infiltrating NK-cell numbers. Our data reveal that NK-cell differentiation influences their antitumor potential and that CD57 þ NK cells may be a biomarker useful for tailoring HER2 antibody-based therapeutic strategies in breast cancer.
BackgroundAplastic anaemia comes from a bone marrow failure which affects all blood lineages. Treatment is based on immunosuppression or allogeneic transplant, but some patients are refractory to these options. Eltrombopag, a thrombopoietin receptor agonist administered orally, promotes megakaryopoiesis and platelet release.PurposeTo assess eltrombopag effectiveness as off-label treatment for immunosuppression-refractory aplastic anaemia.Material and methodsA 10-month (1/12/2013–30/09/2014) retrospective study was carried out including immunosuppression-refractory aplastic anaemia patients who weren’t allotransplantation candidates. After approval by the Regional Committee for drug use under Special Circumstances, each patient received different eltrombopag doses. In order to assess the effect, data were gathered from platelet count at baseline and subsequently, considering the response positive when the platelet count increased enough to avoid transfusion. Clinical data were obtained from the patient’s history and from Outpatient records.ResultsWe recovered data from two patients (male, aged 26 and 34) diagnosed with aplastic anaemia refractory to anti-thymocyte globulin, ciclosporin and high-dose steroids. Neither of them were candidates for allotransplantation. Initial dose was 50 mg/day, causing a platelet count increase of 7 and 272 mill/mm3 after three weeks. Then, doses were modified according to current response to an average of 6.25 mg/day, reaching counts of 5–125 mill/mm3 (average 44.33 mill/mm3) in one patient and 1–553 mill/m3 (average 139.76 mill/mm3) in the other. The average treatment length was 6.75 months. Those results are similar, even better, to the ones shown in a phase-II study (Olnes et al, 2012) involving 25 patients with the same diagnosis and dose (response in 44%, average increase 44.0 mill/mm3, nine of them transfusion independent).ConclusionBoth patients reached platelet counts higher than 100 mill/mm3, avoiding transfusions and their associated risks, with an improvement in their quality of life. Because of the unavailability of other treatments for this kind of patients, the off-label use of eltrombopag is a promising alternative when there’s little chance of cure.References and/or acknowledgementsNo conflict of interest.
Background Axillary hyperhidrosis is based on a continuous, symmetric sweating of axillae that often leads to emotional distress and occupational disability. It affects 0.6–1% of younger people in the western world. When topical treatment doesn’t relieve the sweating, surgical botulinum toxin treatment, which prevents calcium-dependent acetylcholine release from the sympathetic sweat glands, is an attractive alternative to ganglion sympathectomy. Last year, fifteen patients took this treatment in the Thoracic Surgery service of our hospital. Purpose To investigate how the quality of life changes after botulinum toxin surgery in axillary hyperhidrosis patients, as a way to qualitatively assess its effect. Materials and methods Patient information was collected from our hospital databases. In October 2013, using a standardised dermatological life-quality questionnaire (DLQI, Finlay & Khan), we asked patients ten questions by phone covering their emotional, clinical, interpersonal and work issues before and after surgery. Finally, we performed a Shapiro-Wilk test (normality) on SPSS and a paired Student’s t-test (comparing means). Results Data were gathered from ten patients (seven women, average age of 35.4 ± 6.69). For six of them, the disease started in childhood; and for the remaining four after puberty or in their early twenties. All of them had tried aluminium-based products, with no results. Using a scale of 30 points (the higher the score, the worse the quality of life), the average score decreased by 16 ± 2.82 points (p-value < 0.001, from 19.4 before surgery to 3.4 after). This reduction was marked in all issues considered except for interpersonal relationships (positive opinion before and after). All but one mentioned a significant decrease in sweating, which now only happens when practicing sports. Conclusions Despite the effect only lasting for about six months, botulinum toxin surgery clearly improves quality of life in axillary hyperhidrosis patients, who are satisfied with the intervention and were keen to repeat it when the effect disappears. No conflict of interest.
BackgroundEnzalutamide, an androgen receptor inhibitor administered orally, is approved for use in metastatic prostate cancer refractory to castration, when disease progresses during docetaxel treatment or after finishing it.PurposeTo describe the results of using enzalutamide in terms of effectiveness and safety.Material and methodsWe conducted a retrospective study over eleven months (1/10/2014–30/09/2014), including every patient being treated with enzalutamide. Age, disease stage, previous treatment lines, enzalutamide start date and adverse effects were gathered from the patient’s clinical history and our Farmatools outpatient records module. In order to assess enzalutamide effectiveness, baseline and end-of-study prostatic specific antigen (PSA) levels were measured to calculate percentage PSA decrease; a response higher than 50% was considered positive.ResultsWe gathered data from five patients (average age 67.8 years, 80 maximum and 61 minimum), all diagnosed with stage IV (bone metastases) prostate cancer, refractory to chemical castration and docetaxel chemotherapy. Before starting, all of them received abiraterone (1 g, average treatment length 5.8 months). Average enzalutamide dose was 160 mg. Three patients experienced a PSA decrease of greater than 50% compared to baseline (95.2% maximum), while the remaining two dropped out of treatment because of ineffectiveness. Average length of enzalutamide treatment was 5 months. With regard to safety and adverse events, diarrhoea and asthenia were found in one patient, improving after a 25% dose reduction for 2.5 months, returning to the original dose after complete recovery.ConclusionIn this study, enzalutamide showed a response rate and safety profile similar to those observed in clinical trials and other available clinical evidence resources.References and/or AcknowledgementsNo conflict of interest.
BackgroundDespite using steroid premedication before administering potentially highly allergenic chemotherapy (taxanes, platinum drugs, biological macromolecules, etc.), some patients get sensitised during the first cycles and tend to develop hypersensitivity reactions. This leads to early treatment interruption, which could be critical for the patient’s outcome. Once identified, the allergen may be re-administered under a desensitisation protocol, inducing a tolerance state in which the patient doesn’t react again. During each session, the whole dose is administered starting at a very low infusion rate, which is periodically increased until the regular rate is achieved. Patients with a positive skin test, severe reaction despite negative test, and those who react again during controlled administration are candidates for desensitisation.PurposeTo describe the management and outcomes of patients who reacted to chemotherapy, and how oncologists changed their prescriptions to available options.Material and methodsWe carried out a retrospective study (period 2011–2014), obtaining data from patients’ clinical histories and chemotherapy records. SPSS20 was used for data coding and statistical processing.ResultsSixteen patients (81.2% female, average 62.9 ± 7.3 years, diagnosed with ovarian cancer) experienced mild (9), moderate (3) or severe (4) hypersensitivity reactions to chemotherapy (68.8% platinum drugs). Five patients had a positive skin test; only three were enrolled on desensitisation programmes, the remaining two switched treatment line. Two patients had a severe reaction but a negative test, one of them was enrolled and the other switched treatment. The remaining nine (negative test, mild-moderate reaction) didn’t experience a second reaction during controlled infusions, so they kept the same treatment; just one reacted and was proposed for the programme. Four desensitisations were carried without incident, the remaining one had to be stopped due to a reaction when the infusion reached the top rate during the first session.ConclusionDesensitisation, provided by Drug Allergy and Hospital Pharmacy departments, allows standard treatment lines to be continued, modifying oncologists’ decisions and improving patient outcomes.References and/or AcknowledgementsNo conflict of interest.
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