A Rare Case of Sezary Syndrome Cutaneous T-Cell Lymphoma with Complete Response

Cutaneous T cell lymphoma is one of non-Hodgkin’s lymphoma. Several types of cutaneous T-cell lymphoma exist. The most common type is mycosis fungoides. Sezary syndrome is a less common type that causes skin redness over the entire body. The common symptoms of Sezary syndrome are erythroderma, leukemia with circulating mononuclear cells having convoluted nuclei and lymph node enlargement due to infiltration by similar cells. Lymphoma starts in the lymphocytes, or the cells in the immune system that are normally found in the lymphatic system. If lymphocytes start growing out of control, they can build up and form a cancerous collection of cells in the skin that can lead to lymphoma. Patients with skin lymphoma might experience a variety of vague or unusual symptoms, including: 1. Peeled skin 2. Rash, which sometimes can itch 3. Mushroom-like skin lesions 4. Swollen lymph nodes, or painless lumps, in the skin 5. Unexplained fevers and weight loss Skin lymphoma usually is well behaved and doesn’t spread throughout the body. However, it has the potential to do so in approximately 15 to 20 percent of cases. At the specialized skin lymphoma clinic at UT Southwestern, we offer a range of treatment options to effectively beat the two specific types of skin lymphoma and their various subtypes [1-4]. Sezary syndrome is an aggressive form of cutaneous T-cell lymphoma which is a group of disorders that occur when T-cells (a type of white blood cell) become cancerous and affect the skin. It is characterized by a widespread red rash that may cover most of the body, the presence of cancerous T cells (called Sezary cells) in the blood, and abnormally enlarged lymph nodes. Other signs and symptoms may include intense itchiness, scaling and peeling of the skin; fever; weight loss; hair loss; outward turning of the eyelids (ectropion); palmoplantar keratoderma; malformation of the nails; and hepatosplenomegaly. The exact cause of Sezary syndrome is currently unknown. Treatment varies based on the signs and symptoms present in each person and the severity of the condition. Prognosis: The long-term outlook (prognosis) for people with Sezary syndrome is generally poor. Sezary syndrome is difficult to cure. Treatment is usually palliative, with the intention of relief of symptoms and improvement in the quality of life. Median survival for patients with Sezary syndrome has been reported to be 2 to 4 years after development of the condition, although survival has improved with newer treatments. The disease-specific 5-year survival rate has been reported to be 24%. We present 1 case of Sezary syndrome which happened in our hospital with complete response

Using Telemedicine for Providing Supportive and Palliative Care Patients with Advanced Cancer During The COVID‐19 Pandemic in Ukraine

COVID‐19 has overwhelmed the capacity of health care systems, limiting access to supportive and palliative care for patients with advanced cancer. Telemedicine has emerged as a tool to provide care continuity to patients while limiting the risk of contagion. However, implementing telemedicine in resource‐limited settings is challenging. We report the results of a multidisciplinary patient‐navigator‐led telemedicine supportive care program in Dnipro City. One‐hundred sixty‐five telemedicine interventions were provided to 50 patients (median age 67, 47% female). A quarter of the patients had less than or equal to elementary school education, and 18% lived in a rural area. The most com-mon interventions were psychological care (30%), pain and symptom control (27%), and nutritional counseling (10%). Half of the interventions were pro-vided by video conferencing. The most common patient‐reported barrier was limited experience using communication technology. Our results demonstrate the feasibility of providing supportive and palliative care interventions using telemedicine in resource‐limited settings

Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer

BACKGROUND The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced breast cancer. We report the results of a prespecified analysis of overall survival. METHODS We randomly assigned patients with hormone-receptor–positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety. RESULTS Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib– fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo–fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16% of the patients in the placebo–fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib–fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo–fulvestrant group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib– fulvestrant group, as compared with 8.8 months in the placebo–fulvestrant group (hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up. CONCLUSIONS Among patients with hormone-receptor–positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib–fulvestrant resulted in longer overall survival than treatment with placebo– fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135.

Results of Molecular Monitoring in Posttransplant Period by Means of Series Investigation of WT1 Gene Expression in Patients with Acute Myeloid Leukemia

Aim. To demonstrate diagnostic and prognostic significance of series measurement of WT1 expression in patients with acute myeloid leukemia (AML) after allogenic hematopoietic stem cell transplantation (allo-HSCT). Materials & Methods. The clinical trial included 88 AML patients (38 females (43 %) and 50 males (57 %) aged 2–68, median 30 years). All the patients received allo-HSCT. Bone marrow was aspirated before (D0) and after HSCT (D+30, D+60, and D+100). Results. The univariate analysis showed statistically significant differences in 2-year overall survival with respect to the following factors: with and without remission at the moment of HSCT (p 250 copies before HSCT (p < 0.001) and at time points D+60 (p = 0.012), and D+100 (p < 0.001). Multivariate analysis revealed similar statistical significance of differences among patients transplanted in remission (p = 0.041) and with cGVHD (p = 0.03). In univariate analysis statistically significant differences in 2-year event-free survival (EFS) were found: a) in patients with allo-HSCT, either in remission or not (p < 0.001); b) using HSC, but not bone marrow, as transplant source (p < 0.026); c) with normal or high WT1 expression at the stage of HSCT (p < 0.001) and at time point D+100 (p < 0.001); d) using HSC from related or unrelated donor (p = 0.006); e) in patients with cGVHD (p = 0.05). In multivariate analysis independent positive effect on EFS was observed only in patients with normal WT1 expression at D+100 (p = 0.011) and with cGVHD (p = 0.038). Cumulative incidence of posttransplant relapse (PTR) in AML patients with normal or high WT1 expression at the stage of HSCT within the 2-year follow-up was significantly different (28.2 vs. 58.9 %; p = 0.002), also in measurements of this parameter at D+60 and D+100 (p = 0.015 and p < 0.001, respectively). In 1/4 of patients cytological relapses (cPTR) appeared considerably later than molecular relapses (mPTR), i.e. 13–489 days later (median 35 days), which is accounted for by early preventive therapy aimed at cPTR prophylaxis against the background of already recorded mPTR. According to our data, GVHD plays a crucial role in cPTR management. Conclusion. Phenomenon of WT1 expression normalization after allo-HSCT in AML patients proves to have a high diagnostic and prognostic significance. Introduction of this approach into clinical practice seems highly advisable for national oncohematological centers

Bevacizumab plus paclitaxel versus placebo plus paclitaxel as first-line therapy for HER2-negative metastatic breast cancer (MERiDiAN): A double-blind placebo-controlled randomised phase III trial with prospective biomarker evaluation

Aim: MERiDiAN evaluated plasma vascular endothelial growth factor-A (pVEGF-A) prospectively as a predictive biomarker for bevacizumab efficacy in metastatic breast cancer (mBC). Methods: In this double-blind placebo-controlled randomised phase III trial, eligible patients had HER2-negative mBC previously untreated with chemotherapy. pVEGF-A was measured before randomisation to paclitaxel 90 mg/m2 on days 1, 8 and 15 with either placebo or bevacizumab 10 mg/kg on days 1 and 15, repeated every 4 weeks until disease progression, unacceptable toxicity or consent withdrawal. Stratification factors were baseline pVEGF-A, prior adjuvant chemotherapy, hormone receptor status and geographic region. Co-primary endpoints were investigator-assessed progression-free survival (PFS) in the intent-to-treat and pVEGF-Ahigh populations. Results: Of 481 patients randomised (242 placeboepaclitaxel; 239 bevacizumabepaclitaxel), 471 received study treatment. The stratified PFS hazard ratio was 0.68 (99% confidence interval, 0.51e0.91; log-rank p Z 0.0007) in the intent-to-treat population (median 8.8 months with placeboepaclitaxel versus 11.0 months with bevacizumabepaclitaxel) and 0.64 (96% con-fidence interval, 0.47e0.88; log-rank p Z 0.0038) in the pVEGF-Ahigh subgroup. The PFS treatment-by-VEGF-A interaction p value (secondary end-point) was 0.4619. Bevacizumab was associated with increased incidences of bleeding (all grades: 45% versus 27% with placebo), neutropenia (all grades: 39% versus 29%; grade 3: 25% versus 13%) and hypertension (all grades: 31% versus 13%; grade 3: 11% versus 4%). Conclusion: The significant PFS improvement with bevacizumab is consistent with previous placebo-controlled first-line trials in mBC. Results do not support using baseline pVEGF-A to identify patients benefitting most from bevacizumab. Clinical trials registration: ClinicalTrials.gov NCT01663727

Overall Survival with Palbociclib and Fulvestrant in Advanced Breast Cancer.

Background The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib, in combination with fulvestrant therapy, prolongs progression-free survival among patients with hormone-receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. We report the results of a prespecified analysis of overall survival.Methods We randomly assigned patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had progression or relapse during previous endocrine therapy to receive palbociclib plus fulvestrant or placebo plus fulvestrant. We analyzed overall survival; the effect of palbociclib according to the prespecified stratification factors of presence or absence of sensitivity to endocrine therapy, presence or absence of visceral metastatic disease, and menopausal status; the efficacy of subsequent therapies after disease progression; and safety.Results Among 521 patients who underwent randomization, the median overall survival was 34.9 months (95% confidence interval [CI], 28.8 to 40.0) in the palbociclib-fulvestrant group and 28.0 months (95% CI, 23.6 to 34.6) in the placebo-fulvestrant group (hazard ratio for death, 0.81; 95% CI, 0.64 to 1.03; P=0.09; absolute difference, 6.9 months). CDK4/6 inhibitor treatment after the completion of the trial regimen occurred in 16% of the patients in the placebo-fulvestrant group. Among 410 patients with sensitivity to previous endocrine therapy, the median overall survival was 39.7 months (95% CI, 34.8 to 45.7) in the palbociclib-fulvestrant group and 29.7 months (95% CI, 23.8 to 37.9) in the placebo-fulvestrant group (hazard ratio, 0.72; 95% CI, 0.55 to 0.94; absolute difference, 10.0 months). The median duration of subsequent therapy was similar in the two groups, and the median time to the receipt of chemotherapy was 17.6 months in the palbociclib-fulvestrant group, as compared with 8.8 months in the placebo-fulvestrant group (hazard ratio, 0.58; 95% CI, 0.47 to 0.73; P<0.001). No new safety signals were observed with 44.8 months of follow-up.Conclusions Among patients with hormone-receptor-positive, HER2-negative advanced breast cancer who had sensitivity to previous endocrine therapy, treatment with palbociclib-fulvestrant resulted in longer overall survival than treatment with placebo-fulvestrant. The differences in overall survival in the entire trial group were not significant. (Funded by Pfizer; PALOMA-3 ClinicalTrials.gov number, NCT01942135 .)

Overall survival (OS) with palbociclib plus fulvestrant in women with hormone receptor-positive (HR1), human epidermal growth factor receptor 2-negative (HER22) advanced breast cancer (ABC): Analyses from PALOMA-3

Background: Endocrine therapy (ET)–resistant ABC is dependent on cyclin dependent kinase (CDK) 4/6. In the prospective, randomized, double-blind, phase 3 PALOMA-3 study, the CDK4/6 inhibitor PAL in combination with FUL significantly improved progression-free survival (PFS) vs placebo (PBO)þFUL (median PFS, 11.2 vs 4.6 mo; absolute difference, 6.6 mo; hazard ratio [HR] 0.50 [95% CI, 0.40–0.62]; P < 0.000001). Here, we report OS analysis with a median follow up of 44.8 mo. Methods: HRþ/HER2– ABC (N ¼ 521) patients (pts) who had relapsed or progressed on prior ET were randomized 2:1 to PAL (125 mg/d orally, schedule 3/1) þ FUL (500 mg per standard of care) or PBOþFUL. Primary endpoint was investigator-assessed PF

Efficacy of Chemotherapy in Acute Leukemia Patients Resistant to Previous Standard Treatment According to the Series Measurement of WT1 Gene Expression

Aim. To estimate the efficacy of chemotherapy in acute leukemia patients resistant to previous standard treatment according to the series measurement of WT1 expression. Materials & Methods. The series measurement of WT1 expression formed the basis of the efficacy estimation of induction chemotherapy in 31 patients (15 men and 16 women aged from 3 months to 68 years; the median age was 28 years) with prognostically unfavourable variants of acute myeloid (AML) and lymphoblastic leukemia (ALL) (23 AML and 8 ALL patients). The WT1 gene expression was measured at baseline and 2–3 weeks after the treatment by the quantitative real-time PCR. The threshold level for detection was 250 copies of WT1/104 copies of ABL. The cytogenetic profile of leukemia cells was assessed by standard cytogenetics and FISH. Results. The baseline expression level of WT1 varied from 305 to 58,569 copies/104 copies of ABL. The expected reduction of WT1 expression after the first induction chemotherapy treatment was reported in 22/23 (96 %) AML patients and in 6/8 (75 %) ALL patients. According to our results WT1 expression reached the threshold in 13/31 (42 %) patients, including 9 AML patients and 4 ALL patients. After 11/31 (35 %) patients received the second course of treatment, WT1 expression level became normal in 8 cases (5 ALL and 3 AML patients). Despite high dose chemotherapy, HSCT and such agents as blinatumomab and gemtuzumab, an unfavourable outcome was observed in 18/31 (58 %) patients including 6 patients with complex karyotype (CK+) and 2 patients with monosomal karyotype (MK+). Once the MK+ and CK+ combination was observed, in another case the MK+ was combined with the prognostically unfavourable inv(3)(q21q26) inversion. Conclusion. Our results show that the molecular monitoring should be included as part of treatment of the prognostically unfavourable acute leukemia. The WT1 gene was shown to be the most appropriate marker. WT1 expression was shown to correlate with the common fusion genes allowing to estimate the blast cell count at the molecular level

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration