Impact of Rituximab On the Treatment of Waldenström's Macroglobulinemia (WM).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2734-2734
Author(s):  
Sheeba K. Thomas ◽  
Kay B Delasalle ◽  
Jatin J. Shah ◽  
Luhua Wang ◽  
Robert Z. Orlowski ◽  
...  

Abstract Abstract 2734 Background: Rituximab was first approved by the FDA for use in relapsed and/or refractory low grade or follicular B cell non-Hodgkin's lymphoma in 11/1997. Since that time it has been widely used in WM, and is the backbone of drug combinations developed for treatment of this disease. Methods: To evaluate the impact of rituximab on overall survival (OS), we retrospectively evaluated patients (pts) treated at our center who received primary therapy for symptomatic WM with combinations of either alkylating agents (AA), nucleoside analogs (NA) +/− AA, or bortezomib (B), each with or without rituximab (R). The effect of primary therapy on OS was compared between patients receiving primary therapy before and after rituximab use for WM began at our center (11/11/1998). OS was calculated from the date of initial treatment until date of death or last follow-up. Due to small patient numbers, those who received vincristine-doxorubicin-dexamethasone (2 pts), single agent rituximab (3 pts), or rituximab-alkylating agent combinations (11 pts) as primary therapy, were excluded from the analysis. Results: Among 315 patients with previously untreated symptomatic WM treated since 3/1966, 118 received AA alone; 137 received NA +/− AA alone (85 pts) or with R (52 pts), and 44 received B + R. Median age, hemoglobin, platelet count and β2 microglobulin were comparable between all treatment groups (AA alone, NA +/− AA alone, NA +/− AA + R, B + R). Only median albumin differed significantly, with levels of 3.7 g/dL (AA alone), 4.1 g/dL (NA+/− AA alone), 4.3 g/dL (NA+/− AA + R) and 4.4 g/dL (B + R), respectively (p < 0.01). The median OS of pts treated with AA was 4.5 years, and 6.5 years with NA +/− AA, while the median OS of pts treated with NA+/− AA + R (median follow-up: 8 years) and B + R (median follow-up: 2.6 years) has not been reached. Comparing all patients treated with vs. without R, median OS is >13 years vs. 5.6 years (p<0.01). Conclusions: While pts with WM have most certainly benefitted from improvements in supportive care and the greater availability of salvage therapy options in the modern era, the addition of rituximab to available therapies appears to have significantly improved the OS of patients with WM compared with AA or NA +/− AA alone. Our data supports the role of rituximab as an indispensable component of modern therapy for this disease. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4383-4383
Author(s):  
Clayton B Hess ◽  
W. Christopher Ehmann

Abstract Abstract 4383 Here we describe a case of acute promyelocytic leukemia (APL) (M3 leukemia) which developed in a patient treated with single-agent fludarabine for lymphoplasmacytic lymphoma (Waldenstrom's macroglobulinemia [WM]). This 69-year-old male was diagnosed with WM in 2003. He received single-agent therapy with 4 cycles of fludarabine, after having an adverse reaction to his first and only dose of rituximab. Therapy was completed in 2007, with the patient in a complete remission. Two years later, he presented with leukocytosis and a consumptive coagulopathy. A bone marrow biopsy showed 90% abnormal promyelocytes with prominent Auer rods. PML/RARA fusion was positive by FISH. PCR was positive for t(15;17) (PML/RAR long (bcr1 and bcr2) and short (bcr3) form translocations. Cytogenetic studies showed abnormal 3q, monosomy 15 and 17, 2 unidentified marker chromosomes and a complex insertional translocation of chromosomes 15 and 17, with a PML/RARA fusion. The patient's APL was treated with ATRA and 7+ 3 chemotherapy because of a rising number of blasts in his peripheral blood. His subsequent clinical course was complicated by refractory atrial fibrillation, renal failure, a catheter-related upper-extremity deep venous thrombosis, and severe deconditioning. The patient died four months later from probable sepsis. A marrow performed two weeks prior to his death showed a complete hematologic remission, and no evidence of either Waldenstrom's or acute promyelocytic leukemia. There are forty-eight cases published of hematologic malignancies which occurred after single-agent nucleoside-analog treatment: none were APL. Twenty-four of these cases consisted of a lymphoid transformation to a more aggressive histology and twenty-four cases described development of a myeloid leukemia or myelodysplastic syndrome. In these patients, a variety of chromosomal changes were demonstrated with abnormalities of chromosome 7 being the most frequently observed (exclusively in those with myeloid disorders). There were no cases of a t(15;17) reported. We then reviewed all documented cases of therapy-related APL. No cases implicating nucleoside analogs were found. Topoisomerase inhibitors were the most common agents implicated as were radiation, anthracyclines, and alkylating agents. Because fludarabine was the only chemotherapy agent to which the patient was exposed, and the patient developed APL within the time frame expected for therapy-related leukemogenesis, we conclude that this is the first reported case of fludarabine-associated APL. Disclosures: No relevant conflicts of interest to declare.


2015 ◽  
Vol 123 (5) ◽  
pp. 1244-1246 ◽  
Author(s):  
Gentian Kaloshi ◽  
Ermir Roci ◽  
Arben Rroji ◽  
Francois Ducray ◽  
Mentor Petrela

OBJECT The aim of this study was to evaluate the impact of CCNU chemotherapy alone on low-grade glioma (LGG) growth dynamics. METHODS The authors measured the evolution of the mean tumor diameter (MTD) in adult patients with LGG before (n = 28 patients) and after (n = 38 patients) CCNU administration. RESULTS Natural (spontaneous) growth of LGG in the present study was 4.3 mm/year (range 2.1–6.6 mm/year). The median MTD decrease after CCNU was 5.1 mm/year (range 1–8.9 mm/year). MTD decrease was noted in 30 patients (late decrease in 4 patients, and ongoing decrease in 24 patients with oligodendroglial tumors and 2 with astrocytic tumors). The median duration it took for the MTD to decrease after initiation of CCNU treatment was 619 days (1038 days for oligodendroglial tumors vs 377 days for astrocytic tumors; p = 0.003). CONCLUSIONS These results show that CCNU as a single agent has a significant impact on LGG tumor growth. The impact of CCNU seems to be comparable to the previously reported impact of temozolomide therapy and of combined procarbazine, CCNU, and vincristine chemotherapy.


2005 ◽  
Vol 23 (22) ◽  
pp. 5061-5066 ◽  
Author(s):  
Michaël Lévy ◽  
Christiane Copie-Bergman ◽  
Christine Gameiro ◽  
Marie-Thérèse Chaumette ◽  
Marie-Hélène Delfau-Larue ◽  
...  

Purpose To determine the impact of translocation t(11;18) on response to oral alkylating agents in gastric mucosa-associated lymphoid tissue lymphoma (GML). Patients and Methods Fifty-three patients with a GML were studied. Helicobacter pylori--positive patients (n = 34) received anti–H pylori treatment and H pylori–negative patients (n = 19) or patients who failed to respond to anti–H pylori treatment received oral alkylating agents. t(11;18) was detected by reverse transcription polymerase chain reaction from frozen gastric biopsies. Results t(11;18) was detected in 32% of patients. It was more prevalent in H pylori--negative as compared with H pylori--positive patients (12 of 19 v five of 34 patients; P = .0005). Among 31 H pylori–eradicated patients, t(11;18) was detected in three patients, all of whom experienced treatment failure, and it was absent in 28 patients: 21 patients (75%) were in remission and seven patients (25%) experienced treatment failure (P = .03). Among 21 patients who received an alkylating agent, t(11;18) was detected in 12 patients: five patients (42%) were in remission and seven patients (58%) experienced treatment failure. t(11;18) was absent in nine patients: eight patients (89%) were in remission and one patient (11%) experienced treatment failure by the end of treatment. Four patients in remission relapsed during follow-up (median, 7 years): they all had t(11;18). Durable remission was obtained in eight (89%) of the nine patients without t(11;18) versus one of the 12 patients (8%) with t(11;18) (P = .0003). Conclusion Presence of t(11;18) in GML is predictive of resistance to oral alkylating agents, with less than 10% of durable remission at long-term follow-up.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Giulia Brigante ◽  
Giorgia Spaggiari ◽  
Barbara Rossi ◽  
Antonio Granata ◽  
Manuela Simoni ◽  
...  

AbstractTrying to manage the dramatic coronavirus disease 2019 (COVID-19) infection spread, many countries imposed national lockdown, radically changing the routinely life of humans worldwide. We hypothesized that both the pandemic per se and the consequent socio-psychological sequelae could constitute stressors for Italian population, potentially affecting the endocrine system. This study was designed to describe the effect of lockdown-related stress on the hypothalamic-pituitary-thyroid (HPT) axis in a cohort of young men. A prospective, observational clinical trial was carried out, including patients attending the male infertility outpatient clinic before and after the national lockdown for COVID-19 pandemic. The study provided a baseline visit performed before and a follow-up visit after the lockdown in 2020. During the follow-up visit, hormonal measurements, lifestyle habits and work management were recorded. Thirty-one male subjects were enrolled (mean age: 31.6 ± 6.0 years). TSH significantly decreased after lockdown (p = 0.015), whereas no significant changes were observed in the testosterone, luteinising hormone, follicle-stimulating hormone, estradiol and prolactin serum levels. No patient showed TSH serum levels above or below reference ranges, neither before nor after lockdown. Interestingly, TSH variation after lockdown was dependent on the working habit change during lockdown (p = 0.042). We described for the first time a TSH reduction after a stressful event in a prospective way, evaluating the HPT axis in the same population, before and after the national lockdown. This result reinforces the possible interconnection between psychological consequences of a stressful event and the endocrine regulation.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1760
Author(s):  
Novella Pugliese ◽  
Marco Picardi ◽  
Roberta Della Pepa ◽  
Claudia Giordano ◽  
Francesco Muriano ◽  
...  

Background: Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare variant of HL that accounts for 5% of all HL cases. The expression of CD20 on neoplastic lymphocytes provides a suitable target for novel treatments based on Rituximab. Due to its rarity, consolidated and widely accepted treatment guidelines are still lacking for this disease. Methods: Between 1 December 2007 and 28 February 2018, sixteen consecutive newly diagnosed adult patients with NLPHL received Rituximab (induction ± maintenance)-based therapy, according to the baseline risk of German Hodgkin Study Group prognostic score system. The treatment efficacy and safety of the Rituximab-group were compared to those of a historical cohort of 12 patients with NLPHL who received Doxorubicin, Bleomycin, Vinblastine, Dacarbazine (ABVD) chemotherapy followed by radiotherapy (RT), if needed, according to a similar baseline risk. The primary outcome was progression-free survival (PFS) and secondary outcomes were overall survival (OS) and side-effects (according to the Common Terminology Criteria for Adverse Events, v4.03). Results: After a 7-year follow-up (range, 1–11 years), PFS was 100% for patients treated with the Rituximab-containing regimen versus 66% for patients of the historical cohort (p = 0.036). Four patients in the latter group showed insufficient response to therapy. The PFS for early favorable and early unfavorable NLPHLs was similar between treatment groups, while a better PFS was recorded for advanced-stages treated with the Rituximab-containing regimen. The OS was similar for the two treatment groups. Short- and long-term side-effects were more frequently observed in the historical cohort. Grade ≥3 neutropenia was more frequent in the historical cohort compared with the Rituximab-group (58.3% vs. 18.7%, respectively; p = 0.03). Long-term non-hematological toxicities were observed more frequently in the historical cohort. Conclusion: Our results confirm the value of Rituximab in NLPHL therapy and show that Rituximab (single-agent) induction and maintenance in a limited-stage, or Rituximab with ABVD only in the presence of risk factors, give excellent results while sparing cytotoxic agent- and/or RT-related damage. Furthermore, Rituximab inclusion in advanced-stage therapeutic strategy seems to improve PFS compared to conventional chemo-radiotherapy.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 429.2-429
Author(s):  
L. Hu ◽  
X. Ji ◽  
F. Huang

Background:Obesity population are rising rapidly and have become a major health issue. Studies have shown that obesity is a low-grade inflammatory status characterized by increase in proinflammatory cytokines.Objectives:To examine the impact of overweight or obesity on disease activity and treatment responses to biologics in patients with ankylosing spondylitis (AS) in a real-world setting.Methods:Body mass index (BMI) is available in 1013 patients from the Chinese Ankylosing Spondylitis Imaging Cohort (CASPIC). Differences in clinical outcomes (such as BASDAI, ASDAS, BASFI, and ASAS HI) and treatment responses to biologics (ΔBASDAI and ΔASDAS) over 3, 6, 9, and 12 months are assessed between BMI categories (normal weight BMI <24 kg/m2; overweight BMI=24-28 kg/m2; obesity BMI ≥28 kg/m2) using Kruskal-Wallis test. The association between BMI and clinical characteristics and treatment responses to biologics was determined, and multivariate median regression analyses were conducted to adjust for confounders (such as age, gender, smoke, and HLA-B27).Results:Among 1013 patients with AS, overweight accounts for 33%, while obesity for 12.4%. There were significant differences between patients who were obese or overweight and those with a normal weight regarding clinical outcomes (BASDAI: 2.90/2.56 vs 2.21; ASDAS-CRP: 2.20/1.99 vs 1.81; BASFI: 2.13/1.69 vs 1.38; ASAS HI: 6.87/5.29 vs 5.12 and BASMI: 2.35/1.76 vs 1.62; all P<0.05). After adjusting for age, gender, smoke, and HLA-B27, obesity remained associated with higher disease activity (BASDAI: β=0.55, P=0.005; ASDAS-CRP: β=0.40, P<0.001), poorer functional capacity (BASFI: β=0.58, P=0.001), worse health index (ASAS HI: β=1.92, P<0.001) and metrology index (BASMI: β=0.71, P=0.013). For TNFi users, BMI was found to be negatively correlated with changes in disease activity (ΔBASDAI and ΔASDAS) in the multivariate regression model (all P<0.05), and overweight and obese patients showed an unsatisfactory reduction in disease activity during 3-month, 6-month, 9-month, and 12-month follow-up period, compared to normal weight patients (all P<0.05).Conclusion:Overweight or obesity impacts greatly on clinical outcomes and treatment responses to biologics in patients with ankylosing spondylitis, which argues strongly for obesity management to become central to prevention and treatment strategies in patients with AS.References:[1]Maachi M, Pieroni L, Bruckert E, et al. Systemic low-grade inflammation is related to both circulating and adipose tissue TNFalpha, leptin and IL-6 levels in obese women. Int J Obes Relat Metab Disord 2004;28:993–7.Figure 1.Changes of disease activity for TNFi users during 3-, 6-, 9- and 12-month follow-up according to BMI categories. a: vs. normal weight, P<0.05 in 3 months; b: vs. normal weight, P<0.05 in 6 months; c: vs. normal weight, P<0.05 in 9 months; d: vs. normal weight, P<0.05 in 12 months.Acknowledgments:We appreciate the contribution of the present or former members of the CASPIC study group.Disclosure of Interests:None declared


Vascular ◽  
2020 ◽  
pp. 170853812098369
Author(s):  
Stefano Fazzini ◽  
Giovanni Torsello ◽  
Martin Austermann ◽  
Efthymios Beropoulis ◽  
Roberta Munaò ◽  
...  

Objectives The results of branched endovascular repair of thoracoabdominal aneurysms are mainly dependent on durability of the graft used. The purpose of this study was to evaluate postoperative aortic main body and bridging stent-graft remodeling, and their impact on bridging stent-graft instability at one year. Methods Computed tomoangiographies of 43 patients (43 aortic main body mated with 171 bridging stent-grafts) were analyzed before and after branched endovascular repair as well as after a follow-up of 12 months. Primary endpoint was aortic main body remodeling (migration >5 mm, shortening >5 mm, scoliosis >5° or lordosis >5°). Shortening was defined as a reduced length in the long axis, scoliosis as left-right curvature, and lordosis as antero-posterior curvature. Aortic main body remodeling, aneurysm sac changes, and bridging stent-graft tortuosity were evaluated to study their correlations and the impact on the bridging stent-graft instability. Results At 12 months, aortic main body remodeling was observed in 72% of the cases, migration in 39.5% (mean 5.21 mm), shortening in 41.9% (mean 5.79 mm), scoliosis in 58.1%, (mean 10.10°), lordosis in 44.2% (mean 5.78°). Migration, shortening, and scoliosis were more frequent in patients with larger aneurysms ( p = .005), while scoliosis was significantly more frequent in type II thoracoabdominal aneurysm ( p = .019). Aortic main body remodeling was significantly associated to bridging stent-graft remodeling (r: 0.3–0.48). The bridging stent-graft instability rate was 9.3%. Despite a trend toward significance ( p = .07), none of the evaluated aortic main body and bridging stent-graft changes were associated with bridging stent-graft instability at 12 months. Conclusions Aortic main body remodeling is frequent especially in large and extended thoracoabdominal aneurysm aneurysms. Aortic main body and bridging stent-graft remodeling was significantly correlated. While these geometric changes had no significant impact on bridging stent-graft instability at one year, a close long-term follow-up after branched endovascular repair could predict bridging stent-graft failures.


2021 ◽  
Vol 108 (Supplement_7) ◽  
Author(s):  
Hannah Elkadi ◽  
Eleanor Dodd ◽  
Theodore Poulton ◽  
William Bolton ◽  
Joshua Burke ◽  
...  

Abstract Aims Despite being the most common surgical procedure, there is wide variation that exists in the management of simple subcutaneous abscesses with no national guideline describing best practice. During the COVID-19 Pandemic national guidelines promoted the use of regional or local anaesthetic (LA) instead of general anaesthesia (GA) to avoid aerosol generating intubation associated with GA. This study aimed to assess the impact of anaesthetic choice in outcomes following incision and drainage of subcutaneous abscesses. Methods Two cohorts of patients undergoing abscess incision and drainage at St. James’ University Hospital Leeds were retrospectively identified over a 14-week period before and after the introduction of the new COVID-19 anaesthetic guidelines. Wound healing surrogate endpoints were used: i) total number of follow up appointments and ii) attendance to healthcare services after 30 days from I&D. Result 133 patients were included. Significantly more procedures were performed under LA after the intervention (84.1% vs 5.7%; p &lt; 0.0001) with a significant reduction in wound packing (68.3% vs 87.1%. p=0.00473). Follow up data found no significant difference in the average number of follow-up appointments (7.46 vs 5.11; p = 0.0731) and the number of patients who required ongoing treatment after 30 days (n = 14 vs n = 14, p = 0.921). Conclusion Drainage of simple subcutaneous abscess under 5 cm is safe under local anaesthetic with no significant difference in surrogate endpoints of wound healing observed in this patient cohort. Recurrent packing may not be required. Future work should explore patient reported measures such as pain management and the health economics of this intervention.


Author(s):  
Caitlin R. Semsarian ◽  
Gabrielle Rigney ◽  
Peter A. Cistulli ◽  
Yu Sun Bin

University students consistently report poor sleep. We conducted a before-and-after study to evaluate the impact of an online 10-week course on undergraduate students’ sleep knowledge, attitudes, and behaviours at 6-month follow-up. Data were collected via baseline course surveys (August–September 2020) and follow-up surveys distributed via email (February–March 2021). n = 212 students completed baseline surveys and n = 75 (35%) completed follow-up. Students retained to follow-up possessed higher baseline sleep knowledge and received higher course grades. At the 6-month follow-up, sleep knowledge had increased (mean score out of 5: 3.0 vs. 4.2, p < 0.001). At baseline, 85% of students aimed to increase their sleep knowledge and 83% aimed to improve their sleep. At follow-up, 91% reported being more knowledgeable and 37% reported improved sleep. A novel Stages of Change item revealed that 53% of students’ attitudes towards their sleep behaviours had changed from baseline. There was a reduction in sleep latency at follow-up (mean 33.3 vs. 25.6 min, p = 0.015), but no change in the total Pittsburgh Sleep Quality Index score. In summary, completion of an online course led to increased sleep and circadian knowledge and changed sleep attitudes, with no meaningful change in sleep behaviours. Future interventions should consider components of behavioural change that go beyond the knowledge–attitudes–behaviour continuum.


2003 ◽  
Vol 48 (2) ◽  
pp. 43-45 ◽  
Author(s):  
E F Shen ◽  
S Gladstone ◽  
G Milne ◽  
S Paterson-Brown ◽  
I D Penman

Management of columnar lined oesophagus (CLO; Barrett s oesophagus) is controversial. We prospectively audited surveillance practices in Scotland and prospectively assessed the impact of introducing local guidelines for Barrett s surveillance in Edinburgh. Most respondents were gastroenterologists. The majority take random, not four quadrant, biopsies from the CLO. In Edinburgh during 2000, 80 patients underwent surveillance. The guideline protocol was not followed in 30 (37.5%) patients. Follow up of patients without dysplasia generally conformed to the guidelines. Follow up of patients with low grade dysplasia was highly variable while management of those with high grade dysplasia followed the guidelines. Overall we found a wide variability in the management and surveillance of CLO. Early experience suggests that implementation of guidelines is helpful but there is still variation in practice.


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