scholarly journals Rituximab in Remission Induction and Maintenance Therapy for Microscopic Polyangiitis Associated with Gastric Cancer: A Case Report

2021 ◽  
Author(s):  
Takafumi Aritomi ◽  
Masao Nawata ◽  
Aya Nawata ◽  
Yoshihisa Himeno ◽  
Kazuyoshi Saito ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Maintenance Therapy ◽  
Microscopic Polyangiitis ◽  
Early Stage ◽  
High Titer ◽  
Immunosuppressive Agents ◽  
Remission Induction ◽  
Upper Gastrointestinal Endoscopy ◽  
High Dose ◽  
Protein Levels

Abstract We herein report a case of a patient with gastric cancer-associated microscopic polyangiitis (MPA) who was treated with combination glucocorticoids and rituximab (RTX) for remission induction and maintenance, and finally to discontinue glucocorticoids without recurrence of gastric cancer or MPA in a year. A 69-year-old man was suspected of having MPA because of fever, high C-reactive protein levels, neuritis, and a high titer of myeloperoxidase-anti-neutrophil cytoplasmic antibody (MPO-ANCA). Upper gastrointestinal endoscopy indicated early-stage gastric cancer, for which he underwent surgery preceded by immunosuppressive therapy for vasculitis. Histopathological images showed vasculitis in the vicinity of the cancerous tissue, suggesting an association between gastric cancer and vasculitis. Postoperatively, fever and inflammatory response improved, but MPO-ANCA increased further and the patient developed alveolar hemorrhage. He resulted in remission with high-dose glucocorticoids and RTX, and he received maintenance therapy with RTX without additional immunosuppressive agents. After 1 year of treatment, he was able to discontinue glucocorticoids without recurrence of gastric cancer or vasculitis. There is no established treatment for malignancy-associated vasculitis other than glucocorticoids. Although more cases need to be accumulated in the future, RTX is expected to be useful in malignancy-associated vasculitis.

Risk Factors Associated with Relapse in Japanese Patients with Microscopic Polyangiitis

2011 ◽  
Vol 39 (3) ◽  
pp. 545-551 ◽  
Author(s):  
TAKASHI WADA ◽  
AKINORI HARA ◽  
YOSHIHIRO ARIMURA ◽  
KEN-EI SADA ◽  
HIROFUMI MAKINO ◽  
...  
Keyword(s):  
Risk Factors ◽  
Maintenance Therapy ◽  
Regression Coefficient ◽  
Microscopic Polyangiitis ◽  
Damage Index ◽  
Reduction Rate ◽  
European Medicines Agency ◽  
Remission Induction ◽  
Factors Associated ◽  
Cell Counts

Objective.We retrospectively studied the risk factors associated with relapse during remission maintenance therapy for myeloperoxidase-antineutrophil cytoplasmic autoantibody (MPO-ANCA)-positive microscopic polyangiitis (MPA).Methods.Sixty-two patients diagnosed with MPA according to the European Medicines Agency classification algorithm during a 2-year period from January 1, 2005, to December 31, 2006, and who achieved remission after the first remission-induction therapy, were examined (registration no. UMIN000001785).Results.The patient group comprised 25 men and 37 women aged 70.0 ± 8.9 years. The mean observation period was 30.2 ± 15.9 months. The rate of relapse was 24.2% (15/62), and mean interval between remission and relapse was 16.9 ± 13.5 months. During maintenance therapy following remission, the risk of relapse increased when the reduction rate of prednisolone increased above 0.8 mg/month (OR 12.6, 95% CI 2.2–97.9). Proteinuria at the start of maintenance therapy (regression coefficient 1.991 ± 0.758, p < 0.05) and the change in red blood cell counts in urine during the period from the start of maintenance therapy to the final observation (regression coefficient 0.126 ± 0.040, p < 0.01) were identified as risk factors influencing the vasculitis damage index.Conclusion.In Japan, relapse of MPO-ANCA-positive MPA may be associated with the reduction rate of oral prednisolone administration during maintenance therapy.

Sorafenib Is Contributing to Salvage Chemotherapy and Is Effective Given Alone for Maintenance in AML FLT3 ITD Patients Relapsing Post Allo Hematopoietic Stem Cell Transplantation

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5265-5265 ◽  
Author(s):  
Emilia Jaskula ◽  
Janusz Lange ◽  
Mariola Sedzimirska ◽  
Andrzej Lange
Keyword(s):  
Maintenance Therapy ◽  
Low Dose ◽  
Liver Toxicity ◽  
Conflicts Of Interest ◽  
Normal Karyotype ◽  
Salvage Chemotherapy ◽  
Remission Induction ◽  
Comparative Genomic ◽  
High Dose ◽  
Hematopoietic Stem

Abstract Normal karyotype AML patients with FLT3 ITD have a higher risk of relapse than those lacking this mutation (Estey EH, Am J Hematol. 2013). Our comparative genomic hybridization study (77 patients) showed that AML cases with as compared to those without FLT3 ITD had significantly lower number of amplifications or deletions (number of total CNV aberrations: 18±4 vs 51±8, p=0.003). The latter observation in concert with that of others (Thiede, Blood 2002) suggest that FLT3 ITD mutation if present in normal karyotype patients is a key player in the pathogenesis of leukaemia and targeting this mutation may be used successfully in FLT3 ITD positive patients relapsing post HSCT. This was also the case in the two patients presented in this study. Patient UPN 952, male, 53 years old, AML M4 (FAB), normal karyotype, received alloHSCT in 2 CR after completion of two lines of remission induction therapies (first: DA3+7 (Daunorubicin, Ara-C), HAM, high dose Ara-C; second: ICE (IDA, Ara-C, VP-16)) and then promptly transplanted. He relapsed 56 days after transplantation. Patient UPN 938, female, 50 years old, AML, normal karyotype, received as an induction DA 3+7, and for consolidation HAM and high dose Ara-C and completed only one course of the maintenance therapy and transplanted in CR. Both cases were transplanted from unrelated donors (10/10 HLA A, B, C, DR and DQ alleles matched), they received myeloablative conditioning (i.v. Busulfan and Cyclophosphamide) and Cyclosporin A as GvHD prophylaxis. At relapse they received salvage chemotherapy tailored to their biological performance (UPN 938 having Age Adjusted Charlson Comorbidity Index 3 received FLAG and UPN 952 with the index 9, ECOG 3, DA2+5). Both cases received in addition Sorafenib (two times 400 mg per day). The response was prompt and the marrow was free from blasts beginning from 11 day post chemotherapy. UPN 952 received as a maintenance only one course of 6-TG with low dose of Ara-C. Due to the substantial comorbidity and liver toxicity WHO3 further chemotherapy treatment was terminated. The patient was left only on Sorafenib (2 times 200 mg per day). UPN 938 was receiving the maintenance therapy (AML protocol) in 6 – 8 weeks intervals based on low dose Ara-C with 6TG or DNR and also Sorafenib (2 times 200 mg per day). In both cases FLT3 signalling pathway (FLT3 Pathway Mutation PCR Array, SABiosciences, Qiagen) revealed a lack of any additional mutation at the check points in FLT3, KRAS, HRAS, NRAS, MEK1, PIK3CA, BRAF and PTEN genes. UPN 938 had in addition to FLT3 ITD mutation c.1807_1808insATGAATATGATCTCAAAT (p.K602_W603insYEYDLK) insertion which relevance was not so far describe. Sorafenib resistance mutations were not found. The patients were on Sorafenib for 8 (UPN 938) and 9 months (UPN 952). The course of UPN938 was uncomplicated. The second case showed mild aGvHD symptoms evolving into cGvHD (skin lesions and dry eye) slowed down with rapamicine. Up to now the patients are in CR and free from FLT3 ITD. The main observation points: - Sorafenib with chemotherapy tailored to the biologic performance of patients contributes to the efficient salvage in patients with relapsing FLT3 ITD positive AML post HSCT and is also effective given alone as a maintenance. - Side effects were seen in one out of two patients likely associated with the blocking of VEGFR signalling transmission (hand foot skin rash, von Willebrandt factor activity – 388%). Conclusion: The use of multikinase inhibitor (Sorafenib) contributes effectively to salvage therapy in FLT3+ AML patients relapsing post alloHSCTSorafenib given alone is able to maintain long-lasting remissionSide effects are individually dependent Supported by NBiR CellsTherpy grant and Byer Health Care Disclosures No relevant conflicts of interest to declare.

scholarly journals Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer

Cancers ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 789
Author(s):  
Eizaburou Hideura ◽  
Yutaka Suehiro ◽  
Jun Nishikawa ◽  
Takuya Shuto ◽  
Hiroyuki Fujimura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Gastric Cancer ◽  
Early Stage ◽  
False Negative ◽  
Digital Pcr ◽  
Median Number ◽  
Small Sample ◽  
Upper Gastrointestinal Endoscopy ◽  
Dna Testing ◽  
Diagnostic Strategies

The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer.

scholarly journals High Dose Intravenous Vitamin C for Preventing The Disease Aggravation of Moderate COVID-19 Pneumonia. A Retrospective Propensity Matched Before-After Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Bing Zhao ◽  
Min Liu ◽  
Ping Liu ◽  
Yibing Peng ◽  
Jun Huang ◽  
...  
Keyword(s):  
Vitamin C ◽  
Inflammatory Response ◽  
Early Stage ◽  
Treatment Options ◽  
Control Group ◽  
High Dose ◽  
Protein Levels ◽  
Number Of Patients ◽  
Significant Difference ◽  
Intravenous Vitamin

Background: Coronavirus disease 2019 (COVID-19) pandemic is continuing to impact multiple countries worldwide and effective treatment options are still being developed. In this study, we investigate the potential of high-dose intravenous vitamin C (HDIVC) in the prevention of moderate COVID-19 disease aggravation.Methods: In this retrospective before-after case-matched clinical study, we compare the outcome and clinical courses of patients with moderate COVID-19 patients who were treated with an HDIVC protocol (intravenous injection of vitamin C, 100 mg/kg/day, 1 g/h, for 7 days from admission) during a one-month period (between March 18 and april 18, 2020, HDIVC group) with a control group treated without the HDIVC protocol during the preceding two months (January 18 to March 18, 2020). Patients in the two groups were matched in a 1:1 ratio according to age and gender.Results: The HDIVC and control groups each comprised 55 patients. For the primary outcomes, there was a significant difference in the number of patients that evolved from moderate to severe type between the two groups (HDIVC: 4/55 vs. control: 12/55, relative risk [RR] = 0.28 [0.08, 0.93], P = 0.03). Compared to the control group, there was a shorter duration of systemic inflammatory response syndrome (SIRS) (P = 0.0004) during the first week and lower SIRS occurrence (2/21 vs 10/22, P = 0.0086) on Day 7 (6–7 days after admission). In addition, HDIVC group had lower C-reactive protein levels (P = 0.005) and higher number of CD4+ T cells from Day 0 (on admission) to Day 7 (P = 0.04).” The levels of coagulation indicators, including activated partial thromboplastin time and D-dimer were also improved in the HDIVC compared to the control group on Day 7.Conclusion: HDIVC may be beneficial in limiting disease aggravation in the early stage of COVID-19 pneumonia, which may be related to its improvements on the inflammatory response, immune function and coagulation function. Further randomized controlled trials are required to augment these findings.

P0410SIGNIFICANT BURDEN OF DISEASE DURING MAINTENANCE TREATMENT OF ANCA-ASSOCIATED VASCULITIS (AAV) PATIENTS IN REAL WORLD PRACTICE IN EUROPE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Peter Rutherford ◽  
Dieter Götte
Keyword(s):  
Adverse Events ◽  
Maintenance Therapy ◽  
Induction Therapy ◽  
Remission Induction ◽  
Induction Treatment ◽  
High Dose ◽  
Full Remission ◽  
Anca Associated Vasculitis ◽  
Active Disease

Abstract Background and Aims ANCA associated vasculitis (AAV) is a relapsing remitting long term condition and patients are at risk of organ damage from both active AAV and its therapy in particular high dose and/or prolonged glucocorticoids (GC). The remission maintenance phase of AAV is critical for good long term outcomes including renal preservation as well as preventing AAV relapse. This retrospective study aimed to examine the definition of maintenance, therapy and clinical outcomes in patients managed in routine practice. Method 1478 AAV patients (France, Germany, Italy, Spain and UK) managed by 493 physicians (61% Nephrologists) who completed induction therapy for organ or life threatening AAV and initiated maintenance therapy between 2014-16 were studied. Data were collected retrospectively at the time maintenance was determined to begin by the physician and then at 6, 12, 18 and 36 months. Results 49% had granulomatosis with polyangiitis,; mean age 54.2 years with 56% male. 49% had incident AAV and 51% were studied from the time of a relapse requiring remission induction therapy. 70% received cyclophosphamide and GC and 30% received rituximab and GC as induction treatment with 28% receiving plasma exchange. Physicians defined time of the start of maintenance from induction treatment start with mean of 5.7 months on the basis of fixed time point 40%, starting new drug for maintenance 26%, reaching full remission 26% and no specific criteria 8%. At this time of maintenance start 43% were in full remission vs 50% in partial and 7% refractory. Various maintenance regimes were used, 21% received rituximab (88% 6 monthly and 8% 12 monthly, 4% other) at varying planned doses 34% 1g, 40% 500 mg and 23% 375 mg/m2, 4% other regime. Remission rates varied with patients experiencing disease relapse and many patients experienced adverse events (AE) and infections with prolonged GC use being common. Renal function was relatively unchanged and some patients had worsening eGFR, protein excretion or blood pressure. At the most recent clinical review patients had been followed for a mean of 50.7 months – 6% had died, 38% had relapsed at least once, and 11% required renal replacement therapy. 54% had no vasculitis activity, 26% were ANCA positive without active disease and 19% were still experiencing active disease. 32% were still receiving GCs - 22% of them receiving &gt; 5mg/ day. Conclusion Maintenance therapy is variably defined but typically at 6 months from start of remission induction therapy. Achieving full remission and preventing relapse are still clinical problems and many patients require ongoing GC therapy to maintain remission. Infectious complications and adverse events are common and renal disease remains an ongoing clinical problem.

Impact of high-dose cytarabine and asparaginase intensification on childhood acute myeloid leukemia: a report from the Childrens Cancer Group.

1993 ◽  
Vol 11 (3) ◽  
pp. 538-545 ◽  
Author(s):  
R J Wells ◽  
W G Woods ◽  
B C Lampkin ◽  
M E Nesbit ◽  
J W Lee ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Maintenance Therapy ◽  
Myeloid Leukemia ◽  
Survival Rates ◽  
Remission Induction ◽  
High Dose ◽  
Cancer Group ◽  
High Dose Cytarabine ◽  
Childhood Acute Myeloid Leukemia ◽  
Acute Myeloid

PURPOSE The purpose of this review was to determine the impact of high-dose cytarabine and asparaginase intensification, administered shortly after remission induction, on the outcome of childhood acute myeloid leukemia (AML). MATERIALS AND METHODS Three consecutive Childrens Cancer Group (CCG) trials of acute myeloid leukemia, CCG 251 (1979 to 1983), CCG 213P (1983 to 1985), and CCG 213 (1985 to 1989) with a total of 1,294 patients, were reviewed and provide the basis of this report. RESULTS CCG 213P demonstrated the importance of dose interval, in that two courses of cytarabine and asparaginase administered at 7-day intervals gave superior 5-year survival rates (58% v 41% from the end of induction, P < .04) to the same therapy administered at 28-day intervals. CCG 213 showed that there was no advantage to the maintenance therapy used for patients who received two courses of cytarabine and asparaginase at 7-day intervals (5-year survival, 68% [no maintenance] v 44% [maintenance] from the end of consolidation, P < .01). Inclusion of the 7-day interval cytarabine/asparaginase intensification was accompanied by an overall improvement in 5-year survival rates from diagnosis when compared with historical controls (CCG 213, 36% v CCG 251, 29%, P < .02) although other differences between these studies could also be responsible for the improvement seen. CONCLUSION High-dose cytarabine and asparaginase intensification eliminated the benefit of prolonged maintenance therapy in childhood AML and was accompanied by an overall improvement in survival.

scholarly journals AS WE SAY “PREVENTION IS ALWAYS BETTER THAN CURE”

2020 ◽  
pp. 70-72
Author(s):  
Guru Prasad ◽  
Anjana Vasudevan ◽  
Vivek Bala ◽  
Prabhakaran Subbaramiah ◽  
Nithyaraj Prakasam ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Early Stage ◽  
Cross Sectional Study ◽  
Upper Gastrointestinal Endoscopy ◽  
Cross Sectional ◽  
Disease Symptoms ◽  
Incidence And Mortality ◽  
Upper Gi Endoscopy ◽  
Ethical Clearance ◽  
Better Than

Background and Objectives: Gastric cancer remains one of the most common and deadly cancers worldwide. Based on GLOBOCAN 2018 data, stomach cancer is the 5th most common neoplasm and the 3rd most deadly cancer, with an estimated 783,000 deaths in 2018. Gastric cancer incidence and mortality are highly variable by region and highly dependent on diet and Helicobacter pylori infection. Hence the aim of this study was to analyze the benefits of upper gastrointestinal endoscopy (UGI Scopy) among patients with Gastro Esophageal Reflux Disease symptoms (GERD) and analyze the results of the same, in an attempt to find and diagnose patients with early stage gastric cancer. Materials and Methods: A cross-sectional study of all patients attending general surgical outpatient department for dyspepsia, GERD and associated symptoms during the year 2019-2020. After institutional ethical clearance, patients written informed consent was obtained after explaining the procedure to them. A through history and examination was done and following this UGI scopy was performed and the findings recorded. Results: there were a total of 2038 cases. Among these patients 95.78% of them had significant findings. Reflux esophagitis was found in 13.7%, Antral gastritis in 26.4% and Pangastritis in 39.6%, Duodenitis was found in 10.69%, esophageal varices in 4.31% and esophageal candidiasis was 3.72%. 7.2% of the patients were diagnosed with malignancies. Conclusion: Upper GI endoscopy is therefore an effective tool to facilitate earlier diagnosis and treatment in patients with GERD like symptoms.

ITI with high-dose FIX and combined immunosuppressive therapy in a patient with severe haemophilia B and inhibitor

2009 ◽  
Vol 29 (02) ◽  
pp. 155-157 ◽  
Author(s):  
H. Hauch ◽  
J. Rischewski ◽  
U. Kordes ◽  
J. Schneppenheim ◽  
R. Schneppenheim ◽  
...  
Keyword(s):  
Nephrotic Syndrome ◽  
Immunosuppressive Agents ◽  
Tolerance Induction ◽  
Intravenous Immunoglobulins ◽  
Factor Ix ◽  
High Dose ◽  
Allergic Reactions ◽  
Success Rates ◽  
Serious Infections ◽  
History Of

SummaryInhibitor development is a rare but serious event in hemophilia B patients. Management is hampered by the frequent occurrence of allergic reactions to factor IX, low success rates of current inhibitor elimination protocols and the risk of development of nephrotic syndrome. Single cases of immune tolerance induction (ITI) including immunosuppressive agents like mycophenolat mofetil (MMF) or rituximab have been reported. We present a case of successful inhibitor elimination with a combined immune-modulating therapy and high-dose factor IX (FIX). This boy had developed a FIX inhibitor at the age of 5 years and had a history of allergic reactions to FIX and to FEIBA→. Under on-demand treatment with recombinant activated FVII the inhibitor became undetectable but the boy suffered from multiple joint and muscle bleeds. At the age of 11.5 years ITI was attempted with a combination of rituximab, MMF, dexamethasone, intravenous immunoglobulins and high-dose FIX. The inhibitor did not reappear and FIX half-life normalized. No allergic reaction, no signs of nephrotic syndrome and no serious infections were observed.

Inhibitorentwicklung nach früher hoher Exposition und Hirnblutung

2010 ◽  
Vol 30 (S 01) ◽  
pp. S115-S118
Author(s):  
C. Moorthi ◽  
A. Bade ◽  
C. Niekrens ◽  
G. Auerswald ◽  
K. Haubold
Keyword(s):  
High Titer ◽  
Cerebral Haemorrhage ◽  
High Dose ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Intron 22 Inversion ◽  
Neurosurgical Intervention

SummarySevere haemophilia A was diagnosed postpartum in a newborn. The mother was known as a conductor (intron 22 inversion) and an uncle had a persistently high titer inhibitor after failed ITI.Due to a cephalhaematoma, a high-dose pdFVIII substitution was given within the first days after birth. At the age of six month a severe cerebral haemorrhage occurred, making a high-dose pdFVIII substitution and neurosurgical intervention necessary. Several days later a porth-a-cath-system was implanted. The development of a high titer inhibitor occured six days later, an ITI was started according to the Bonn Protocol. Initially rFVIIa was given in addition to the pdFVIII substitution. Seven days after the beginning of treatment the inhibitor was no longer detectable. At monthly intervals the FVIII dosage was reduced until the dosage complied with a prophylaxis in severe haemophilia A.The duration of the ITI was nine months. A total of 30 mg rFVIIa and 276 000 IU pdFVIII were used; costs in total: 280 173.60 Euro.

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