Bruton tyrosine kinase inhibitors (BTKi) therapies in chronic lymphocytic leukemia (CLL): Review of multiple trials data for incidence of lymphocytosis and designation of partial response with lymphocytosis (PRL).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19502-e19502
Author(s):  
Jayant Narang ◽  
Christiana Caplan ◽  
Katarina Ludajic ◽  
Sambit Ray ◽  
Surabhi Bajpai ◽  
...  
Keyword(s):  
Partial Response ◽  
Kinase Inhibitors ◽  
Absolute Lymphocyte Count ◽  
Lymphocytic Leukemia ◽  
Additional Parameter ◽  
True Incidence ◽  
Overall Response ◽  
Group A ◽  
Definition Of ◽  
Group B

e19502 Background: In trials with BTKi, lymphocytosis alone may not be a sign of progression but rather treatment related redistribution of lymphocytes from tissues into the peripheral blood (Cheson et al 2012). This observation was later incorporated in iwCLL 2018 criteria. However, no clear details were provided on how to assess lymphocytosis along with other parameters to derive an overall timepoint response (OTR) in a clinical trial setting. While PRL is a response category used to assess lymphocytosis in many clinical trials, it has not been defined in iwCLL 2018. Furthermore, iwCLL 2018 defines Absolute Lymphocyte Count (ALC) progression (PD) as an increase of ALC ≥ 50% compared to baseline whereas conventionally progression is defined in comparison to nadir, which may lead to under reporting of ALC PD. Methods: Data from multiple (8) phase II/III CLL trials with BTKi (frontline and relapsed/refractory setting), were retrospectively analyzed. Subjects with a post baseline (post-BL) timepoint (TP) were analyzed for the incidence of ALC PD and an OTR designation of PRL, PD and other non-PD assessments (Stable Disease (SD), Non-PD and Unknown (UNK)). Results: We identified 1976 subjects with a total of 17134 post BL TPs. There were 1182 TPs (6%) with ALC PD. Out of these TPs with ALC PD, 497 TPs had OTR of PRL (42% TPs with ALC PD), 365 TPs (31%) were assessed as non-PD and 320 (27%) TPs were assessed as PD. 104 TPs (33%) of subjects with OTR of PD had at least one additional parameter driving PD. Thus, ALC PD is a common occurrence with BTKi and in line with the Cheson 2012 guidance, ALC PD alone should not be considered as overall progression. We propose that initial ALC PD with BTKi should not be considered a sign of progression but rather a treatment effect and should be assessed as PRL. However, PRL should only be assessed if Partial Response (PR) is achieved in at least 2 other involved iwCLL group A parameters (nodes, liver or spleen) and 1 group B parameter (hemoglobin or platelets). An initial decrease/normalization of the ALC compared to baseline with a subsequent progression compared to nadir, may be considered true progression in a setting of continued BTKi. If only one other group A parameter is involved and is PR with associated ALC PD, SD may be a more appropriate overall response than PRL. Conclusions: ALC PD and PRL are common in BTKi, but there is a need for standardization of the definition of ALC PD and its role in determination of OTR of PRL. We propose that ALC PD should be assessed by comparing ALC with nadir and not baseline. If PRL is assigned only when PR is met by other criteria along with ALC PD, PRL could be a part of determining Overall response rate (ORR) in protocols. Future prospective studies are needed to estimate the true incidence of ALC PD and its impact on ORR with BTKi as well as other agents which induce lymphocytosis.

COMPARATIVE STUDY IN BETWEEN INTRALESIONAL VITAMIN D3 AND INTRALESIONAL BLEOMYCIN IN THE TREATMENT OF CUTANEOUS VERRUCAE

2020 ◽  
Vol 4 (8) ◽  
Author(s):  
Shrikant . ◽  
R.D. Mehta ◽  
B.C. Ghiya
Keyword(s):  
Partial Response ◽  
Comparative Study ◽  
Recurrence Rate ◽  
Vitamin D3 ◽  
Complete Response ◽  
Recurrence Rates ◽  
Additional Advantage ◽  
Cost Effective Treatment ◽  
Group A ◽  
Group B

Background: Verruca is one of the common dermatopathologies which has multiple therapeutic options but with variable success rates, refractory cases and high recurrence rates. Nowadays, treatment with intralesional injections has gained recognition due to its effectiveness in clearing verrucae. These act by stimulating the cell-mediated immunity. Out of scores of options available for intralesional therapeutics, Vitamin D3 appears to be more promising but least evaluated. Therefore, we planned to evaluate the efficacy of intralesional Vitamin D3 in various types of cutaneous verrucae. Simultaneously the results were compared with intralesional bleomycin, also. Methods: A total of 200 patients of cutaneous verrucae with varying size and duration were included in the experimental randomized comparative study. We divided them into two groups. Group A, comprising of 100 patients, received 0.2-0.5 ml intralesional Vitamin D3 (600,000 IU, 15mg/ml) and Group B, also of hundred subjects, received intralesional Bleomycin (1 mg/ml) into the base of verrucae. A maximum of 5 verrucae were injected per session at 3 weeks interval until resolution or for a maximum of 4 sessions. Patients were followed up for 6 months after the last injection to assess the clearance status and detect any recurrence. Results: In Group A (Vitamin D3), 'Complete response', 'Partial response' and 'No response' were observed in 85.07%, 6.74% and 8.17% respectively after 4 sessions. Recurrence rate was 0.81% after 6 months. In Group B (Bleomycin), 'Complete response', 'Partial response' and 'No response' were found in 77.99%, 10.47% and 11.53% in the series. Recurrence rate was 1.71%, comparatively higher in group B. Conclusion: The efficacy of intralesional Vitamin D3 was found significantly higher as compared to intralesional Bleomycin in the treatment of cutaneous verrucae with less recurrence rates. Vitamin D3 has an additional advantage of cost-effective treatment over Bleomycin. We purpose its use, as a primary mode of treatment in various types of cutaneous verrucae. Keywords: Bleomycin, Vitamin D3, Verrucae.

Immunity to Diphtheria, Pertussis, Tetanus, and Poliomyelitis in Children with Acute Lymphocytic Leukemia After Cessation of Chemotherapy

PEDIATRICS ◽  
1981 ◽  
Vol 67 (2) ◽  
pp. 222-229 ◽  
Author(s):  
A. van der Does-van den Berg ◽  
J. Hermans ◽  
J. Nagel ◽  
G. van Steenis
Keyword(s):  
Acute Lymphocytic Leukemia ◽  
Lymphocytic Leukemia ◽  
First Year ◽  
Healthy Children ◽  
Healthy Control ◽  
Antibody Titers ◽  
Group A ◽  
One Year ◽  
Group B ◽  
Antibody Levels

Antibody titers to diphtheria, pertussis, tetanus, and poliomyelitis (types I to III) were measured in previously vaccinated children with acute lymphocytic leukemia in remission after cessation of therapy. The response to revaccination one year after therapy was stopped was also studied. The patients' antibody titers were compared with those of healthy children, matched for age and sex. Two groups of patients were studied: one group (group A, N = 30) was given two drugs (6-mercaptopurine, methotrexate); the other group (group B, N= 19) was given three drugs (6-mercaptopurine, methotrexate, and cyclophosphamide) for maintenance treatment. In general, the patients' antibody titers were lower than those of healthy children, but in most patients they were still at levels considered to be protective. No significant differences in antibody levels between the two patient groups were found. A spontaneous rise in antibody titers in the first year after termination of therapy was not observed. After revaccination the rise in antibody titers was correlated with preexisting antibody titers in the same way in patients as in healthy children, and the antibody titers in patients and in healthy control subjects were on roughly the same level.

Allogeneic Transplant in Patients with Poor Prognosis B-Chronic Lymphocytic Leukemia (B-CLL): Comparative Study between Myeloablative(M) and Non-Myeloablative(NM) Conditioning Regimen.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2306-2306 ◽  
Author(s):  
M.D. Caballero ◽  
J.A. García-Marco ◽  
R. Martino ◽  
J. Esteve ◽  
M.V. Mateos ◽  
...  
Keyword(s):  
At Risk ◽  
Poor Prognosis ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Lymphocytic Leukemia ◽  
Allogeneic Transplant ◽  
Peripheral Blood Stem Cells ◽  
Group A ◽  
Group B ◽  
Patients With Poor Prognosis

Abstract Sustained complete remissions (CR) have been reached with allogeneic transplant in patients with poor prognosis B-CLL; however, mortality rates are high (20–50%); in order to reduced TRM, NM conditioning are widely used in haematological malignancies; however it is not clear if the use of NM regimens can maintain the efficacy reducing the toxicity. IN this report we performed a retrospective comparison between 30 patients (group A) who have received myeloablative conditioning consisted of TBI plus Cy in 23 pts (74%), TBI, Cy plus VP-16 in 6 pts (19%) and BuCy in 1 patient and 31 patients (Group B) who have received a NM transplant. Conditioning regimens in Group B included: Fludarabine plus Melphalan, 20 pts (64%), Fludarabine, Busulphan and ATG, 5 pts (16%), Fludarabine, TBI and ATG, 4 pts (13%) and Fludarabine plus TBI, 1 patient. All patients received peripheral blood stem cells from a HLA related identical donor. T-cell depletion was performed in 14 patients of the group A. Median age at transplant was significantly higher in the group B patients (53 versus 45, respectively) (p<0,005); no differences were observed in terms of status at transplant and n° of previous chemotherapy lines as well in the risk of graft versus host disease (GVHD) and transplant related mortality (TRM) (See Table, below). With a median follow-up of 71 and 36 months for groups A and B respectively,Overall Survival and Event Free Survival are similar for both groups (53% versus 64% and 60% versus 68%, respectively). Although patients in the NM transplant group were older toxicity was similar in both groups; moreover a similar efficacy has been observed suggesting the clear role of graft versus tumour effect in B-CLL probably more important that the type ofconditining. Table 1 GROUP A Myeloablative Group B Non-myeloablative p Number of previuous chemotherapy lines 2 (1-6) 2 (1-8) NS Acute GVHD 15/30 (48%) 20/31 (64%) NS Grade II-IV 11/30 (35%) 12 /31(38%) NS Chronic GVHD 12/26pts at risk (46%) 18/27 pts at risk (66%) NS Extense 8 pts (30%) 9 pts (33%) NS TRM 7/30 (23%) 7/31 (22%) NS

Rituximab in the Treatment of Adults with Chronic Idiopathic Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3930-3930 ◽  
Author(s):  
Ghassan Zalzaleh ◽  
Ahmad Jajeh ◽  
Diemante Tamoseviciene
Keyword(s):  
Partial Response ◽  
Hemolytic Anemia ◽  
Complete Response ◽  
Pure Red Cell Aplasia ◽  
Lymphocytic Leukemia ◽  
Overall Response ◽  
Medical Centers ◽  
History Of ◽  
Refractory Itp

Abstract Corticosteroids have been the first line of treatment of ITP since 1950, however some patients do not respond to this treatment (refractory) and some will relapse after its discontinuation. For such patients second line treatments were introduced. Some patients will continue to be refractory to this treatment and need other therapy modality. Rituximab is a chimeric monoclonal antibody directed against the CD20 antigen exposing B Lymphocytes, causing its depletion. This could alter the production of auto-antibodies in some Auto-Immune diseases and thus could be used in their treatment. Few medical centers had reported using Rituximab in the treatment of refractory (ITP) and (AIHA), yet its definite role could not be determined, and here we share our experience. Patients with documented diagnosis of ITP or AIHA who were refractory to at least two lines of therapy including steroids were offered to receive Rituximab (375mg/m2 weekly for 4 weeks). 15 patients were enrolled, 10 with ITP, 4 with AIHA, 1 with Coombs negative Hemolytic anemia, and 1 with pure red cell aplasia. One had both ITP and AIHA. 10 were females and 5 males. 5 were >60 years old and 10 were < 60 years old. 2 out of the 10 patients with ITP had also Chronic Lymphocytic Leukemia (CLL). Duration of follow up ranged from 2 months to 17 months (average 7 mos). Of the 10 patients with refractory ITP treated with Rituximab overall response was 60%. 4 were NR (no response), 2 were MR (minimal response: Platelets increased to <50000), 2 were PR (Partial response: Platelets increased to <100000) and 2 were complete response (Platelets became normal). 3 patients of 6 with Hemolytic anemia or PRC aplasia had NR, 1 had MR (Hct <30), and 2 had partial response (Hct 30–35). No complete response was observed in this group. In 3 patients with hemolytic anemia and CLL 1 had MR, 1 had PR and 1 had NR. 2 patients with hemolytic anemia who had NR died as a complication of their disease (one with septic shock and one with severe autoimmune flare up). Only one patient with refractory ITP had mild allergic side effects and did not complete 4 doses. No Rituximab related mortality was observed. CONCLUSION: Rituximab therapy had a variable but valuable effect in the treatment of patients with chronic refractory ITP and refractory/ relapsed AIHA. Overall response in our group reached 60%. No clinical or laboratory parameters were found to predict response, although there was a suggestion that males, younger age, and no history of splenectomy have a better chance of response. As we lack an effective alternative treatment in chronic refractory ITP and AIHA, Rituximab use could be a valid option in view of its mild toxicity. Further follow up of our patients and input from other institutions in this regard are needed.

In Patient with Chronic Lymphocytic Leukemia the Overall SURVIVAL Is NOT Different WHEN Analysed by Cause of Death, Related or NOT Related to the Disease

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4587-4587
Author(s):  
Luca Laurenti ◽  
Francesco Autore ◽  
Barbara Vannata ◽  
Idanna Innocenti ◽  
Francesco Santini ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Survival Time ◽  
Cause Of Death ◽  
Causes Of Death ◽  
Lymphocytic Leukemia ◽  
Overall Survival Time ◽  
Group A ◽  
Group B ◽  
Age Of Death

Abstract Abstract 4587 Chronic Lymphocytic Leukemia (CLL) is the most common lymphoprolipherative disorder of the elderly population in Western countries. It shows a highly variable clinical course. In fact, some patients may die within few months from the diagnosis because of CLL itself or disease-related complications. Other patients do not require any treatment for many years and have a long-standing disease. Many of them could die because of disease different from CLL. The identification of subgroups of patients with peculiar features predictive of the clinical behaviour of the disease is important. This retrospective analysis has the purpose to study patients affected by CLL, diagnosed and followed at our single centre of Haematology, focusing our attention on their causes of death. We selected 340 patients affected by CLL from our data-base, diagnosed from January 1999 to December 2010 and followed until March 2012. We distinguished the causes of death in two groups: one related to CLL (as progression of the disease, evolution to Richter's Syndrome, infections due to chemotherapy) and the other not related to CLL (i.e. cardiovascular diseases, solid tumours, old age). Statistical analysis, conducted using SPSS version 16.0 for Windows and “GraphPad Prism” GraphPad Software Inc., compared these two groups and tried to select other subgroups. We recorded 69 deaths: 47 related to CLL (68.1%) and 22 unrelated to CLL (31.9%). The median age of death of our cohort of patients was 76 years (range 40–92); those patients with a CLL-related death (related pts) died at a median age of 76 years (range 40–89) and the patients with a CLL-unrelated death (unrelated pts) died at a median age of 76 years (range 61–92). No differences in terms of median age of death were found analysing the data by gender. Also, considering the overall survival time from diagnosis to death, it was 58 months (range 9–155) in the related group and 43 months (range 14–121) in the unrelated group (p=0.185). When divided our population by the disease behaviour, we obtained 3 subgroups of patients: patients who progressed and died for CLL related causes (group A), patients who progressed and died for CLL unrelated causes (group B) and patients who did not progress and died for CLL unrelated causes (group C) (Table 1). The only statistical significant difference was found among the median overall survival times in un-progressive patients who died for non CLL related causes (p=0.043). The median age of death was not affected by the cause of death in our CLL population. Moreover, patients with un-progressive CLL showed an overall survival time shorter than the progressive CLL subgroups. Patients with un-progressive CLL probably had a shorter survival because unrelated CLL diseases could are more difficult aggressive than CLL itself. Table 1. group A group B group C p N° patients 47 13 9 Median age at diagnosis (years) (range) 70 (39–85) 71 (56–83) 77 (67–86) n.s. Median age at death (years) (range) 76 (40–89) 75 (61–84) 79 (68–92) n.s. Overall survival time (months) (range) 58 (9–155) 48 (18–121) 22 (14–78) 0.043 Disclosures: No relevant conflicts of interest to declare.

The Prognostic Value of Serum APRIL Levels in Patients with Chronic Lymphocytic Leukemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5648-5648
Author(s):  
Sinem Nihal Esatoglu ◽  
Dilek Keskin ◽  
Muge Kutnu ◽  
Tugrul Elverdi ◽  
Ayse Salihoglu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Demographic Data ◽  
Lymphocytic Leukemia ◽  
Rank Test ◽  
Healthy Controls ◽  
Log Rank Test ◽  
Treatment Naïve ◽  
Group A ◽  
Group B ◽  
Time To First Treatment

Abstract Introduction: Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with variable clinical course. Several studies have been conducted to predict outcome in patients with CLL and also have been going on. A proliferation inducing ligand (APRIL) has been shown to involve in survival and resistance to apoptosis in CLL, and APRIL molecule has been investigated as a prognostic marker in CLL patients. However, there are limited and controversial data regarding APRIL and its impact on prognosis in CLL. We aimed to compare serum APRIL levels in CLL patients with those of age and gender matched healthy subjects, and to investigate the relationship between APRIL and the other common prognostic factors, and to determine whether serum APRIL levels predict time to first treatment in CLL. Methods: After ethical approval and informed consent were obtained, between May and December 2012, venous blood samples were driven from 96 CLL patients’ and 25 healthy controls’, and serum APRIL levels were measured by ELISA. Demographic data and the prognostic markers were obtained from the patients’ files, and patients have been followed for a minimum of 12 months. We tested the correlation between APRIL with the, clinical and biological parameters, and used the log rank test to compare their Kaplan Meier curves. Results: Patients were divided into three groups: Treatment naive (group A, n=49), chemotherapy receiving (group B, n=25) and who had previously received chemotherapy (group C, n=22). Median APRIL level was higher in group A (2.78 vs 1.29; p=0.034) and group C (3.54 vs 1.29; p=0.001) when compared to healthy controls, but was not different in group B (1.56 vs 1.29; p=0.3) (Figure 1). Serum APRIL level in group A was negatively correlated with hemoglobin levels (r=-0.298; p=0.037) and platelet counts (r=-0.321; p=0.025) whereas no correlation with age, Rai and Binet stages, lymphocyte counts, β2-microglobulin and CD38 levels were detected. Group A patients were also divided into 2 subgroups (APRIL levels low, n=20 and APRIL levels high, n=29) using median natural logarithm of serum APRIL level as cut off. April low and high subgroups were similar with respect to demographic data and prognostic factors. Median time to first treatment was not reached in the APRIL low group, but was 104 months in the APRIL high group (p=0.13, log-rank test). Conclusions: Among the treatment naive patients, serum APRIL levels only negatively correlate with hemoglobin levels and platelet counts. These correlations seem to be associated with tumor burden rather than the prognosis, because APRIL levels were not different in chemotherapy receiving patients compared to healthy controls. Since a median survival time could not be reached in the APRIL low group, short follow up time might be an explanation why the APRIL levels did not predict the time to first treatment. In conclusion, our findings let us to think APRIL levels are not a useful marker to predict prognosis in patients with CLL. Figure 1. Median APRIL levels of CLL patients and healthy controls (ng/mL) Figure 1. Median APRIL levels of CLL patients and healthy controls (ng/mL) Disclosures No relevant conflicts of interest to declare.

scholarly journals Phenotypic and Genotypic Characterization ofMycobacterium africanum Isolates from West Africa

1999 ◽  
Vol 37 (6) ◽  
pp. 1921-1926 ◽  
Author(s):  
Richard Frothingham ◽  
Percy L. Strickland ◽  
Gisela Bretzel ◽  
Srinivas Ramaswamy ◽  
James M. Musser ◽  
...  
Keyword(s):  
Sierra Leone ◽  
Tandem Repeats ◽  
Drug Resistant ◽  
Polymorphic Genes ◽  
Intergenic Regions ◽  
Group A ◽  
Definition Of ◽  
Group B ◽  
Vntr Analysis ◽  
Simple Definition

The Mycobacterium tuberculosis complex includesM. tuberculosis, M. bovis, M. africanum, and M. microti. Most clinical isolates areM. tuberculosis or M. bovis. These species can be distinguished by phenotypes and genotypes. However, there is no simple definition of M. africanum, and some authors question the validity of this species. We analyzed 17 human isolates from Sierra Leone, identified as M. africanum by biochemical and growth characteristics. We sequenced polymorphic genes and intergenic regions. We amplified DNA from six loci with variable numbers of tandem repeats (VNTRs) and determined the exact number of repeats at each locus in each strain. All M. africanumisolates had the ancestral CTG Leu at katG codon 463. Drug-resistant M. africanum isolates had katGand rpoB mutations similar to those found in drug-resistantM. bovis and M. tuberculosis. Fourteen Sierra Leone M. africanum isolates (designated group A) hadkatG codon 203 ACC Thr, also found in M. africanum T (the T indicates type strain) from Senegal. Group A isolates clustered with M. africanum T by VNTR analysis. Three M. africanum isolates (group B) had katG codon 203 ACT Thr, found in M. tuberculosis T, and clustered with M. tuberculosis T by VNTR analysis. Phenotypic identification of M. africanumyielded a heterogeneous collection of strains. Genotypic analyses identified a cluster (M. africanum group A) which includedM. africanum T and was distinct from the rest of the M. tuberculosis complex. Future studies ofM. africanum should include both phenotypic and genotypic analyses.

scholarly journals Comparison of the efficacy of 3-weekly chop with CHOEP for treatment of patients with aggressive non-Hodgkin’s lymphoma.

2020 ◽  
Vol 27 (03) ◽  
pp. 631-634
Author(s):  
Tahir Mehmood ◽  
Muhammad Khalid ◽  
Nasir Mehmood ◽  
Shahbaz Ahmed ◽  
Saeed Ahmed ◽  
...  
Keyword(s):  
Partial Response ◽  
Hodgkin’S Lymphoma ◽  
Complete Response ◽  
Hodgkin's Lymphoma ◽  
Female Patients ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Group A ◽  
Group B

Objectives: To compare the efficacy of 3-weekly CHOP with CHOEP for the treatment of patients with aggressive Non-Hodgkin’s Lymphoma. Study Design: Randomized control trial. Setting: Department of Medical Oncology, Jinnah Hospital Lahore. Period: From January 2016 to June 2016. Material & Methods: Conducted on 200 patients of biopsy confirmed aggressive non-Hodgkin’s lymphoma. The cases were allocated into two groups by using random numbers table i.e. group A & B having 100 patients each. Group A received CHOP-21 regimen which is defined as cyclophosphamide (750mg/m2 intravenously), doxorubicin (50mg/m2 intravenously), vincristine (2mg i/v) & prednisone (100mg/m2 d1-5 PO). Group B received CHOEP-21 regimen which is defined same as CHOP-21 but with the addition of etoposide 100mg/m2 intravenously for day 1-3. Observation regarding efficacy was including all the number of cases in which complete remission of disease was noted one month after completion of chemotherapy. Results: The mean age of the patients in group A was 44.6±13.9 years and in group B was 45.6±11.5 years. In group A, 74 (74%) male and 26 (26%) female patients and in group B, 72 (72%) male and 28 (28%) female patients. In the distribution of patients by complete response after 6 cycles, in group A, 66 (66%) patients had complete response, 30 (30%) patients had partial response, 1 (1%) patient expired, 2 (2%) patients had progressive disease (shifted to salvage therapy) and 1 (1%) patient lost the follow up. In group B, 80 (80%) patients had complete response, 16 (16%) patients had partial response, 2 (2%) patients expired, and 2 (2%) patients lost the follow up. Conclusion: It is concluded from this study that viability was accomplished in a greater number of patients treated with CHOEP-21 than those treated with CHOP-21 in the management of patients with aggressive Non hodgkin's lymphoma.

372 ESOPHAGEAL BODY PERISTALSIS CORRELATES FOR DYSPHAGIA AND REGURGITATION: AN ASSESSMENT BASED ON BARIUM ESOPHAGRAM

2020 ◽  
Vol 33 (Supplement_1) ◽  
Author(s):  
L Giulini ◽  
D Razia ◽  
S Mittal
Keyword(s):  
Clinical Symptoms ◽  
Objective Assessment ◽  
Esophageal Peristalsis ◽  
High Resolution Manometry ◽  
Number Of Patients ◽  
Barium Esophagram ◽  
Group A ◽  
The Mean ◽  
Definition Of ◽  
Group B

Abstract   Because it offers real-time assessment, barium esophagram should be the modality of choice when studying esophageal peristalsis. However, no standard reporting method is available for BE results. Presently, peristaltic disorders are defined according to high-resolution manometry (HRM), but HRM findings do not correlate with clinical symptoms. The aim of this study was to stratify esophageal peristaltic function via standardized evaluation of BE, and to define the association between esophageal peristalsis and dysphagia and regurgitation. Methods After IRB approval, a prospectively maintained database was reviewed for patients who underwent both HRM and BE from 08/01/2016 to 12/31/2019. Patients with conditions associated with outflow impairment were excluded. BEs were re-examined in blinded fashion and assigned subjective scores (0, 1, or 2) for dilation grade (DG) and contractility grade (CG). Patients were categorized according to the sum of the DG and CG: Group A = 0, Group B = 1–2, and Group C = 3–4. Mean distal contractile integral (DCI), number of failed contractions on HRM, and number of patients with dysphagia/regurgitation in each group were analyzed and compared. Results In all, 124 patients were included. The mean DCI (mmHg*cm*s) was 2539.1 ± 1357.8 in Group A, 884.4 ± 916.9 in Group B, and 77.4 ± 192.3 in Group C (p &lt; 0.001). The mean number of failed contractions were 0.7 ± 1.3, 3.4 ± 3.4, and 8.6 ± 3.2, respectively (p &lt; 0.001). Table 1 shows the distribution of patients with dysphagia or regurgitation across groups. The proportion of patients with dysphagia in Group C was higher than in Groups A or B (OR 3.75, p = 0.02; and OR 2.58, p = 0.07, respectively). Similarly, Group C was significantly more often associated with regurgitation than in Groups A or B (OR 4.69, p = 0.009; and OR 4.42, p = 0.005). Conclusion The combined DG and CG allowed us to identify the patients with a grade of peristaltic disfunction that was significantly more associated with dysphagia or regurgitation (Group C). However, in order to achieve a clearer definition of the different peristaltic disfunction levels according to their propensity to cause dysphagia or regurgitation, a more objective assessment of both DG and CG should be provided; therefore, further studies are required.

scholarly journals Emerging role of kinase-targeted strategies in chronic lymphocytic leukemia

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 88-96 ◽  
Author(s):  
Adrian Wiestner
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Absolute Lymphocyte Count ◽  
Cell Receptor ◽  
Lymphocytic Leukemia ◽  
Cell Trafficking

Abstract Chronic lymphocytic leukemia (CLL) is a malignancy of mature B cells that depend on host factors in the tissue microenvironment for survival and proliferation. In vitro, CLL cells rapidly undergo apoptosis unless microenvironmental factors are provided that support their survival. Signaling pathways activated in the microenvironment in vivo include the B-cell receptor (BCR) and NF-κB pathways. Thus, CLL is a disease “addicted to the host” and is dependent on pathways that promote normal B-cell development, expansion, and survival; this is particularly true in the case of the BCR signaling cascade. Small-molecule inhibitors of kinases that are essential for BCR signal transduction abrogate the stimulating effects of the microenvironment on CLL cells. The orally administered tyrosine kinase inhibitors fostamatinib and ibrutinib and the phosphatidylinositol 3-kinase inhibitor GS-1101 have induced impressive responses in relapsed and refractory CLL patients, mostly with moderate side effects. Reductions in lymphadenopathy and splenomegaly are seen within weeks and are frequently accompanied by a transient rise in absolute lymphocyte count that is asymptomatic and probably the result of changes in CLL cell trafficking. This review discusses the biologic basis for kinase inhibitors as targeted therapy of CLL and summarizes the exciting early clinical experience with these agents.

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