Deletion 11q Abnormality in Patients with Chronic Lymphocytic Leukemia (CLL) May Not Have Poor Clinical Outcomes and Bulky Disease (clinical and radiological) At Presentation – Clinical Characteristics of (n=172) Previously Untreated Patients with CLL and del11q Cytogenetic Abnormality.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2890-2890
Author(s):  
Preetesh Jain ◽  
Long Xuan Trinh ◽  
Ohad Benjamini ◽  
Susan Lerner ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Ct Scan ◽  
Clinical Features ◽  
Research Funding ◽  
Clinical Characteristics ◽  
Ct Scans ◽  
Chromosome 11 ◽  
Bulky Disease ◽  
Β2 Microglobulin ◽  
Risk Of Death ◽  
Significant Difference

Abstract Abstract 2890 Introduction: Del11q aberration is universally considered as an adverse prognostic marker in patients with CLL. However, large studies describing the clinical characteristics of del11q in CLL patients (pts) have never been reported. We studied the clinical features, outcomes and treatment responses among (172) previously untreated pts with CLL and del11q. Methods: This is a retrospective analysis of CLL pts (n=172) with del11q, who presented at our institution between 2003–2012. All pts signed an informed consent as per the declaration of Helsinki and IRB approval. Del11q was determined from bone marrow (BM) aspirate or blood samples by FISH (Fluorescent in-situ hybridization) technique. Detection of the 11q22.3 (ATM gene) on chromosome 11 used a multi-color FISH technique. Pts were divided into five categories – One – 57; del11q alone, Two – 105; del11q and del13q, others – 10 (4; del11q with +12, 1; del11q with del17p and 5; del11q, del13q with +12). Baseline bulky lymphadenopathy by CT scan or physical exam (PE) was also analysed. The probabilities of OS, PFS and TTFT (time to first treatment) were estimated using KM plots (log rank). PFS was assessed in 121 treated pts, from date of starting therapy to date of progression or death on therapy. The Cox proportional hazards regression model was used to assess the association between pt characteristics and OS, PFS or TTFT. Results: At the baseline, majority of pts with del11q were young (median age <60 years), males (81.4%) without very high white cell count (median 33.8 K/UL), absolute lymphocyte count – (median 27.1 K/UL) and β2 microglobulin (3 mg/L). Only 16.7% (n=28) patients had advanced Rai stage (3, 4). Majority were IGHV unmutated (n=112; 89.6%), CD38 high (n=88; 51.8%), Zap-70 high (n=100; 75.8%). Status of bulky disease was assessed by PE and baseline CT scans. Bulky disease by PE was observed in n=11 (6.4%) only. Baseline CT scans were performed for 108 patients out of whom only 16 patients (14.8%) had bulky disease. Thus, majority of del11q pts did not have bulky disease by PE or by CT scanning. Analysis of time dependent variables was performed. Among the total 172 pts, 19 (11%) have died. and median time to death has not been reached (NR) - OS. 48/125 (38%) pts who were treated died or progressed and median PFS time was 49.2 months. Overall, 123 (71%) patients received therapy after initial presentation at MDACC. The median TTFT was 10.6 months. FCR based therapies were given in (91; 73 %) pts. Median PFS on FCR based therapy was 32 mo (Figure -1). CR was achieved in (70%; n=64) and overall response was 89%. Pts who received fludarabine based therapy had a significantly shorter TTFT as compared to non fludarabine based therapy (P<0.0001). Other pts (32) were treated with single agent rituximab and lenalidomide protocols. To address whether del11q has any influence over presence of deletion 13 q abnormality we compared (del11q alone; n=57) vs (del11 and del13q; n=105) patients. Patients with sole del11q had significant proportions of younger patients, lesser WBC count, and ALC and β2 microglobulin. Furthermore, there was no significant difference in OS, PFS and TTFT among the two categories. In the multivariate analysis for OS and PFS among the two categories, β2 microglobulin was significantly predictive of increased risk of death or progression among the two categories and FISH categories were not significantly predictive of OS or PFS or TTFT. Bulky disease by PE (and not by CT scan) was significantly associated with a shorter TTFT (HR=2.93; 95%CI -1.5–5.69 and P=0.002). Furthermore, a separate cohort of (n=500) patients with sole del13q was compared with del11q alone (n=57) and del11q with del13q (n=105). There was no significant difference in OS but the TTFT was significantly shorter in del11q alone (data not shown). Conclusions: We describe the clinical features of del11q in CLL patients. This study suggests that occurrence of del11q is frequent with del13q abnormality. The majority of patients with del11q did not have bulky disease as assessed by PE or by CT scan. Presence of bulky disease by PE predicted for a shorter TTFT. β2 microglobulin level significantly predicted for OS and PFS. FCR based therapy has good responses. Del11q is similar to del13q in terms of OS, PFS and TTFT. Del11q may not have very poor adverse outcomes in patients with CLL inspite of a shorter TTFT. Disclosures: Burger: Pharmacyclics: Consultancy, Research Funding. Wierda:Abbott: Research Funding; Genentech: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; AmGen: Research Funding; Merck: Consultancy; Celgene: Consultancy; Pharmacyclics: Consultancy; Genzyme: Consultancy. Kantarjian:Genzyme: Research Funding.

scholarly journals Clinical Features and Surgical Treatment of Synchronous Multiple Primary Lung Adenocarcinomas With Different EGFR Mutations

2022 ◽  
Vol 11 ◽  
Author(s):  
Rirong Qu ◽  
Fan Ye ◽  
Dehao Tu ◽  
Yixin Cai ◽  
Xiangning Fu
Keyword(s):  
Clinical Features ◽  
Mutation Rate ◽  
Surgical Outcomes ◽  
Clinical Characteristics ◽  
Egfr Mutations ◽  
Driver Gene ◽  
Invasive Adenocarcinoma ◽  
Significant Difference ◽  
Multiple Primary ◽  
Lung Adenocarcinomas

BackgroundWith the popularity of lung cancer screening and advances in imaging technology, more and more synchronous multiple primary lung adenocarcinomas (SMPLA) are being diagnosed clinically, however, the clinical characteristics and prognosis of SMPLA with different EGFR mutations remains unclear. We aimed to explore clinical features and surgical outcomes of these patients to aid in the diagnosis and treatment of SMPLA.MethodsMedical records of patients with different EGFR mutations who have been diagnosed as SMPLA and underwent surgical resection from March 2015 to December 2019 were retrospectively analyzed. Clinical characteristics, surgical outcomes, recurrence-free survival (RFS) and overall survival (OS) were investigated.ResultsA total of 70 patients (68.6% female and 77.1% non-somkers) were included. Total of 161 lesions in all patients, 84.4% were ground-glass opacity (GGO) lesions. EGFR mutations were detected in 108 lesions, most of which were L858R (35.4%) and 19Del (20.5%). The mutation rate of mixed GGO is significantly higher than that of pure GGO and solid nodules (SN); the mutation rate of invasive adenocarcinoma is significantly higher than that of other histology subtypes; the mutation rate of lesions &gt;20 mm was significantly higher than that of ≤20 mm. However, there is no significant difference in the mutation rate of specific driver gene between different radiological features, pathological characteristics and sizes. After a median follow-up time of 29 months, the 3-year OS and RFS were 94.4% and 86.0%, respectively.ConclusionsA high discordance of EGFR mutations were identified between tumors in patients with SMPLA. Synchronous multiple lung adenocarcinomas with predominantly multiple GGO should be considered as SMPLA, and surgery may be aggressively performed for these patients due to a good prognosis.

Clinical Characteristics of T-Cell Lymphoma Associated Hemophagocytic Syndrome: Comparison of T-Cell Lymphoma with and without Hemophagocytic Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3576-3576
Author(s):  
Hongyan Tong ◽  
Yanling Ren ◽  
Feng Xiao ◽  
Wenyuan Mai ◽  
Haitao Meng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Median Survival ◽  
Clinical Characteristics ◽  
Hemophagocytic Syndrome ◽  
Cell Lymphoma ◽  
Initial Therapy ◽  
T Cell Lymphoma ◽  
Β2 Microglobulin ◽  
Significant Difference

Abstract T-cell lymphoma associated hemophagocytic syndrome (T-LAHS) has been regularly reported in Asia countries and is considered with extremely poor prognosis. The rate of definite diagnosis during early stage is low and the therapeutic outcome has been disappointed. We therefore compared T-cell lymphoma patients with and without hemophagocytic syndrome (HPS) in order to have a better understanding of the clinical characteristics of T-LAHS. One hundred and thirteen patients (66 men and 47 women, age from 12 to 80 years with the median age of 42) with aggressive T-cell lymphoma admitted to our department between January 2000 and December 2005 were included in this study, while 28 of them were with T-LAHS. The patients were divided into LAHS group and no-LAHS group. The clinical data including clinical manifestations and laboratory findings were compared between the two groups by using Chi-square test. The method of Kaplan and Meier was used to analyze overall survival (OS). The results showed that LAHS occured in about 1/4 of all the patients with T-cell lymphoma, which were all aggressive type. The elevated rates of lactate dehydrogenase (LDH) and ferritin were much higher in LAHS group than in no-LAHS group. β2-microglobulin and ovarian cancer antigen (CA125) were also elevated in both groups, but there was no significant difference. The rate of hypo-fibrinogen and liver dysfunction were higher in LAHS group than that in no-LAHS group. The rate of bone marrow infiltration in LAHS group is remarkably higher than that in no-LAHS group (57% vs 32%, p&lt;0.05). The median survival was 40 days (16 days - 22 months) in the LAHS group, and the median survival of 11 patients accepted chemotherapy more than 2 courses was 6 months. By contrast, the 2-year survival for no-LAHS group was 43%. There was significant difference between the two groups. Three patients undergoing plasmapheresis as initial therapy had survived for 3–6 months. These results indicate that high suspicion is required for early diagnosis of T-LAHS. In patients with fever, hepatosplenomegaly and cytopenia, simultaneously with serum markers such as LDH, ferritin, TG, CA125, and β2-microglobulin constantly increasing, T-LAHS should be considered. For patients without extranodal invasion or enlargement of lymph nodes, repeating biopsy of multiple sites of bone marrow may help improving the diagnosis rate. As for treatment, other more intensive regimens were not superior to CHOP regimen. While the overall outcome of treatment is still unsatisfied, plasmapheresis as initial therapy is worth considering.

A Detailed Analysis of Myelodysplastic Syndrome Complicated By Autoimmune or Inflammatory Disorders: A Possible Efficacy of Low-Dose Lenalidomide

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3256-3256
Author(s):  
Yasunobu Takeoka ◽  
Akiko Miura ◽  
Koji Nakamura ◽  
Junko Nakamura ◽  
Ryosuke Yamamura ◽  
...  
Keyword(s):  
Myelodysplastic Syndrome ◽  
Clinical Features ◽  
Steroid Therapy ◽  
Research Funding ◽  
Low Dose ◽  
Progression Rate ◽  
Trisomy 8 ◽  
Inflammatory Disorders ◽  
Kaplan Meier ◽  
Significant Difference

Abstract [Background] Approximately 10-20 % of the patients with myelodysplastic syndrome (MDS) are known to be complicated by autoimmune or inflammatory disorders (ADs) such as vasculitis. However, most of the reports on such MDS were published before 2000, in which the diagnosis of MDS was made with previous criteria; about 20% (range 9-43%) of the patients in these reports may not be diagnosed as MDS with the present criteria. In addition, many of these reports do not offer sufficient information on cytogenetic analysis, a presently known critical factor that affect pathophysiology of MDS. These facts could make difficult to discuss its characteristics, prognosis and treatment options. Therefore, we made a detailed retrospective analysis on clinical features and treatment outcomes of MDS complicated by ADs based on more recent knowledge. [Results] A total of 102 Japanese patients with MDS (70 males and 32 females, median age of 73), diagnosed between June 2007 and June 2014, were evaluated. The diagnosis was made with WHO (2008) classification. Bone marrow G-band chromosome analysis was available in 95 % of the patients. "Very High" risk category of IPSS-R criteria comprised 29% of the patients. As summarized in Table 1, 14 episodes of AD were observed in 13 (13%) patients; 4 with Sweet syndrome, 2 each with Bechet like symptoms, interstitial pneumonia, large vessel vasculitis and myelitis, and 1 each with HPS and seronegative arthritis. As in the previous reports, the patients who developed ADs (AD group) were characterized by younger age and higher frequency of complex cytogenetics compared with those who did not (non-AD group). In addition, patients of AD group showed lower neutrophil count and higher frequency of trisomy 8 (p=.034 and <.01, respectively). Of note, despite no significant difference in median IPSS-R score, the progression rate to AML in AD group was more than two-times higher compared with non-AD group (p=.01). Survival rates were not significantly different between two groups. Corticosteroids were given to 8 patients of AD group and 6 of them (75 %) showed a certain degree of responses. Six patients with relapsed or refractory AD after the steroid therapy were treated with low-dose Lenalidomide (LEN) (10mg/day for 21 days). Interestingly, 5 of them responded to LEN with 3 achieving complete remission. Furthermore, the patients of AD group received LEN showed better survival compared with those treated without LEN (1.2y vs. 3.1y, p=.017) (Figure 1). [Conclusion] The present observation indicated that MDS with AD may be associated with cytogenetic abnormalities including trisomy 8 and higher progression rate to AML. Of note, LEN might be a possible treatment option for those resistant to steroid therapy. Table 1. Clinical features of the patients who were complicated by autoimmune or inflammatory disorders (AD) and those who were not (non-AD) Table 1. Clinical features of the patients who were complicated by autoimmune or inflammatory disorders (AD) and those who were not (non-AD) Figure 1 Comparison of Kaplan-Meier estimates of survival in the presence or absence of Lenalidomide treatment Figure 1. Comparison of Kaplan-Meier estimates of survival in the presence or absence of Lenalidomide treatment Disclosures Nakamae: Novartis: Honoraria, Research Funding, Speakers Bureau, Travel/accomidations/meeting expenses Other. Hino:Nippon Shinyaku CO.,LTD: Research Funding; astellas CO.,LTD: Research Funding.

scholarly journals Chest CT Imaging Characteristics of COVID-19 Pneumonia in Surviving and Non-Surviving Hospitalized Patients: A Retrospective Study in a Referral Center in Tehran, Iran

2021 ◽  
Vol 18 (2) ◽  
Author(s):  
Sara Besharat ◽  
Fatemehsadat Rahimi ◽  
Siamak Afaghi ◽  
Farzad Esmaeili Tarki ◽  
Fatemeh Pourmotahari ◽  
...  
Keyword(s):  
Pleural Effusion ◽  
Ct Scan ◽  
Chest Ct ◽  
Ct Scans ◽  
Early Management ◽  
Ct Findings ◽  
Imaging Characteristics ◽  
Significant Difference ◽  
Chest Ct Scan ◽  
Lung Lobes

Background: Coronavirus disease 2019 (COVID-19) has several chest computed tomography (CT) characteristics, which are important for the early management of this disease, because viral detection via RT-PCR can be time-consuming, resulting in a delayed pneumonia diagnosis. The Radiological Society of North America (RSNA) proposed a reporting language for CT findings related to COVID-19 and defined four CT categories: typical, indeterminate, atypical, and negative. Objectives: To retrospectively evaluate the chest CT characteristics of patients with COVID-19 pneumonia. Patients and Methods: A total of 115 hospitalized laboratory-verified COVID-19 cases, underdoing chest CT scan, were included in this study from April 30 to May 15, 2020. Of 115 cases, 53 were discharged from the hospital, and 62 expired. The initial clinical features and chest CT scans were assessed for the type, pattern, distribution, and frequency of lesions. Moreover, the findings were compared between ward-hospitalized, ICU-admitted, and non-surviving (expired) patients. Results: Of four CT categories, typical CT findings for COVID-19 were more frequent in the expired group (77.4%), compared to the ward-admitted (44.8%) and ICU-admitted (70.8%) groups (P = 0.017). However, no significant difference was observed in the prevalence of intermediate or atypical CT findings between the groups. Negative CT scans for the diagnosis of COVID-19 were significantly fewer in the expired group (0%) as compared to the ward-admitted (10.3%) and ICU-admitted (8.3%) groups (P = 0.0180). Also, the mean number of involved lung lobes and segments was significantly higher in the expired group compared to the other two groups (P = 0.032 and 0.010, respectively). The right upper lobe involvement, right middle lobe involvement, bilateral involvement, central lesion, air bronchogram, and pleural effusion were among CT scan findings with a significantly higher prevalence in non-surviving cases (P < 0.0001, 0.047, 0.01, 0.036, 0.038, and 0.047, respectively). Conclusion: The increased number of involved lung lobes and segments, bilateral and central distribution patterns, air bronchogram, and severe pleural effusion in the initial chest CT scan can be related to the increased severity and poor prognosis of COVID-19.

scholarly journals Comparison of Dorsal-to-Ventral Ratios of the Cervical Paraspinal Musculature in French Bulldogs With and Without Cervical Intervertebral Disk Disease and Two Other Breeds Based on CT Scan Measurements

2021 ◽  
Vol 8 ◽  
Author(s):  
Julia Hart ◽  
Stefan Rupp ◽  
Katinka Hartmann ◽  
Carolin Fischer ◽  
Pia Düver ◽  
...  
Keyword(s):  
Cervical Spine ◽  
Ct Scan ◽  
Body Length ◽  
Vertebral Body ◽  
Influencing Factor ◽  
Intervertebral Disk ◽  
Ct Scans ◽  
Height Ratio ◽  
Significant Difference ◽  
Major Factors

Objective: To objectively assess the cervical paraspinal musculature of French bulldogs (FBs) using computed tomography (CT) scan-based measurements, outline differences in other breeds published in the literature, and investigate the potential influence of its cervical paraspinal musculature on predisposed sites for intervertebral disk disease.Animals: Thirty FBs that underwent CT scans of the cervical spine from the skull to C7/T1 were enrolled. Fifteen dogs were patients suffering from intervertebral disk herniation (IVDH group), and 15 dogs underwent CT scans due to brachycephalic obstructive airway syndrome (BOAS group).Methods: At the level of each cervical intervertebral disk from C2/C3 to C7/T1, measurements were performed and statistically analyzed. On the sagittal CT scan reconstruction, the height ratio of the dorsal to ventral paraspinal musculature and the angle of the disk axis to vertebral body length were assessed. On the transverse plane, the area ratio of the dorsal and ventral paraspinal musculature and the ratio of force moments were determined at each intervertebral disk level. Finally, ratios were compared to the values of Labrador retrievers and dachshunds published by Hartmann et al. (1).Results: Comparing the two FB groups, one significant difference was detected in the mean height ratio of the dorsal to ventral paraspinal musculature at the level of C5/C6 (P = 0.0092) and C6/C7 (P = 0.0076), with IVDH FBs having the more prominent dorsal paraspinal musculature. At the level of C3/C4, a significantly less prominent dorsal paraspinal musculature in FBs than in dachshunds (P = 0.0058) and a significantly steeper disk to vertebral body angulation were observed (P = 0.0005).Conclusion: Although some incidental differences were found, most parameters did not significantly differ between the BOAS and IVDH FBs. Significant conformational differences in the cervical paraspinal musculature and disk to vertebral body length angulation were found between FBs and two other breeds (chondrodystrophic and non-chondrodystrophic). This study's findings suggest that the paraspinal musculature is an additional biomechanical influencing factor on the preferential sites of IVDH in the cervical spine and that other major factors exist in IVDH development, especially in FBs.

scholarly journals Anatomical and Radiological Study of Jugular Foramen

2019 ◽  
Vol 08 (03) ◽  
pp. 121-125
Author(s):  
Ajay Kumar ◽  
Alok Tripathi ◽  
Shobhit Raizaday ◽  
Shilpi Jain ◽  
Satyam Khare ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Ct Scan ◽  
Skull Base ◽  
Jugular Foramen ◽  
Ct Scans ◽  
Transverse Diameter ◽  
Radiological Study ◽  
Significant Difference ◽  
Human Skulls ◽  
The Right

Abstract Background and Aim The purpose of present study was to obtain comprehensive data of morphometric and anatomical details of jugular foramen. Materials and Methods The study was performed on 30 dry adult human skulls along with computed tomography (CT) scans from 30 adult patients. The parameters observed were dimensions, shape, margins, confluence, septations, and distance from jugular foramen to mastoid base. Result In the dry skull observations, only anteroposterior diameter (APD) was significantly different between the right and left side, while for the CT scan observations both transverse diameter and APD exhibit significant difference. Conclusion We believe that data from the present study will help radiologists and neurosurgeons for diagnosis and treatment of skull base pathology around jugular foramen.

scholarly journals Different clinical features between patients with ROS1-positive and ALK-positive advanced non-small cell lung cancer

2021 ◽  
Vol 49 (2) ◽  
pp. 030006052199364
Author(s):  
Xianxiu Ji ◽  
Huikang Xie ◽  
Ren Zhu ◽  
Bin Chen ◽  
Sen Jiang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Features ◽  
Cell Lung Cancer ◽  
Clinical Characteristics ◽  
Small Cell ◽  
Imaging Features ◽  
Small Cell Lung ◽  
Significant Difference ◽  
Alk Positive

Objective To compare the baseline clinical characteristics between patients with ROS1-positive and ALK-positive advanced non-small cell lung cancer (NSCLC), and the correlations of these subtypes with the distribution of metastases. Methods We compared the clinical characteristics and imaging features of patients with ROS1-positive and ALK-positive NSCLC using statistical methods. Results Data for 232 patients were analyzed. Compared with ALK-positive NSCLC, ROS1-positive NSCLC was more likely to occur in women (71% vs 53%), and primary lesions ≤3 cm were more common in patients with ROS1-positive compared with ALK-positive NSCLC (58% vs 37%). There was no significant difference in the distribution of metastases between the two groups. Subgroup analysis within the ROS1-positive group showed that, compared with primary lesions >3 cm, primary lesions ≤3 cm were more likely to present as peripheral tumors (72% vs 43%) and more likely to exhibit non-solid density (44% vs 4%). Conclusions Although ROS1-positive and ALK-positive NSCLCs show similar clinical features, the differences may help clinicians to identify patients requiring further genotyping at initial diagnosis.

scholarly journals COMPARATIVE ANALYSIS IMAGE RESULTS OF PANCREAS IN PORTAL VEIN PHASE ON CT SCAN ABDOMEN CONTRAST WITHOUT AND WITH MINIMUM INTENSITY PROJECTION IN CT SCAN 64 SLICE

2019 ◽  
Vol 2 (3) ◽  
pp. 101
Author(s):  
Maria Ramandita ◽  
Lailatul Muqmiroh ◽  
Pramono Pramono
Keyword(s):  
Ct Scan ◽  
Ct Scans ◽  
Analytic Method ◽  
Portal Venous Phase ◽  
Minimum Intensity Projection ◽  
Significant Difference ◽  
Venous Phase ◽  
Spss Software ◽  
Contrast Ct ◽  
Minimum Intensity

Background: Minimum Intensity Projection is a post-proccesing technique on CT Scan that useful for showing structures with low Hounsfiled Unit (HU) values such as pancreas. To demonstrate the anatomy and pathology of the pancreatic organs, a contrast CT scan was performed on pancreatic phase but pancreatic phase was rarely used, so it was replaced by the portal venous phase, but this technique is still rarely used among the radiographers. Objective: This study aimed to prove the image of the portal venous pancreatic vein on contrast contrast CT scan by using minimum intensity projection (MinIP) on CT scan 64 slices will produce a more optimal image than without the minimum intensity projection (MinIP). Methods: This study is a retrospective study with an observational analytic method to assess differences of pancreatic image in contrasting contrast CT scans with and with MinIP reforms on CT 64 slice modalities Philips Briliance. 30 images as samples, with the criteria set by the researchers. The image will be post proccesing without and by using MinIP reformat. Image results will be evaluated by two radiologist, then the data obtained will be tabulated and processed using SPSS software version 17. Result: From this research obtained the result that MinIP reformat able to produce pancreas image more optimal than image without MinIP reformat on CT scan 64 slice and shows a significant difference. Overall assessment of the image has an improvement with the MinIP but for the homogeneity of pancreatic images decreased. Conclusions: There was a significant difference between pancreatic venous porta port results in contrasting CT scans of the abdomen without and with MinIP reformat.

scholarly journals Durable Responses in Fit Elderly Patients with Chronic Lymphocytic Leukemia (CLL) in a Randomised, Fludarabine-Based, Immunochemotherapy Dose De-Escalation Study - Long-Term Follow-up By Treatment Arm and Mutational Status

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4432-4432
Author(s):  
Stephen P. Mulligan ◽  
Devinder Gill ◽  
Gavin Cull ◽  
Leanne Berkahn ◽  
David Simpson ◽  
...  
Keyword(s):  
Research Funding ◽  
Lymphocytic Leukemia ◽  
Hematological Toxicity ◽  
Early Stopping ◽  
Full Dose ◽  
Treatment Regimens ◽  
Risk Of Death ◽  
Mutational Status ◽  
Significant Difference

Abstract BACKGROUND: Immunochemotherapy (ICT) with fludarabine (F), cyclophosphamide (C) and rituximab (R) provides prolonged progression free (PFS) and overall survival (OS) in fit younger patients with CLL. The Australasian Leukaemia and Lymphoma Group (ALLG) CLL5 study previously showed FCR based therapy was safe, tolerable and effective in fit older CLL patients. We now assess the PFS and OS status by treatment arm and mutational status after a minimum of 5 years following final recruitment. METHODS: Previously untreated patients with progressive CLL aged ≥65 were randomised to one of three treatment regimens FR5, FCR3 and FCR5 (= full dose) as follows: (i) F 24mg/m2 po D1-5 + R (375mg/m2 C1, 500mg/m2 C2-6) iv D1 (FR5), (ii) F 24mg/m2 po and C 150mg/m2 po D1-3 + R iv D1 (FCR3) or (iii) F 24mg/m2 po+ C 150mg/m2 po D1-5 + R iv D1 (FCR5), all given at 4 weekly intervals for an intended 6 cycles. Early cessation of therapy was mandated for grade 3+ toxicity that delayed the next cycle >2 weeks on >2 occasions. RESULTS: The ITT population comprised 119 patients: 40 female and 79 male. Mean age was 71.6 years (range 64-83). The distribution by treatment arm was even with 38 patients on FR5, 41 on FCR3, and 40 on FCR5. As previously presented (ASH 2014), the overall response rate (ORR) was comparable at 95%, 95% and 97%, and the bone marrow confirmed complete remission (CR) rates 27%, 44% and 44% respectively. ORR and CR were not statistically significant. Toxicity was tolerable, and mainly hematological with neutropenia and thrombocytopenia. Early stopping due to toxicity occurred in 5.6%, 2.4% and 34% respectively, mainly hematological toxicity without complications. After a minimum of 5 years follow-up, no significant difference by OS (p=0.48) or PFS (p=0.93) (figure 1) was seen by treatment arm. Overall 51 patients (of 117 - 43.6%) died, hence the survival rate was 56.4%. Causes of death by treatment arm for FR5, FCR3 and FCR5 respectively were disease progression 4, 4, 1; Richter transformation 2, 0, 0; infection 2, 0, 7; and second malignancy 2, 4, 4. Of the 119 patients, 61 (51%) had data on immunoglobulin variable gene (IGHV) mutational status. In 33 (54%), IGHV were mutated (M-CLL) and 28 (46%) had unmutated IGHV (UM-CLL). The distribution by mutation status by treatment arm was even, with 10 each in FR5 and FCR3 and 13 in FCR5. Patients with M-CLL had a 61% lower risk of death and a significantly better PFS (p=0.0079; HR 0.39 [95% CL, 0.19 to 0.80]) than UM-CLL (M-CLL median PFS 110 months vs UM-CLL median PFS 48 months) (figure 2). CONCLUSIONS: Oral F(C)R therapy is generally safe and well tolerated in CLL patients aged ≥65 years requiring first-line treatment, when early stopping is utilized if prolonged toxicity is encountered; one third on full dose FCR5 stopped early with this rule, mainly with neutropenia. Response rates were high with ORR of 96% and CR rate of 56%. After a minimum of 5 years follow-up, OS and PFS outcomes by the treatment arms FR5 (full dose F, no C), FCR3 (40% FC dose reduction) and FCR5 (full-dose FCR) are essentially identical in this randomized dose de-escalation study. The median PFS overall was 53 months. CLL patients with M-CLL had a significantly superior PFS compared to UM-CLL. Disclosures Gill: Janssen: Other: TRAVEL, ACCOMMODATIONS, EXPENSES, Speakers Bureau. Cull:Takeda Australia: Other: Travel Expenses; Amgen Australia: Other: Travel Expenses; AbbVie (Australia): Membership on an entity's Board of Directors or advisory committees. Simpson:Novartis: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Celgene: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Bristol-Myers Squibb: Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Sanofi: Research Funding; BeiGene: Research Funding; Merck: Honoraria, Research Funding; Acerta: Research Funding; Pharmacyclics LLC, an AbbVie Company: Research Funding; Roche: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; Amgen: Research Funding, TRAVEL, ACCOMMODATIONS, EXPENSES; MSD: Honoraria; Janssen: Honoraria, Research Funding. Tam:Pharmacyclics: Honoraria, Travel funding; Gilead: Honoraria; Janssen: Honoraria, Research Funding; AbbVie: Honoraria, Research Funding; Roche: Honoraria; AbbVie: Honoraria, Research Funding; Roche: Honoraria; Gilead: Honoraria; Pharmacyclics: Honoraria; Beigene: Honoraria, Other: Travel funding; Beigene: Honoraria, Other: Travel funding. Badoux:Roche: Research Funding.

scholarly journals Impact of Bortezomib- or Lenalidomide-Based Induction Treatment on High Risk Cytogenetic Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Enrolled in the Gimema-MM-03-05 and EMN01 Trials

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 744-744 ◽  
Author(s):  
Alessandra Larocca ◽  
Massimo Offidani ◽  
Pellegrino Musto ◽  
Francesca Patriarca ◽  
Lorenzo De Paoli ◽  
...  
Keyword(s):  
Sensitivity Analysis ◽  
High Risk ◽  
Board Of Directors ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Risk Of Death ◽  
Significant Difference ◽  
Reduced Risk

Abstract Introduction : Cytogenetic abnormalities by fluorescence in situ hybridization (FISH) are clinically relevant prognostic factors in MM. Data in transplant ineligible patients treated with bortezomib or lenalidomide in first-line therapy for high-risk (HiR) patients is limited. Careful analysis of cytogenetic subgroups in trials comparing different treatments remains an important goal. This sub-analysis evaluates the impact of cytogenetics on outcomes in transplant-ineligible patients with newly diagnosed MM (NDMM) treated with bortezomib-based induction (BORT) or lenalidomide-based (LEN) treatment. Methods : In the GIMEMA-MM-03-05-trial, patients were randomized to bortezomib-melphalan-prednisone-thalidomide for 9 cycles followed by maintenance with bortezomib-thalidomide (VMPT-VT) vs VMP for 9 cycles, without maintenance. In the EMN01-trial, patients were randomized to melphalan-prednisone-lenalidomide (MPR) or cyclophosphamide-prednisone-lenalidomide (CPR) or lenalidomide plus low-dose dexamethasone (Rd) for 9 cycles, followed by maintenance with lenalidomide alone or plus prednisone continuously. Results of these studies have previously been reported (Palumbo A et al JCO 2010 and 2014; Magarotto V et al Blood 2016 127(9)). Cytogenetics were assessed using FISH. Patients were categorized into cytogenetic risk groups according to International Myeloma Working Group criteria. HiR cytogenetics included del(17p), t(4;14), and t(14;16); all other patients were categorized as standard risk (StR). Subgroup analyses were performed to determine the consistency of treatment effects of BOR vs LEN in the different subgroups using interaction terms between treatment and FISH, ISS, age, sex, Karnofsky PS and LDH. The different effect of BORT vs LEN in cytogenetic subgroups was confirmed by one sensitivity analysis where the follow-up of the BORT study was reduced to make the follow-up times similar; and by another sensitivity analysis with multiple imputation method for missing cytogenetic value. Results : 902 of 1165 patients from the intent-to-treat population had available cytogenetic profiles, with 243 (27%) patients in the HiR group and 659 (73%) in the StR group. In the BORT vs LEN groups, median age was 71 vs 73 years (p&lt;0.001), ISS3 20% vs 27% (P=0.65), HiR patients were 29% vs 26%, StR patients were 71% vs 74% (p=0.32) and the median follow-up was 72.3 and 63.6 months, respectively. In the subgroup analysis, a significant difference was found in the cytogenetic subgroup with a superior advantage of BORT versus LEN in HiR group, whereas no significant difference was found between BORT and LEN in the other subgroups analyzed (ISS, age, sex, Karnofsky PS and LDH) (interaction-p=0.01) (Fig. 1 B). BORT treatment resulted in a reduced risk of death or progression compared with LEN in patients with HiR. In HiR patients, median PFS was 30.8 with BORT compared with 14.8 months with LEN (HR: 0.54; 95% CI: 0.41-0.72); in StR, median PFS was 29.1 with BORT compared with 22.1 months with LEN (HR: 0.87; 95%; CI: 0.72-1.05) (Fig. 1 A). Considering the standard of care VMP and Rd, in the HiR group (n=95) VMP resulted in a 48% reduced risk of death or progression compared with Rd (HR: 0.53; 95% CI: 0.34-0.83), whereas no significant difference in PFS was found in the StR group (n=273) (HR: 1.00; 95% CI: 0.75-1.33), interaction-p=0.02. BORT treatment resulted in a reduced risk of death in patients with HiR cytogenetics: median OS was 62.4 months with BORT compared with 43.2 months with LEN (HR: 0.68; 95% CI: 0.47-0.96); in StR, median OS was 78.1 months with BORT and was not reached with LEN (HR: 1.06; 95% CI: 0.82-1.36), interaction-p=0.04 (Fig. 1 A). In patients with del(17p) (n=131) median PFS was 18.0 vs 12.9 months for BORT vs LEN (HR: 0.71; 95% CI: 0.49-1.04), interaction-p=0.73. In patients with t(4;14) (n=118) median PFS was 31.5 vs 15.2 months for BORT vs LEN (HR: 0.41; 95% CI: 0.27-0.62) interaction-p=0.002. In patients with t(14;16) (n=31) median PFS was 36.2 vs 9.8 months for BORT vs LEN treated patients (HR: 0.34; 95% CI: 0.16-0.76), interaction-p=0.045. Conclusions : BORT treatment resulted in a PFS and OS benefit vs LEN in patients with HiR cytogenetics. Treatment with VMP led to a significant reduction of the risk of death or progression vs Rd in HiR patients. These results support VMP induction as a standard treatment option for patients with NDMM who are ineligible for transplant with HiR cytogenetics. Disclosures Larocca: Celgene: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Amgen: Honoraria. Offidani: celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees. Musto: Janssen: Honoraria; Celgene: Honoraria. Patriarca: MSD Italia: Honoraria; Janssen: Honoraria. Corradini: Gilead: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Roche: Honoraria; Celgene: Honoraria; Sanofi: Honoraria; Takeda: Honoraria; Novartis: Honoraria. Bosi: Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Takeda: Membership on an entity's Board of Directors or advisory committees. Petrucci: Celgene: Honoraria; Janssen: Honoraria; Bristol-Myers Squibb: Honoraria; Takeda: Honoraria; Amgen: Honoraria. Boccadoro: Bristol-Myers Squibb: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Mundipharma: Research Funding; AbbVie: Honoraria.

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