scholarly journals Effect of BCR-ABL1 Transcript Type and Body Weight on Outcome in Chronic Myeloid Leukemia

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4611-4611
Author(s):  
Mohammad Abdul-Jaber Abdulla ◽  
Prem Chandra ◽  
Susana El akiki ◽  
Mahmood B Aldapt ◽  
Sundus Sardar ◽  
...  

Abstract Introduction The hallmark of CML is BCR-ABL1 (breakpoint cluster region gene-Abelson murine leukemia viral oncogene homolog 1) on Philadelphia chromosome, which is the result of a reciprocal translocation between the long arms of chromosomes 9 and 22 (t[9;22][q34;q11]) [1]. Chromosome 22 breakpoints influence the BCR portions preserved in the BCL-ABL1 fusion mRNA and protein and are mainly localized to one of three BCRs, namely major-BCR (M-BCR), minor BCR (m-BCR) and micro-BCR (µ-BCR). In comparison, breaks in chromosome 9 arise most frequently by alternative splicing of the two first ABL1 exons, and can also be generated in a large genetic region, upstream of exon Ib at the 5' end, or downstream of exon Ia at the 3' end. In the majority of CML cases, the breakpoint lies within the M-BCR and gives rise to e13a2 or e14a2 fusion mRNAs (previously denoted as b2a2 and b3a2) and a p210BCR-ABL fusion protein [2]. [3] Methodology We conducted a retrospective analysis of the files of 79 patients being treated in our center for CML with known BCR-ABL1 breakpoints; there were few more patients with known transcript type but excluded because either travelled immediately on diagnosis or had a failure due to confirmed compliance issues. Patients' management and response assessment was done based on ELN 2013 guidelines. The analysis is done based on two main groups, obese versus normal BMI, and then based on BCR-ABL1 transcripts: e13a2 versus e14a2. Ethical approval was obtained from Medical Research Center for Hamad Medical Corporation (MRC-01-18-337). Results Patients included 62 males (78.5%) and 17 females (21.5%) with the mean age at diagnosis 38.8±11.8 years (median, 38; range 21 to 69 years). The characteristics (demographics, anthropometric, hematological and clinico-pathological) of the patients and their association with transcript types and obesity are summarized in Table 1. Patient outcomes, cytogenetic and molecular responses The median follow-up was 30 months (range 6 to 196 months) and 38 months (range 3 to 192 months) in normal weight and obesity groups, respectively. The median follow-up was 28 months (range 3 to 196 months) and 39 months (range 10 to 192 months) in e14a2 and e13a2 patients, respectively. A total of 22 patients distributed among different groups ended up leaving the country (censored) after a variable duration of follow-up (6 - 196 months), 18 of them CML-CP, and 4 CML-AP. 3 patients died in our cohort, all of them had e14a2 transcript, one of them was in the normal weight/BMI group, two were in the obesity group. In e14a2 group, more patients were on imatinib at the time of analysis (15 (39.5%) vs 7 (17.1%) in e13a2 group, p = 0.026). The percentage of patients of had to switch TKI was similar in both groups (47.4% vs 53.7%, p = 0.576). However, less patients in e14a2 group had to switch TKI because of failure/progression (10 (55.6%) vs 17 (77.3%), p = 0.145); however, this didn't translate into a significant difference of achieving MMR at 1 year, where in e14a2 group, 10 patients achieved MMR at 1 year (31.3%), same as in e13a2 group (10 patients = 29.3%) p 0.331 (all shown in table 1). When comparing long-term outcomes, there was also no significant difference between groups based on transcript type with regards to MMR (44.7% vs 46.3% in e14a2 vs e13a2 respectively) or DMR (26.3% vs 22% respectively) as shown in figure. In the obesity group, there were 2 patients using ponatinib due to T315I mutation, compared to none in normal weight group. However, there were no significant differences in TKI used, switch of TKI, or reason for switch. Same applies for achieving MMR at 1 year, as 11 patients in the obesity group achieved MMR (28.2%) compared to 9 patients in normal weight group (33.3%), p = 0.778 (as shown in table 1). Regarding the long-term outcomes, more patients in the obesity group achieved MMR (53.2%) compared to normal weight group (34.3%), and this response was faster, but not statistically significant. This difference was less clear with regards to DMR (25.5% in the obesity group compared to 21.9% in normal weight group) as shown in figure. Conclusion In the patient-cohort studied there were no significant differences in molecular response based on transcript type or body weight/BMI. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

2021 ◽  
Vol 8 ◽  
Author(s):  
Yue Yin ◽  
Yiling Li ◽  
Lichun Shao ◽  
Shanshan Yuan ◽  
Bang Liu ◽  
...  

Objective: At present, the association of body mass index (BMI) with the prognosis of liver cirrhosis is controversial. Our retrospective study aimed to evaluate the impact of BMI on the outcome of liver cirrhosis.Methods: In the first part, long-term death was evaluated in 436 patients with cirrhosis and without malignancy from our prospectively established single-center database. In the second part, in-hospital death was evaluated in 379 patients with cirrhosis and with acute gastrointestinal bleeding (AGIB) from our retrospective multicenter study. BMI was calculated and categorized as underweight (BMI <18.5 kg/m2), normal weight (18.5 ≤ BMI < 23.0 kg/m2), and overweight/obese (BMI ≥ 23.0 kg/m2).Results: In the first part, Kaplan–Meier curve analyses demonstrated a significantly higher cumulative survival rate in the overweight/obese group than the normal weight group (p = 0.047). Cox regression analyses demonstrated that overweight/obesity was significantly associated with decreased long-term mortality compared with the normal weight group [hazard ratio (HR) = 0.635; 95% CI: 0.405–0.998; p = 0.049] but not an independent predictor after adjusting for age, gender, and Child–Pugh score (HR = 0.758; 95%CI: 0.479–1.199; p = 0.236). In the second part, Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between the overweight/obese and the normal weight groups (p = 0.094). Cox regression analyses also demonstrated that overweight/obesity was not significantly associated with in-hospital mortality compared with normal weight group (HR = 0.349; 95%CI: 0.096-1.269; p = 0.110). In both of the two parts, the Kaplan–Meier curve analyses demonstrated no significant difference in the cumulative survival rate between underweight and normal weight groups.Conclusion: Overweight/obesity is modestly associated with long-term survival in patients with cirrhosis but not an independent prognostic predictor. There is little effect of overweight/obesity on the short-term survival of patients with cirrhosis and with AGIB.


2021 ◽  
Vol 10 (5) ◽  
pp. 995
Author(s):  
Marja Perhomaa ◽  
Tytti Pokka ◽  
Linda Korhonen ◽  
Antti Kyrö ◽  
Jaakko Niinimäki ◽  
...  

The preferred surgical fixation of forearm shaft fractures in children is Elastic Stable Intramedullary Nailing (ESIN). Due to known disadvantageous effects of metal implants, a new surgical method using biodegradable polylactide-co-glycolide (PLGA) intramedullary nails has been developed but its long-term outcomes are unclear. The aim of this study was to compare the long-term outcomes of Biodegradable Intramedullary Nailing (BIN) to ESIN and assess the biodegradation of the study implants via magnetic resonance imaging (MRI). The study population of the prospective, randomized trial consisted of paediatric patients whose forearm shaft fractures were treated with BIN (n = 19) or ESIN (n = 16). Forearm rotation at minimally four years’ follow-up was the main outcome. There was no clinically significant difference in the recovery of the patients treated with the BIN as compared to those treated with the ESIN. More than half of the implants (57.7%, n = 15/26) were completely degraded, and the rest were degraded almost completely. The PLGA intramedullary nails used in the treatment of forearm shaft fractures in this study resulted in good function and anatomy. No unexpected disadvantages were found in the degradation of the implants. However, two implant failures had occurred in three months postoperatively.


2020 ◽  
Vol 8 (4_suppl3) ◽  
pp. 2325967120S0017
Author(s):  
Julien T Aoyama ◽  
Joshua T Bram ◽  
John Todd R. Lawrence ◽  
Theodore J Ganley

Background: Studies on pediatric anterior cruciate ligament reconstructions (ACLRs) often focus on graft choice, as rates of these injuries have risen in recent years. Large multicenter studies have found younger age and smaller graft size to be risk factors for graft failure and contralateral tears, but despite large sample sizes these studies have not looked specifically at graft strand number. Therefore the purpose of this study was to use a large sample size to ask whether ACLR graft strand number affects long-term outcomes. Hypothesis/Purpose: Examine long-term effects of ACLR graft strand number using a large cohort. Methods: This was a retrospective comparison study of all patients presenting between 1/1/2008 and 12/31/16 for a first-time ACLR at a single pediatric hospital. After querying medical records for all ACLRs using CPT codes, graft strand number, graft diameter, and other variables were abstracted. Long-term outcomes on graft rupture, contralateral ACL tear, and subsequent meniscus injury were collected via phone calls and REDCap emails. Patient groups were compared for differences in graft strand number and diameter using bivariate analyses, and differences in long-term outcomes were analyzed using multivariate regression. Results: 436 patients met the inclusion criteria also completed the long-term follow-up on outcomes. Long-term follow-up ranged from 18 months post surgery to 10 years post surgery. Patients with larger graft diameter were significantly less likely to suffer a complication (graft rupture, contralateral ACL tear, or subsequent meniscus injury) in multivariate regression (p=0.03), while strand number, sex, weight, and age showed no significant difference. Transphyseal reconstructions had larger graft diameters (8.8mm) than partial hybrid (8.6mm) and all-epiphyseal reconstructions (8.3mm) (p<0.001), but had no differences in graft strand number. Males had larger graft diameters (8.9mm) than females (8.6mm) (p=0.03), but also had no differences in graft strand number. Obese patients had larger graft diameters (9.1mm) than overweight (8.9mm) and normal weight patients (8.6mm) (p=0.002). Obese patients also had more graft strands (6.9) than overweight (6.2) or normal weight patients (6.1), but this difference was not significant (p=0.051). Conclusion: This data supports the existing literature that pediatric ACLR patients with larger graft diameters are less likely to suffer long-term complications. Using both a large patient cohort and long-term follow-up, this data also showed that graft strand number was not significantly correlated with outcomes. This suggests that strand number is not important when constructing ACLR grafts, as long as sufficient graft diameter can be achieved.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Wei Chen ◽  
Dipesh Kumar Yadav ◽  
Xueli Bai ◽  
Jianying Lou ◽  
Risheng Que ◽  
...  

Background. In China, the cases of liver transplantation (LT) from donation after citizens’ death have rose year by year since the citizen-based voluntary organ donor system was initiated in 2010. The objective of our research was to investigate the early postoperative and late long-term outcomes of LT from donation after brain death (DBD) and donation after circulatory death (DCD) according to the current organ donation system in China. Methods. Sixty-two consecutive cases of LT from donation after citizens’ death performed in our hospital between February 2012 and June 2017 were examined retrospectively for short- and long-term outcomes. These included 35 DCD LT and 27 DBD LT. Result. Subsequent median follow-up time of 19 months and 1- and 3-year graft survival rates were comparative between the DBD group and the DCD group (81.5% and 66.7% versus 67.1% and 59.7%; P=0.550), as were patient survival rates (85.2% and 68.7% versus 72.2% and 63.9%; P=0.358). The duration of ICU stay of recipients was significantly shorter in the DBD group, in comparison with that of the DCD group (1 versus 3 days, P=0.001). Severe complication incidence (≥grade III) after transplantation was identical among the DBD and DCD groups (48.1% versus 60%, P=0.352). There was no significant difference in postoperative mortality between the DBD and DCD groups (3 of 27 cases versus 5 of 35 cases). Twenty-one grafts (33.8%) were lost and 18 recipients (29.0%) were dead till the time of follow-up. Malignancy recurrence was the most prevalent reason for patient death (38.8%). There was no significant difference in incidence of biliary stenosis between the DBD and DCD groups (5 of 27 cases versus 6 of 35 cases, P=0.846). Conclusion. Although the sample size was small to some extent, this single-center study first reported that LT from DCD donors showed similar short- and long-term outcomes with DBD donors and justified the widespread implementation of voluntary citizen-based deceased organ donation in China. However, the results should be verified with a multicenter larger study.


2020 ◽  
Author(s):  
Fatema Tabak ◽  
Guo-Zhong Ji ◽  
Lin Miao

AbstractBackground/AimsTranspancreatic sphincterotomy (TPS) can be an alternative approach of biliary access in difficult cannulation cases. We aimed to prospectively evaluate the efficacy and safety of TPS compared to needle-knife precut (NKP), considering the late consequences of both techniques.MethodsA total of 122 enrolled patients have been divided into three groups based on the applied secondary cannulation techniques. Selective cannulation success, ERCP procedure findings, and immediate adverse events were compared between groups. We investigated the long-term outcomes during six-month after the procedure.ResultsSuccessful selective cannulation was achieved in 92.9% with TPS similarly to other groups. The mean procedure time was shorter in the TPS group without significant difference. Using TPS did not affect the rate of post-ERCP pancreatitis (PEP) with less frequent post-ERCP bleeding and perforation after TPS compared to NKP, without significant difference. Patients who received TPS, NKP, or both had no symptoms related to papillary stenosis or chronic pancreatitis during the follow-up period.ConclusionsUsing TPS was useful to achieve success cannulation in difficult cases with an acceptable PEP rate. Furthermore, it was associated with reducing bleeding and perforation rates comparing with NKP and no differences related to the long term consequences within the follow-up period.


2019 ◽  
Vol 10 (5) ◽  
pp. 543-551 ◽  
Author(s):  
Pasangi Madhuka Wijayarathne ◽  
Peter Skillington ◽  
Samuel Menahem ◽  
Amalan Thuraisingam ◽  
Marco Larobina ◽  
...  

Background: Following corrective surgery in infancy/childhood for tetralogy of Fallot (TOF) or its variants, patients may eventually require pulmonary valve replacement (PVR). Debate remains over which valve is best. We compared outcomes of the Medtronic Freestyle valve with that of the pulmonary allograft valve following PVR. Methods: A retrospective study was undertaken from a single surgical practice of adult patients undergoing elective PVR between April 1993 and March 2017. The choice of valve was at the surgeon’s discretion. There was a trend toward the almost exclusive use of the more readily available Medtronic Freestyle valve since 2008. Results: One hundred fifty consecutive patients undergoing 152 elective PVRs were reviewed. Their mean age was 33.8 years. Ninety-four patients had a Medtronic Freestyle valve, while 58 had a pulmonary allograft valve. There were no operative or 30-day mortality. The freedom from reintervention at 5 and 10 years was 98% and 98% for the pulmonary allograft and 99% and 89% for the Medtronic Freestyle. There was no significant difference in the rate of reintervention, though this was colored by higher pulmonary gradients across the Medtronic Freestyle despite its shorter follow-up. Conclusions: Pulmonary valve replacement following previous surgical repair of TOF or its variants was found to be safe with no significant differences in mortality or reintervention between either valve. Although the Medtronic Freestyle valve had a greater tendency toward pulmonary stenosis, additional follow-up is needed to further document its long-term outcomes.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Hannah Fraser ◽  
Julia Geppert ◽  
Rebecca Johnson ◽  
Samantha Johnson ◽  
Martin Connock ◽  
...  

Abstract Background Mitochondrial trifunctional protein (MTP) and long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiencies are rare fatty acid β-oxidation disorders. Without dietary management the conditions are life-threatening. We conducted a systematic review to investigate whether pre-symptomatic dietary management following newborn screening provides better outcomes than treatment following symptomatic detection. Methods We searched Web of Science, Medline, Pre-Medline, Embase and the Cochrane Library up to 23rd April 2018. Two reviewers independently screened titles, abstracts and full texts for eligibility and quality appraised the studies. Data extraction was performed by one reviewer and checked by another. Results We included 13 articles out of 7483 unique records. The 13 articles reported on 11 patient groups, including 174 people with LCHAD deficiency, 18 people with MTP deficiency and 12 people with undifferentiated LCHAD/MTP deficiency. Study quality was moderate to weak in all studies. Included studies suggested fewer heart and liver problems in screen-detected patients, but inconsistent results for mortality. Follow up analyses compared long-term outcomes of (1) pre-symptomatically versus symptomatically treated patients, (2) screened versus unscreened patients, and (3) asymptomatic screen-detected, symptomatic screen-detected, and clinically diagnosed patients in each study. For follow up analyses 1 and 2, we found few statistically significant differences in the long-term outcomes. For follow up analysis 3 we found a significant difference for only one comparison, in the incidence of cardiomyopathy between the three groups. Conclusions There is some evidence that dietary management following screen-detection might be associated with a lower incidence of some LCHAD and MTP deficiency-related complications. However, the evidence base is limited by small study sizes, quality issues and risk of confounding. An internationally collaborative research effort is needed to fully examine the risks and the benefits to pre-emptive dietary management with particular attention paid to disease severity and treatment group.


Author(s):  
Shinji Ohno ◽  
Shigehira Saji ◽  
Norikazu Masuda ◽  
Hitoshi Tsuda ◽  
Futoshi Akiyama ◽  
...  

Abstract Purpose To evaluate the efficacies of cyclophosphamide, methotrexate, and fluorouracil (CMF) and tegafur–uracil (UFT) as adjuvant therapy in patients with resected stage I–IIIA breast cancer by immunohistochemistry (IHC)-based subtype and to determine the relationships between clinicopathological factors and long-term outcomes. Methods A pooled analysis of the randomized controlled N·SAS-BC 01 and CUBC studies was conducted. Expression of hormone receptors (HRs; estrogen and progesterone receptors), human epidermal growth factor receptor 2 (HER2), and Ki67were assessed by IHC. Tumor-infiltrating lymphocytes (TILs) and nuclear/histological grades were determined by hematoxylin and eosin staining. Relapse-free survival (RFS) and overall survival (OS) were estimated by Kaplan–Meier analysis and hazard ratios were determined by Cox model adjusted for baseline tumor size and nodal status. Results A total of 689 patients (342 CMF and 347 UFT) were included in the analyses with a median follow-up of 11.1 years. There was no significant difference in RFS or OS between the two cohorts (RFS: 0.96 [95% confidence interval: 0.71–1.30], log-rank test p = 0.80; OS: 0.93 [0.64–1.35], p = 0.70). There was no difference in RFS or OS between the two cohorts for HR+/HER2− and HR+/HER2+ subtypes. RFS was significantly longer in patients treated with UFT compared with CMF in patients with HR−/HER2+ subtype (0.30 [0.10–0.88], p = 0.03). A high TILs level was associated with a better OS compared with low TILs level (p = 0.02). Conclusions This long-term follow-up study showed that RFS and OS were similar in patients with luminal-type breast cancer treated with CMF and UFT.


2020 ◽  
Vol 14 (Supplement_1) ◽  
pp. S491-S492
Author(s):  
S Lawrence ◽  
H Huynh ◽  
W El-Matary ◽  
J DeBruyn ◽  
M Carroll ◽  
...  

Abstract Background There is a paucity of data regarding long-term outcomes for adalimumab (ADA) in pediatric Crohn’s disease (CD). We describe the long-term effectiveness of ADA, in achieving clinical and biochemical remission in a Canadian multi-centre pediatric CD cohort. Moreover, we report the effects of prior anti-TNF exposure and use of a concomitant immunomodulator (IM) on durability of clinical and biochemical response. The primary outcome was 24-month corticosteroid (CS) free remission. Secondary objectives included biochemical and faecal calprotectin response over the study period. Methods Retrospective review of electronic records of all children aged 3–18 years with CD requiring ADA at 4 centres across Canada (Vancouver, Edmonton, Winnipeg and Calgary) between January 2005 and December 2017. Results One hundred and nine children (68% male; median age 13.07 [IQR 10.6–15.1]) with CD (L1 21.7%, L2 28.3%, L3 50%) were included with a median follow-up of 15.9 months [IQR 7.6–24]. Seventy-four patients (67.9%) were anti-tumour necrosis factor (TNF) naïve. Concomitant IM therapy was used in 51 (46.8%). CS free clinical remission at 24 months was observed in 45/66 (68%). Over time, the median PCDAI, CRP, ESR and faecal calprotectin significantly improved (Table 1). During follow-up, 36 (33%) patients discontinued ADA; 6 (5.5%) had primary non-response, 28 (25.7%) had secondary LOR and 2 (1.8%) had intolerance. At 24 months, clinical remission was achieved more frequently in patients who were Anti-TNF naïve (81% vs. 43.5% p 0.002). There was no significant difference in biochemical or faecal calprotectin outcomes between those who were bio-naive or experienced. There was no significant difference in the time to loss of response between those on monotherapy and combination therapy with an IM and ADA (HR 0.64 [95% CI 0.33–1.26] p0.2). Conclusion This study demonstrates that ADA is effective and durable in pediatric CD. Over 24 months, clinical, biochemical and faecal calprotectin improvement was seen. In our cohort, clinical response to ADA was greater in anti-TNF naïve compared with anti-TNF experienced patients; however,, biochemical and faecal calprotectin outcomes did not differ. ADA response appears durable with no significant difference in patients on monotherapy or combination therapy.


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yong-Sheng Liu ◽  
Mei Wei ◽  
Le Wang ◽  
Gang Liu ◽  
Guo-Ping Ma ◽  
...  

Abstract Background Subclinical hypothyroidism (SCH) is reportedly associated with an increased risk of adverse events in patients undergoing percutaneous coronary intervention (PCI). The prognostic significance of SCH in the elderly was poorly defined. The purpose of this study was to evaluate the association between SCH and long-term outcomes in older patients undergoing PCI. Methods Three thousand one hundred sixty-eight patients aged 65 years or older who underwent PCI from January 2012 to October 2014 were included. Patients were divided into SCH group (n = 320) and euthyroidism (ET) group (n = 2848) based on thyroid function test. Cox proportional hazard regression analyses were used to estimate the relative risks (RRs) of all-cause death and cardiac death for patients with SCH during a 4-year follow-up period. Results There were 227 deaths during the follow-up period including 124 deaths caused by cardiac events. There was no significant difference in mortality rate between the SCH group and the ET group (p > 0.05). After adjustment for covariates, compared with patients with ET, the RRs of death from all-cause and cardiac in patients with SCH were 1.261 (95%CI: 0.802–1.982, p = 0.315) and 1.231 (95%CI: 0.650–2.334, p = 0.524), respectively. When SCH was stratified by age, gender, and degree of thyroid-stimulating hormone elevation, no significant associations were also found in any stratum. Conclusion Our investigation revealed that SCH was negatively associated with the outcome of PCI in older patients.


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