scholarly journals Prognostic Significance of Thyroglobulin Antibodies in Differentiated Thyroid Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-6 ◽  
Author(s):  
Jordi L. Reverter ◽  
Irene Rosas-Allende ◽  
Carlos Puig-Jove ◽  
Carles Zafon ◽  
Ana Megia ◽  
...  
Keyword(s):  
De Novo ◽  
Prognostic Significance ◽  
Differentiated Thyroid Carcinoma ◽  
Thyroglobulin Antibodies ◽  
Incomplete Response ◽  
Initial Cohort ◽  
Risk Condition ◽  
Thyroglobulin Autoantibodies ◽  
Design And Methods

Objective. To investigate whether variations in thyroglobulin autoantibodies (TgAb) are related to the recurrence or persistence of differentiated thyroid carcinoma (DTC) and may therefore be useful as surrogate tumor markers. Design and Methods. We retrospectively studied 98 subjects (83 women, 47 ± 15 years old) from an initial cohort of 1017 patients treated for DTC in five hospitals, with positive TgAb at any time during the follow-up. Patients presented five different patterns of evolution of serum TgAb concentrations: (1) stable positive TgAb, (2) de novo appearance, (3) an increase of more than 50%, (4) TgAb levels from positive to negative, and (5) a decrease of more than 50%. Results. In the group of 11 patients with stable TgAb, four cases presented persistence of the disease with structural incomplete response. In the group of 22 patients with sustained increasing trend rising more than 50% or de novo detectable TgAb levels, three patients were diagnosed with structural incomplete response. There was no evidence of recurrence or persistence of the disease in any of the 65 patients who showed a significant decrease in (n = 35) or disappearance of (n = 30) TgAb. Conclusions. Our results suggest that not only the appearance of a significant increase in TgAb but also stable concentrations of TgAb should be regarded as a sufficient risk condition for an active search for recurrent or persistent disease. Conversely, a significant decrease in TgAb levels can represent a good prognostic sign.

scholarly journals MBCL-04. 5 – AZACYTIDINE IN TREATMENT OF CHILDREN WITH DE NOVO AND RELAPSED METASTATIC MEDULLOBLASTOMA: RESULTS OF INTERCENTER PILOT STUDY

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii387-iii387
Author(s):  
Andrey Levashov ◽  
Dmitry Khochenkov ◽  
Anna Stroganova ◽  
Marina Ryzhova ◽  
Sergey Gorelyshev ◽  
...  
Keyword(s):  
Gene Amplification ◽  
De Novo ◽  
Prognostic Significance ◽  
N Gene ◽  
Free Survival ◽  
Tumor Bed ◽  
Craniospinal Radiation ◽  
Therapeutic Program ◽  
Grade 3

Abstract The aim of this study was to estimate treatment toxicity and event-free survival (EFS) according to therapeutic program, MYC/MYC-N gene amplification and MGMT/DNMT (1, 3a, 3b) proteins expression in tumor cells. From 2016 to 2018 twenty four patients were included in trial. Children underwent adjuvant therapy: craniospinal radiation (CSI) or local radiation therapy (RT) to the relapsed site up to 23.4Gy with 5-azacytidine, 2 cycles methotrexate/5-azacytidine/cisplatin/etoposide, 3 cycles 5-azacytidine/temozolomide - for relapsed group (arm A, n = 5); for patients with de novo medulloblastoma: arm B, n = 11 – vincristine/cyclophosphamide/cisplatin/etoposide (OPEC) - based induction, CSI 36Gy + local RT to the tumor bed up to 54Gy with 5-azacytidine, 1 cycle OPEC and 2 cycles thiophosphamide/carboplatin with auto stem cell transplantation (auto-SCT); arm C, n = 8 – cyclophosphamide/cisplatin - based induction, CSI 23.4 Gy followed by 2 cycles 5-azacytidine/thiophosphamide/carboplatin with auto-SCT, local RT with 5-azacytidine. The combination of 5-azacytidine with local RT or temozolomide was safety and tolerability. Arm C was discontinued due to severe gastrointestinal grade 3/4 toxicity, hemorrhagic syndrome after combination of 5-azacytidine with thiophosphamide/carboplatin. EFS was 0% in arm A, 53.0 ± 15.5%, 50.0 ± 17.7% in arms B and C, a median follow-up 8.8 ± 1.1 months (arm A), 18.8 ± 2.5 months (arm B), 25.0 ± 4.4 months (arm C). Addition of 5-azacytidine to RT or chemotherapy did not improve EFS of patients with MYC/MYC-N gene amplification positive tumor. There was not determined any prognostic significance of MGMT/DNMT (1, 3a, 3b) proteins expression in this cohort.

scholarly journals Significance of “de novo” appearance of thyroglobulin antibodies in patients with differentiated thyroid cancer

2020 ◽  
Vol 35 (3) ◽  
pp. 41-49
Author(s):  
Lorenzo Scappaticcio ◽  
Pierpaolo Trimboli ◽  
Frederik A. Verburg ◽  
Luca Giovanella
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
De Novo ◽  
Disease Free Survival ◽  
Thyroglobulin Antibodies ◽  
Free Survival ◽  
Similar Disease ◽  
Structural Disease ◽  
Disease Free

Objective Clinical and laboratory guidelines recommend thyroglobulin antibodies (TgAbs) measurement with every thyroglobulin (Tg) measurement for the follow-up of differentiated thyroid cancer (DTC) patients. However, no evidence exists on the need for perpetual TgAbs testing in patients who are TgAb-negative at baseline. Our study was carried out to evaluate the prevalence, the dynamic changes, and the clinical significance of TgAbs that appeared de novo during the follow-up of DTC patients who were TgAb-negative at baseline. Methods The data of DTC patients with negative pre-ablation TgAbs were reviewed retrospectively. The main characteristics of patients with both transient and sustained de novo TgAbs appearance were analyzed. DTC patients with persistently negative TgAbs served as controls. Results Among 119 patients with pre-ablation negative TgAbs, 14 cases (11.7%) with de novo TgAbs appearance (10 and 4 patients with a transient and sustained de novo TgAbs appearance, respectively) were detected. No differences in disease-free survival were observed in patients with de novo TgAbs appearance compared to controls. The TgAbs peak value was higher in patients with sustained de novo appearance compared to patients with transient de novo. Two of 14 patients with de novo TgAbs developed structural disease with concurrently detectable Tg in both cases. Conclusions Transient de novo TgAbs appearance is not infrequent during DTC patients’ follow-up, and it has no apparent clinical impact. Sustained de novo TgAbs appearance is rare and may predict structural recurrences; however, similar disease-free survival was observed in patients with sustained de novo TgAbs and TgAb-negative DTC patients.

Prognostic Significance of Serial Determinations of LDH Levels in Primary (De Novo) Myelodysplastic Syndromes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4828-4828
Author(s):  
Friedrich Wimazal ◽  
Wolfgang R. Sperr ◽  
Anja Vales ◽  
Michael Kundi ◽  
Alexandra Boehm ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lactate Dehydrogenase ◽  
Disease Progression ◽  
Myelodysplastic Syndromes ◽  
Prognostic Value ◽  
De Novo ◽  
Prognostic Significance ◽  
Bone Marrow Examination ◽  
Probability Of Survival

Abstract An increased lactate dehydrogenase (LDH) level at diagnosis is associated with a reduced probability of survival and an enhanced risk of AML development in primary (de novo) myelodysplastic syndromes (MDS). However, so far, little is known about the prognostic value of an increase in LDH levels during the follow up in these patients. We have serially determined LDH levels in 221 patients (102 males, 119 females) with de novo MDS (median age 70 years; FAB-types: RA, n=62; RARS, n=46; RAEB, n=48; RAEBT, n=36; CMML, n=29), and examined the prognostic value of LDH as a follow-up parameter. Confirming previous data, an elevated LDH level at diagnosis was found to be associated with a significantly increased probability of AML evolution and a significantly decreased probability of survival (p<0.05). In the follow up, an increase in LDH (from normal to elevated) was found to be associated with progression of MDS and AML evolution in most cases. Moreover, in those patients who progressed to AML, LDH levels were found to be significantly higher in the two three-months-periods preceding progression compared to the two initial three-months-periods examined (p<0.005). In most patients, the increase in LDH was accompanied or followed by other signs of disease progression, such as the occurrence of thrombocytopenia or an increase in blasts. Together, our data show that LDH can be employed as a prognostic follow-up variable in patients with MDS. In those patients in whom an increase in LDH is noted, a thorough re-evaluation of the progression-status of the disease including a bone marrow examination should be considered.

ASXL1 Mutations in AML: Molecular Biomarker for Secondary AML?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2343-2343
Author(s):  
Jingmei Hsu ◽  
Anita J. Kumar ◽  
Martin P. Carroll ◽  
Noelle V. Frey ◽  
Nirav N. Shah ◽  
...  
Keyword(s):  
Overall Survival ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Myeloproliferative Neoplasm ◽  
Molecular Characteristics ◽  
Intermediate Risk ◽  
Kaplan Meier ◽  
The Impact

Abstract Background: Additional sex combs like transcription factor 1 (ASXL1) is a member of the polycomb group protein. ASXL1 mutation has been implicated in myeloid malignancy transformation. It is hypothesized that mutated ASXL1 leads to the loss of polycomb repressive complex 2 (PRC2) mediated gene repression and subsequent transforming events. Recent studies identify ASXL1 mutation as a poor prognostic marker in patients (pts) with de novo acute myeloid leukemia (AML) who present with intermediate–risk cytogenetic lesions (Patel, NEJM 2012; Schnittger, Leukemia2013). To study the impact of ASXL1 mutations in an unselected AML population, we analyzed clinical and molecular characteristics of patients with untreated AML who express ASXL1 mutation at presentation. Methods: Using next generation sequencing, 254 adult patients with AML seen at the Hospital of the University of Pennsylvania were analyzed for mutations, including ASXL1, using a 33-gene hematologic malignancy panel. Clinical characteristics were obtained from retrospective chart review. Kaplan-Meier estimates were used to calculate overall survival (OS) from time of diagnosis. Living patients were censored at date last seen. Results: ASXL1 mutations were detected in 36/254 (14%) AML pts. There were 29 known pathologic mutations, 1 benign, 1 probable pathologic, and 9 variants of unknown clinical significance (VUS). In 6/36 (16.7%) pts, ASXL1 was the sole mutation identified. Of the 30 pts with additional mutations (Figure 1), 6/30 (20%) pts harbored 2 independent ASXL1 mutations. When the 27 patients with pathologic ASCL mutations were analyzed for co-mutations, TET2 (13/27, 48%) was the most frequent ASXL1 co-mutation. FLT3 (0/27, 0%) and NPM1 (1/27, 3.7%) were notable for their absence. Median age of pts at diagnosis was 69 years (range 23-80). Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) was noted in 9/36 (25%) and 11/36 (30.6%) pts, respectively. Four pts (11.1%) had received chemotherapy and/or radiation therapy for a prior non-myeloid neoplasm. Karyotype was normal in 18/36 (50%) pts, and 7 additional pts had intermediate cytogenetic lesions. There were 7 pts (19.4%) with unfavorable cytogenetics (complex karyotype (3 pts), 7q- (3 pts), and 5q- (1 pt)). Four pts (11.1%) had a favorable karyotype, with t(8;21) in 3 pts and t(15;17) in 1 pt. At presentation, median white blood cell count (WBC) was 6.4x103/uL (1.0 x -103). In pts whose AML transformed from prior MPN, median WBC was 50 X103/uL (3.3-140). Standard induction chemotherapy with an anthracycline and cytarabine was given to 17/36 (47%) pts. An additional 3/36 (8.3%) pts underwent induction therapy with clofarabine. Complete remission (CR) was documented in 14/20 (70%) evaluable pts. Of the remaining pts, 11 received a hypomethylating agent, and 5 received other therapies. Thirty-day treatment mortality for all 36 pts and for 27 pts with known ASXL1 pathologic mutation was 13.4% and 18.5% respectively. Kaplan-Meier estimate showed a median overall survival of 349 days (median follow up of 107 days (range 15-1570)). For the 27 pts with a pathologic ASXL1 mutation, the OS was 276 days (Figure 2, median follow up of 145 days (range 18-1570)). Conclusion: ASXL1 mutations in de novo AML with intermediate-risk cytogenetics is associated with poor clinical outcome in cooperative group trials. Strikingly we demonstrate in a single institution, retrospective analysis that 66.7% of pts who present with ASXL1 mutations in the setting of previously untreated AML had documented MDS, MPN and/or prior chemotherapy/radiation. Further studies are necessary to evaluate if ASXL1 mutation has independent prognostic significance in AML or if it is primarily a marker for secondary leukemia. Figure 1: ASXL1 and co-mutations Figure 1:. ASXL1 and co-mutations Figure 2: Overall survival for AML patients with ASXL1 pathologic mutation Figure 2:. Overall survival for AML patients with ASXL1 pathologic mutation Disclosures No relevant conflicts of interest to declare.

Glutathione S-Transferases (GSTT1 and GSTM1) Genes Polymorphisms and Response and Prognosis of Chinese Patients with De Novo Acute Myeloid Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4293-4293
Author(s):  
Lin Yang ◽  
Zhijian Xiao ◽  
Jianxiang Wang ◽  
Yushu Hao
Keyword(s):  
Overall Survival ◽  
Induction Therapy ◽  
De Novo ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Chinese Patients ◽  
Lower Probability ◽  
Acute Monocytic Leukemia ◽  
Monocytic Leukemia

Abstract The GSTT1 and GSTM1 genes are polymorphic in humans, with the phenotypic absence of enzyme activity caused by a homozygous inherited deletion of the gene. A number of prior studies have reported on GST genotype and outcome of therapy for AML. In this study, we analyzed the prognostic significance of gene polymorphism of GSTT1, GSTM1 in Chinese patients with de novo AML other than M3. A total of 254 cases were entered. There are 157 males and 97 females, ranging in age from 15 to 75 years (median: 32 years). Patients were diagnosed following WHO criteria, 81 were AML with t(8;21) AML1/ETO, 54 were AML with inv(16) or t(16;16) CBF-β/MYH11, 4 were AML with 11q23 abnormalities (MLL), 1 was minimally differentiated, 3 were AML without maturation, 44 were AML with maturation, 17 were acute myelomonocytic leukemia, 42 were acute monocytic leukemia, and 8 were acute erythroid leukemia. All the patients were treated with HAD regimen (Homoharringtonine, HHT, 2.5mg/m2 intravenously on days 1 to7; Ara-c, 150 mg/m2/d continuous infusion on days 1 to 7, and DNR,45 mg/m2 intravenously on days1 to 3.) as induction therapy. Postremission therapy consisted of HA regimen (HHT and Ara-c)(course 1 and 4), DA regimen (DNR and Ara-c)(courses 2 and 5), and MA regimen (MTZ and Ara-c) or HAM (Ara-c 1g/m2,q12h, intravenously on days 1 to 4, combined with MTZ 8mg/m2, intravenously on days 5 to 7(courses 3 and 6). The multiplex PCR method was used to simultaneously amplify and analyze GSTM1,GSTT1, and β-globin from patients. 21 patients died before marrow recovery or adequate assessment of response. 165 (68.5%) achieved a CR after the first course of chemotherapy and 194 (80.5%) achieved a CR after the second course of chemotherapy. Median follow-up was 36 months (11 to 111 months). 104 patients were last known to be alive after entering the study, the other 138 patients are now decease. Twelve patients lost to follow-up are censored at the date they were last known to be alive. Median OS and median RFS was 22 months and 19 months, respectively. OS rates at 3 years and 5 years were 38.9%±3.5% and 25.2%±6.5%, respectively. RFS rates at 3 years and 5 years were 32.8%±3.9% and 22.4%±5.2%, respectively. The rate of early death after the initiation of chemotherapy was similar between the GSTT1+/ GSTM1+ group and GSTT1− / GSTM1- group. The CR rates was higher in GSTM1+ group(71.9%) than GSTM1− group(60.8%) (OR=1.882; P =0.034) after the initiation of chemotherapy, and The CR rates was higher in GSTT1+ group(82.6%) than GSTT1− group (70.75)(OR=2.204; P =0.024) after the second course of chemotherapy. Overall survival and disease-free survival of patients who achieved complete remission (CR) in GSTT1 and GSTM1 double present group(50.1%±9.6% and 43.1%±9.6% at 5 years, respectively) was better than GSTT1- and/or GSTM1- group(27.2%±4.6% and 15.7%±6.3% at 5 years, respectively) (p=0.03 and p=0.022, respectively). For patients with AML with inv(16)(p13q22) or t(16;16)(p13;q22)(CBFβ/MYH11), Overall survival was better in GSTT1+ group than GSTT1− group(69.7%±10.5% v 27.5%±13.0% at 5 years)(p=0.013). Our data showed AML patients with deletions of GSTM1 or GSTT1 or both had a lower probability to achieve CR on induction therapy as compared to patients with intact GST genes and a shorter survival.

Reduced Intensity Conditioned Volunteer Unrelated Donor Transplants Using Alemtuzumab Are Safe and Effective in Older Patients with Myelodysplastic Syndromes.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 444-444 ◽  
Author(s):  
ZiYi Lim ◽  
Aloysius Ho ◽  
Michelle Kenyon ◽  
Stephen Devereux ◽  
Rafael Duarte ◽  
...  
Keyword(s):  
Older Patients ◽  
Response Rate ◽  
De Novo ◽  
Chronic Gvhd ◽  
Prognostic Significance ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Donor Chimerism ◽  
Select Group

Abstract Use of myeloablative conditioning HSCT regimens have been limited to a select group of patients with MDS. This is due in part to the high transplant related mortality, which is closely associated with increasing recipient age as well as the degree of HLA parity. We have conducted a prospectively designed, single-center study to assess the efficacy of an RIC regimen consisting of fludarabine, busulphan, and alemtuzumab (FBC) in 75 patients with MDS utilizing hematopoietic stem cells (HSC) from VUD. The RIC protocol consisted of 30 mg/m2 fludarabine iv from day −9 to −5; 4 mg/kg oral busulphan from day −3 to −2; and 20 mg alemtuzumab iv from day −8 to −4. Patients received cyclosporine A for GvHD prophylaxis. All patients possessed relative or absolute contraindications to conventional myeloablative HSCT. 30 patients received RIC on the basis of advanced age alone. 13 patients had been treated for IPA within 3 months of transplantation. Median age of patients was 52 years (range 24–68 years). The stem cell source was BM in 28 patients and PBSC in 47 patients; median CD34 cell doses were 2.25 x 106/kg (range:0.7–9.7) and 6.2 x 106/kg (range:0.7–17.8), respectively. 23 (31%) donor-recipients were mismatched on 1 or more HLA loci. 49 patients (65%) had an IPSS stage of ≥Int-2, and 55 (73%) had received induction chemotherapy prior to HSCT. 67 patients (89%) had stable disease or were in complete morphological remission at time of transplant. Mean time to engraftment was 13 days for neutrophil count >0.5 x 109/L, and 16 days for an unsupported platelet count >20 x 109/L. Three patients had primary graft failure. With a median follow-up of 315 days (range:36–2096), 38 patients (51%) were alive at the time the data were censored. The median follow-up for survivors was 752 days (range:74–2096). The Kaplan-Meier estimates of OS at years 1 and 2 were 55% and 47%, respectively. Similarly, at years 1 and 2, NRM was 10% and 30%, respectively, and DFS was 48% and 40%, respectively. Significantly, the OS and DFS curves plateau at day+902 and day+799, respectively, suggesting that longer term disease eradication can be achieved. The prognostic significance of IPSS, cytogenetic risk and disease status at transplantation was maintained in our cohort. 20 patients received DLI post transplantation. DLI was given for falling donor chimerism in 10 recipients, with re-establishment of full-donor chimerism in 9 patients. While DLI was effective against cytogenetic relapses (response rate 50%), it was less effective against established morphologic relapse (response rate 33%). Limited and extensive de novo chronic GVHD occurred in 14 patients (18%) and 12 patients (17%) respectively. Following DLI, the overall cumulative incidence of acute grade III-IV GvHD at 2 years was 25%. When chronic extensive GvHD was present in the study, it significantly correlated with a lower relapse rate (p<0.05). CMV reactivation occurred in 21 (28%) patients at a median time of 59 days (range:29–215 days) following transplantation, with 2 patients developing CMV disease. Two patients had IPA post-transplant; however, none of the 13 patients with recent IPA pre-transplant experienced progression of the infection. In our cohort of older patients with a high degree of HLA disparity and significant co-morbidities, RIC HSCT regimen utilizing FBC, can serve as a platform for durable engraftment, with a low incidence of GVHD, favorable TRM, and long-term DFS.

scholarly journals Frequency of 11q23/MLL gene rearrangement in Egyptian childhood acute myeloblastic leukemia: Biologic and clinical significance

2014 ◽  
Vol 03 (04) ◽  
pp. 206-208
Author(s):  
Adel Abdelhaleim Hagag ◽  
Shebl S. Shebl ◽  
Nabih H. El-Fadaly
Keyword(s):  
De Novo ◽  
Fusion Gene ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Cytogenetic Abnormalities ◽  
Blast Count ◽  
Laboratory Investigations ◽  
De Novo Aml

Abstract Background: Molecular cytogenetic abnormalities involving 11q23 are among the most common cytogenetic abnormalities in acute myeloid leukemia (AML) patients. Aim of the work: we aimed to evaluate the frequency of MLL/AF9 fusion gene in de novo AML patients, its impact on clinical features, and its prognostic significance. Patients and Methods: Twenty-eight children patients with AML and 20 healthy controls were subjected to complete clinical examination and laboratory investigations including, complete hemogram and bone marrow (BM) examination. Diagnosis was based on FAB morphologic and immunophenotypic criteria. Detection of (MLL/AF9) fusion gene was assessed by dual color fluorescent in situ hybridization (FISH). Follow-up were carried out clinically and by blast count in BM, and response to therapy to detect the outcome of the disease. Results: The incidence of MLL-fusion gene MLL/AF9 in AML cases was about (6/28) (21%). Four patients with MLL/AF9 fusion gene were newly diagnosed, two cases were at relapse and no patient at remission showed positivity. As regard the clinical outcome, five out of six MLL positive cases died, three of them during induction and two during relapse. The FAB AML subtypes with MLL/AF9 fusion were one M2, three M4, and two M5. Conclusion: MLL-fusion gene MLL/AF9 was found in about 21% of studied AML patients when assessed by FISH technique and this is of high clinical relevance as most of these abnormalities have been associated with poor prognosis.

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