Autograft Followed by Allograft Without Myeloablative Conditioning Regimen: A New Approach for Resistant Hematologic Neoplasia and Breast Cancer

2000 ◽  
pp. 211-216
Author(s):  
A. M. Carella ◽  
E. Lerma ◽  
A. Dejana ◽  
M. T. Corsetti ◽  
L. Celesti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Conditioning Regimen ◽  
Myeloablative Conditioning ◽  
New Approach ◽  
Hematologic Neoplasia

Long-Term Survival and Late Events After Allogeneic Stem-Cell Transplantation with Reduced-Intensity Conditioning (RIC) for AML and Mds; Comparable Results with Myeloablative Conditioning.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 518-518
Author(s):  
Avichai Shimoni ◽  
Avital Rand ◽  
Noga Shem-Tov ◽  
Izhar Hardan ◽  
Yulia Volchek ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Advanced Age ◽  
Cumulative Probability ◽  
High Dose ◽  
Myeloablative Conditioning ◽  
History Of ◽  
Predicting Factor

Abstract Abstract 518 Allogeneic stem cell transplantation (SCT) is a potentially curative therapy for patients (pts) with AML and MDS. SCT is associated with substantial mortality during the first 2 years after treatment due to relapse and non-relapse causes, whereas after 2 years survival curves often reach a plateau. However, late mortality and late events continue to cause treatment failures through the late post-transplant course. The pattern of late events has been reported following myeloablative conditioning (MAC) but is not well defined in the RIC setting. To explore late outcomes we retrospectively analyzed SCT results in a cohort of 298 pts with AML/MDS given allogeneic SCT with various regimens. As a general role, pts meeting standard eligibility criteria were given MAC, consisting of high dose intravenous busulfan (Bu) and cyclophosphamide (BuCy). Pts considered at excessive risk for non-relapse mortality (NRM), mostly due to advanced age, were given a reduced toxicity regimen such as fludarabine with high-dose Bu (FB4) or treosulfan (FT) or a RIC regimen of fludarabine and reduced doses of Bu (FB2). The 2-year and 5-year overall survival (OS) for this cohort was 48% (95CI, 42-54) and 38% (95CI, 31-44), respectively. We identified 93 pts who were alive and leukemia-free 2 years after SCT. The median age at SCT was 52 years (17-72), 52 male, 41 female. The donors were HLA-matched siblings (n=57) or unrelated donors (n=36. The conditioning regimen was FB2 (n=28), FB4 (n=21, FT (n=15) or BuCy (n=29). At the 2-year time-point, 28 pts had a history of acute GVHD, 68 had a history of chronic GVHD, 43 had active chronic GVHD which still required immune suppressive therapy (IST) in 37. Among pts surviving leukemia-free 2 years after SCT, the probability of remaining alive and leukemia-free, for the next 5 years, was 81% (95CI, 71-91) and 79% (95CI, 69-88), respectively. The probability of OS was 75%, 84%, 92% and 79%, after the various regimens, respectively (p=NS). There were 14 deaths beyond 2 years, 8 deaths due to relapse and 6 due to NRM. NRM included 3 deaths due to solid cancers, 2 due to breast cancer (both in pts transplanted for therapy related AML relapsing with the primary malignancy) and one due to colon cancer. There were 3 additional secondary cancers; breast cancer, squamous cell skin cancer and Kaposi sarcoma (1 pt each; all currently alive). Two pts died of myocardial infarction and one of chronic GVHD. In all, the cumulative incidence of late NRM was 10% (4-24). Interestingly, unlike the early post-transplant period, with current supportive care regimens, late deaths from GVHD and infections are rare. Twelve pts relapsed, 24-59 months after SCT, cumulative incidence 12% (6-23); 8 died, 4 are alive following further therapies, 3 long-term. The kinetics of late relapses was similar with MAC and RIC. Advanced age (>50) was the most significant predicting factor for shortened survival. OS was 64% and 92%, in the older and younger groups, respectively (p=0.03). All deaths due to NRM, and all secondary cancers occurred in the older group (p=0.01). Multivariate analysis (MVA) identified advanced age as the only independent predicting factor for OS; HR 3.1 (1-11.3). The conditioning regimen, disease status at SCT and donor type were not predictive. A history of acute or chronic GVHD predicted improved leukemia-free survival. Age was the most important predicting factor for NRM Active chronic GVHD was the most important factor predicting for reduced relapse risk. The cumulative probability of stopping IST by 7 years post SCT, for the entire cohort, was 73% (63-82). This probability was related to the conditioning regimen and was 80%,76%,80% and 63%, after FB2,FB4,FT and BuCy, respectively (p=0.06 for BuCy versus others). MVA identified conditioning with BuCy (HR 1.8, p=0.06) and male gender (HR 1.7, p=0.04) as predicting for prolonged need for IST. Among the 37 pts who were still on IST 2 years after SCT, the cumulative probability of stopping IST during the following 5 years was only 35%. It was higher in younger pts (59% Vs 15%, p=0.05) and in pts given FB2 (42% Vs. 31%, p=NS). In conclusion the pattern of late outcome is similar after MAC and RIC. Younger pts with AML/MDS who are leukemia-free 2 years after SCT can expect a very good outcome, while older pts are at higher risk for NRM and second cancers, which may not always relate directly to SCT. Pts given RIC are more likely to be able to stop IST, which may be associated with a better quality of life. Disclosures: No relevant conflicts of interest to declare.

A New Approach to Eliciting Meaning in the Context of Breast Cancer

2003 ◽  
Vol 26 (3) ◽  
pp. 169-178 ◽  
Author(s):  
Lesley F. Degner ◽  
Thomas Hack ◽  
John O’Neil ◽  
Linda J. Kristjanson
Keyword(s):  
Breast Cancer ◽  
New Approach

scholarly journals Breast Cancer Prediction and Diagnosis through a New Approach based on Majority Voting Ensemble Classifier

2021 ◽  
Vol 191 ◽  
pp. 481-486
Author(s):  
Mohammed Amine Naji ◽  
Sanaa El Filali ◽  
Meriem Bouhlal ◽  
EL Habib Benlahmar ◽  
Rachida Ait Abdelouhahid ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ensemble Classifier ◽  
Majority Voting ◽  
New Approach ◽  
Cancer Prediction

scholarly journals Allogeneic Hematopoietic Cell Transplantation with Myeloablative Conditioning Regimen of Reduced Toxicity Is Associated with Favorable Survival in Patients with Secondary Acute Myeloid Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 21-22
Author(s):  
Eleni Gavriilaki ◽  
Chrysavgi Lalayanni ◽  
Ioanna Sakellari ◽  
Christos Varelas ◽  
Despina Mallouri ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Conditioning Regimen ◽  
Transplant Recipients ◽  
Myeloablative Conditioning ◽  
Comorbidity Index ◽  
Reduced Toxicity ◽  
Reduced Intensity

Background: Secondary or treatment-related acute myeloid leukemia (sAML) is associated with poor outcomes. Although allogeneic hematopoietic cell transplantation (alloHCT) is the treatment of choice, patient eligibility criteria and optimal conditioning regimen remain under study. We have previously shown an advantage of a myeloablative conditioning regimen with reduced toxicity (Fludarabine 150mg/m2, Treosulfan 42g/m2, FluTreo) compared to a reduced intensity regimen. However, the long-term effects of this regimen remain unknown, especially in comparison to patients not receiving alloHCT. Aims: We hypothesized that patients transplanted with FluTreo would have a long-term survival advantage over other treatment alternatives. Methods: We retrospectively studied consecutive patients treated for sAML in our center over the last two decades (1998-2018). Exclusion criteria were: age>70 years, ECOG performance status≥3 at presentation, induction regimens≤2, and autologous or haploidentical HCT because these were performed in individual patients. Since 2013, we have introduced FluTreo for patients with a suitable donor that would have been previously eligible only for reduced intensity conditioning/RIC. The following factors were studied in the whole cohort: age, type of disease (treatment-related or post myelodysplastic syndrome/MDS), previous intensive chemotherapy cycles, cytogenetic risk, overall (OS) and disease-free survival (DFS). In transplant recipients, we also recorded HCT-comorbidity index/CI score, cumulative incidence (CI) of graft-versus-host disease (GVHD), and treatment-related mortality (TRM). Follow-up was calculated from diagnosis in the whole cohort; and from date of transplant in the sub-group analysis of transplant recipients. Results: We studied 19 FluTreo recipients compared to 46 recipients of other conditioning regimens (38 myeloablative and 8 RIC), and 52 patients treated only with chemotherapy. Complete remission (CR) had been achieved in all FluTreo recipients before HCT, compared to 53% of other transplants, and 44% of chemotherapy only patients (p<0.001). As expected, median age was increased in FluTreo and chemotherapy only patients (59 and 58 years respectively), compared to other transplants (48 years, p<0.001). There was no other difference in baseline characteristics. With a median follow-up of 43 (range 13-204) months in surviving patients, 4-year OS was 40.3% in FluTreo versus 31.3% in other transplants and 11.8% in chemotherapy only patients (p<0.001, Figure 1A). In the multivariate analysis, achieving CR (p<0.001) and the FluTreo group (p<0.001) were associated with favorable OS, independently of age and cytogenetic risk. 4-year DFS was 32.3% in FluTreo, versus 29.3% in other transplants and 10.2% in chemotherapy only patients (p=0.001, Figure 1B). Within transplanted patients, there was no significant difference in GVHD, relapse and TRM between FluTreo and other transplants. Within the FluTreo group, acceptable rates of CI in severe acute and extensive chronic GVHD were observed (15.2% and 18.4%, respectively). Similarly, 4-year CI of TRM reached 30.4%, despite a median HCT-CI of 3 (0-7), age of 59 (51-67) years, 4 lines of treatment (3-6), and a majority of matched unrelated donors (13/19). Conclusion: Our real-world study confirms that alloHCT with FluTreo expands the transplant population with similar safety and efficacy to previous transplant modalities in sAML patients. Achievement of CR remains a major predictor of OS in these patients. The choice of alloHCT in this unique patient population of a rather older age and comorbidity index needs to be revisited. Figure 1 Disclosures Gavriilaki: Omeros Pharmaceuticals: Consultancy.

scholarly journals The Antiasthma Medication Ciclesonide Suppresses Breast Cancer Stem Cells through Inhibition of the Glucocorticoid Receptor Signaling-Dependent YAP Pathway

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6028 ◽  
Author(s):  
Su-Lim Kim ◽  
Hack Sun Choi ◽  
Ji-Hyang Kim ◽  
Dong-Sun Lee
Keyword(s):  
Breast Cancer ◽  
Glucocorticoid Receptor ◽  
Underlying Mechanism ◽  
Tissue Growth ◽  
New Approach ◽  
Ru 486 ◽  
Mammosphere Formation ◽  
Cysteine Rich Protein ◽  
Anti Cancer ◽  
Interfering Rna

Ciclesonide is an FDA-approved glucocorticoid used to treat asthma and allergic rhinitis. However, whether it has anticancer and anti-cancer stem cell (CSC) effects is unknown. This study focused on investigating the effect of ciclesonide on breast cancer and CSCs and determining its underlying mechanism. Here, we showed that ciclesonide inhibits breast cancer and CSC formation. Similar glucocorticoids—dexamethasone and prednisone—did not inhibit CSC formation. Ciclesonide-induced glucocorticoid receptor (GR) degradation was dependent on ubiquitination. We showed via GR small interfering RNA (siRNA) that GR plays an important role in CSC formation. We showed via western blot and immunofluorescence assays that ciclesonide reduces the nuclear level of GR. The GR antagonist RU-486 also inhibited CSC formation. Ciclesonide reduced the protein level of the Hippo transducer Yes-associated protein (YAP). GR siRNA induced a decrease in YAP protein expression and inhibited mammosphere formation. The YAP inhibitor verteporfin inhibited CSC formation and transcription of the connective tissue growth factor and cysteine-rich protein 61 genes. The GR/YAP1 pathway regulated breast CSC formation. We showed that the GR/YAP signaling pathway regulates breast CSC formation and revealed a new approach for targeting GR and YAP to inhibit CSC formation.

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