scholarly journals Impact of Post-Remission Maintenance Therapy (MT) on Outcomes in Patients (pts) with Newly Diagnosed Acute Myeloid Leukemia (AML) in Real-World Practice

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4140-4140
Author(s):  
Ravi Potluri ◽  
David Rotter ◽  
Zephirin Kiendrebeogo ◽  
Clara Chen
Keyword(s):  
Bone Marrow ◽  
Maintenance Therapy ◽  
Induction Chemotherapy ◽  
Real World ◽  
Cox Regression ◽  
The United States ◽  
Hazard Ratio ◽  
Newly Diagnosed ◽  
Ecog Ps ◽  
Bone Marrow Blasts

Abstract INTRODUCTION : Therapeutic advances have led to improved survival outcomes in patients (pts) with AML. Consolidation therapy helps to eradicate residual leukemia and prevent relapse. However, relapse remains a major concern and contributes to suboptimal outcomes in pts with newly diagnosed AML who attain remission following induction chemotherapy (IC). Strategies for maintenance therapy (MT) attempt to prolong AML remission and extend survival. MT approaches have included chemotherapy, hypomethylating agents (HMAs), and targeted small-molecule drugs. Overall, the evidence in favor of MT is limited. The oral formulation of azacitidine (Oral-AZA), an HMA, is the first and only MT to demonstrate significant overall survival (OS) and relapse-free survival (RFS) benefits in pts with a broad range of AML subtypes (Wei, NEJM 2020), leading to regulatory approvals in the United States (2020), Canada (2021), and European Union (2021). This study aimed to determine in real-world practice whether the use of MT after IC, with or without consolidation, conferred any clinical advantage before Oral-AZA became available. METHODS: This study included pts in the US-based Flatiron TM Health cancer-specific electronic health record-derived database diagnosed with AML between January 2014 and December 2020. Eligible pts in this study obtained remission (< 5% bone marrow blasts) from first-line (1L) induction chemotherapy or venetoclax (VEN)-based therapy, had not previously taken Oral-AZA or any clinical study drug, and did not undergo transplant prior to relapse. Pts were grouped into 2 cohorts: Cohort A comprised pts who did not receive MT, and Cohort B comprised pts who did receive MT. RFS and OS were estimated using Kaplan-Meier (KM) methods. Multivariate Cox regression models that retained baseline (BL) characteristics (age, sex, BMI, ECOG performance status [PS], and cytogenetic risk) were used to examine the relationships between use of MT and relapse (> 5% bone marrow blasts), and MT and survival. RESULTS: A total of 952 pts met the selection criteria: 808 pts (84.9%) in Cohort A and 144 pts (15.1%) in Cohort B. The most commonly received MTs for pts in Cohort B were injectable AZA (34.7%; n = 50), decitabine (24.3%; n = 35), and VEN-based regimens (21.5%; n = 31). Cohorts A and B were comparable for sex, BL BMI, ECOG PS score, and practice type (Table). Pts who did not receive MT (Cohort A) were younger (mean age 62.1 vs 66.0 years; P = 0.006) and more commonly presented with favorable cytogenetic risk (17.2% vs 6.9%; P = 0.011) compared with pts who received MT (Cohort B). The percentage of pts receiving IC in a 7+3 regimen was similar between Cohort A and Cohort B (69.1% vs 67.4%, respectively; P = 0.685), as were the proportions of pts receiving VEN + an HMA (23.3% vs 17.4% P = 0.118). The KM analysis indicated that although median RFS of Cohort A was longer than Cohort B, differences between cohorts were not statistically significant (303 vs 276 days, P = 0.175). In a subanalysis of pts with intermediate/poor cytogenetic risk, median RFS was 201 days for Cohort A and 230 days for Cohort B (P = 0.952). In the multivariate Cox model, treatment with MT was not a significant predictor of improved RFS vs no MT (hazard ratio [95% CI]: 0.97 [0.79, 1.20]). Age and cytogenetic risk were significantly associated with RFS. The median OS was 659 days for Cohort A and 389 days for Cohort B (P = 0.006). In the subanalysis excluding pts with favorable or unknown cytogenetic risk, median OS was 400 days for Cohort A and 366 days for Cohort B (P = 0.561). A multivariate Cox regression model suggested that treatment with MT was not a significant predictor of improved OS (hazard ratio [95% CI]: 0.88 [0.70, 1.10]). Age, sex, ECOG PS, and cytogenetic risk were all significantly associated with OS. CONCLUSIONS: These Flatiron data provide real-world evidence that despite decades of study, optimal MT in AML had remained elusive. Prior to approval of Oral-AZA, the most common MT options for pts with AML in first remission after 1L induction therapy were limited and appeared to lack clinical benefit. Pts with AML need an MT that prolongs remission and improves long-term survival. Further research is needed to elucidate the benefits and disadvantages of different MT options and may lead to establishment of optimal MT as standard of care. Figure 1 Figure 1. Disclosures Potluri: Bristol Myers Squibb: Consultancy. Rotter: SmartAnalyst Inc.: Current Employment. Chen: Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.

Probability of Eventual CR After Course 1 of Induction Therapy for Newly-Diagnosed AML As a Function of Platelet and Neutrophil Recovery.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2598-2598
Author(s):  
Laura F Newell ◽  
Hu Xie ◽  
John M. Pagel ◽  
Ravinder K Sandhu ◽  
Pamela S Becker ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Platelet Count ◽  
Induction Chemotherapy ◽  
Induction Therapy ◽  
Blood Count ◽  
Newly Diagnosed ◽  
Platelet Recovery ◽  
Platelet Counts ◽  
Bone Marrow Blasts ◽  
Count Recovery

Abstract Abstract 2598 Background: After initial induction chemotherapy for acute myeloid leukemia (AML), it is commonplace that reinduction or intensified therapy is not indicated if the bone marrow has <5% blasts, even despite persistently low neutrophil (ANC) and/or platelet counts. This practice suggests that complete remission (CR), i.e. ANC >1000/μl and platelet count >100,000/μl per standard criteria (Cheson BD, et al. J Clin Oncol. 1990;8(5):813-9), might still occur and that the lack of blood count recovery may not bear prognostic significance. However, the time to CR after the first induction has been shown to be inversely related to subsequent duration of disease-free survival (DFS) and survival (OS), independent of age, treatment, and cytogenetics (Estey EH, et al. Blood. 2000;95(1):72-7). Additionally, the level of ANC and platelet recovery at time of CR is prognostic, with significantly better DFS among patients with higher counts (Yanada M, et al. Leuk Res. 2008;32(10):1505-9). Newly-diagnosed AML patients often present with below normal neutrophil and platelet counts, suggesting that persistence of such cytopenias after induction may be a clinical indicator of minimal residual disease (MRD) in the marrow. We therefore examined whether blood count recovery affected the probability of subsequent CR in patients with <5% bone marrow blasts. Methods: We included 85 patients who, by day 21 or thereafter of induction therapy for newly-diagnosed AML, had not met blood count criteria for CR despite a bone marrow in the prior week with <5% blasts by morphology. Patients were classified by type of induction therapy based on cytarabine dosing. G-CSF was not systematically administered. Marrows were planned for day 21 after chemotherapy and/or weekly thereafter to assess for disease status and evidence of marrow recovery. Because patients were often managed as outpatients, counts and marrows were not uniformly available and thus “day 28” included days 21–28, “day 35” included days 29–35, etc. If a patient had more than one marrow evaluation after day 21, we included only the first one. Results: Overall cohort CR rate was 64%. Eventual CR rate was significantly affected by platelet count, with 44% eventual CR for patients with platelets <30,000, 66% CR for platelets 30,000–100,000, and 95% CR for platelets >100,000. The effect of ANC recovery on eventual CR was less dramatic, with an OR 0.4 (0.2–1.0, p=0.049), for ANC <0.1 vs. >0.1 in the univariate analysis. By day 28, patients with either ANC or platelet recovery were significantly more likely to obtain CR than patients with neither count recovery (89% vs. 51%), OR 8.05 (2.2–30, p=0.002). In the multivariate analysis, (a) lack of platelet recovery to >30,000 was associated with significantly lower incidence of CR, OR 0.26 (0.1–0.8, p=0.02), and was independent of cytogenetic risk, antecedent hematologic disorder, and induction regimen, and (b) there was a suggested association between earlier count recovery and CR (>28 days vs. day 21–28), OR 0.31 (0.1–1.0, p=0.051). Conclusion: Persistence of low peripheral blood counts, despite the presence of <5% bone marrow blasts, is predictive of low eventual CR rates after induction chemotherapy. These results suggest that initiation of further and possibly different therapy, rather than continued observation, should be investigated in this setting. Disclosures: Becker: Sanofi: Research Funding.

Real-world patterns and predictors of first-line maintenance use among patients with newly diagnosed advanced ovarian cancer: Is there an opportunity for change?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e18710-e18710
Author(s):  
Jinan Liu ◽  
Premal H. Thaker ◽  
Janvi Sah ◽  
Eric M. Maiese ◽  
Oscar Bee ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Maintenance Therapy ◽  
Real World ◽  
Index Date ◽  
Advanced Ovarian Cancer ◽  
Newly Diagnosed ◽  
First Line ◽  
Receive Maintenance Therapy ◽  
Platinum Based Chemotherapy ◽  
To Receive

e18710 Background: With the advent of poly(ADP-ribose) polymerase inhibitors (PARPi), options for first-line (1L) maintenance therapy in ovarian cancer (OC) have evolved in the US. This study described the use of 1L maintenance and assessed predictors of 1L maintenance use among PARPi-eligible patients (pts) with OC in a real-world setting. Methods: This retrospective cohort study included pts with newly diagnosed stage III/IV epithelial OC who received 6–9 cycles of 1L platinum-based chemotherapy (PBC) and primary or interval debulking surgery following neoadjuvant chemotherapy between Jan 1, 2016, and Feb 29, 2020, from the nationwide Flatiron Health electronic health record–derived deidentified database. The end of the last cycle of 1L PBC was defined as the index date. Those pts who started second-line chemotherapy within 2 months of the index date were excluded. Logistic regression was used to analyze variables with regard to 1L maintenance use. Results: In total, 463 pts were included; 21% received maintenance therapy, 79% received active surveillance. Baseline characteristics are shown in the table. Overall maintenance therapy use increased over the study period, from 7.7% to 37.7%. Pts with BRCA wild type were significantly less likely to receive maintenance therapy (odds ratio [OR]: 0.30; 95% CI, 0.16–0.59) than pts with BRCA mutation. Pts treated in 2018 (OR: 2.73; 95% CI, 1.25–5.98) and 2019 (OR: 8.78; 95% CI, 4.15–18.55) were significantly more likely to receive maintenance therapy than pts treated in 2017. Age, race, practice type, ECOG score, and residual disease status were not significant predictors of 1L maintenance use. Conclusions: Nearly 40% of pts with advanced stage OC received upfront maintenance therapy with an increasing trend over time, particularly in those with biomarker guidance. Research is warranted toward addressing barriers to the appropriate use of maintenance therapy.[Table: see text]

scholarly journals Dietary Fat Intake and Risk of Uterine Leiomyomata: A Prospective Ultrasound Study

2020 ◽  
Vol 189 (12) ◽  
pp. 1538-1546 ◽  
Author(s):  
Theodore M Brasky ◽  
Traci N Bethea ◽  
Amelia K Wesselink ◽  
Ganesa R Wegienka ◽  
Donna D Baird ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Black Women ◽  
Confidence Interval ◽  
Dietary Fat ◽  
Cox Regression ◽  
Transvaginal Ultrasound ◽  
The United States ◽  
Hazard Ratio ◽  
Uterine Leiomyomata ◽  
Ultrasound Study

Abstract Uterine leiomyomata (UL) are associated with severe reproductive morbidity and are the primary indication for hysterectomy in the United States. A recent prospective cohort study of Black women reported positive associations between intakes of marine-sourced ω-3 fatty acids and UL risk. We examined whether intakes of dietary fat were associated with UL incidence in a 5-year prospective study of premenopausal Black women living in Detroit who underwent serial ultrasound. At baseline (2010–2012) and 20, 40, and 60 months of follow-up, participants underwent transvaginal ultrasound. Among 1,171 UL-free women at baseline, incident UL were detected in 277 women. Cox regression was used to estimate hazard ratios and 95% confidence intervals for the association of dietary fat and UL incidence. Intakes of total fat and saturated, monounsaturated, polyunsaturated, and trans-fat were not appreciably associated with UL incidence. Intake of the marine ω-3 polyunsaturated fatty acid, docosahexaenoic acid, was associated with 49% higher UL incidence (quartile 4 vs. 1: hazard ratio = 1.49, 95% confidence interval: 1.04, 2.14; P for trend = 0.01). Intakes of total marine ω-3 polyunsaturated fatty acids were similarly associated with elevated UL incidence (hazard ratio = 1.35, 95% confidence interval: 0.94, 1.93; P for trend = 0.03). It remains unclear whether the fatty acids or persistent environmental pollutants drive the association.

scholarly journals Mobilized Peripheral Blood Stem Cells Versus Unstimulated Bone Marrow As a Graft Source for T-Cell–Replete Haploidentical Donor Transplantation Using Post-Transplant Cyclophosphamide

2017 ◽  
Vol 35 (26) ◽  
pp. 3002-3009 ◽  
Author(s):  
Asad Bashey ◽  
Mei-Jie Zhang ◽  
Shannon R. McCurdy ◽  
Andrew St. Martin ◽  
Trevor Argall ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Peripheral Blood ◽  
Cox Regression ◽  
The United States ◽  
Platelet Recovery ◽  
Post Transplant ◽  
Transplant Outcomes ◽  
Prospective Comparison ◽  
Mobilized Peripheral Blood

Purpose T-cell–replete HLA-haploidentical donor hematopoietic transplantation using post-transplant cyclophosphamide was originally described using bone marrow (BM). With increasing use of mobilized peripheral blood (PB), we compared transplant outcomes after PB and BM transplants. Patients and Methods A total of 681 patients with hematologic malignancy who underwent transplantation in the United States between 2009 and 2014 received BM (n = 481) or PB (n = 190) grafts. Cox regression models were built to examine differences in transplant outcomes by graft type, adjusting for patient, disease, and transplant characteristics. Results Hematopoietic recovery was similar after transplantation of BM and PB (28-day neutrophil recovery, 88% v 93%, P = .07; 100-day platelet recovery, 88% v 85%, P = .33). Risks of grade 2 to 4 acute (hazard ratio [HR], 0.45; P < .001) and chronic (HR, 0.35; P < .001) graft-versus-host disease were lower with transplantation of BM compared with PB. There were no significant differences in overall survival by graft type (HR, 0.99; P = .98), with rates of 54% and 57% at 2 years after transplantation of BM and PB, respectively. There were no differences in nonrelapse mortality risks (HR, 0.92; P = .74) but relapse risks were higher after transplantation of BM (HR, 1.49; P = .009). Additional exploration confirmed that the higher relapse risks after transplantation of BM were limited to patients with leukemia (HR, 1.73; P = .002) and not lymphoma (HR, 0.87; P = .64). Conclusion PB and BM grafts are suitable for haploidentical transplantation with the post-transplant cyclophosphamide approach but with differing patterns of treatment failure. Although, to our knowledge, this is the most comprehensive comparison, these findings must be validated in a randomized prospective comparison with adequate follow-up.

Thrombin Generation and D-Dimer Significantly Predict for Early Disease Progression and Mortality in Patients with Gastrointestinal Cancer

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Marina Pesenti ◽  
Marina Marchetti ◽  
Cinzia Giaccherini ◽  
Cristina Verzeroli ◽  
Laura Russo ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Cox Regression ◽  
Newly Diagnosed ◽  
Early Disease ◽  
Gi Cancer ◽  
Independent Risk Factors ◽  
Ecog Ps ◽  
D Dimer

Background: Abnormalities of laboratory coagulation tests are common in cancer patients, underlying a subclinical hypercoagulable state. Due to the reciprocal interaction between coagulation and cancer, the biomarkers of hemostatic system activation are under evaluation as a tool for predicting cancer outcomes, disease progression, and mortality. Aim: In this analysis of a prospective cohort of patients with newly diagnosed metastatic gastro-intestinal (GI) cancer, we wanted to evaluate whether the pre-chemotherapy abnormalities of hemostatic biomarkers may predict for early-disease progression (E-DP), i.e. within 6 months from cancer diagnosis, and for 1-year overall survival (1-year OS). Methods: The study cohort included 304 newly diagnosed metastatic GI cancer patients, candidate to chemotherapy associated or not with immunotherapy, enrolled from March 2012 to March 2019 in the HYPERCAN study (ClinicalTrials.gov, ID# NCT02622815), an ongoing Italian prospective, multicenter, observational study; 191 healthy subjects acted as a control group. At diagnosis, before starting any curative chemotherapy, plasma samples were collected and tested for the following hypercoagulation biomarkers: D-dimer and fibrinogen by an automated coagulometer analyzer (ACL TOP500, Werfen Group), and prothrombin fragment 1+2 (F1+2) by ELISA (Siemens). In addition, thrombin generation (TG) potential was evaluated by Calibrated Automated Thrombogram (CAT) assay at 5 pM tissue factor and endogenous thrombin potential (TG ETP) and TG peak were analyzed. Clinical data [i.e. age, sex, BMI, ECOG Performance Status (ECOG-PS), relevant comorbidies] and the hemochromocytometric parameters were recorded at enrollment, whereas E-DP was clinically monitored every 3 chemotherapy cycles and during follow-up. Results: A cohort of 304 (205M/99F) metastatic GI cancer patients (206 colorectal and 98 gastric cancers) with a median age of 66 years (min-max: 29-85) was available for analysis. At enrollment, patients presented with a hypercoagulable state, as shown by significantly higher (p&lt;0.001) plasma levels of D-dimer, fibrinogen and F1+2, and significantly higher (p&lt;0.01) TG peak and TG ETP values than controls. After 6 months from the start of chemotherapy, E-DP had occurred in 80 patients, providing a cumulative incidence of 29.6% (CI 95% 24.1-35.1). E-DP subjects had significantly (p&lt;0.05) higher baseline D-dimer levels and TG ETP value than non-E-DP patients. Correlation analyses showed that pre-chemotherapy fibrinogen (β = -0.127; p=0.048), D-dimer (β = -0.198; p=0.002) and TG ETP (β = -0.133; p=0.034) levels were significantly and inversely associated with time to E-DP. By Multivariate Cox regression analysis, gastric cancer diagnosis (HR=1.546), pre-chemotherapy D-dimer (HR=1.001) and TG ETP values (HR=1.001) were identified as independent risk factors for E-DP. After 1 year from the start of chemotherapy, 228 patients were dead and the OS was 66.6% (CI 95% 61.3-71.9). Patients who died within 1 year showed higher baseline D-dimer, F1+2, fibrinogen, TG peak and TG ETP values compared to the remaining subjects. Multivariate Cox regression identified independent risk factors for 1-year OS the followings: gastric cancer diagnosis (HR=2.237), D-Dimer (HR=1.001) and TG ETP (HR=1.001) levels, white blood cell count (HR=1.094), ECOG-PS&gt;1 (HR=3.858), and chemotherapy plus immunotherapy treatment (HR=2.274). Conclusion: Our results show that, in newly diagnosed metastatic gastrointestinal cancer patients, before the start of antitumor treatment, a procoagulant state exists. Among the different hemostatic parameters evaluated, D-dimer and TG ETP appear as candidate biomarkers to predict for 6-month DP and 1-year OS. In particular, in this setting, the role of TG as a prognostic biomarker emerges for the first time in a large prospective cohort of GI cancer patients. Project funded by "5xMILLE" n. 12237 grant from the "Italian Association for Cancer Research (AIRC)" Disclosures Santoro: Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy; Arqule, Sanofi: Consultancy; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Takeda, Roche, Abbvie, Amgen, Celgene, AstraZeneca, ArQule, Lilly, Sandoz, Novartis, Bristol-Myers Squibb, Servier, Gilead Sciences, Pfizer, Eisai, Bayer, MSD: Speakers Bureau; Bristol Myers Squibb, Servier, Gilead, Pfizer, Eisai, Bayer, MSD: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy, Speakers Bureau; Bristol-Myers Squibb, SERVIER, Gilead Sciences, Pfizer, Eisai, Bayer, MSD, Sanofi, ArQule: Consultancy.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Hypercvad Induction Chemotherapy Is Associated with Higher Rates of Stem Cell Mobilization Failure in Mantle Cell Lymphoma ( MCL)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 3849-3849 ◽  
Author(s):  
Amandeep Salhotra ◽  
Shan Yuan ◽  
Joycelynne Palmer ◽  
Ibrahim Aldoss ◽  
Ni-Chun Tsai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Induction Chemotherapy ◽  
Bone Marrow Involvement ◽  
Median Number ◽  
The Other ◽  
High Dose ◽  
Newly Diagnosed ◽  
Cd34 Cells ◽  
Pbsc Mobilization

Abstract Background: MCL patients deemed fit for high dose regimens undergo induction therapy with rituximab and chemotherapy (HyperCVAD/CHOP/bendamustine) followed by consolidation with ASCT (autologous stem cell transplantation). R-HyperCVAD is a dose intense regimen with high response rates for MCL when used in the upfront setting (ORR 97%; CR 38%; Romaquera JE, JCO 2005). R-bendamustine and R-CHOP are contemporary regimens with similar efficacy (ORR 85-93%; Rummel MJ, Lancet 2013). In a recent randomized phase II trial (SWOG 1106) accrual to the HyperCVAD arm was stopped due to higher than expected rates of peripheral blood stem cell (PBSC) mobilization failure. Methods: To assess the impact of these regimens on PBSC collection, we performed a retrospective analysis of newly diagnosed MCL patients undergoing induction chemotherapy with R-HyperCVAD versus R-CHOP/R-bendamustine and referred to transfusion medicine for PBSC collection prior to ASCT from 01/2009 to 12/2013. Patients were not allowed any salvage chemotherapy. The primary end point was successful stem cell collection defined as ability to collect ≥2.1 million CD34 cells/Kg. Secondary endpoints were number of days of apheresis, use of pleraxifor as mobilization salvage and total number of CD34+ cells collected. Results: A total of 91 MCL patients were eligible for analysis (Table 1). Patients who received HyperCVAD were younger at the time of collection (median: 56 vs 62 years; p <0.01) and were referred for collection earlier (median time from diagnosis to collection start: 4.5 vs. 6.4 months; p<0.01). There were no other baseline differences between the two groups in terms of gender, bone marrow involvement, stage of disease at presentation and use of plerixafor. While the median number of apheresis days were comparable: 4 (range: 1-9) for the HyperCVAD group and 3 (range: 2-8) for the other group (p=0.21), 18% patients in the Hyper-CVAD group failed to collect adequate numbers of PBSC (defined as < 2.1 ×10 6/Kg) compared to 4% in the other group (p=0.05). Additionally, the median number of CD34+ cells collected was lower in HyperCVAD group (p=0.05). After adjusting for baseline differences in age and timing of collection, for a patient who received HyperCVAD, the odds of failing to collect were 7.28 times higher (95% CI: 1.01, 52.57) than the odds for a patient who received a non-HyperCVAD induction regimen (p=0.05). Ultimately, 81/91 (89%) patients proceeded to high dose chemotherapy and ASCT [82% in HyperCVAD versus 96% in non-HyperCVAD (p=0.06)]. Four of the remaining 10 patients with mobilization failure (all from HyperCVAD arm) proceeded to Allogeneic HCT, the remaining 6 patients did not receive any further treatment. Conclusion: Patients with MCL receiving R-HyperCVAD chemotherapy in the frontline setting have a significantly higher rate of PBSC mobilization failure and collect significantly fewer CD34+ PBSCs when compared to patients treated with comparable regimens. R-HyperCVAD should be used with caution in patients with newly diagnosed MCL who are eligible for ASCT. Some patients failing mobilization may be salvaged with use of plerixafor. Table 1: Patient, Transplant Characteristics Variable Hyper-CVAD, n=45Median (Range)N (%) Other, n=46Median (Range)N (%) Patient Gender Female Male 9 (20) 36 (80) 12 (26) 34 (74) Age at Collection Completion (years) 56 (40 – 68) 62 (36 – 74) Time from Diagnosis to Start of Collection (months) 4.5 (2.3 – 65.3) 6.4 (3.9 – 69.4) Stage at Diagnosis I II III IV 1 (2) 3 (7) 2 (4) 39 (87) 2 (4) 1 (2) 6 (13) 37 (81) Bone Marrow Involvement at Diagnosis No Yes Not Done 9 (20) 35 (78) 1 (2) 13 (28) 32 (70) 1 (2) Treatment after Chemotherapy Auto Transplant Allo Transplant No Transplant 37 (82) 4 (9) 4 (9) 44 (96) 0 (0) 2 (4) Mozobil Era (08/16/2009) Pre Post 8 (18) 37 (82) 3 (7) 43 (93) Mozobil Usage No Yes 29 (64) 16 (36) 30 (65) 16 (35) Number of Collections 4 (1 – 9) 3 (2 – 8) Total CD34 4.5 (0.3 – 100.5) 5.3 (0.7 – 76.6) Total CD34 (Failure Rate) < 2.1 >/= 2.1 8 (18) 37 (82) 2 (4) 44 (96) Disclosures Chen: Seattle Genetics: Honoraria, Research Funding, Speakers Bureau.

Tandem high-dose therapy with autologous stem cell support for small-cell lung cancer (SCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17033-17033
Author(s):  
J. N. Machatschek ◽  
G. Kobbe ◽  
R. Haas ◽  
U. P. Rohr
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Induction Chemotherapy ◽  
Cox Regression ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
High Dose Therapy ◽  
Platelet Recovery ◽  
Dose Therapy

17033 Background: We evaluated the therapeutic efficacy of tandem high-dose chemotherapy followed by autologous peripheral stem-cell transplantation (PBSCT) in patients with newly diagnosed SCLC in complete remission or very good partial response after induction chemotherapy. Methods: Between 1996 and 2000, 19 patients with newly diagnosed SCLC in CR or very good PR after two cycles of induction chemotherapy (cisplatin 90 mg/m2 day 1, etoposide 120 mg/m2 day 1–3, ifosfamide 1500 mg/m2 day 1–4) received a tandem high-dose chemotherapy (cyclophosfamide 2000 mg/m2 day 1 and 2, etoposide 700 mg/m2 day 1–3, carboplatin 1200 mg/m2 day 1) followed by PBSCT. Following transplantation, patients received concurrent chest and cranial radiotherapy to a total dose of 45 Gy and 30 Gy, respectively. Results: Of 19 patients with SCLC, 18 had stage III and one stage IV disease. The median age was 50.7 years. Median time to leukocyte-recovery above 1000/μl and platelet-recovery above 20.000/μl was 12 days and 9 days, respectively. The median follow-up was 6.38 years (range 5.11–7.23) for surviving patients. There were no transplant-related deaths and toxicity was moderate. Using the Kaplan-Meier method, the 2- and 5-year survival rates after high-dose therapy were 42% and 32% respectively. Median time to relapse was 0.7 years (range 0.2–4.6). The mean survival was 36.8 months. This outcome compared favourably to a group of 77 patients who did not receive high-dose therapy but responded to conventional chemotherapy (mean survival 11.4 months). Using the Cox regression model, among all patients response to induction, normal LDH and PBSCT were associated with favourable outcome. Conclusions: Our findings suggest that patients with or near complete response after conventional therapy might benefit from tandem high-dose therapy with PBSCT with tolerable toxicicity. No significant financial relationships to disclose.

Improving the care of acute lymphocytic leukemia (ALL) at a large county hospital.

2013 ◽  
Vol 31 (31_suppl) ◽  
pp. 213-213 ◽  
Author(s):  
Meghan Sri Karuturi ◽  
Jeffrey Thomas Yorio ◽  
Annie Titus ◽  
Stephenie Jeanette Pharr ◽  
Alyssa G. Rieber
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Underserved Populations ◽  
Philadelphia Chromosome ◽  
The United States ◽  
Lymphocytic Leukemia ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed

213 Background: The treatment of ALL involves complex chemotherapy regimens that are difficult to deliver to underserved populations. Lyndon B. Johnson General Hospital (LBJGH) provides care to uninsured and underinsured patients in Harris County, the third largest county in the United States. Our goal is to achieve 80% adherence to National Comprehensive Cancer Network guidelines in the care of newly diagnosed ALL patients at LBJGH. Methods: The charts of 14 patients with newly diagnosed ALL were reviewed. Demographics, initial work-up (e.g., bone marrow biopsy and aspirate), type of treatment, adherence to scheduled treatment, use of supportive medications, outpatient follow-up, stem cell transplant referral and quality of provider documentation were collected. Areas of potential improvement were then identified using provider focus groups and Ishikowa Diagram. The project was approved by the MD Anderson Quality Improvement Assessment Board. Results: 12/14 patients were evaluable, having received their full course of care at LBJGH. The median age was 35, 9/12 (75%) were female and 9/12 (75%) were Hispanic. 6/11 (55%) cases expressed CD20 (CD20+) and 3/11 (27%) were Philadelphia chromosome positive (Ph+). All 12 patients received induction and consolidation therapy with the HyperCVAD regimen (cyclophosphamide/vincristine/doxorubicin/dexamethasone alternating with high-dose methotrexate/cytarabine). Bone marrow biopsy at time of diagnosis, use of a tyrosine kinase inhibitor for Ph+ ALL, and use of supportive medications occurred >80% of the time. Administration of outpatient chemotherapy, use of rituximab for CD20+ ALL, outpatient lab follow-up, intrathecal chemotherapy and appropriate referral for allogeneic transplant occurred 50-80% of the time. Provider documentation was appropriate <50% of the time. Conclusions: Based on these findings, we established a standard algorithm of care for ALL patients at LBJGH, enhanced provider education through the design and distribution of teaching tools, created a checklist to facilitate handoffs between providers and established expectations for documentation. In the future, we would also like to add a patient navigator to further improve coordination of care.

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