European MCL Network: An Update on Current First Line Trials.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 388-388 ◽  
Author(s):  
Martin H. Dreyling ◽  
Eva Hoster ◽  
Olivier Hermine ◽  
J.C. Kluin-Nelemans ◽  
Jan Walewski ◽  
...  
Keyword(s):  
Overall Survival ◽  
Febrile Neutropenia ◽  
Elderly Patients ◽  
Response Rate ◽  
Response Rates ◽  
High Dose ◽  
High Dose Cytarabine ◽  
The Impact ◽  
Grade Iii

Abstract Background: Conventional chemotherapy achieves only short term remission despite high initial response rates of 70%–80%. In the current study generation, the European MCL Network investigates the impact of various combined immuno-chemotherapy regimens. Additionally, in elderly patients the role of rituximab maintenance is being evaluated, whereas in younger patients dose-intensified regimens with implementation of high dose cytarabine are investigated based on the excellent results of the HyperCVAD regimen. Methods: In MCL elderly, patients are initially randomized between 8 cycles of R-CHOP or 6 cycles of R-FC (experimental arm). Patients who achieve either an PR or CR, receive subsequently either interferon maintenance (standard arm) or a single rituximab dose every 2 months. In MCL younger, the standard arm (R-CHOP induction followed by myeloablative consolidation: 12 Gray TBI, 2x 60mg/kg cyclophosphamide) is compared to the implementation of high dose cytarabine into induction (R-CHOP/R-DHAP) and consolidation (10 Gray TBI, 4x1,5 g/m2 Ara-C, 140mg/m2 melphalan). Results: In MCL elderly, 222 of 263 patients were evaluable based on the annual interim analysis. Median age was 70 years with 66% of patients displaying an intermediate high/high risk IPI. Induction was well tolerated with mainly hematological toxicity (grade III/IV in R-CHOP/R-FC): Leukocytopenia 62/72%, thrombocytopenia 13%/40%, but only rare febrile neutropenia (23%/7%) or infections (19%/23%). Despite the poor risk profile, combined immuno-chemotherapy (total group) achieved a remarkable 84% response rate (51% CR/CRu). Although the impact of maintenance is not yet evaluable, both progression-free and overall survival were encouraging with 77% and 86% at 12 months, respectively. In MCL younger, 247 of 271 patients were evaluable. Again, toxicity (grade III/IV in R-CHOP/alternating R-DHAP) was mainly hematological: leukocytopenia 58/77%, thrombocytopenia 14%/74%, but only rare febrile neutropenia (11%/22%) or infections (5%/7%). Combined immuno-chemotherapy achieved a 93% response rate (60% CR/CRu) before subsequent high dose consolidation. Again, both progression-free and overall survival are remarkable with both 90% at 12 months, respectively. Discussion: Combined immuno-chemotherapy results in high response rates in two prospective international trials. Further recruitment and follow-up will determine the role of rituximab maintenance and high dose cytarabine in this distinct subtype of malignant lymphoma.

High Dose Chemotherapy (HD CHT) Followed by Autologous PBPC Transplant in Elderly ANLL Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 881-881
Author(s):  
Debora Capelli ◽  
Emanuela Troiani ◽  
Giancarlo Discepoli ◽  
Antonella Poloni ◽  
Mauro Montanari ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Response Rate ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Poor Tolerance ◽  
Cytoprotective Agent ◽  
Grade Iii

Abstract Poor tolerance of aggressive chemotherapy and intrinsic disease resistance of ANLL in Elderly patients strongly impair the achievement of successful responses in this setting. Moreover, even after the achievement of CR, the intensive consolidation with autotransplantation is feasible in very few cases. We used Amifostine as cytoprotective agent in addition to a regimen containing HD Idarubicine (40 mg/sqm) and HD ARA-C (3 g/sqm for 5 days), the so-called “Memorial”. We treated 35 elderly patients (median age: 66, range: 56–78). Amifostine (740 mg/sqm IV) was administered at day 3, followed by Idarubicin. Patients aged more than 70 yrs received 30% reduced schedule. Karyotype was normal in 18 pts, unfavorable in 12 pts, unevaluable in 5 pts. Complete remission was observed in 24 patients (70.6%). The response rate was 78% (14/18) and 41% (5/12) in the intermediate and the poor prognosis cytogenetic groups respectively. Neutrophil (> 1500/ml) and platelet (>50,000/ml) recoveries were achieved at day 16 (range: 12–36) and 17 (range: 11–52) respectively. We observed one toxic induction death due to infection and other 21 grade III infectious episodes which responded to antibiotic treatment. Grade III–IV oral mucositis was observed in 3 patients. Twentyfour patients underwent a consolidation course with FLAG + Daunoxome (80 mg/sm i.v. day 1 and 2); a successful mobilization was achieved in 12 out of the 20 responder patients with a median collection of 6.6 x 106 CD34+/kg (range 4–14). All these patients were successfully autotransplanted with a conditioning regimen including Busulfan 9 mg/m2, Melphalan 120 mg/m2 in combination with Amifostine and Daunoxome 160 mg/m2. Transplant related mortality was 25% (infectious complication in one patient, congestive hearth failure in one case and severe mucositis in the other case). Haematological recovery was complete and fast in all patients. Grade III–IV extrahematological toxicity was mainly due to mucositis (8%), and infections (33%). The sequence HD CHT and autologous transplant determined a final CCR rate of 23% with a median follow-up of 12 months (range 1–31); two relapsed patients are still alive while 25 patients died, 5 for treatment related causes (14%), 20 for disease progression. We observed a 21% 3 years OS with a 27% in patients with intermediate prognosis kariotype versus 16% in the unfavorable group (p=0.03). The prognostic role of kariotype was not confirmed when 3 years DFS was analysed in the 24 responder patients: 25% vs 22% in the intermediate prognosis kariotype group. Induction response rate is surprisingly high for this setting but we still have high relapse incidence, probably due to the low mobilization rate and the consequent moderately low transplant feasibility. Alternative consolidation regimen, possibly not including Fludarabine, should therefore be explored.

Impact of G-CSF for Outcomes of Non-M3 AML Patients Who Were Treated By Anthracycline-Based Induction (7+3 regimen) Chemotherapies

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4889-4889
Author(s):  
Ka-Won Kang ◽  
Yong Park ◽  
Dae Sik Kim ◽  
Se Ryeon Lee ◽  
Hwa Jung Sung ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Febrile Neutropenia ◽  
Confidence Interval ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Solid Cancer ◽  
Therapeutic Group ◽  
High Dose Cytarabine ◽  
The Impact

Abstract Granulocyte colony-stimulating factor (G-CSF) has been known to reduce the duration of neutropenia and the incidence of infection-related death in patients with solid cancer who were treated by cytotoxic chemotherapies. A few randomized trials addressed these benefits in patients with non-M3 acute myelogenous leukemia (AML). However, long-term effects of G-CSF exposure in these patients were not reported. We analyzed the impact of G-CSF for outcomes of non-M3 AML patients who were treated by anthracycline-based induction and high-dose cytarabine consolidation chemotherapies. The patients enrolled in the Korea University AML registry from September 2002 to December 2014 were analyzed. AML patients who were treated by anthracycline-based inducton (7+3 regimen) and high-dose cytarabine consolidation (cytarabine 3g/m2 q 12 hours on D1, 3, 5) chemotherapies were included for this analysis. Patients with acute promyelocytic leukemia were excluded. The enrolled patients were classified into 3 subgroups based on G-CSF administration strategies during induction chemotherapies; 1) patients without G-CSF exposure during induction (no G-CSF group), 2) patients with G-CSF administration which was initiated immediately after development of neutropenia (absolute neutrophil counts < 1000) but before development of febrile neutropenia (preemptive group), 3) patients with G-CSF administration which was initiated after development of febrile neutropenia (therapeutic group). 285 patients were included in this analysis. The median follow-up duration was 18 months. The number of no G-CSF, preemptive and therapeutic group were 83, 70, and 132, respectively. The impacts of G-CSF administration strategies for treatment outcomes were summarized in table 1. The incidence and duration of chemotherapy-induced febrile neutropenia (CIFN) was not statistically different in no G-CSF group and preemptive group (p=0.700 and p=0.103, respectively). According to the median duration of neutropenia, preemptive G-CSF group (20.5 days) showed marginal benefit compared to the other groups (24 days in no G-CSF group and 23 days in therapeutic group) (p=0.052). The median time to ANC recovery (>1000) was significantly shorter in preemptive group (23 days) and therapeutic group (23 days) compared to no G-CSF group (27 days) (p<0.001). Infection-related mortality was significantly lower in preemptive group (2.9%) compared to no G-CSF group (9.6%) and therapeutic group (15.9%) (p=0.020). Complete remission rate and cumulative incidence of relapse were not significantly different between groups (p=0.151 and p=0.423, respectively). In multivariate analysis for incidence of CIFN, quinolone prophylaxis was independently significant factor for reducing the incidence of CIFN (HR 0.222, 95% confidence interval 0.054-0.911, p=0.037). In multivariate analysis for infection-related death, young age (°Â60) and preemptive group were independently significant factors for reducing the development of infection-related death (HR 0.284, 95% confidence interval 0.120-0.676, p=0.004 and HR 0.108, confidence interval 0.012-0.934, p=0.043 respectively). According to the survival, there were no significant differences among groups in overall survival and relapse free survival (figure 1). Preemptive G-CSF administration during induction treatments in non-M3 AML patients was considered to be effective in reducing infection-related deaths without affecting remission, relapse and overall survival. Because quinolone prophylaxis was showed to be effective in reducing the incidence of CIFN, combination of preemptive G-CSF administration and quinolone prophylaxis might be considered to provide synergistic benefit in non-M3 patients with intensive chemotherapy. Disclosures No relevant conflicts of interest to declare.

A Direct Comparison of High Dose Cytarabine to Combination of Gemtuzumab and High Dose Cytarabine for Acute Myeloid Leukemia Patients in First Relapse Confirmed the Benefit of Gemtuzumab Based Regimens.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2051-2051
Author(s):  
Thomas Prébet ◽  
Aude Charbonnier ◽  
Anne Etienne ◽  
Evelyne D'Incan ◽  
Sabine Fürst ◽  
...  
Keyword(s):  
Overall Survival ◽  
Response Rate ◽  
Standard Of Care ◽  
Allogeneic Transplantation ◽  
Control Group ◽  
High Dose ◽  
Current Standard ◽  
Advanced Phase ◽  
High Dose Cytarabine ◽  
First Relapse

Abstract Abstract 2051 Poster Board II-28 Acute meyloid leukemia (AML) in first relapse is associated with a poor outcome when treated with standard dose cytarabine regimens and intermediate to high dose cytarabine (IHDAraC) is the current standard of care. During the last years, Gemtuzumab Ozogamycin (GO) has demonstrated a relevant clinical activity in relapsed and refractory AML. This antibody directed against CD33 is conjugated to calicheamycin that triggers apoptosis when hydrolyzed in the leukemic blasts. Combination regimen of GO are currently extensively studied in both frontline and advanced phase disease. Nevertheless, analysis of the litterature showed that only few data are available regarding a direct comparison of IHDAraC and IHDAraC+GO regimen. To this respect, we conduced a retrospective analysis of response (CR and CRi) and survival for patients with first relapse AML treated in our centre with either IHDAraC or IHDAraC+GO regimen. A total of 84 patients were included in the analysis: 28 were induced in the IHDAraC+GO group (mean GO dose: 6mg/m2, range:[3-9], including 82% of combination with anthracyclines or etoposide) and 56 in the IHDAraC group (including 57% of combination with other agents, mostly etoposide and anthracyclines). Patients characteristics were comparable between the IHDAraC+GO group and the control group in terms of median age (51y vs 49y), Performance Status at relapse (1 vs 1), median time to relapse (221 days vs 280 days), cytogenetic risk group clustering and previous allogeneic transplantation in first CR (21% vs 16%). Median Follow-up was 24 months. Univariate analysis showed that IHDAraC+GO induction, as compared with IHDAraC, was associated with a better response rate (68% vs 48%, p=0.08), a lower relapse rate (31% vs 66%, p=0.02), a better Overall Survival (median 35 months vs 19 months, p=0.02) and a better Event Free Survival (median Not Reached vs 10 months, p=0.02). Of note, the better response rate in the IHDAraC+GO group allowed to bring more patients to allogeneic transplantation in second CR (33% vs 16% respectively, p=0.08).Multivariate analysis using logistic regression method for response evaluation and Cox model for survival showed that treatment in the IHDAraC+GO group was an independent prognosis factor with a favorable impact on both response (HR:2.8, 95%CI:[1.1-7.7], p=0.048) and Overall Survival (HR:1.9, 95%CI:[1.1-3.4], p=0.047). It is already known that combination of IHDAraC and GO could give good results for advanced phase AML patients but, to our knowledge, this report is the first that directly compared the results of IHDAraC+GO with the current standard of care regimen on an homogeneous sample of patients in first relapse. This report also underline the importance of a prospective comparison in order to define the best combination therapy. Disclosures: No relevant conflicts of interest to declare.

Outcome of Elderly Patients with Acute Myeloid Leukemia (AML) Post Hypomethylating Agent (HMA) Failure.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2627-2627 ◽  
Author(s):  
Koichi Takahashi ◽  
Hagop M. Kantarjian ◽  
Hady Ghanem ◽  
Farhad Ravandi ◽  
Jorge E. Cortes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Salvage Therapy ◽  
Research Funding ◽  
Objective Response ◽  
Induction Treatment ◽  
High Dose ◽  
Cell Transplant ◽  
Investigational Agents ◽  
The Impact

Abstract Abstract 2627 Background and Aims: HMA such as 5-azacitadine or decitabine have been increasingly used as induction therapy in elderly patients with AML. The prognosis of such patients who failed initial HMA and the impact of subsequent chemotherapy on outcome are unknown. Therefore the aims of the current analysis are 1) to evaluate the prognosis of elderly patients with AML post HMA failure and 2) to evaluate the efficacy of using intensive cytarabine-based salvage therapy vs. low intensity investigational therapy. Methods: We analyzed 54 patients older than 60 years old with AML who received induction treatment with HMA using either 5-azacitadine (n=17; 31%) or decitabine (n=37; 69%) under various clinical trials. Result: Median age of the group was 68 years (range; 60–84); 39% patients were female. Forty three patients (77%) had performance status (PS) ≤1 and 11 patients had PS of 2 (23%). Mean initial white blood cell count was 10.9 ± 3.2 (x103/μl), hemoglobin 9.9 ± 0.2 (g/dl), platelet count 77 ± 9 (x103/μl), and bone marrow blast count 44 ± 2.9 (%). Cytogenetic category was classified as intermediate in 30 (55%) patients and poor in 24 (45%) based on the MRC criteria. Six patients (11%) carried FLT3-ITD mutation and 1 carried FLT3 D835 mutation. Complete remission (CR) was achieved in 24 patients (44%) with median numbers of cycles required to achieve CR being 3 (range; 1–6). All patients received further salvage therapies, at the time of failure, with a median of 2.5 (range, 2–5) salvage regimens. As part of the salvage regimen, high-dose cytarabine-based regimen (HDAC) was given to 32 patients (59%). Objective response rate to HDAC was 53%, with 18 pts achieving CR. Median number of courses given was 2 (range, 1–7) with a median duration of response of 3 months. No induction death was reported. Stem cell transplant was performed in total of 9 patients (17%) as a consolidation post HDAC (n=4) or as salvage therapy (n=5). With a median follow-up of 5 months post HMA failure, 5 (9%) patients remained alive receiving therapy. The median overall survival (OS) was 5.4 months (range, 2.3–8.5). The 1-year overall survival rate was 26%. There was no difference in OS between patients who received HDAC versus those who received investigational agents (p=0.25). Conclusion: The outcome of untreated elderly patients with AML who failed HMA is poor with a median survival of 5 months. HDAC based regimen, although active with low treatment related morbidity, yielded no survival improvement compared to investigational agents. Such patients should benefit from more innovative approaches. Disclosures: Ravandi: Celgene: Honoraria, Research Funding; Eisai: Honoraria, Research Funding.

Graft-Versus-Host Disease (GVHD) and Survival Outcomes after HLA-Haploidentical (Haplo) Bone Marrow Transplant (BMT) Compare Favorably with Matched Related Donor (MRD), and Matched Unrelated Donor (MUD) BMT Utilizing High-Dose Posttransplantation Cyclophosphamide (PTCy)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 730-730 ◽  
Author(s):  
Shannon R. McCurdy ◽  
Christopher G. Kanakry ◽  
Yvette L. Kasamon ◽  
Javier Bolanos Meade ◽  
Hua-Ling Tsai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Chronic Gvhd ◽  
Lower Probability ◽  
Survival Outcomes ◽  
High Dose ◽  
Grade Ii ◽  
The Impact ◽  
Grade Iii

Abstract Background: High-dose PTCy has been shown to effectively reduce acute (a) and chronic (c) GVHD after MRD and MUD BMT and to enable the safe implementation of haplo BMT. However, GVHD-related risk factors and survival outcomes, the impact of donor type, and novel composite endpoints, such as cGVHD-free relapse-free survival (cGFRFS), have not been fully characterized in BMT with PTCy. Methods: We retrospectively analyzed 582 consecutive adult pts with advanced or poor-risk hematologic malignancies who received allogeneic BMT with PTCy at Johns Hopkins from 2002-2012. All pts received a T-cell replete bone marrow graft and PTCy (50 mg/kg/d IV) on D+3 and +4. Platforms consisted of: 1) myeloablative conditioning (MAC) with Busulfan/Fludarabine or Busulfan/Cy followed by MRD (n = 193; 33%) or MUD (n=119; 20%) allografting and PTCy as sole GVHD prophylaxis; or 2) nonmyeloablative (NMA) conditioning with Fludarabine/Cy/TBI followed by related haplo (n = 270; 46%) allografting and PTCy, mycophenolate mofetil D5-35, and tacrolimus D5-180. Results: The median follow up was 4 (range 0.3-11.4) years (y). The median pt age at time of BMT was 49 (range 18-66) in the MAC cohort and 54 (range 18-73) in the NMA cohort. On competing risk analysis, the D200 probability of grade II-IV aGVHD was 27% after haplo, 37% after MRD, and 50% after MUD BMT, and grade III-IV aGVHD was 4%, 11%, and 14% respectively. The 3-y probability of cGVHD was 12% after haplo, 8% after MRD, and 19% after MUD BMT. On multivariate analysis adjusted for age and original disease risk index (DRI), MRD and MUD BMT were associated with a statistically significantly higher risk of grade II-IV and grade III-IV aGVHD compared to haplo BMT (each p ≤ 0.001). Compared to haplo BMT, MUD, but not MRD, BMT was also associated with a significantly higher risk of cGVHD (p = 0.009). On multivariate analysis, female into male allografting was independently associated with a higher risk of cGVHD (p = 0.007), whereas age and CMV serostatus of the pt and donor were not statistically significantly associated with risks of acute or chronic GVHD. Pts with grade II-IV aGVHD or cGVHD had a lower probability of relapse, but a higher probability of nonrelapse mortality (NRM) at 3 y compared to pts without GVHD. Among pts with GVHD, an HCT-CI score ≥ 5 was associated with significantly inferior overall survival compared to lower HCT-CI scores. Although MAC matched BMT was associated with less relapse risk than NMA haplo BMT, the 3-y probabilities of NRM, DFS, and overall survival were comparable between the transplant platforms (Table). On multivariate analysis adjusted for pt age and DRI, there were no statistically significant differences in DFS, OS, or cGFRFS in MAC related or unrelated BMT compared to NMA haplo BMT. Conclusions: High-dose PTCy safely modulates acute and chronic GVHD across multiple BMT platforms. The apparently lower risk of aGVHD after NMA haplo BMT with PTCy likely reflects the reduced conditioning intensity and longer duration of immunosuppression utilized. Despite the limitations inherent to a retrospective analysis, these data suggest that key outcomes after BMT with PTCy are comparable across donor types and conditioning intensities. Notably, in all these settings, 3-y estimates of cGFRFS appeared to approach those of DFS. Thus, PTCy may minimize the late morbidity and mortality of cGVHD and allow earlier implementation of novel posttransplantation strategies for relapse prevention. TableOutcomes of BMT with PTCy3-y probabilitiesNMA HaploMAC MRD*MAC MUD*NRM141717DFS384144OS495856cGFRFS313533 * p = NS for all comparisons to haplo BMT on multivariate analysis Disclosures Off Label Use: High-dose posttransplantation cyclophosphamide.

scholarly journals The Dose-Dependent Efficacy of Cefepime in the Empiric Management of Febrile Neutropenia: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 4 (3) ◽  
Author(s):  
Nikolaos Andreatos ◽  
Myrto Eleni Flokas ◽  
Anna Apostolopoulou ◽  
Michail Alevizakos ◽  
Eleftherios Mylonakis
Keyword(s):  
Febrile Neutropenia ◽  
Low Dose ◽  
Meta Analysis ◽  
Treatment Discontinuation ◽  
High Dose ◽  
First Line ◽  
The Impact ◽  
Dose Dependent ◽  
Overall Mortality

Abstract Background Despite reports questioning its efficacy, cefepime remains a first-line option in febrile neutropenia. We aimed to re-evaluate the role of cefepime in this setting. Methods We searched the PubMed and EMBASE databases to identify randomized comparisons of (1) cefepime vs alternative monotherapy or (2) cefepime plus aminoglycoside vs alternative monotherapy plus aminoglycoside, published until November 28, 2016. Results Thirty-two trials, reporting on 5724 patients, were included. Clinical efficacy was similar between study arms (P = .698), but overall mortality was greater among cefepime-treated patients (risk ratio [RR] = 1.321; 95% confidence interval [CI], 1.035–1.686; P = .025). Also of note, this effect seemed to stem from trials using low-dose (2 grams/12 hours, 100 mg/kg per day) cefepime monotherapy (RR = 1.682; 95% CI, 1.038–2.727; P = .035). Cefepime was also associated with increased mortality compared with carbapenems (RR = 1.668; 95% CI, 1.089–2.555; P = .019), a finding possibly influenced by cefepime dose, because carbapenems were compared with low-dose cefepime monotherapy in 5 of 9 trials. Treatment failure in clinically documented infections was also more frequent with cefepime (RR = 1.143; 95% CI, 1.004–1.300; P = .043). Toxicity-related treatment discontinuation was more common among patients that received high-dose cefepime (P = .026), whereas low-dose cefepime monotherapy resulted in fewer adverse events, compared with alternative monotherapy (P = .009). Conclusions Cefepime demonstrated increased mortality compared with carbapenems, reduced efficacy in clinically documented infections, and higher rates of toxicity-related treatment discontinuation. The impact of cefepime dosing on these outcomes is important, because low-dose regimens were associated with lower toxicity at the expense of higher mortality.

Salvage Autologous Hematpoeitic Stem Cell Transplants (AHSCT2) for Myeloma: Single Center Experience.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4591-4591
Author(s):  
Bishoy Faltas ◽  
Jane L. Liesveld ◽  
Michael Becker ◽  
Jainulabdeen J. Ifthikharuddin ◽  
Gordon L. Phillips
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
Median Overall Survival ◽  
Progressive Disease ◽  
Conflicts Of Interest ◽  
High Dose ◽  
The Impact

Abstract Abstract 4591 Although the role of AHSCT1 is well established in multiple myeloma therapy, the role of the salvage (not “tandem”) AHSCT2 is less clear. However, most pts. undergo initial stem cell harvests with plans for eventual AHSCT2. To clarify the indications, the prognostic factors and the outcomes of AHSCT2 in relapsed myeloma, we analyzed our experience in 19 pts. (pts.) who underwent salvage AHSCT2 between the 1994–2008. Mean age at AHSCT1/2 was 54.58 (SD 7.96)/57.03 (SD 8.10) respectively; 15 (79.0%) were males. At the time of diagnosis, 7 (36.8%) pts. had ISS stage I, 6 (31.6%) stage II, 3(15.8%) stage III and in 3 (15.8%) the ISS stage could not be determined. Isotypes: IgG 11 (57.9%), IgA 4 (21.1%), 1 (5.3%) pt. had IgM and 3 (15.8%) had light chain myeloma. Cytogenetics were normal in 6 (31.6%), abnormal in 5 (26.3%) and unavailable for 8 (42.1%) pts. The most common therapy received prior to AHSCT1 was Vincristine/Adriamycin/Dexamethasone in 11 (57.9%) pts.; 7 pts. were exposed to novel agents. One pt. achieved complete response (CR), 15 (79.0%) pts. achieved partial response (PR) and 3 (15.8%) pts. had stable or progressive disease after receiving the initial treatment. All pts. proceeded to receive high dose therapy with Melphalan (MEL), 2 pts received fTBI in addition to MEL. Mean MEL dose was 190.00 mg/m2 (SD 23.01); 15 pts. received 200 mg/m2. All pts. received >2×10e6/kg of CD34+ cells in the first and second transplants. At D+100 after AHSCT1, responses were: 4 (21.1%) CR, 1 (5.3%) VGPR, 8 (42.1%) PR and 6 (31.6 %) with lesser responses. Therapy to prolong response or for salvage after AHSCT1 was given in all pts before AHSCT2, including Thalidomide in 6 (31.6%), Bortezomib in 4 (21.1%) and Lenalidomide in 2 (10.5) pts. Median time to progression after AHSCT1 was 318 days [95 % CI 110– 573]. Median interval between AHSCT1 and AHSCT2 was 896.74 days (SD: 698.34 days). At the time of AHSCT2, 4 (21.1%) were in PR, 15 (79.0%) had progressive disease. For AHSCT2, all pts. Received MEL, one pt. received MEL + Cytoxan and one pt. received MEL + Bortezomib. The median MEL dose/m2 was 175.56 (52.04).All pts. survived AHSCT2 to D+100, responses were as follows: 3 (15.8%) VGPR, 9 (47.4%) in PR; 7 (36.9) pts. had lesser responses. After AHSCT2, nine (47.4%) pts. had grade III toxicity and only one pt. had grade IV toxicity (avascular necrosis). Maintenance therapy after AHSCT2 included Bortezomib in 7 (36.8%) pts., Lenalidomide in 5 (26.3%) pts. and Thalidomide in 4 (21.1%) pts. After AHSCT2, the median overall survival (OS) was 658 days [95 % CI 326–1330] and progression free survival (PFS) after AHSCT2 was 237 days [95 % CI 121– 397] (Figure 1). OS probability at 6, 12, 24 months after AHSCT2 was 81.3, 75.0, 39.3 % respectively. For all pts., the median OS time (i.e. time from diagnosis to death or last follow-up) was 2187 days [95% CI 1413– 4126]. At the end of the follow up period, a total of 14 pts. had died. Causes of death were progression in 12 (63.2%) and sepsis in 2 pts. (10.5%). The number of previous lines of chemotherapy, interval between transplants, disease status at the time of AHSCT1/2, type of myeloma and MEL dose were not predictive of OS and PFS. In the multivariate analysis, only age by decade at AHSCT2 and male gender were independent predictors of OS after AHSCT2 (HR 4.037, P= 0.01), (HR 3.74, P=0.07) respectively. Similarly, in the multivariate analysis for PFS after AHSCT2, age at AHSCT2 was an unfavorable independent predictor (HR 3.48, P=0.009) whereas relapse free response more than 18 months after AHSCT1 was an independent favorable predictor (HR 0.198, P=0.007).Our results are consistent with the few studies examining the impact of salvage transplants for myeloma which report a median overall survival ranging from 20.7 to 38.1 months from the time of AHSCT2.We conclude that salvage AHSCT2 can positively impact PFS and OS but efforts to improve outcomes are mandatory.FigureSEQ Figure ≂,* ARABIC 1Figure. SEQ Figure ≂,* ARABIC 1 X-axis represents time from AHSCT2 in days. Y axis represents survival distribution. Blue line = OS, Red = PFS. Disclosures: No relevant conflicts of interest to declare.

Age-Dependent Influence of TNF-α Polymorphism on Progression Free Survival of ASCT In Multiple Myeloma Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1829-1829
Author(s):  
Gabriele Buda ◽  
Alessandro Martino ◽  
Enrico Orciuolo ◽  
Valentina Maggini ◽  
Francesco Lapi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Elderly Patients ◽  
Progression Free Survival ◽  
The Elderly ◽  
High Dose ◽  
Transcriptional Level ◽  
Free Survival ◽  
Response To Chemotherapy ◽  
The Impact

Abstract Abstract 1829 Proinflammatory cytokines are suspected to play a role in the pathogenesis of multiple myeloma (MM). TNF-a, a potent mediator of inflammation, is involved in the malignant transformation of plasma cells and plasma cell proliferation. TNF-a determination was also reported to be a good parameter for monitoring therapy outcome during treatment with different protocols. Variation in TNF-a levels can be related to gene expression, which is regulated at transcriptional level, as well as to genetic polymorphism (SNP). Specifically, a G to A substitution at position -308 is associated with higher levels of TNF-a. From September 2006 to April 2010 we selected 202 MM patients and 234 control cases matched for age and sex. TNF-a SNP at position -308 was determined on genomic DNA extracted from blood samples. These genotypes frequencies obtained were in Hardy-Weinberg equilibrium. Our results indicate that the cytokine TNF-a gene SNP do not confer differences in the susceptibility of MM. Then, we studied the correlation between the SNPs of TNF-a -308 and the outcome of 91 MM patients that underwent to autologous bone marrow transplantation (ASCT) after a similar induction therapy (DAV or TAD). Melphalan 200 mg/mq (or 100 mg/mq, for the elderly patients) was used as conditioning regimen (table I). In the MM carrying the rarest A allele of TNF-a the overall response to chemotherapy and outcome to ASCT were similar to patients carriers G allele. On the contrary TNF-a seems to be an independent factor to predict the outcome in patients affected by MM modifying the progression free survival age related, if patients are > 60 yrs (p= 0.02). In particular pts > 60 years carrying the G/G genotype showed a better progression free survival compared to the same age patients carrying A/A or G/A genotypes (table II and table III ). Previous studies demonstrated that an higher plasma TNF-a concentration is significantly associated with advancing age and the combination of TNF-a and melphalan results in high response rates. Several mechanisms could be responsible for this, in particular a direct effect of TNF-a on the anti-tumour activity of melphalan. In our population the high dose of melphalan used in the youngest population is able to mask the role of TNF-a, but in the elderly patients it is clear as the impact of polymorphism plays a role in the better PFS of patients carrying the G/G genotype. To conclude we confirm the interesting role of TNF-a SNP in the outcome of MM in particular in the subset of pts characterized by a physiological high production of TNF-a. Disclosures: No relevant conflicts of interest to declare.

Induction chemotherapy with high-dose cytarabine and mitoxantrone in elderly acute myeloid leukemia (AML) patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6569-6569
Author(s):  
Muthalagu Ramanathan ◽  
Jan Cerny ◽  
Glen Raffel ◽  
William Vincent Walsh ◽  
Bruce Woda ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Median Time ◽  
Induction Chemotherapy ◽  
Progression Free Survival ◽  
High Dose ◽  
Refractory Disease ◽  
Platelet Recovery ◽  
Free Survival ◽  
High Dose Cytarabine

6569 Background: Induction chemotherapy is often not used in elderly patients with AML due to poor prognosis and inferior outcomes. We present here our experience in treating 20 patients age>70yrs with an induction regimen consisting of high dose cytarabine and mitoxantrone (HiDAC/MITO). Methods: We analyzed all patients age > 70 years who underwent induction with HiDAC/MITO at our institution from January 2009 to December 2011. 20 patients received HiDAC at 3 g/m2 daily on days 1-5 and mitoxantrone 80mg/m2* once on day 2(*one patient received 60mg/m2). The end points analyzed were complete remission (CR) and induction mortality at day 30, overall survival and progression free survival. Results: Median age was 75 years (70-83). 11 (55%) patients were male and 9 (45%) patients were female. Median duration of follow up of 10 (50%) patients who are still alive at the time of this analysis is 439 days (38-1095). High risk cytogenetics was noted in 11 (55%) patients including two patients with FLT3 mutated cytogenetics. Intermediate risk cytogenetics was noted in 9 (45%) patients including 2 patients with NPM1 mutated FLT 3 WT AML. 12 (60%) patients had secondary AML. The age unadjusted charlson comorbidity index (CCI) was 3 (2-9). 15 (75%) patients attained CR and 3 (15%) patients attained a CR with incomplete platelet recovery (CRp). CR +CRp rate was 90%. Two (10%) patients were refractory to induction and 5 (25%) patients relapsed at a later time point after induction. Median duration of hospital stay was 28 days (22-60). Median time to ANC >1K was 23.5 days (18-29), excluding 2 patients who had refractory disease. Median time to platelet recovery >100K was 25 days (20-44), excluding 2 patients with refractory disease and 3 patients with CRp. Regimen related toxicity included cardiac toxicity in 4 patients and bacteremia in 11 patients. Five (25%) patients were consolidated with stem cell transplant. Median overall survival (OS) was 151 days (38-1095) and progression free survival (PFS) was 131 days (38-1049). Conclusions: HiDAC/MITO induction is well tolerated by elderly patients with AML and demonstrates an overall response (CR+CRp) rate of 90% coupled with no induction deaths.

Role of employer branding in enhancing the talent management strategies: applied study at commercial banks of Jordan

2021 ◽  
Vol 12 (7) ◽  
pp. 1962-1983
Author(s):  
Atif Badri Al-Qura'an
Keyword(s):  
Commercial Banks ◽  
Response Rate ◽  
Relevant Literature ◽  
Management Strategies ◽  
Talent Management ◽  
Employer Branding ◽  
Applied Study ◽  
The Impact ◽  
Descriptive Method

The main aim of this study is to identify to what extent the managerial leaderships in top, middle, and lower levels of commercial banks at Jordan practice the employer branding dimensions and talent management strategies. Also, it aims to explore the impact of employer branding dimensions on talent management strategies. The researcher relied on analytical-descriptive method to analyze and classify the data to achieve the objectives and to identify the variables of the study. To collect data a questionnaire was developed based on relevant literature and scales, (226) questionnaires were distributed, out of which (187) were returned and analyzed using SPSS (version 19), with response rate (82.7%). The results of the study showed that the relative importance of employer branding dimensions and talent management strategies practices in commercial banks of Jordan was high. Also, the results revealed that there is a positive relationship and significant impact of employer branding dimensions on talent management strategies among managers of commercial banks in Jordan.

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