Maintenance Therapy with Low-Dose Subcutaneous 5-Azacitidine in Older Patients with AML in 1st Remission.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1029-1029
Author(s):  
Jeffrey E Lancet ◽  
Rami S. Komrokji ◽  
HuiYi Lin ◽  
Carlos M. de Castro ◽  
David A. Rizzieri ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Maintenance Therapy ◽  
Older Patients ◽  
Research Funding ◽  
Low Dose ◽  
Disease Free Survival ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free ◽  
Risk Categories

Abstract Abstract 1029 Poster Board I-51 Background: Elderly patients with AML have a poor outcome, with low complete response (CR) rates and durations of CR that are typically less than 1 year, highlighting the need for more effective post-remission therapy. 5-azacitidine (AZA) is a nucleoside analogue/DNA methyltransferase inhibitor approved for use in all FAB subtypes and risk categories of myelodysplastic syndromes (MDS). In higher-risk patients with MDS, including those with AML (former RAEB-T subtype), AZA improves overall survival and delays the time to leukemia transformation. We undertook a phase 2 pilot study of low-dose subcutaneous (SC) AZA in older adult patients with AML in 1st CR or CR with incomplete platelet recovery (CRp) following standard induction therapy. Methods: Study objectives included the following: 1) determine the one year disease-free survival in elderly patients with acute myeloid leukemia (AML) in first CR/ CRp treated with low-dose SC AZA as post-remission therapy. 2) determine safety and tolerability of SC AZA administered in the post-remission setting. 3) investigate the relationship between bone marrow genomic promoter methylation with 1-year disease-free survival. Eligibility included age ≥ 60 with AML in 1st CR/ CRp following 1-2 cycles of induction chemotherapy and 1-2 cycles of consolidation therapy, ECOG PS 0-2, adequate end-organ function. AZA was administered subcutaneously on 1 of 2 different dosing schedules: A) 50 mg/m2/d x 5d (d 1-5), or B) 50 mg/m2/d x 7d (d 1-5, 8-9). Cycles were repeated every 4 weeks, and up to 12 cycles. Results: As of August 2009, 16 patients have been enrolled on the study and 15 are currently evaluable. Nine patients received dosing schedule A and 6 received schedule B. Median age was 69 years (range 62-81); M/F was 13/2; baseline cytogenetic risk categories at initial diagnoses: poor (6), intermediate (8), and unknown/not done (1). Two of 15 patients had a history of antecedent MDS. Nine of 15 patients (60%) required 2 cycles of induction chemotherapy to achieve CR/CRp. The median time from achievement of CR/CRp to AZA initiation was 13.6 weeks (range 7 – 21.9 weeks). To date, the median number of AZA cycles received was 4, ;5 patients have received ≥ 6 cycles, 2 of whom have received the 12 planned cycles and another who remains on-study after 11 cycles. Median duration of CR/CRp was 54.8 weeks (95% CI: 28.1-96.4 weeks) estimated using the Kaplan-Meier method. Only 2 of 15 (13%) patients developed grade 3-4 non-hematologic adverse events (colitis, headache). Six of 15 (40%) patients developed reversible grade 3-4 neutropenia or thrombocytopenia, but only 3 required dose reduction. No patients discontinued AZA due to toxicity, and there were no deaths that occurred on-study. Criteria for early stoppage, based upon toxicity, have not been reached. Methylation array analyses are ongoing. SC AZA administered as maintenance therapy in older patients with AML in 1st CR/CRp appears feasible and safe. Extended treatment was possible in a high proportion of patients, with encouraging early signs of durable remissions. Accrual to this trial is ongoing and updated results will be presented. Disclosures: Lancet: Celgene: Research Funding. Komrokji:Celgene: Research Funding, Speakers Bureau. de Castro:Celgene: Speakers Bureau. Rizzieri:Celgene: Research Funding, Speakers Bureau. List:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

scholarly journals Combined Treatment of Bortezomib, Continuous Low-Dose Cyclophosphamide and Dexamethasone Followed By One Year of Maintenance Treatment for Refractory or Relapsed Multiple Myeloma Patients: A Prospective Phase II Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4733-4733
Author(s):  
Esther GM Waal de ◽  
Linda Munck de ◽  
Gerhard Woolthuis ◽  
Annet velden Van Der ◽  
Yvonne Tromp ◽  
...  
Keyword(s):  
Overall Survival ◽  
Maintenance Therapy ◽  
Research Funding ◽  
Low Dose ◽  
Progression Free Survival ◽  
Free Survival ◽  
First Relapse ◽  
Grade 3 ◽  
One Year

Abstract Introduction: Combination therapy for longer periods but at low dose, also called metronomic scheduling, might be an effective manner to treat patients with relapsing myeloma. In particular if the used agents attack the malignant clone in an alternative manner. Therefore we used the combination of bortezomib, dexametasone and daily low dose of oral cyclophosphamide as an induction regimen followed by one year of maintenance therapy consisting of bortezomib and cyclophosphamide. Methods: Relapsing myeloma patients, bortezomib naïve, were treated with three cycles of 1.3 mg/m2 bortezomib at day 1, 4, 8 and 11, cyclophosphamide 50 mg daily, and 20 mg dexamethasone at day 1, 2, 4, 5, 8, 9, 11 and 12 followed by three cycles of bortezomib 1.6 mg/m2 (day 1, 8, 15 and 2), cyclophosphamide (50 mg) daily and dexamethasone (20 mg) at day 1, 2, 8, 9, 15, 16, 22 and 23. Maintenance therapy consisting of bortezomib 1.3 mg/m2 every two weeks and daily dose of 50 mg cyclophosphamide for one year was applied to patients in partial or complete remission. Primary endpoints were toxicity during re-induction and maintenance therapy. Secondary endpoints were response to treatment and progression free and overall survival. Results: 59 patients with relapsing multiple myeloma were included of whom 69% were in first relapse (Table 1). The upfront treatment consisted mainly of thalidomide-based and vincristine-based chemotherapy and 40% of the patients have been treated with an autologous stem cell transplantation. All 6 cycles of induction chemotherapy could be given in 49% of the patients. Premature discontinuation before starting maintenance therapy was due to toxicity (31%), progressive disease (7%), death (7%) or other reasons (6%). Myelosuppression was the most common side effect with WHO grade 3-4 in 31% of the patients. Neuropathy grade 3-4 was observed in 16% of patients, partially due to the fact that bortezomib was given intravenously during the first 2 yrs of the protocol which included 76% of the patients. Maintenance therapy was started in 47% of the patients with a median duration of 7.3 months (range 0.36.-13.4). Grade 3-4 toxicity was observed in 25% of the patients including infections (n=3) and myelosuppression (n=3) which did not resulted in discontinuation of therapy. Median follow up time was 29 months with an overall response of 62%, and a very good partial response (VGPR), complete remission (CR) in 21% and 7% of the patients respectively. During the maintenance phase an improvement in responsiveness was observed in 25% of the patients. The CR rate increased with 9% to a total of 16%. VGPR rate was 20% and 16% of the patient had a PR. At end of the maintenance therapy 50% of patients started with maintenance had stable disease. The median progression free survival (PFS) was 17.2 months (range 0.13 – 43.5) as depicted in figure 1. and the median overall survival was 21.6 months (range 0.46-54.4, figure 2). During follow up 33 % of the patients died due to progression of MM. Conclusion: The present study demonstrates that combination therapy with bortezomib, continuous low dose cyclophosphamide and dexamethasone is an effective and manageable regimen. Adding a year of maintenance was feasible with limited side effects and an increase in CR rate. Table 1: patient characteristics Patients (%) Age, mean (min,max) 69 (46-86) Sex Male 56 Female 44 Relapse number First relapse 75 Second relapse 20 Third relapse 5 Performance status 0 65 1 29 2 5 M-protein heavy chain IgA 18 IgG 65 Light chain disease 18 Polyneuropathy No 61 Yes 39 Figure 1: Progression free survival Figure 1:. Progression free survival Figure 2: Overall survival Figure 2:. Overall survival Disclosures Waal de: Jansen Cilag: Research Funding. Munck de:Jansen Cilag: Research Funding. Woolthuis:Jansen Cilag: Research Funding. velden Van Der:Jansen Cilag: Research Funding. Tromp:Jansen Cilag: Research Funding. Hoogendoorn:Jansen Cilag: Research Funding. Vellenga:Jansen Cilag: Research Funding. Hovenga:Jansen Cilag: Research Funding.

Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study

2017 ◽  
Vol 35 (4) ◽  
pp. 387-393 ◽  
Author(s):  
Arnaud Pigneux ◽  
Marie C. Béné ◽  
Philippe Guardiola ◽  
Christian Recher ◽  
Jean-Francois Hamel ◽  
...  
Keyword(s):  
Overall Survival ◽  
Acute Myeloid Leukemia ◽  
Elderly Patients ◽  
Maintenance Therapy ◽  
Myeloid Leukemia ◽  
Disease Free Survival ◽  
Event Free Survival ◽  
Free Survival ◽  
Disease Free ◽  
Acute Myeloid

Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older. Patients and Methods A total of 330 patients with AML de novo or secondary to chemotherapy or radiotherapy were enrolled in the study. Induction therapy included idarubicin 8 mg/m2 on days 1 to 5, cytarabine 100 mg/m2 on days 1 to 7, and lomustine 200 mg/m2 on day 1. Patients in complete remission or partial remission received six reinduction courses, alternating idarubicin 8 mg/m2 on day 1, cytarabine 100 mg/m2 on days 1 to 5, and a regimen of methotrexate and mercaptopurine. Patients were randomly assigned to receive norethandrolone 10 or 20 mg/day, according to body weight, or no norethandrolone for a 2-year maintenance therapy regimen. The primary end point was disease-free survival by intention to treat. Secondary end points were event-free survival, overall survival, and safety. This trial was registered at www.ClinicalTrials.gov identifier NCT00700544. Results Random assignment allotted 165 patients to each arm; arm A received norethandrolone, and arm B did not receive norethandrolone. Complete remission or partial remission was achieved in 247 patients (76%). The Schoenfeld time-dependent model showed that norethandrolone significantly improved survival for patients still in remission at 1 year after induction. In arms A and B, respectively, 5-year disease-free survival was 31.2% and 16.2%, event-free survival was 21.5% and 12.9%, and overall survival was 26.3% and 17.2%. Norethandrolone improved outcomes irrelevant to all prognosis factors. Only patients with baseline leukocytes > 30 × 109/L did not benefit from norethandrolone. Conclusion This study demonstrates that maintenance therapy with norethandrolone significantly improves survival in elderly patients with AML without increasing toxicity.

scholarly journals EPEN-49. RESPONSE OF RECURRENT EPENDYMOMA TO MEMMAT BASED METRONOMIC ANTIANGIOGENIC COMBINATION THERAPY UTILIZING TAPERED BEVACIZUMAB AND MAINTENANCE THERAPY WITH CELECOXIB AND FENOFIBRATE

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii317-iii317
Author(s):  
Eileen Gillan
Keyword(s):  
Combination Therapy ◽  
Maintenance Therapy ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Time To Progression ◽  
Free Survival ◽  
Dismal Prognosis ◽  
Recurrent Ependymoma ◽  
Disease Free

Abstract Recurrent ependymomas have a dismal prognosis (2 year survival rates 29% OS and 23% EFS) and are relatively resistant to conventional chemotherapy. We previously reported five relapsed ependymoma patients treated with a MEMMAT based metronomic antiangiogenic combination therapy. All patients are currently alive, including four patients who were multiply relapsed with at least three recurrences. These four patients received between 44–52 weeks of therapy with minimal toxicity. Three had recurrent disease within an average of 44 months (median 42 months) after discontinuation of therapy. One patient who received the following tapering bevacizumab schedule: q3 weeks x 3, q4 weeks x 4 and q5 weeks x 5 followed by maintenance therapy with fenofibrate and celecoxib is in complete remission 12 months post treatment. This regimen was well tolerated with good quality of life in this patient population. Our results suggest that the chosen anti-angiogenic drug combination prolonged the time to progression in these multiply relapsed patients and thus may be particularly beneficial for patients with recurrent ependymoma. Tapered bevacizumab and maintenance therapy with celecoxib and fenofibrate may be modifications worth further investigation for prolonged disease free survival in relapsed ependymoma patients.

scholarly journals Stem Cells Inhibition by Bevacizumab in Combination with Neoadjuvant Chemotherapy for Breast Cancer

2019 ◽  
Vol 8 (5) ◽  
pp. 612 ◽  
Author(s):  
Renaud Sabatier ◽  
Emmanuelle Charafe-Jauffret ◽  
Jean-Yves Pierga ◽  
Hervé Curé ◽  
Eric Lambaudie ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Tumor Cells ◽  
Disease Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Open Label ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free

Preclinical works have suggested cytotoxic chemotherapies may increase the number of cancer stem cells (CSC) whereas angiogenesis inhibition may decrease CSC proliferation. We developed a proof of concept clinical trial to explore bevacizumab activity on breast CSC. Breast cancer patients requiring preoperative chemotherapy were included in this open-label, randomized, prospective, multicenter phase II trial. All received FEC-docetaxel combination, and patients randomized in the experimental arm received concomitant bevacizumab. The primary endpoint was to describe ALDH1 (Aldehyde dehydrogenase 1) positive tumor cells rate before treatment and after the fourth cycle. Secondary objectives included safety, pathological complete response (pCR) rate, disease-free survival (DFS), relapse-free survival (RFS), and overall survival (OS). Seventy-five patients were included. ALDH1+ cells rate increase was below the predefined 5% threshold in both arms for the 32 patients with two time points available. Grade 3 or 4 adverse events rates were similar in both arms. A non-significant increase in pCR was observed in the bevacizumab arm (42.6% vs. 18.2%, p = 0.06), but survival was not improved (OS: p = 0.89; DFS: p = 0.45; and RFS: p = 0.68). The increase of ALDH1+ tumor cells rate after bevacizumab-based chemotherapy was less than 5%. However, as similar results were observed with chemotherapy alone, bevacizumab impact on breast CSC cells cannot be confirmed.

Improved Disease Survival without Increased GVHD Using Low Dose Cyclosporine and Prednisone in Allogeneic Stem Cell Transplantation - a Case Control Study.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5148-5148
Author(s):  
John J. Moore ◽  
David D. Ma ◽  
Tony Dodds ◽  
Sam Milliken ◽  
Keith Fay ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Survival Benefit ◽  
Low Dose ◽  
Disease Free Survival ◽  
Prophylactic Regimen ◽  
Free Survival ◽  
Allogeneic Hsct ◽  
Disease Free

Abstract Allogeneic stem cell transplantation (HSCT) can cure numerous malignant and non-malignant diseases but this is offset by significant morbidity and mortality from graft versus host disease (GVHD). The standard prophylactic regimen contains cyclosporine, methotrexate and/or prednisone however doses and the timing of tapering remain unclear. Recently Ruutu et al demonstrated reduced GVHD using a prednisone based prophylactic regimen without a survival benefit whereas Baclgalupo et al demonstrated an increased survival benefit with 1mg/kg cyclosporine over 3mg/kg which strongly correlated with cyclosporine levels. Since early 2002 we have adopted both these strategies in an attempt to reduce GVHD in myeloblative HSCT but still maintain disease free survival. Consecutive myeloblative allogeneic HSCT patients (n=47, median age 41 yrs, 28 sibling or family, 19 unrelated) underwent HSCT using cyclosporine 1mg/kg, standard dose methotrexate and prednisone commencing at D14 0.5mg/kg, according to Ruutu et al. All sibling allograft patients underwent conditioning with Bu/Cy whereas unrelated recipients received Cy/TBI. This group was compared with 94 historical controls for age and disease status (median age 36 yrs, 63 sibling or family, 31 unrelated). At a median of 1 year follow up (range 100–600 days), overall and disease free survival is significantly increased in the low dose cyclosporine/prednisone arm (OS: 75% vs 50% at 1 yr, p=0.04). Acute GVHD (II–IV) was similar in both arms at D100 with a trend to less GVHD in the low dose cyclosporine/prednisone arm (20% vs 30%, p=0.1). These results suggest that the low dose cyclosporine/prednisone regimen has controlled GVHD whilst maintaining an adequate GVL effect. Randomised trials using this regimen may be warranted to fully determine its place in allogeneic HSCT prophylaxis.

Long-Term Disease-Free Survival of Patients with AML Relapse After T-Cell-Depleted Allogeneic Stem Cell Transplantation by Re-Induction Therapy and Subsequent Interferon-Boosted Donor Lymphocyte Infusion

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3064-3064
Author(s):  
M. Eefting ◽  
C.J.M. Halkes ◽  
S. Kersting ◽  
W.A.F. Marijt ◽  
P.A. von dem Borne ◽  
...  
Keyword(s):  
Immune Response ◽  
Induction Therapy ◽  
Acute Gvhd ◽  
Disease Free Survival ◽  
Remission Induction ◽  
Free Survival ◽  
Grade 3 ◽  
Disease Free

Abstract Abstract 3064 Relapse of AML after allogeneic stem cell transplantation (alloSCT) has a very poor prognosis. Salvage re-induction chemotherapy leads to clinical remissions in a substantial number of patients, but these remissions tend to be of short duration. In contrast, donor lymphocyte infusions (DLI) have the potential to effect long-lasting remissions, but the interval of several weeks to months that is required to develop a DLI-induced anti-leukemia response may prevent efficient control of a highly proliferative leukemia. In addition, a high tumor burden may suppress the immune response. In contrast, the combination of efficient cytoreduction by chemotherapy with DLI administered in rapid succession under circumstances favoring the development of an early and profound immune response might have the potential to eradicate otherwise resistant leukemia cells. We therefore adopted an institutional therapeutic strategy for relapsed myeloid leukemia post-allogeneic SCT based on administration of DLI at the anticipated end of the neutropenic phase after salvage re-induction chemotherapy. At this time point, the high prevalence of a pro-inflammatory milieu should favor the induction of the immune response, and an expected state of lymphopenia should promote the expansion of infused T cells by homeostatic proliferation. If 3 weeks after DLI no graft versus host disease (GvHD) was observed, the potential anti-leukemia immune response was further amplified by treatment with interferon- α (IFN- α) until GvHD occurred. Between January 2000 and December 2009 44 patients with relapsed myeloid malignancy after alloSCT were treated at our hospital. Pre-transplant diagnoses were AML n=40, CMML n=1 and MDS n=3. Median time from SCT to relapse was 187 days. Median follow-up after relapse was 3.1 years. 5 patients had a smouldering relapse (<10% bone marrow blasts) and 39 patients had an overt relapse. Of 39 patients with overt relapse, 7 patients (18%) did not receive re-induction therapy due to poor performance status (n=5) or patient choice (n=2). 32 patients received remission-induction therapy consisting of gemtuzumab ozogamycin (n=9), cytosine arabinoside-containing chemotherapy (n=17), or both (n=6). Following this treatment, 7 of 32 patients had rapidly progressive disease during induction therapy (n=6) or died due to toxicity (n=1) and did not receive DLI. The remaining 25 patients received DLI at a dose of 5.0×10 ^6 CD3+ cells/kg for related and 2.5×10 ^6 CD3+ cells/kg for unrelated donors 3 weeks after the start of remission-induction therapy. In 16 of these patients DLI was boosted with IFN- α 3.0×10 ^6 IE once daily. This strategy resulted in acute GvHD in 17 of 25 patients (n=8 grade 1–2, n=9 grade 3–4). At 6 weeks after DLI, 16 patients had reached CR, 5 patients had failed to reach CR (2 with GvHD) and 4 suffered treatment-related mortality (3 with GvHD). Of the 16 patients in CR, 4 had no signs of GvHD and developed a second relapse during the follow-up period. Only 3 of 12 patients in CR with signs of acute GvHD at 6 weeks after DLI developed a second relapse. In total, 9 of 17 patients (53%) with acute GvHD after DLI had long term survival versus none without acute GvHD. During follow-up, 8 patients developed chronic GvHD (n=4 limited, n=4 extensive). Finally, 5 patients with an early detected smouldering relapse received DLI, which was boosted with IFN- α in 2 patients, without salvage re-induction therapy. All 5 patients developed GvHD (n=2 grade 1–2, n=3 grade 3–4) and 3 patients achieved a CR of whom 1 patient died from GvHD. Our results indicate that treatment of relapsed AML after alloSCT with salvage re-induction therapy followed by DLI at the end of the neutropenic phase during minimal residual disease, with additional boosting of the immune response with IFN- α, can result in long-term disease-free survival. Disclosures: Off Label Use: Interferon: DLI-boosting.

Selection of Unrelated Allogeneic Hematopoietic Cell Donors Based on KIR3DL1 Allotypes Is Feasible and Results in Improved Disease-Free Survival in Transplant Recipients with MDS and AML

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 990-990
Author(s):  
Brian C. Shaffer ◽  
Glenn Heller ◽  
Jean-Benoit Le Luduec ◽  
Jack Vahradian ◽  
Miguel Perales ◽  
...  
Keyword(s):  
Research Funding ◽  
Disease Free Survival ◽  
Hematopoietic Cell ◽  
No Donors ◽  
Free Survival ◽  
Inhibitory Signal ◽  
Improved Outcomes ◽  
High Degree ◽  
Disease Free ◽  
Selection Of

Abstract Donor natural killer (NK) cells impart a potent anti-leukemia effect after allogeneic hematopoietic cell transplantation (allo HCT). The killer Ig-like receptors (KIR) play a central role in modulating NK effector function. Chief among them, the inhibitory KIR3DL1 exhibits a high degree of allelic polymorphism. We previously demonstrated that highly expressed KIR3DL1 alleles (KIR3DL1 allele groups *001 and *002) bind preferentially to HLA-Bw4 with I80 to confer a high degree of inhibitory signaling. Similarly, poorly expressed KIR3DL1 alleles (KIR3DL1 allele groups *005 and *007) bind to HLA-Bw4 with T80 to confer a strong inhibitory signal. In a retrospective cohort of 299 patients undergoing allo HCT for AML, we demonstrated that these highly inhibitory donor KIR3DL1/recipient HLA-Bw combinations (KIR3DL1-HIGH) resulted in a greater incidence of recipient relapse when compared to other donor/recipient KIR3DL1/HLA-Bw pairings with low or absent inhibitory signal (KIR3DL1-LOW/NO). (Giglio F et al, ASH Annual Meeting Abstracts, 2012) Here, we evaluated whether it was feasible to prospectively type and use KIR3DL1 allotypes in unrelated allo HCT donor selection, and whether this intervention would result in improved outcomes in patients undergoing transplant for AML and MDS. We performed PCR-SSP based intermediate resolution KIR3DL1 allele typing on all unrelated adult donors evaluated for patients with MDS and AML at our center from 2013 to present as previously described. (Boudreau J et al, PLoS One, 2014) KIR3DL1 status was provided to the treating physicians, who made the final donor selection. A total of 941 prospective allo HCT donors underwent high resolution HLA typing and KIR3DL1 allotyping for 252 patients (median per patient = 4, range 1-12). Among all donors evaluated, 27% were found to be KIR3DL1-HIGH when considering the respective recipient HLA-Bw. Having multiple donors evaluated improved the likelihood of avoiding a KIR3DL1-HIGH donor: Among recipients with one donor evaluated, 27% had only KIR3DL1-HIGH donors available compared to 12% in recipients with 2-3 donors evaluated and 4% for recipients with >3 donors evaluated (P < 0.0001). Among all evaluated patients, 41% had both KIR3DL1-HIGH and KIR3DL1-LOW/NO donors available, indicating a potential selection based on KIR3DL1 was possible. Among 252 patients evaluated, 115 proceeded to allo HCT (48 with MDS, 67 with AML). The median age at transplant was 62 years (range 3.6-78). Donors were HLA matched in 105 transplants and were single loci mismatched in 10 transplants. Conditioning was myeloablative in 73 (11 with total body irradiation). GVHD prophylaxis was with ex vivo CD34+ selection in 65 patients and with tacrolimus/methotrexate in the remaining patients. The median follow-up in transplanted patients was 13.1 months (range 0.5-43.3 months). On univariate analysis, the 2-year disease-free survival was 64% (95% confidence interval: 54-76%) in those with KIR3DL1-LOW/NO donors versus 39% (22-68%) in recipients with KIR3DL1-HIGH donors (P = 0.05). The incidence of relapse was similar but favored patients with KIR3DL1-LOW/NO donors (26% [15-37%] versus 35% [13-57%], P = 0.5). 2-year overall survival was similar between those with KIR3DL1-LOW/NO versus KIR3DL1-HIGH donors (75% [65-86%] versus 69% [52-91%], P = 0.43). The time from the initiation of a formalized donor search to transplant did not differ between recipients with KIR3DL1-LOW/NO versus KIR3DL1-HIGH donors (median 81 v. 83 days, respectively, P = 0.97). Recipients with KIR3DL1-LOW/NO donors were CIBMTR Transplant Risk Score low = 53, intermediate = 6, and high = 33; whereas recipients of KIR3DL1-HIGH donors were low = 17, intermediate = 2, and high = 4 (P = 0.15). These results indicate that disease severity and transplant urgency did not influence whether a KIR3DL1-LOW/NO donor was able to be selected. In summary, these prospective data on 115 patients from a single center support improved outcomes in patients with AML and MDS undergoing unrelated donor allo HCT using a donor with low or absent KIR3DL1 inhibition. A multi-center, prospective study to evaluate the prospective use of HLA and KIR genotype based selection of URDs for patients undergoing allo HCT for AML is underway (NCT02450708). Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Kernan: Gentium: Research Funding; The National Cancer Institute of the National Institutes of Health: Research Funding.

Adjuvant systemic therapy in elderly patients with breast cancer: A Brazilian single center experience

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20711-e20711
Author(s):  
G. Ismael ◽  
A. L. Coradazzi ◽  
C. A. Beato ◽  
P. Milhomem ◽  
J. Oliveira ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Elderly Patients ◽  
Systemic Therapy ◽  
Systemic Treatment ◽  
Disease Free Survival ◽  
Adjuvant Systemic Therapy ◽  
Free Survival ◽  
Adjuvant Systemic Treatment ◽  
Disease Free

e20711 Background: Breast cancer is the leading cause of cancer in women in Brazil and in the western world. Despite the high incidence of breast cancer in elderly women, there is no solid information regarding the real impact of the adjuvant systemic therapy in this population, considering the underrepresentation of patients with 65 years of age or older in cancer-treatment trials. Moreover, elderly patients may face some difficulties to receive adequate adjuvant systemic treatment in the routine clinical practice. Methods: Two hundred fifty eight patients with 65 years of age or older at the time of diagnosis of operable breast cancer and treated in our Institution from February 2000 to December 2005 were retrospectively studied. Clinical and pathological data were recorded as well as the type of adjuvant systemic therapy: hormonal therapy (HT), chemotherapy (CT) or both. We evaluated the disease free survival and overall survival and compared the results between the group of patients treated with HT only and the group of patients treated with both HT and CT. Results: Ninety five (37.5%) patients were stage I, 150 (58.1%) were stage II and 6 (2.3%) were stage III, while 5 (1.9%) patients were diagnosed with DCIS. Ductal carcinoma was the most frequent histological type (81%) and grade II were reported in the majority of patients (47.3%). Mostly of patients were hormonal sensible (74.4% were ER+ and 64% were PR+) and HER 2 negative (81.8%). One hundred seventy eight (69%) patients received any kind of adjuvant HT while 91 (35.3%) received any kind of adjuvant CT. There was no statistical difference between patients treated with HT when compared with the group of patients treat with HT and CT, regarding disease free survival and overall survival. However, a higher rate of high risk patients were observed in the group treated with both HT and CT. Conclusions: Despite the age, a considerable part of this elderly breast cancer patient's population has received adjuvant systemic treatment. Benefits from HT and/or CT may be considered in this group of patients. No significant financial relationships to disclose.

Sign in / Sign up

Export Citation Format

Share Document