scholarly journals A Novel Intermediate Intensity Conditioning Regimen Achieves High Rates of Long-Term Outpatient Progression-Free Survival Offsetting the Disadvantage of Early Post-Transplant Complications in Adult Cord Blood (CB) Transplant Recipients

2017 ◽  
Vol 23 (3) ◽  
pp. S176-S177
Author(s):  
Ioannis Politikos ◽  
Sean M. Devlin ◽  
Chris Mazis ◽  
Molly Maloy ◽  
Andromachi Scaradavou ◽  
...  
Keyword(s):  
Cord Blood ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Transplant Recipients ◽  
Free Survival ◽  
Post Transplant ◽  
Transplant Complications

A Novel Intermediate Intensity Conditioning Regimen Achieves High Rates of Long-Term Outpatient Progression-Free Survival Offsetting the Disadvantage of Early Post-Transplant Complications in Adult Cord Blood (CB) Transplant Recipients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2193-2193
Author(s):  
Ioannis Politikos ◽  
Sean Devlin ◽  
Yeon Yoo ◽  
Christopher Mazis ◽  
Molly A. Maloy ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Acute Leukemia ◽  
B Cell ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Free Survival ◽  
Post Transplant ◽  
Time Period ◽  
Transplant Complications

Abstract Background: CB transplantation (CBT) can be associated with early post-transplant complications resulting in prolonged hospitalization, but this disadvantage may be offset by the later benefits of low rates of chronic GVHD & relapse, & high rates of long-term immune recovery. Our center is investigating CBT after a novel intermediate intensity, reduced toxicity myeloablative conditioning regimen in an effort to reduce early complications/ toxicities while maximizing disease control. However, the determinants of both progression-free survival (PFS) & the complications that compromise the time spent outpatient & progression-free after this therapy are not established. Methods: We analyzed factors contributing to 2-year PFS & the composite endpoint of being both outpatient & progression-free by post-transplant time period in adult recipients of intermediate intensity CBT. Eligible patients (pts) were 1st allograft recipients ≤ 65 years conditioned with cyclophosphamide 50 mg/kg, fludarabine 150 mg/m2, thiotepa 5-10 mg/kg, 400 cGy TBI for the treatment of acute leukemia/ MDS/ MPD (≤ 10% blasts pre-CBT), B-cell NHL or HL. GVHD prophylaxis was with CSA/ MMF (no ATG). Results: Pts [n = 110, 55% non-European, 62% CMV seropositive, median age 51 years (range 18-65)] had diagnoses of acute leukemia (83), MDS/MPD (11), B-cell NHL (14) & HL (2). 109 received double & 1 single unit grafts [median donor recipient 8-allele HLA-match 5/8 (range 2-8); median infused CD34+ dose 0.95 x 105/kg/unit (range 0.17-3.72)]. 96% of pts engrafted. Day 180 incidence of grades II-IV & III-IV aGVHD was 75% (95%CI: 66-83) & 21% (95%CI: 14-29), respectively; 8% (95%CI: 4-15) of pts had cGVHD by 1 year. Day 180 TRM incidence was 15% (95%CI: 8-22), & 10% (95%CI: 5-17) of pts relapsed by 2 years post-CBT. With a median survivor follow-up of 2.7 years (range 6 months-8.5 years), the 2-year OS is 72% (95%CI: 64-81) & PFS is 69% (95%CI: 61-79). Revised disease risk index (rDRI) & age adjusted hematopoietic cell transplant-comorbidity index (aaHCT-CI) were significant determinants of 2-year PFS (Figure 1), whereas pt age (< 51 vs ≥ 51 years), CMV serostatus, European vs non-European ancestry, dominant unit-recipient HLA-match (< 5/8 vs ≥ 5/8) & infused CD34+ cell dose (< 0.95 vs ≥ 0.95) were not. In multivariate analysis, only aaHCT-CI was significant [HR 2.15 (95%CI: 1.01-4.59) if aaHCT-CI ≥ 3 (p = 0.047)]. The HR if high-very high rDRI was 2.03 (95%CI: 0.92-4.48) (p = 0.079). We then analyzed if recipient & graft factors were associated with the endpoint of being outpatient & progression-free by time period post-CBT. The median initial length of stay was 37 days (range 14-77) post-CBT. 101/110 (92%) pts survived to first discharge. Within the first 180 days, 60/101 (59%) of these pts were re-admitted for transplant-related complications at least once [111 readmissions, median 1/pt (range 1-9), & most commonly due to infection or aGVHD (± infection)]. However, when the distribution of pts who were outpatient/ progression-free vs inpatient vs dead/ relapsed was analyzed by post-transplant month over the first 2 years (Figure 2), high proportions of pts are outpatient & progression-free after 6 months post-CBT. Finally, we found that low-intermediate rDRI, 0-2 aaHCT-CI & CMV seronegativity were associated with a higher mean number of outpatient progression-free days in the first 6 months (Table), and only aaHCT-CI was significant through-out the 2 years post-CBT. Age, ancestry & graft variables were not significant at any time. In multivariate analysis for days 0-180, only aaHCT-CI was significant (p = 0.015). Conclusions: The 2-year PFS in this adult pt population (median age 51 years) is very promising after Cy/Flu/Thio/TBI intermediate intensity CBT. Not only is the incidence of late TRM and relapse low, the burden of hospitalization is low after 6 months resulting in high rates of being outpatient and progression-free long-term. Patients with low aaHCT-CI scores do especially well and PFS with quality of life comparisons of this pt population as compared to allografting with other stem cell sources is indicated.Nonetheless, new strategies are required to reduce early post-CBT complications, and further investigation is required to understand which comorbidities specifically dictate increased risk for complications and mortality, as well as how to improve CBT safety in pts with high aaHCT-CI. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Predictive Value of PET/CT for Post-Transplant Outcomes in T Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2914-2914
Author(s):  
Nancy Kaddis ◽  
Eric D Jacobsen ◽  
Ailbhe O'Neill ◽  
Nikhil Ramaiya ◽  
Robert A. Redd
Keyword(s):  
Predictive Value ◽  
Progression Free Survival ◽  
Ct Images ◽  
Negative Group ◽  
Free Survival ◽  
Positive Group ◽  
Post Transplant ◽  
Pet Ct

Abstract Objective 18F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) is used routinely for response assessment and treatment decision making in Hodgkin lymphoma and B cell non-Hodgkin lymphoma. The predictive value of PET/CT in patients with peripheral T-cell lymphomas (PTCL) is not well defined. We performed a retrospective single institution analysis to determine the utility of pre-transplant PET/CT to predict outcomes following autologous stem cell transplant (ASCT) for PTCL. Materials and Methods PET/CT patient population We screened the Dana-Farber Cancer Institute database for patients undergoing ASCT between 2005 and 2015 and identified 109 PTCL patients. Patients had PET/CT performed within 3 months prior to transplant and follow up PET/CT within one year of ASCT. 38 patients met the inclusion criteria (17 women, 21 men, mean age at transplant 56 years, SD ±14.6, range 22-73). Image interpretation The FDG-PET/CT images were reviewed on HERMES GOLD (Hermes Medical Solutions AB, Stockholm, Sweden) workstation by a radiologist (AON) blinded to clinical details. Pre-transplant PET/CT images were read initially and then one week later the post-transplant PET/CT images were read with the reader blinded to the pre-transplant PET/CT findings. The Deauville five-point scale was used for staging and assessment of treatment response and recurrence. A Deauville score of 3 or less was considered a complete response (CR). Results There was mean of 1.3 months between the initial PET/CT and transplant. Mean of 5 months between transplant and follow up PET/CT. A total of 30 patients had a CR on pre-transplant PET/CT. There were 8 patients with persistent sites of FDG uptake on PET/CT with Deauville 4 (n=4), Deauville 5 (n=2) consistent with partial response to treatment. Pre-transplant PET/CT did not correlate with long term survival outcomes including 3-year PFS in our data; a negative pre-transplant PET/CT was not associated with improved 3-year PFS as compared to a positive pre-transplant PET/CT. A total of 26 patients (68%) had no evidence of disease on post-transplant PET or negative post treatment PET/CT. Of those, 23 (88%) had a 3 -year progression free survival, 13 (50%) had a 5-year progression free survival, and 5 (19%) had died of recurrent disease at the time of our analysis. On post-transplant, a total of 12 patients had positive PET/CT with 6 achieving partial remission and 6 having progressive disease on post-transplant PET/CT. In terms of outcome, the 3-year PFS for the PET positive group was 42% (5/12). Of those, 2 (17%) had durable 5-year PFS with treatment after transplant while the other 10 (83%) eventually died of their disease. The 3-year PFS rate in the PET negative group was 88% (23/26) (95% CI: 70 - 98%) and 42% (5/12) (95% CI: 15 - 72%%) for PET positive group. The difference in the 3-year PFS in the PET negative group is significantly larger than that of the PET negative group (p<0.005). The 5-year PFS in the PET negative group was 50% (13/26) and 17% (2/12) for the PET positive group with a marginally significant difference (p=0.08) Conclusions: Patients with a negative post-transplant PET/CT had a 3-year PFS of 88% and 5-year PFS of 50% compared to a 3-year PFS of 42% and a 5-year PFS of 17% in patients with a positive post-transplant PET/CT. This suggests that post-transplant PET/CT is a clinically meaningful predictor of long-term disease-free survival. The PFS data in the patients with a negative post-transplant PET/CT compares favorably to that of patients not stratified by PET/CT in prospective trials including a 5-year PFS of 44% in the NLG-T-01 study which looked at 115 PTCL patients who underwent ASCT in the up-front setting (d'Amore F, et al. J Clin Oncol. 2012 Sep 1;30(25):3093-9). Our findings that negative pre-transplant PET/CT are not predictive of survival or associated with an improved 3-year PFS in comparison to positive pre-transplant PET/CT was in keeping with the findings of another retrospective analysis of 48 patients, which compared the 3-year PFS and OS of patients with positive and negative pre-transplant PET/CT studies (Shea L, et al. Leuk Lymphoma. 2015 January; 56(1): 256-259). Disclosures Jacobsen: Merck: Consultancy; Seattle Genetics: Consultancy.

scholarly journals Long-term progression-free survival of patients with metastatic melanoma or renal cell carcinoma following high-dose interleukin-2

2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Melanoma ◽  
Systemic Therapy ◽  
Renal Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Dose ◽  
Free Survival

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.

scholarly journals A phase I/Ib trial targeting the Pi3k/Akt pathway using perifosine: Long-term progression-free survival of patients with resistant neuroblastoma

2016 ◽  
Vol 140 (2) ◽  
pp. 480-484 ◽  
Author(s):  
Brian H. Kushner ◽  
Nai-Kong V. Cheung ◽  
Shakeel Modak ◽  
Oren J. Becher ◽  
Ellen M. Basu ◽  
...  
Keyword(s):  
Phase I ◽  
Progression Free Survival ◽  
Akt Pathway ◽  
Free Survival

Alkylating agent rechallenge in metastatic pancreatic neuroendocrine tumours

2021 ◽  
Author(s):  
Ophelie De Rycke ◽  
Thomas Walter ◽  
Marine Perrier ◽  
Olivia Hentic ◽  
Catherine Lombard-Bohas ◽  
...  
Keyword(s):  
Neuroendocrine Tumours ◽  
Objective Response ◽  
Multivariable Analysis ◽  
Progression Free Survival ◽  
Tumor Control ◽  
Free Survival ◽  
Mgmt Expression ◽  
Pancreatic Neuroendocrine Tumours

A rechallenge is common after initial efficacy of alkylating-based chemotherapy (ALK) in pancreatic neuroendocrine tumors (PanNET). High MGMT expression seems associated with lower response to ALK. We aimed to evaluate the efficacy and toxicity of ALK rechallenge in PanNET. Secondly, to assess the evolution of MGMT expression under ALK. All consecutive patients with advanced PanNETs who received initial ALK (achieving tumor control) followed by a pause > 3 months, then an ALK rechallenge (ALK2) upon progression were retrospectively studied (Cohort A). Primary endpoint was progression-free survival under ALK2 (PFS2). The MGMT expression was retrospectively assessed by immunohistochemistry (H-score) in consecutive PanNET surgically resected following ALK (Cohort B). We foud that cohort A included 62 patients (median Ki67 8%), for which ALK1 followed by pause achieved an objective response rate of 55%, and a PFS1 of 23.7 months (95% IC, 19.8-27.6). ALK2 achieved no objective response, and stability in 62% of patients. The median PFS2 was 9.2 months (IC 95% 7.1-11.3). At multivariable analysis, a hormonal syndrome (p=0.032) and a pause longer than 12 months (p=0.041) were associated with a longer PFS2. In the cohort B (17 patients), the median MGMT H-score increased from 45 (IQR 18-105) before ALK, to 100 (IQR 56-180) after ALK (p=0.003). We conclude that after initial efficacy of ALK treatment, a pause followed by ALK rechallenge might be appropriate to prolong tumor control, improve quality of life and limit long-term adverse events. Increased MGMT expression under ALK might explain low efficacy of ALK rechallenge.

The association between albumin-globulin ratio (AGR) and survival in patients treated with immune checkpoint inhibitors

2021 ◽  
pp. 1-11
Author(s):  
Deniz Can Guven ◽  
Oktay Halit Aktepe ◽  
Melek Seren Aksun ◽  
Taha Koray Sahin ◽  
Gozde Kavgaci ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Multivariate Analyses ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Free Survival ◽  
Patients With Cancer ◽  
Early Progression ◽  
Term Benefit

BACKGROUND: The albumin-globulin ratio (AGR) could be a prognostic biomarker in patients with cancer, although the data is limited in patients treated with immune-checkpoint inhibitors (ICIs). OBJECTIVES: We aimed to evaluate the association between AGR and survival in ICI-treated patients. METHODS: The data of 212 advanced-stage patients were retrospectively evaluated in this cohort study. The association between AGR with overall (OS) and progression-free survival (PFS) were evaluated with multivariate analyses. Additionally, receptor operating curve (ROC) analysis was conducted to assess the AGR’s predictive power in the very early progression (progression within two months) and long-term benefit (more than twelve months survival). RESULTS: The median AGR was calculated as 1.21, and patients were classified into AGR-low and high subgroups according to the median. In the multivariate analyses, patients with lower AGR (< 1.21) had decreased OS (HR: 1.530, 95% CI: 1.100–2.127, p= 0.011) and PFS (HR: 1.390, 95% CI: 1.020–1.895, p= 0.037). The area under curve of AGR to detect early progression and long-term benefit were 0.654 (95% CI: 0.562–0.747, p= 0.001) and 0.671 (95% CI: 0.598–0.744, p< 0.001), respectively. CONCLUSIONS: In our experience, survival with ICIs was impaired in patients with lower AGR. Additionally, the AGR values could detect the very early progression and long-term benefit ICIs.

scholarly journals Progression-Free Survival: An Important Prognostic Marker for Long-Term Survival of Small Cell Lung Cancer

2014 ◽  
Vol 76 (5) ◽  
pp. 218 ◽  
Author(s):  
Myoung-Rin Park ◽  
Yeon-Hee Park ◽  
Jae-Woo Choi ◽  
Dong-Il Park ◽  
Chae-Uk Chung ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Prognostic Marker ◽  
Cell Lung Cancer ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Term Survival ◽  
Free Survival
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