Allogeneic Hematopoietic Stem Cell Transplantation Improves Outcome of Elderly Patients with Acute Myeloid Leukemia in First Complete Remission: A Time-Dependent and Multistate Analysis from the French Innovative Leukemia Organization

Abstract Allogeneic stem cell transplantation (AlloSCT) is a curative option for acute myeloid leukemia (AML) patients. In first complete remission (CR1), young patients (< 60 years) with intermediate or unfavorable ELN disease risk are usually considered for AlloSCT. In contrast, because of the expected higher toxicity in older patients, the benefit of this treatment remains a matter of debate after 60 years, especially in the intermediate ELN risk group. In this multicenter analysis from the French Innovative Leukemia Organization (FILO), we investigated whether AlloSCT was beneficial for AML patients over 60 years old in CR1. Inclusion criteria were: patients between 60 and 70 years of age diagnosed with AML from 2007 to 2017; CR1 after intensive chemotherapy; ELN-2010 intermediate or unfavorable risk group. AlloSCT was evaluated as a time dependent variable in survival calculations and in a multivariate Cox model adjusted on age, ELN group, transplantation period and stratified by transplantation center. We also used a multistate model as follow: initial state for all patients was "No Allo - CR" with time 0 at the time of CR. From initial state, patients can transit to "Allo-CR", or move through 2 absorbing states (non-relapse death (No Allo-NRM) or relapse (No Allo-Relapse). Similarly, once transplanted (i.e. in the state "Allo-CR"), patients can move to "Allo-Relapse" or "Allo - NRM" when such events occurred. The model allows the dynamic prediction of probability for a patient to be in a specific state considering specific initial state and time. We analyzed 521 consecutive patients in 6 centers who matched inclusion criteria. Median age was 65 years (range: 60-70). ELN-2010 risk was intermediate and unfavorable in 376 (72%) and 145 (28%) patients, respectively. While all patients had a theoretical indication for AlloSCT in CR1, 199 (38%) were actually transplanted (129 (34%) and 70 (48%) in the intermediate and unfavorable risk group, respectively). In the whole cohort, AlloSCT as time-dependent variable significantly improved relapse-free survival ([RFS] at 5 years, No AlloSCT vs. AlloSCT: 14% vs. 47% p < 0.001) and overall survival ([OS] at 5 years, No AlloSCT vs. AlloSCT: 24% vs. 51% p < 0.001). In subgroup analysis based on ELN-2010 risk classification, AlloSCT significantly improved outcome of both ELN intermediate (No AlloSCT vs. AlloSCT: 5-y RFS: 16% vs. 50% p < 0.001; 5-y OS: 26% vs. 54% p < 0.001) and unfavorable (No AlloSCT vs. AlloSCT: 5-y RFS: 7% vs. 44% p < 0.001; 5-y OS: 17% vs. 46% p < 0.001) risk group patients (Figure A and B). By multivariate time-dependent Cox model, AlloSCT significantly decreased the risk of relapse (HR [95%CI]: 0.29 [0.20-0.41] p < 0.001) and increased the risk of NRM (HR [95%CI]: 2.61 [1.38-4.94] p = 0.003). This led to a significant advantage for AlloSCT in both RFS (HR [95%CI]: 0.48 [0.36-0.64] p < 0.001) and OS (HR [95%CI]: 0.60 [0.44-0.81] p = 0.001). This benefit was observed in both intermediate and unfavorable ELN-2010 risk groups, with lower risk of relapse (intermediate: HR [95%CI]: 0.30 [0.19-0.46] p < 0.001; unfavorable: HR [95%CI]: 0.37 [0.19-0.72] p = 0.004) and better OS (intermediate: HR [95%CI]: 0.67 [0.47-0.96] p = 0.028; unfavorable: HR [95%CI]: 0.51 [0.29-0.91] p = 0.022). Multistate model showed that 5 years after CR1, few patients were still alive in CR without AlloSCT (i.e. in the initial "No Allo-CR" state), whatever the ELN-2010 risk group (intermediate: 9%; unfavorable: 1% Figure C and D). Among patients who were transplanted, the probability for transiting to Allo-NRM state within 5 years post CR1 was 17% and 24% in intermediate and unfavorable ELN-2010 groups, respectively. Corresponding values for patients without AlloSCT transiting to No Allo-NRM state were 11% and 12%. Moreover, considering a landmark at 6 months after CR1, the multistate model showed that patients who received AlloSCT had lower probability of relapse at 5 years (22% and 33% in intermediate and unfavorable ELN-2010 groups, respectively) compared to those who did not (68% and 78% in intermediate and unfavorable groups, respectively). AlloSCT for CR1 AML patients over 60 years of age is routinely feasible and significantly improves outcome in both intermediate and unfavorable ELN-2010 risk groups. Less than 10% of patients are long term disease free survival without AlloSCT, even in intermediate risk group, supporting that AlloSCT remains the first curative option for these patients. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Clinical value of event-free survival (EFS) in acute myeloid leukemia (AML).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e18513 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e18513-e18513

Author(s):

Abhishek Maiti ◽

Hagop M. Kantarjian ◽

Vinita Popat ◽

Carlos Blanco ◽

Miguel Velasquez ◽

...

Keyword(s):

Myeloid Leukemia ◽

Blood Product ◽

Risk Groups ◽

Care Utilization ◽

Newly Diagnosed ◽

Inclusion Criteria ◽

Event Free Survival ◽

Imaging Studies ◽

Clinical Value ◽

Free Survival

e18513 Background: EFS is not considered a robust end-point for AML trials. We hypothesized that rather than a surrogate for overall survival (OS), improvement in EFS may be valuable due to patients (pts) staying in remission and thus decreasing health care utilization (HCU). Methods: In this retrospective study we identified AML pts treated on frontline therapy trials at our institute from 2003-2013 with EFS ≥2 months (mo) and OS of 12-36 mo. We captured the amount of HCU from diagnosis till death, including number of clinic and emergency room (ER) visits, hospitalizations, consultations, blood product transfusions, invasive procedures, laboratory and imaging studies. Linear regression and product-moment correlation were used to determine the relation between these parameters and EFS. Results: Among 337 pts meeting inclusion criteria, the median age was 65 years, 30% had adverse risk AML, 47% received intensive chemotherapy (IC) and 27% received hypomethylating agents (HMA). The median EFS was 10.8 mo. Increasing EFS led to statistically significant decline in HCU for all patients regardless of OS and the correlations were stronger for pts achieving a complete remission (CR, Table). These observations held true across European LeukemiaNet risk groups, younger and older pts, and those receiving IC, HMA, and non-IC, with or without other agents. Conclusions: In newly diagnosed AML, improvement in EFS is correlated with decrease in all HCU irrespective of OS duration. [Table: see text]

Download Full-text

In-depth time-dependent analysis of the benefit of Allo-HSCT for elderly patients with CR1 AML: a FILO study

Blood Advances ◽

10.1182/bloodadvances.2021004435 ◽

2021 ◽

Author(s):

Raynier Devillier ◽

Edouard Forcade ◽

Alice Garnier ◽

Sarah Guenounou ◽

Sylvain Thepot ◽

...

Keyword(s):

Myeloid Leukemia ◽

Risk Group ◽

Time Dependent ◽

Multistate Model ◽

Dynamic Prediction ◽

Hematopoietic Stem ◽

Landmark Model ◽

The Impact ◽

Time Dependent Analysis

The benefit of allogeneic hematopoietic stem cell transplantation (Allo-HSCT) for acute myeloid leukemia (AML) patients over 60 years remains a matter of debate, notably when performed in first complete remission (CR1). In order to clarify this issue, the French Innovative Leukemia Organization (FILO) performed a 10-year real-world time-dependent analysis. The study enrolled patients between 60 and 70 years of age with AML in CR1 after intensive chemotherapy with intermediate (IR) or unfavorable (UR) risk according to the European LeukemiaNet (ELN)-2010. The impact of Allo-HSCT was analyzed through three models, respectively i) time-dependent Cox, ii) multistate for dynamic prediction and iii) super landmark. The study enrolled 369 (73%) IR and 138 (27%) UR AML patients, 203 of whom received an Allo-HSCT. Classical multivariate analysis showed that Allo-HSCT significantly improved relapse-free (RFS; Hazard Ratio/HR [95%CI]: 0.47 [0.35-0.62], p<0.001) and overall (OS; HR [95%CI]: 0.56 [0.42-0.76], p<0.001) survivals, independently of the ELN risk group. With the multistate model, the predicted 5-year probability for IR and UR patients to remain in CR1 without Allo-HSCT was 8% and 1%, respectively. Dynamic predictions confirmed that patients without Allo-HSCT continue to relapse over time. Finally, the super landmark model showed that Allo-HSCT significantly improved RFS (HR [95%CI]: 0.47 [0.36-0.62], p<0.001) and OS (HR [95%CI]: 0.54 [0.40-0.72], p<0.001). Allo-HSCT in CR1 is demonstrated here to significantly improve the outcome of fit older AML patients. Long-term RFS without Allo-HSCT is very low (<10%), supporting Allo-HSCT as being the best curative option for these patients.

Download Full-text

Impact of NPM1/FLT3-ITD genotypes defined by the 2017 European LeukemiaNet in patients with acute myeloid leukemia

Blood ◽

10.1182/blood.2019002697 ◽

2020 ◽

Vol 135 (5) ◽

pp. 371-380 ◽

Cited By ~ 14

Author(s):

Konstanze Döhner ◽

Christian Thiede ◽

Nikolaus Jahn ◽

Ekaterina Panina ◽

Agnes Gambietz ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Hematopoietic Cell Transplantation ◽

Risk Group ◽

Cox Model ◽

Risk Groups ◽

Mutational Status ◽

Genetic Features ◽

Poor Outcomes ◽

Acute Myeloid

Abstract Patients with acute myeloid leukemia (AML) harboring FLT3 internal tandem duplications (ITDs) have poor outcomes, in particular AML with a high (≥0.5) mutant/wild-type allelic ratio (AR). The 2017 European LeukemiaNet (ELN) recommendations defined 4 distinct FLT3-ITD genotypes based on the ITD AR and the NPM1 mutational status. In this retrospective exploratory study, we investigated the prognostic and predictive impact of the NPM1/FLT3-ITD genotypes categorized according to the 2017 ELN risk groups in patients randomized within the RATIFY trial, which evaluated the addition of midostaurin to standard chemotherapy. The 4 NPM1/FLT3-ITD genotypes differed significantly with regard to clinical and concurrent genetic features. Complete ELN risk categorization could be done in 318 of 549 trial patients with FLT3-ITD AML. Significant factors for response after 1 or 2 induction cycles were ELN risk group and white blood cell (WBC) counts; treatment with midostaurin had no influence. Overall survival (OS) differed significantly among ELN risk groups, with estimated 5-year OS probabilities of 0.63, 0.43, and 0.33 for favorable-, intermediate-, and adverse-risk groups, respectively (P < .001). A multivariate Cox model for OS using allogeneic hematopoietic cell transplantation (HCT) in first complete remission as a time-dependent variable revealed treatment with midostaurin, allogeneic HCT, ELN favorable-risk group, and lower WBC counts as significant favorable factors. In this model, there was a consistent beneficial effect of midostaurin across ELN risk groups.

Download Full-text

Umbilical cord blood transplantation can overcome the poor prognosis of KMT2A-MLLT3 acute myeloid leukemia and can lead to good GVHD-free/relapse-free survival

Annals of Hematology ◽

10.1007/s00277-021-04413-2 ◽

2021 ◽

Author(s):

Juan Tong ◽

Lei Zhang ◽

Huilan Liu ◽

Xiucai Xu ◽

Changcheng Zheng ◽

...

Keyword(s):

Myeloid Leukemia ◽

Poor Prognosis ◽

Cord Blood Transplantation ◽

Chronic Gvhd ◽

Relapse Free Survival ◽

Free Survival ◽

Chemotherapy Group ◽

Blood Transplantation ◽

The Poor ◽

First Complete Remission

AbstractThis is a retrospective study comparing the effectiveness of umbilical cord blood transplantation (UCBT) and chemotherapy for patients in the first complete remission period for acute myeloid leukemia with KMT2A-MLLT3 rearrangements. A total of 22 patients were included, all of whom achieved first complete remission (CR1) through 1–2 rounds of induction chemotherapy, excluding patients with an early relapse. Twelve patients were treated with UCBT, and 10 patients were treated with chemotherapy after 2 to 4 courses of consolidation therapy. The 3-year overall survival (OS) of the UCBT group was 71.3% (95% CI, 34.4–89.8%), and that of the chemotherapy group was 10% (95% CI, 5.89–37.3%). The OS of the UCBT group was significantly higher than that of the chemotherapy group (P = 0.003). The disease-free survival (DFS) of the UCBT group was 60.8% (95% CI, 25.0–83.6%), which was significantly higher than the 10% (95% CI, 5.72–35.8%) of the chemotherapy group (P = 0.003). The relapse rate of the UCBT group was 23.6% (95% CI, 0–46.8%), and that of the chemotherapy group was 85.4% (95% CI, 35.8–98.4%), which was significantly higher than that of the UCBT group (P < 0.001). The non-relapse mortality (NRM) rate in the UCBT group was 19.8% (95% CI, 0–41.3%), and that in the chemotherapy group was 0.0%. The NRM rate in the UCBT group was higher than that in the chemotherapy group, but there was no significant difference between the two groups (P = 0.272). Two patients in the UCBT group relapsed, two died of acute and chronic GVHD, and one patient developed chronic GVHD 140 days after UCBT and is still alive, so the GVHD-free/relapse-free survival (GRFS) was 50% (95% CI, 17.2–76.1%). AML patients with KMT2A-MLLT3 rearrangements who receive chemotherapy as their consolidation therapy after CR1 have a very poor prognosis. UCBT can overcome the poor prognosis and significantly improve survival, and the GRFS for these patients is very good. We suggest that UCBT is a better choice than chemotherapy for KMT2A-MLLT3 patients.

Download Full-text

MO048MULTICENTRE PROSPECTIVE VALIDATION OF THE URINARY PEPTIDOME-BASED CLASSIFIER CKD273 AS A PREDICTOR OF RENAL FUNCTION DECLINE IN SUBJECTS WITH TYPE 2 DIABETES

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa140.mo048 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Morten Lindhardt ◽

Nete Tofte ◽

Gemma Currie ◽

Marie Frimodt-Moeller ◽

Heiko Von der Leyen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Renal Function ◽

High Risk ◽

Risk Group ◽

Cox Model ◽

Risk Groups ◽

High Risk Group ◽

Low Risk ◽

Renal Function Decline

Abstract Background and Aims In the PRIORITY study, it was recently demonstrated that the urinary peptidome-based classifier CKD273 was associated with increased risk for progression to microalbuminuria. As a prespecified secondary outcome, we aim to evaluate the classifier CKD273 as a determinant of relative reductions in eGFR (CKD-EPI) of 30% and 40% from baseline, at one timepoint without requirements of confirmation. Method The ‘Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial’ (PRIORITY) is the first prospective observational study to evaluate the early detection of diabetic kidney disease in subjects with type 2 diabetes (T2D) and normoalbuminuria using the CKD273 classifier. Setting 1775 subjects from 15 European sites with a mean follow-up time of 2.6 years (minimum of 7 days and a maximum of 4.3 years). Patients Subjects with T2D, normoalbuminuria and estimated glomerular filtration rate (eGFR) ≥ 45 ml/min/1.73m2. Participants were stratified into high- or low-risk groups based on their CKD273 score in a urine sample at screening (high-risk defined as score > 0.154). Results In total, 12 % (n = 216) of the subjects had a high-risk proteomic pattern. Mean (SD) baseline eGFR was 88 (15) ml/min/1.73m2 in the low-risk group and 81 (17) ml/min/1.73m2 in the high-risk group (p < 0.01). Baseline median (interquartile range) urinary albumin to creatinine ratio (UACR) was 5 (3-8) mg/g and 7 (4-12) mg/g in the low-risk and high-risk groups, respectively (p < 0.01). A 30 % reduction in eGFR from baseline was seen in 42 (19.4 %) subjects in the high-risk group as compared to 62 (3.9 %) in the low-risk group (p < 0.0001). In an unadjusted Cox-model the hazard ratio (HR) for the high-risk group was 5.7, 95 % confidence interval (CI) (3.9 to 8.5; p<0.0001). After adjustment for baseline eGFR and UACR, the HR was 5.2, 95 % CI (3.4 to 7.8; p<0.0001). A 40 % reduction in eGFR was seen in 15 (6.9 %) subjects in the high-risk group whereas 22 (1.4 %) in the low-risk group developed this endpoint (p<0.0001). In an unadjusted Cox-model the HR for the high-risk group was 5.0, 95 % CI (2.6 to 9.6; p<0.0001). After adjustment for baseline eGFR and UACR, the HR was 4.8, 95 % CI (2.4 to 9.7; p<0.0001). Conclusion In normoalbuminuric subjects with T2D, the urinary proteomic classifier CKD273 predicts renal function decline of 30 % and 40 %, independent of baseline eGFR and albuminuria.

Download Full-text

Induction chemotherapy followed by radiotherapy versus concurrent chemoradiotherapy in the treatment of different risk locoregionally advanced nasopharyngeal carcinoma

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920928214 ◽

2020 ◽

Vol 12 ◽

pp. 175883592092821

Author(s):

Li-Ting Liu ◽

Yu-Jing Liang ◽

Shan-Shan Guo ◽

Hao-Yuan Mo ◽

Ling Guo ◽

...

Keyword(s):

High Risk ◽

Nasopharyngeal Carcinoma ◽

Induction Chemotherapy ◽

Concurrent Chemoradiotherapy ◽

Risk Group ◽

Risk Groups ◽

Rank Test ◽

Intermediate Risk ◽

Free Survival ◽

Alternative Treatment Strategy

Background: This study aimed to investigate the efficiency and toxicities of concurrent chemoradiotherapy (CCRT) and induction chemotherapy (IC) followed by radiotherapy (RT) in different risk locoregionally advanced nasopharyngeal carcinoma (NPC). Methods: A total of 1814 eligible patients with stage II–IVB disease treated with CCRT or IC plus RT were included. The overall survival (OS), progression-free survival (PFS) and distant metastasis-free survival (DMFS) were calculated using the Kaplan–Meier method, and the differences were compared using the log-rank test. Results: Nomograms were developed to predict OS, PFS and DMFS (C-index: 0.71, 0.70 and 0.71, respectively). Patients were then divided into three different risk groups based on the scores calculated by the nomogram for OS. In the low and intermediate-risk group, no significant survival differences were observed between patients treated with IC plus RT alone and CCRT (5-year OS, 97.3% versus 95.6%, p = 0.642 and 87.6% versus 89.7%, p = 0.381, respectively; PFS, 95.9% versus 95.6%, p = 0.325 and 87.6% versus 89.0%, p = 0.160, respectively; DMFS, 97.2% versus 94.8%, p = 0.339 and 87.2% versus 89.3%, p = 0.628, respectively). However, in the high-risk group, IC plus RT displayed an unfavorable 5-year OS (71.0% versus 77.2%, p = 0.022) and PFS (69.4.0% versus 75.4%, p = 0.019) compared with CCRT. A significantly higher incidence of grade 3 and 4 adverse events was documented in patients treated with CCRT than in those treated with IC plus RT in all risk groups ( p = 0.040). Conclusion: IC followed by RT represents an alternative treatment strategy to CCRT for patients with low and intermediate-risk NPC, but it is not recommended for patients with high-risk NPC.

Download Full-text

Clinical Useful Prognostic Index for Adult Patients with Acute Myeloid Leukemia in First Relapse.

Blood ◽

10.1182/blood.v104.11.2011.2011 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2011-2011

Author(s):

Dimitri A. Breems ◽

Wim L.J. Van Putten ◽

Bob Lowenberg

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Risk Group ◽

Prognostic Index ◽

Free Interval ◽

First Relapse ◽

One Year ◽

First Complete Remission ◽

Acute Myeloid

Abstract The treatment of acute myeloid leukemia (AML) in first relapse is associated with unsatisfactory rates of complete responses that are usually short lived. Previously proposed prognostic classification methods serving therapeutic decisions and evaluation of investigational treatment strategies at relapse of AML have been based on the duration of the relapse free interval and have largely neglected the influence of other known prognostic factors. Here we present an improved clinically useful prognostic index. This index has been developed from a multivariate analysis of 667 AML patients in first relapse among 1540 newly diagnosed non-M3 AML patients of age 15 to 60 years entered into three successive HOVON/SAKK Collaborative Group trials. The score, which has a range of 0 to 14 points, uses four relevant parameters. The parameters are: length of relapse free interval after first complete remission (more than 18 months: 0 points; 7 to 18 months: 3 points; 6 months or less: 5 points), cytogenetics at diagnosis (t(16;16) or inv(16): 0 points; t(8;21): 3 points; other cytogenetics: 5 points), age at relapse (35 years or younger: 0 points; 36 to 45 years: 1 point; older than 45 years: 2 points) and whether or not a previous stem cell transplantation (SCT) has been undertaken in first complete remission (no SCT: 0 points; previous SCT: 2 points). These points were assigned following estimations of the relative values of each of these factors contributing to outcome. Ultimately, three risk groups were defined: a favorable prognostic group A (0 to 6 points; overall survival of 70% at one year and 46% at five years), an intermediate risk group B (7 to 9 points; overall survival of 49% at one year and 18% at five years), and an unfavorable risk group C (10 to 14 points; overall survival of 16% at one year and 4% at five years). Thus, four commonly applied clinical parameters may identify among patients with AML in first relapse those for salvage or investigational therapy.

Download Full-text

Phase II Study of Allogeneic Transplantation for Older Patients With Acute Myeloid Leukemia in First Complete Remission Using a Reduced-Intensity Conditioning Regimen: Results From Cancer and Leukemia Group B 100103 (Alliance for Clinical Trials in Oncology)/Blood and Marrow Transplant Clinical Trial Network 0502

Journal of Clinical Oncology ◽

10.1200/jco.2015.62.7273 ◽

2015 ◽

Vol 33 (35) ◽

pp. 4167-4175 ◽

Cited By ~ 82

Author(s):

Steven M. Devine ◽

Kouros Owzar ◽

William Blum ◽

Flora Mulkey ◽

Richard M. Stone ◽

...

Keyword(s):

Complete Remission ◽

Older Patients ◽

Myeloid Leukemia ◽

Phase Ii Study ◽

Disease Free Survival ◽

Reduced Intensity Conditioning ◽

Free Survival ◽

Disease Free ◽

First Complete Remission ◽

Reduced Intensity

Purpose Long-term survival rates for older patients with newly diagnosed acute myeloid leukemia (AML) are extremely low. Previous observational studies suggest that allogeneic hematopoietic stem-cell transplantation (HSCT) may improve overall survival (OS) because of lower rates of relapse. We sought to prospectively determine the value of HSCT for older patients with AML in first complete remission. Patients and Methods We conducted a prospective multicenter phase II study to assess the efficacy of reduced-intensity conditioning HSCT for patients between the ages of 60 and 74 years with AML in first complete remission. The primary end point was disease-free survival at 2 years after HSCT. Secondary end points included nonrelapse mortality (NRM), graft-versus-host disease (GVHD), relapse, and OS. Results In all, 114 patients with a median age of 65 years received transplantations. The majority (52%) received transplantations from unrelated donors and were given antithymocyte globulin for GVHD prophylaxis. Disease-free survival and OS at 2 years after transplantation were 42% (95% CI, 33% to 52%) and 48% (95% CI, 39% to 58%), respectively, for the entire group and 40% (95% CI, 29% to 55%) and 50% (95% CI, 38% to 64%) for the unrelated donor group. NRM at 2 years was 15% (95% CI, 8% to 21%). Grade 2 to 4 acute GVHD occurred in 9.6% (95% CI, 4% to 15%) of patients, and chronic GVHD occurred in 28% (95% CI, 19% to 36%) of patients. The cumulative incidence of relapse at 2 years was 44% (95% CI, 35% to 53%). Conclusion Reduced-intensity conditioning HSCT to maintain remission in selected older patients with AML is relatively well tolerated and appears to provide superior outcomes when compared with historical patients treated without HSCT. GVHD and NRM rates were lower than expected. Future transplantation studies in these patients should focus on further reducing the risk of relapse.

Download Full-text

Allogeneic Hematopoietic Stem Cell Transplantation for Acute Myeloid Leukemia Patients in First Complete Remission: Significant Impact of the Interval Between Diagnosis and Transplantation on Different Outcomes

Blood ◽

10.1182/blood.v126.23.5517.5517 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5517-5517 ◽

Cited By ~ 1

Author(s):

Stéphanie Ducreux ◽

Mohamad Sobh ◽

Stéphane Morisset ◽

Marie Balsat ◽

Xavier Thomas ◽

...

Keyword(s):

Board Of Directors ◽

Median Time ◽

Myeloid Leukemia ◽

Conditioning Regimen ◽

Inclusion Criteria ◽

Advisory Committees ◽

Hematopoietic Stem ◽

First Complete Remission ◽

Acute Myeloid

Abstract Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the main therapeutic option for most patients with high risk acute myeloid leukemia (AML). In order to determine whether time between diagnosis and allo-HSCT could have any impact on transplant outcomes, we screened 700 consecutive adult AML patients diagnosed between January 2007 and June 2014 at the Lyon Sud Hospital transplant center. Inclusion criteria were: (1) newly diagnosed AML in patients with age ≤ 65 years, (2) AML classified in the intermediate-2 and unfavorable risk groups according to the Acute Leukemia French Association (3) patients fit for receiving chemotherapy (4) patients candidates for allo-HSCT and in first complete remission (CR1) at transplantation. Two hundred and one patients met the inclusion criteria and were enrolled in the study. Among them, 137 (68%) received allo-HSCT of whom 83 (41%) only received HSCT in CR1 after a median time of 143 days (range: 69-265) from diagnosis. We collected within this interval different delays for donor search, including patients HLA typing and time to unrelated donor identification when a sibling donor was not available. Patients were split into 2 groups based on their time to transplant. An "early transplant group" included 28 (33%) patients transplanted after a median time of 108 days (range: 69-133) after diagnosis. The other 55 (67%) patients transplanted after a median time of 163 days (range: 134-265) were qualified as "late transplant group". Patients and transplantation characteristics according to the timing of transplantation are shown in table 1. After a median follow-up of 16 months (range: 0-60) the 5-year probability of overall survival (OS) and disease-free survival (DFS) for the whole population were respectively, 63.4% and 48.3%. The cumulative incidences of non-relapse mortality (NRM) at 1 and 5 years were constant at 17.5%. The multivariate analysis using proportional hazards modeling showed that conditioning regimen and sex mismatching were independent prognostic factors for DFS, with no significant impact on OS. To evaluate the long term impact of transplantation timing on OS and DFS, we performed a landmark analysis for patients surviving at 1 year post-allo-HSCT. This analysis showed that patients in the early transplant group had a higher probability of OS at 3 and 5 years with 100% survival respectively compared to the late transplantation group with 85.5% and 79.4% respectively (p=0.09); accordingly, we found a significant difference in terms of DFS with 100% probability at 3 and 5 years for the early transplantation group compared to 80% and 56% respectively in the late transplantation group (p=0.02). This difference in terms of OS and PFS was still valid after stratification on the type of conditioning regimen. These results confirm the important impact of allogeneic HSCT timing in high-risk AML patients, early allo-HSCT for patients transplanted in CR1 is associated with a better OS and a very significant benefit in terms of DFS. Further analyses are ongoing including disease monitoring from diagnosis to the last follow-up to identify the potential of transplantation timing on the graft versus leukemia effect. Table 1. Table 1. Disclosures Nicolini: Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Ariad Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Download Full-text

Sera cytokine levels to predict survival in men with progressive castration-resistant prostate cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.5083 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 5083-5083

Author(s):

Sumit Kumar Subudhi ◽

Glenn Heller ◽

Daniel Costin Danila ◽

Aseem Anand ◽

Kristine Peregrino Lacuna ◽

...

Keyword(s):

Risk Group ◽

Cox Model ◽

Tumor Biology ◽

Regression Tree ◽

Risk Groups ◽

Group Classification ◽

Discriminatory Power ◽

Group Model ◽

Castration Resistant Prostate Cancer ◽

Serum Cytokines

5083 Background: Serum cytokines have been proposed as immunologic biomarkers of clinical responses based on their role in tumor biology. Recently, two whole blood mRNA signatures, which included immunomodulatory gene transcripts, were found to be predictive of survival in CRPC. This study explores serum cytokines, measured with analytically valid assays, as prognostic biomarkers in CRCP. Methods: Serum was collected from 75 progressive CRPC patients treated at MSKCC. A panel of 10 cytokines (M-CSF, IFN-γ, TNF-α, IL-1 β, IL-4, IL-5, IL-6, IL-10, IL-12 and IL-13) was measured in a CLIA-certified laboratory by clinically validated ELISAs. To create a risk group classification based on the 10 cytokines, a regression tree methodology was used with the intent to maximize the survival differences between risk groups. In addition to the cytokine risk groups, PSA, LDH, albumin, hemoglobin and CTC enumeration were also independently prognostic. The Cox model was developed to determine the factors that jointly predicted survival. The concordance probability estimate (CPE) was used to determine the discriminatory power of this model. Results: Among the 10 cytokines, M-CSF (stimulates monocytes and macrophages) and IL-10 (suppresses T-cell-mediated anti-tumor responses), were most predictive of overall survival in a 3 risk-group model. The relative risk for log CTC was 1.78 (95% CI 1.43 – 2.21). The combination of the cytokine risk groups and CTC enumeration provided the best discriminatory power for predicting survival, yielding a discrimination index measured by the CPE equal to 0.77 (se = 0.03). Conclusions: A risk group classification, based on two serum cytokines, M-CSF and IL-10, and log CTC measured by analytically valid assays, predicted survival in patients with progressive CRPC. These cytokines may reflect the biology within the tumor microenvironment, and may also serve as biomarker for clinical benefit. Independent validation in a similar cohort of patients is ongoing. [Table: see text]

Download Full-text