Lymphocyte Count on Day 56 Predicts for Reduced Risk of Infection Related Mortality Following Non-Myeloablative Allogeneic Haematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5324-5324
Author(s):  
Caroline Alvares ◽  
Samar Kulkarni ◽  
Pawel Kaczmarek ◽  
Radovan Saso ◽  
Helena Woods ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Lymphocyte Count ◽  
Recursive Partitioning ◽  
Surrogate Marker ◽  
Haematopoietic Stem Cell ◽  
Gvhd Prophylaxis ◽  
Single Antigen ◽  
Risk Patients

Abstract In vivo T-cell depletion using Alemtuzumab containing conditioning regimens are commonly employed in high risk patients undergoing non-myeloablative allogeneic transplants (NMT). The effect of lymphocyte count on mortality due to infection following NMT has not been previously reported. We examined lymphocyte counts as a surrogate marker of immune reconstitution following NMT. Between August 2000 and August 2006, 70 patients (M:48, F: 22, median age:49, range: 17–63) underwent NMTs for haematological malignancies [ALL, n=6; AML, n=24; CML, n=2; HD, n=5; NHL, n=16 and MM, n=17]. Donors were matched siblings in 25 patients and 45 received matched unrelated transplants. All patients received standard induction and consolidation therapy and 39 patients had previously received autologous transplant (31 had 1 procedure and 8 had 2 procedures). Three patients received NMT as a part of tandem transplantation. Fifty two transplants were from HLA identical donors, 16 received single antigen class I mismatched grafts and 2 patients received single antigen class II mismatched transplants. Thirty two patients (32/70, 46%) and 51 donors (51/70, 73%) were CMV sero-negative. Conditioning therapy was Alemtuzumab based in 48 patients (69%), low dose TBI in 14 cases (20%) and 8 patients (11%) received other combinations. All patients received cyclosporine with or without mycophenolate as GVHD prophylaxis. At the time of transplantation 19 patients were in CR1 (27%), 26 were in subsequent CR (37%), 14 had partial remission (20%) and 11 had active disease (16%). Overall 73% patients had high risk disease. With a median follow-up of 10 months (range: 0–46), the probability of overall survival (OS) at 2 yr. was 24% (95% CI: 10.8–36.8, median OS: 10 months). Forty-three patients died and death was attributed to infection in 23/43 (54%), progressive disease in 14/43 (32%), GVHD in 5/43(12%) and secondary cancer in 1/43 (2%). Twenty-seven patients relapsed (38.6%) and the probability of relapse at 2yr. was (37%, 95% CI: 18–56). The median lymphocyte count on day 28 (L28) post transplant was significantly lower with use of Alemtuzumab (0.1 vs. 0.6, p<0.001) but this effect was not seen on the day 56 lymphocyte count (0.2 vs. 0.5, p=0.8). Recursive partitioning of L28 and L56 identified L56 count of 0.4×109/L to have a significant impact on OS. Patients with L56 >0.4 (n=26) had a significantly better survival (median OS: 15 vs. 8 months, p=0.033). This survival advantage was related to reduction in infectious deaths. There was no effect on mortality due to relapse or GVHD. The incidence of CMV reactivation within the first 100 days was independent of L56 (39% vs. 36%, p=0.7). In conclusion, this study shows that lymphocyte count >0.4 on day 56 post-NMT is associated with better overall survival due to reduction in infection related deaths. This finding warrants further investigation in a larger cohort of patients.

scholarly journals A Novel Strategy to Identify Haematology Patients at High Risk of Developing Aspergillosis

2021 ◽  
Vol 12 ◽  
Author(s):  
James S. Griffiths ◽  
P. Lewis White ◽  
Aiysha Thompson ◽  
Diogo M. da Fonseca ◽  
Robert J. Pickering ◽  
...  
Keyword(s):  
High Risk ◽  
Disease Risk ◽  
Low Risk ◽  
Fungal Resistance ◽  
Haematopoietic Stem Cell ◽  
Cell Transplant ◽  
Negative Results ◽  
Risk Patients ◽  
Haematology Patients ◽  
Anti Fungal

Invasive Aspergillosis (IA), typically caused by the fungus Aspergillus fumigatus, is a leading cause of morbidity and mortality in immunocompromised patients. IA remains a significant burden in haematology patients, despite improvements in the diagnosis and treatment of Aspergillus infection. Diagnosing IA is challenging, requiring multiple factors to classify patients into possible, probable and proven IA cohorts. Given the low incidence of IA, using negative results as exclusion criteria is optimal. However, frequent false positives and severe IA mortality rates in haematology patients have led to the empirical use of toxic, drug-interactive and often ineffective anti-fungal therapeutics. Improvements in IA diagnosis are needed to reduce unnecessary anti-fungal therapy. Early IA diagnosis is vital for positive patient outcomes; therefore, a pre-emptive approach is required. In this study, we examined the sequence and expression of four C-type Lectin-like receptors (Dectin-1, Dectin-2, Mincle, Mcl) from 42 haematology patients and investigated each patient’s anti-Aspergillus immune response (IL-6, TNF). Correlation analysis revealed novel IA disease risk factors which we used to develop a pre-emptive patient stratification protocol to identify haematopoietic stem cell transplant patients at high and low risk of developing IA. This stratification protocol has the potential to enhance the identification of high-risk patients whilst reducing unnecessary treatment, minimizing the development of anti-fungal resistance, and prioritising primary disease treatment for low-risk patients.

scholarly journals A Novel Autophagy-Related lncRNA Gene Signature to Improve the Prognosis of Patients with Melanoma

2020 ◽  
Author(s):  
Yi Ding ◽  
Tian Li ◽  
Min Li ◽  
Tuersong Tayier ◽  
MeiLin Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Model ◽  
Risk Group ◽  
Clinical Information ◽  
Low Risk ◽  
Gene Set Enrichment Analysis ◽  
Positive Regulation ◽  
Risk Patients ◽  
Cox Analysis

Abstract Background: Autophagy and long non-coding RNAs (lncRNAs) have been the focus of research on the pathogenesis of melanoma. However, the autophagy network of lncRNAs in melanoma has not been reported. The purpose of this study was to investigate the lncRNA prognostic markers related to melanoma autophagy and predict the prognosis of patients with melanoma.Methods: We downloaded RNA-sequencing data and clinical information of melanoma from The Cancer Genome Atlas. The co-expression of autophagy-related genes (ARGs) and lncRNAs was analyzed. The risk model of autophagy-related lncRNAs was established by univariate and multivariate COX regression analyses, and the best prognostic index was evaluated combined with clinical data. Finally, gene set enrichment analysis was performed on patients in the high- and low-risk groups.Results: According to the results of the univariate COX analysis, only the overexpression of LINC00520 was associated with poor overall survival, unlike HLA-DQB1-AS1, USP30-AS1, AL645929, AL365361, LINC00324, and AC055822. The results of the multivariate COX analysis showed that the overall survival of patients in the high-risk group was shorter than that recorded in the low-risk group (p<0.001). Moreover, in the receiver operating characteristic curve of the risk model we constructed, the area under the curve (AUC) was 0.734, while the AUC of T and N was 0.707 and 0.658, respectively. The Gene Ontology was mainly enriched with the positive regulation of autophagy and the activation of the immune system. The results of the Kyoto Encyclopedia of Genes and Genomes enrichment were mostly related to autophagy, immunity, and melanin metabolism.Conclusion: The positive regulation of autophagy may slow the transition from low-risk patients to high-risk patients in melanoma. Furthermore, compared with clinical information, the autophagy-related lncRNAs risk model may better predict the prognosis of patients with melanoma and provide new treatment ideas.

scholarly journals Expression ofFOXP3,CD14, andARG1in Neuroblastoma Tumor Tissue from High-Risk Patients Predicts Event-Free and Overall Survival

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Sara Stigliani ◽  
Michela Croce ◽  
Fabio Morandi ◽  
Paola Scaruffi ◽  
Valentina Rigo ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Immune Status ◽  
Primary Tumors ◽  
Neuroblastoma Tumor ◽  
Elevated Expression ◽  
Risk Patients ◽  
History Of ◽  
Low Levels ◽  
Positive Correlations

The prognosis of children with metastatic neuroblastoma (NB) > 18 months at diagnosis is dismal. Since the immune status of the tumor microenvironment could play a role in the history of disease, we evaluated the expression ofCD45,CD14,ARG1,CD163,CD4,FOXP3,Perforin-1(PRF1),Granzyme B (GRMB), andIL-10mRNAs in primary tumors at diagnosis from children with metastatic NB and tested whether the transcript levels are significantly associated to event-free and overall survival (EFS and OS, resp.). Children with high expression ofCD14,ARG1andFOXP3mRNA in their primary tumors had significantly better EFS. Elevated expression ofCD14, andFOXP3mRNA was significantly associated to better OS.CD14mRNA expression levels significantly correlated to all markers, with the exception ofCD4. Strong positive correlations were found betweenPRF1andCD163, as well as betweenPFR1andFOXP3. It is worth noting that the combination of high levels ofCD14,FOXP3, andARG1mRNAs identified a small group of patients with excellent EFS and OS, whereas low levels ofCD14were sufficient to identify patients with dismal survival. Thus, the immune status of the primary tumors of high-risk NB patients may influence the natural history of this pediatric cancer.

Quality of Life and Overall Survival in High Risk Patients After Radical Cystectomy With a Simple Urinary Derivation

2015 ◽  
Vol 93 (6) ◽  
pp. 368-374
Author(s):  
Giuseppe Mucciardi ◽  
Luciano Macchione ◽  
Alessandro Galì ◽  
Antonina di Benedetto ◽  
Enrica Subba ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Overall Survival ◽  
High Risk ◽  
Radical Cystectomy ◽  
High Risk Patients ◽  
Risk Patients

Rapamycin blocks hepatoblastoma growth in vitro and in vivo implicating new treatment options in high-risk patients

2012 ◽  
Vol 48 (15) ◽  
pp. 2442-2450 ◽  
Author(s):  
Ferdinand Wagner ◽  
Bente Henningsen ◽  
Christine Lederer ◽  
Melanie Eichenmüller ◽  
Jan Gödeke ◽  
...  
Keyword(s):  
High Risk ◽  
Treatment Options ◽  
High Risk Patients ◽  
Risk Patients ◽  
New Treatment

Utilization of Resources and Overall Outcome in Patients Undergoing Hematopoietic Stem Cell Transplantation Related to Psychosocial Factors as Measured by the Transplant Evaluation Rating Scale (TERS).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3332-3332
Author(s):  
Dawn S. Speckhart ◽  
H.K. Holland ◽  
Scott R. Solomon ◽  
Lawrence E. Morris ◽  
Asad Bashey
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Rating Scale ◽  
Risk Group ◽  
Psychosocial Risk ◽  
Moderate Risk ◽  
Hematopoietic Stem ◽  
Risk Patients ◽  
Transplant Evaluation ◽  
Length Of Hospitalization

Abstract Several studies have begun to examine the relationship between psychosocial variables and outcome in hematopoietic stem cell transplantation (HSCT). Data presented at the 2006 ASH Convention, demonstrated a significant relationship between psychosocial variables, such as those assessed on the Transplant Evaluation Rating Scale (TERS), and objective outcomes, such as length of hospitalization and survival. The 2006 data included 200 consecutive patients (136 autologous, 65 allogeneic) undergoing HSCT. Based on the patient’s TERS score, each patient was stratified into one of two groups (low/moderate risk (n=173) vs. high risk (n=28)) based on their predicted psychosocial risk for problems during transplant. With the addition of 166 patients (Current N=366: 239 autologous, 127 allogeneic) the difference in length of hospitalization between low/moderate risk (10 days) versus high risk (19 days) patients remains significant (p<.02). For allogeneic patients (N=127), there continues to be an improved overall survival in low/moderate risk patients in the first 12 to 18 months following HSCT compared to high risk patients (p = .246). To determine whether similar factors impact utilization of resources in patients undergoing HSCT, we prospectively conducted psychosocial assessments on 112 consecutive allogeneic HSCT patients. An analysis of cost was completed for all patients in both the low/moderate risk group and high risk group. The mean cost differential for high risk patients is noted to be 27% higher than those patients in the low/moderate risk group (p = .122). This trend reinforces earlier data presented and suggests a correlation between pre-transplant psychosocial risk factors and resource utilization in HSCT. Overall Survival Overall Survival

RASGRP1/APTX Ratio Strongly Correlates with Clinical Response and Survival in AML Patients Treated with Tipifarnib-Bortezomib Combination.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1028-1028
Author(s):  
Stefania Paolini ◽  
Emanuela Ottaviani ◽  
Sarah Parisi ◽  
Federica Salmi ◽  
Barbara Lama ◽  
...  
Keyword(s):  
Overall Survival ◽  
Adverse Event ◽  
High Risk ◽  
Clinical Response ◽  
Stable Disease ◽  
Response Rate ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Secondary Aml

Abstract Abstract 1028 Poster Board I-50 Background: Outcome of elderly acute myeloid leukemia (AML) patients is dismal. Targeted-therapies might improve current results by overcoming drug-resistance and reducing toxicity. In particular, the farnesyl-transferase inhibitor Tipifarnib (Zarnestra®), and the proteasome inhibitor Bortezomib (Velcade®), appeared synergistic in AML cells ex vivo, and their association was shown to be safe in vivo in a phase I trial by our group. Aim We conduced a phase II study aiming to assess efficacy and toxicity of Tipifarnib-Bortezomib association in AML patients >18 years, unfit for conventional therapy, or >60 years, in relapse. Furthermore, we aimed to identify biological features potentially predictive of clinical response. In particular, we focused on the RASGRP1/APTX ratio, which was previously found to be effective in predicting treatment response in patients treated with Tipifarnib alone. Methods: Bortezomib (1.0 mg/m2) was administered as weekly infusion for three consecutive weeks (days 1, 8, 15). Tipifarnib was administered at dose of 300-600 mg BID for 21 consecutive days. Response was assessed at the end of each cycle (28 days). Patients' withdrawn was planned in case of progression or stable disease after six cycles. Real-time quantitative-PCR (q-PCR) was used for RASGRP1/APTX quantification. Results: Eighty patients were enrolled (47 male). Median age was 71 years (43-89) and WBC at diagnosis was 4.2 × 109/L (0.5- 42.1). Thirty-two out of 80 patients had a secondary-AML, 14 had a high risk cytogenetic and 42 were previously untreated. Seventy-five patients actually initiated the treatment, 62 completed at least the first cycle while 13 early dropped out for non-leukemia related adverse event. Nine patients achieved complete remission (CR), 1 patients obtained a partial response (PR) and in 2 cases an hematological improvement (HI) was documented for an overall response rate (ORR) of 19%. Eighteen had progressive disease (PD) and the remaining showed stable disease (SD). Median time to response was 112 days, corresponding to 4 cycles (range 2-14). Marrow response (CR+PR) was significantly associated with overall survival (OS) (p<0.0001). RASGRP1/APTX was evaluated before treatment initiation on bone marrow (BM) and/or peripheral blood (PB). The median RASGRP/APTX value on BM was 15.3 (15-19.8) in responder patients and 2.2 (0.5-25.9) in non responders, respectively (p=0.00006). Its median value on PB was 31.6 (19.3-35.5) in responders and 6.4 (0.5-27.1) in non responders, respectively (p=0.00001). Interestingly, no marrow responses were recorded in patients with marrow RASGRP1/APTX ratio <8, while the response rate was 43% in patients with RASGRP1/APTX >8 (p<0.0001). Finally, RASGRP1/APTX levels significantly correlated with OS (p=0.001) with a median OS of 490 days and 162 days in patients with RASGRP1/APTX >8 and <8 respectively. Conversely, there was no correlation between cytogenetics, secondary AML, previous treatment and response or overall survival. Toxicity was overall mild, the most common adverse event being febrile neutropenia. Permanent treatment interruption due to Tipifarnib-Bortezomib related adverse events occurred in 13/75 (17%) of patients. With a median follow-up of 122 days (range 9-737), 57/75 (76%) patients are dead and 18/75 (24%) are alive, six of which in CR. Conclusion: We conclude that the clinical efficacy of the combination Tipifarnib-Bortezomib was similar to what reported for Tipifarnib alone. However, noteworthy, we could confirm that the RASGPR1/APTX BM or PB level is an effective predictor of response. Though higher RASGRP1/APTX is relatively rare (∼10% of cases), Tipifarnib (±Bortezomib) may represent an important option in a subset of high risk/frail AML patients. Acknowledgments: Supported by BolognAIL, AIRC, European LeukemiaNET, COFIN, FIRB 2006, Fondazione del Monte di Bologna e Ravenna. Disclosures: No relevant conflicts of interest to declare.

Survival Disparities in Patients with Lymphoma According to Place of Residence and Treatment Provider: A Population-Based Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 874-874
Author(s):  
Fausto R Loberiza ◽  
Anthony J Cannon ◽  
Dennis D Weisenburger ◽  
Julie M. Vose ◽  
Matt J. Moehr ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Rural Areas ◽  
Urban Areas ◽  
Population Based ◽  
Place Of Residence ◽  
Community Based ◽  
Risk Levels ◽  
Risk Of Death ◽  
Risk Patients

Abstract Objectives: We evaluated the association of the primary area of residence (urban vs. rural) and treatment (trt) provider (university-based vs. community-based) with overall survival in patients with lymphoma, and determined if there are patient subgroups that could benefit from better coordination of care. Methods: We performed a population-based study in 2,330 patients with centrally confirmed lymphoma from Nebraska and surrounding states reported to the Nebraska Lymphoma Study Group between 1982 and 2006. Patient residential ZIP codes at the time to trt were used to determine rural/urban designation, household income and distance to trt center; while trt providers were categorized into university-based or community based. Multivariate analyses were used to group patients into risk levels based on 8 factors found to be associated with survival at the time of trt (age, performance score, Ann Arbor stage, presence of B symptoms, LDH levels, tumor bulk, nodal and extranodal involvement). The following categories were identified: low-risk (1–3 factors), intermediate risk (4–5 factors), and high-risk (≥6 factors). Cox proportional regression analyses, stratified by type of lymphoma (low-grade NHL, high-grade NHL and Hodgkin) were used to evaluate the association between place of residence and trt provider with overall survival. Results: Among urban residents, 321 (14%) were treated by university-based providers (UUB) and 816 (35%) were treated by community-based providers (UCB). Among rural residents, 332 (14%) were treated by university-based providers (RUB) and 861 (37%) were treated by community-based providers (RCB). Patients from rural areas were more likely to be older and Caucasian, with a lower median household income, greater travel distance to seek trt, and more likely to have high-risk disease when compared to patients from urban areas. In multivariate analysis, using all patients regardless of risk level, the relative risk of death (RR) among UUB, UCB and RUB was not statistically different. However, RCB had a higher risk of death RR 1.37, 95% CI 1.14–1.65, p=0.01; RR 1.18, 95% CI 1.04–1.33, p<0.01; and RR 1.26, 95% CI 1.06–1.49, p=0.01 when compared with UUB, UCB and RUB, respectively. This association remained true in both low- and intermediate-risk patients. Among high-risk patients, both RUB and RCB were at higher risk of death when compared with UUB or UCB, while UCB were not different from UUB. We found no differences in progression-free survival according to place of residence and trt provider. The use of stem cell transplantation was significantly higher in patients coming from urban and rural areas treated by university-based providers (UUB 19%, RUB 16%) compared to urban and rural patients treated by community-based providers (UCB 11%, RCB 10%, p < 0.01). Patients from rural areas (RUB and RCB) were slightly less likely to die from lymphoma-related causes than patients from urban areas (75% versus 80%, p=0.04). Conclusion: Overall survival in patients with lymphoma is inferior in patients coming from rural areas. This relationship varies according to treatment provider and pretreatment risk levels. Further studies in patients from rural areas are needed to understand how coordination of care is carried to design appropriate interventions that may improve the disparity noted.

Immunochemotherapy with Rituximab Improves Molecular CR Rate and Outcome In CD20+ B-Lineage Standard and High Risk Patients; Results of 263 CD20+ Patients Studied Prospectively In GMALL Study 07/2003

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 170-170 ◽  
Author(s):  
Dieter Hoelzer ◽  
Andreas Huettmann ◽  
Felix Kaul ◽  
Sebastian Irmer ◽  
Nadja Jaekel ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Complete Remission ◽  
Relapse Rate ◽  
Remission Rate ◽  
Supportive Therapy ◽  
High Risk Patients ◽  
Tumour Load ◽  
Risk Patients ◽  
Standard Risk

Abstract Abstract 170 The effect of Rituximab in conjunction with a chemo induction and consolidation therapy was studied in CD20+, Ph/BCR-ABL negative B-precursor ALL (Pre-B/Common) in the GMALL Study 07/2003. The rationale were encouraging results with combined intensive chemotherapy and Rituximab in CD20+ adult Burkitt lymphoma / leukemia. Furthermore that in previous GMALL studies, improvement of B-precursor ALL by intensification of chemotherapy was limited and the observation that patients with CD20+ cells (antigen expression >20%) had an inferior outcome in adult ALL (Thomas et al. Blood 2009. 113;6330). Aim: In standard risk (SR) patients the aim was to increase the rate of molecular remission (Mol. CR) thereby decreasing the relapse rate and in high risk (HR) patients to reduce the pre-transplant tumour-load and thereby reducing the relapse rate after SCT which was 30–40% in previous GMALL studies. Materials and Methods: Adult ALL patients (15 – 55 years) with standard risk B-precursor ALL being CD20 pos. received Rituximab 375 mg/m2 at day -1 before each induction course (phase I and II), the re-induction course and before each of the six consolidations for a total of 8 doses. High Risk patients, defined as WBC > 30.000 and/or late CR > 4 weeks, which are candidates for a stem cell transplantation in CR 1 after wk 16, received Rituximab three times (d -1 ind. I/II and Cons. I) before SCT. Patients receiving Rituximab were compared with earlier CD20+ patients in the GMALL study 07/2003 with identical chemo- and supportive therapy but no Rituximab. MRD method and chemo backbone was described earlier [Brüggemann, Blood 2006: 107;1116]. Results: A total of 263 CD20 pos. patients were analyzed in the GMALL study 07/2003; 196 were SR and 67 HR patients. 181 received Rituximab (R+ arm) and were compared to a cohort of 82 patients earlier recruited without Rituximab (R- arm). In the SR there was no difference in the results of induction therapy with a CR rate of 94 % and 91 % in the R+ vs. R- patients. There was also no difference in ED rate 5% vs. 3% or failure/PR 1% vs. 5%. However, MRD course differed substantially. Decrease in MRD load in the R+ vs. R- arm was faster with a Mol CR (MRD <10-4) rate of 57% vs. 27% at day 24 and of 90% vs. 59% at wk 16. Probability for continuous complete remission (CCR) at 5 years was 80% vs. 47% for R+ vs. R- pts. and for overall survival 71% vs. 57%. In the cohort of 67 HR patients the CR rate for R+ vs. R- was 81% vs. 88% due to a higher rate of failure/PR 12% vs. 8%. The ED rates in the R+ vs. R- arm were 7% vs. 4%. There was a higher Mol CR rate at wk 16 in the R+ arm vs. R- with 64% vs. 40%. Overall survival for HR patients at 5 yrs was 55% vs. 36% in the R+ vs. R- group. When only the HR cohort with SCT in CR1 is considered (in 69 % +R and 90% -R SCT in CR1 were performed) the CCR probability was superior for the R+ vs. R- with 67% vs. 37%, due to a lower relapse rate. Conclusion: Intensive chemo- plus immunotherapy with Rituximab is feasible in adult patients with B-precursor ALL in the context of the GMALL protocol 07/2003. In standard risk patients, the complete remission rate was comparable. There was however a faster and higher Mol. CR rate in the Rituximab cohort, with an improvement in remission duration and overall survival. In high risk patients the Mol. CR rate was also higher in the R+ arm and the relapse rate after SCT lower, but probably more Rituximab doses are needed in this patient cohort to reduce the tumour load before SCT further. Supported by Deutsche Krebshilfe 70–2657-Ho2 and in part by Hoffmann La Roche. Disclosures: Off Label Use: Rituximab: activity against CD20 pos. ALL cells.

The Absolute Monocyte and Lymphocyte Counts at Diagnosis Predict Survival and Identify High-Risk Patients In Diffuse Large-B-Cell Lymphoma

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3088-3088
Author(s):  
Ryan A. Wilcox ◽  
Kay Ristow ◽  
Thomas M. Habermann ◽  
David James Inwards ◽  
Ivana Micallef ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Confidence Interval ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Hazard Ratio ◽  
Poor Risk ◽  
Large B Cell Lymphoma ◽  
Risk Patients ◽  
Good Risk

Abstract Abstract 3088 Background: Despite the use of modern immunochemotherapy (R-CHOP) regimens, almost 50% of patients with diffuse large-B-cell lymphoma (DLBCL) will relapse. Current prognostic models, most notably the International Prognostic Index, are comprised of patient and tumor characteristics and are unable to identify patients with less than a 50% chance of long-term survival. However, recent observations demonstrate that factors related to host adaptive immunity and the tumor microenvironment are powerful prognostic variables in non-Hodgkin lymphoma Methods: We retrospectively examined the absolute neutrophil count (ANC), monocyte count (AMC) and lymphocyte count (ALC), obtained from an automated complete blood count with differential, as prognostic variables in a cohort of 255 consecutive DLBCL patients that were uniformly treated with R-CHOP between 2000 and 2007 at a single institution. The primary study objective was to assess if ANC, AMC, and ALC at diagnosis were predictors of overall survival (OS) in DLBCL. Results: At diagnosis, the median ANC was 4720/uL (range 1190–17690), the median AMC was 610/uL (range 30–4040), and the median ALC was 1220/uL (range 140–5410). The median follow-up for these patients was 48 months. In the univariate analysis, each of these variables predicted OS as continuous variables. As dichotomized variables, an elevated ANC (≥5500/μL; hazard ratio 1.75, 95% confidence interval 1.14–2.60, p=0.01) and AMC (≥610/μL; hazard ratio 3.36, 95% confidence interval 2.10–5.59, p<0.0001) were each associated with inferior OS. In contrast, the presence of lymphopenia, defined as an ALC ≤1000/uL, was associated with inferior OS (hazard ratio 2.21, 95% confidence interval 1.43–3.39, p=0.0004). When components of the IPI were included on multivariate analysis only the AMC and ALC were independently significant prognostic factors for OS, with hazard ratios of 3.37 (95% confidence interval 2.05–5.74, p<0.0001) and 2.19 (95% confidence interval 1.38–3.44, p=0.0009), respectively. The dichotomized AMC and ALC generated the AMC/ALC prognostic index (PI) and stratified patients into 3 risk groups: very good (AMC <610/uL and ALC >1000/uL), good (AMC ≥610/uL or ALC ≤1000/uL), and poor-risk (AMC ≥610/uL and ALC ≤1000/uL) populations. For both the very good (n=79) and good-risk (n=134) groups median OS has not been reached with estimated 5-year overall survival of 88% and 69%, respectively. Median OS for poor-risk (n=42) patients was 1.7 years (95% confidence interval 1.1–2.7 years) with an estimated 5-year overall survival of 28% (p<0.0001). By comparison, the R-IPI was unable to identify a group of patients with a median survival less than 8 years. The estimated 5-year OS was 93%, 71% and 53% for very good, good and poor-risk patients, respectively. We sought to determine whether the AMC/ALC PI may provide additional prognostic information when combined with the R-IPI. To test this possibility, the 171 very good/good risk and 84 poor risk patients identified by the R-IPI were subsequently risk stratified using the AMC/ALC PI. Among R-IPI very good/good risk patients a subset of poor risk patients (n=21) with a median OS of 2.2 years (95% confidence interval 1.1–6.6 years) and 35% 5-year OS could be identified with the AMC/ALC PI. In contrast, 5-year OS ranged from 75%-88% among very good and good risk patients. Similarly, stratification of R-IPI poor risk patients by the AMC/ALC PI identified subsets of very good (n=19) and good risk (n=44) patients with median OS that had not been reached and 86% and 55% 5-year OS, respectively. High risk (n=21) patients had a median OS of 1.4 years (95% confidence interval 0.9–2.2 years) and an estimated 5-year OS of less than 25%. Conclusions: Measurement of AMC and ALC at diagnosis is widely applicable, cost effective, predicts OS, and identifies high-risk patients with DLBCL. Disclosures: No relevant conflicts of interest to declare.

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