Nomograms to predict lung metastasis probability and lung metastasis subgroup survival in malignant bone tumors

The aim of this study was to construct and validate nomograms for predicting lung metastasis and lung metastasis subgroup overall survival in malignant primary osseous neoplasms. Least absolute shrinkage and selection operator, logistic and Cox analyses were used to identify risk factors for lung metastasis in malignant primary osseous neoplasms and prognostic factors for overall survival in the lung metastasis subgroup. Further, nomograms were established and validated. A total of 3184 patients were collected. Variables including age, histology type, American Joint Committee on Cancer T and N stage, other site metastasis, tumor extension and surgery were extracted for the nomograms. The authors found that nomograms could provide an effective approach for clinicians to identify patients with a high risk of lung metastasis in malignant primary osseous neoplasms and perform a personalized overall survival evaluation for the lung metastasis subgroup.

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Incidence, Survival, and Associated Factors Estimation in Osteosarcoma Patients with Lung Metastasis: A Single-center Experience of 11 Years in Tianjin, China

10.21203/rs.3.rs-1071152/v1 ◽

2021 ◽

Author(s):

Chao Zhang ◽

Haixiao Wu ◽

Guijun Xu ◽

Wenjuan Ma ◽

Lisha Qi ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Regression Analysis ◽

Prognostic Factors ◽

Lung Metastasis ◽

Associated Factors ◽

Cox Regression ◽

Cancer Center ◽

Single Center ◽

Cox Regression Analysis

Abstract Background: Osteosarcoma is the most common primary malignant bone tumor. The current study was conducted to describe the general condition of patients with primary osteosarcoma in a single cancer center in Tianjin, China and to investigate the associated factors in osteosarcoma patients with lung metastasis. Methods: From February 2009 to October 2020, patients from Tianjin Medical University Cancer Institute and Hospital, China were retrospectively analyzed. The Kaplan–Meier method was used to evaluate the overall survival of osteosarcoma patients. Prognostic factors of patients with osteosarcoma were identified by the Cox proportional hazard regression analysis. Risk factor of lung metastasis in osteosarcoma were investigated by the logistic regression model. Results: A total of 203 patients were involved and 150 patients were successfully followed up for survival status. The 5-year survival rate of osteo-sarcoma patients was 70.0%. Surgery, bone and lung metastasis were the significant prognostic factors in multivariable Cox regression analysis. Twenty-one (10.3%) patients showed lung metastasis at the diagnosis of osteosarcoma and 67 (33%) lung metastases during the later course. T3 stage (OR=11.415, 95%CI 1.362-95.677, P=0.025) and synchronous bone metastasis (OR=6.437, 95%CI 1.69-24.51, P=0.006) were risk factors of synchronous lung metastasis occurrence. Good necrosis (≥90%, OR=0.097, 95%CI 0.028-0.332, P=0.000) and elevated Ki-67 (≥50%, OR=4.529, 95%CI 1.241-16.524, P=0.022) were proved to be significantly associated with metachronous lung metastasis occurrence. Conclusion: The overall survival, prognostic factors and risk factors for lung metastasis in this single center provided insight about osteosarcoma management.

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A Web-Based Prediction Model for Overall Survival of Elderly Patients With Malignant Bone Tumors: A Population-Based Study

Frontiers in Public Health ◽

10.3389/fpubh.2021.812395 ◽

2022 ◽

Vol 9 ◽

Author(s):

Jie Tang ◽

JinKui Wang ◽

Xiudan Pan

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Elderly Patients ◽

Prediction Model ◽

Bone Tumors ◽

Receiver Operating Curve ◽

Training Set ◽

Malignant Bone Tumors ◽

Independent Risk Factors ◽

Validation Set

Background: Malignant bone tumors (MBT) are one of the causes of death in elderly patients. The purpose of our study is to establish a nomogram to predict the overall survival (OS) of elderly patients with MBT.Methods: The clinicopathological data of all elderly patients with MBT from 2004 to 2018 were downloaded from the SEER database. They were randomly assigned to the training set (70%) and validation set (30%). Univariate and multivariate Cox regression analysis was used to identify independent risk factors for elderly patients with MBT. A nomogram was built based on these risk factors to predict the 1-, 3-, and 5-year OS of elderly patients with MBT. Then, used the consistency index (C-index), calibration curve, and the area under the receiver operating curve (AUC) to evaluate the accuracy and discrimination of the prediction model was. Decision curve analysis (DCA) was used to assess the clinical potential application value of the nomogram. Based on the scores on the nomogram, patients were divided into high- and low-risk groups. The Kaplan-Meier (K-M) curve was used to test the difference in survival between the two patients.Results: A total of 1,641 patients were included, and they were randomly assigned to the training set (N = 1,156) and the validation set (N = 485). The univariate and multivariate analysis of the training set suggested that age, sex, race, primary site, histologic type, grade, stage, M stage, surgery, and tumor size were independent risk factors for elderly patients with MBT. The C-index of the training set and the validation set were 0.779 [0.759–0.799] and 0.801 [0.772–0.830], respectively. The AUC of the training and validation sets also showed similar results. The calibration curves of the training and validation sets indicated that the observed and predicted values were highly consistent. DCA suggested that the nomogram had potential clinical value compared with traditional TNM staging.Conclusion: We had established a new nomogram to predict the 1-, 3-, 5-year OS of elderly patients with MBT. This predictive model can help doctors and patients develop treatment plans and follow-up strategies.

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Score for the Risk and Overall Survival of Lung Metastasis in Patients First Diagnosed With Soft Tissue Sarcoma: A Novel Nomogram-Based Risk Assessment System

Technology in Cancer Research & Treatment ◽

10.1177/15330338211066240 ◽

2022 ◽

Vol 21 ◽

pp. 153303382110662

Author(s):

Zhiyi Fan ◽

Changxing Chi ◽

Yuexin Tong ◽

Zhangheng Huang ◽

Youxin Song ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Prognostic Factors ◽

Soft Tissue ◽

Soft Tissue Sarcoma ◽

Tumor Size ◽

Training Set ◽

N Stage ◽

Independent Risk Factors ◽

Testing Set

Background: Metastatic soft tissue sarcoma (STS) patients have a poor prognosis with a 3-year survival rate of 25%. About 30% of them present lung metastases (LM). This study aimed to construct 2 nomograms to predict the risk of LM and overall survival of STS patients with LM. Materials and Methods: The data of patients were derived from the Surveillance, Epidemiology, and End Results database during the period of 2010 to 2015. Logistic and Cox analysis was performed to determine the independent risk factors and prognostic factors of STS patients with LM, respectively. Afterward, 2 nomograms were, respectively, established based on these factors. The performance of the developed nomogram was evaluated with receiver operating characteristic curves, area under the curve (AUC) calibration curves, and decision curve analysis (DCA). Results: A total of 7643 patients with STS were included in this study. The independent predictors of LM in first-diagnosed STS patients were N stage, grade, histologic type, and tumor size. The independent prognostic factors for STS patients with LM were age, N stage, surgery, and chemotherapy. The AUCs of the diagnostic nomogram were 0.806 in the training set and 0.799 in the testing set. For the prognostic nomogram, the time-dependent AUC values of the training and testing set suggested a favorable performance and discrimination of the nomogram. The 1-, 2-, and 3-year AUC values were 0.698, 0.718, and 0.715 in the training set, and 0.669, 0.612, and 0717 in the testing set, respectively. Furthermore, for the 2 nomograms, calibration curves indicated satisfactory agreement between prediction and actual survival, and DCA indicated its clinical usefulness. Conclusion: In this study, grade, histology, N stage, and tumor size were identified as independent risk factors of LM in STS patients, age, chemotherapy surgery, and N stage were identified as independent prognostic factors of STS patients with LM, these developed nomograms may be an effective tool for accurately predicting the risk and prognosis of newly diagnosed patients with LM.

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A Web-based Prediction Model for Overall Survival of Elderly Patients With Malignant Bone Tumors: a Population-based Study

10.21203/rs.3.rs-962779/v1 ◽

2021 ◽

Author(s):

Jie Tang ◽

Jinkui Wang ◽

Xiudan Pan

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Elderly Patients ◽

Prediction Model ◽

Bone Tumors ◽

Receiver Operating Curve ◽

Training Set ◽

Malignant Bone Tumors ◽

Independent Risk Factors ◽

Validation Set

Abstract Background: Malignant bone tumors(MBT) are one of the causes of death in elderly patients. The purpose of our study is to establish a nomogram to predict the overall survival(OS) of elderly patients with MBT.Methods: The clinicopathological data of all elderly patients with MBT from 2004 to 2018 were downloaded from the SEER database. They were randomly assigned to the training set (70%) and validation set (30%). Univariate and multivariate Cox regression analysis was used to identify independent risk factors for elderly patients with MBT. A nomagram was built based on these risk factors to predict the 1-, 3-, and 5-year OS of elderly patients with MBT. Then, used the consistency index (C-index), calibration curve, and the area under the receiver operating curve(AUC) to evaluate the accuracy and discrimination of the prediction model. Decision curve analysis(DCA) was used to evaluate the clinical potential application value of nomogram. Based on the scores on the nomogram, patients were divided into high- and low-risk groups. Kaplan-Meier (K-M) curve was used to test the difference in survival between the two groups of patients.Results: A total of 1641 patients were included, and they were randomly assigned to the training set (N=1156) and the validation set (N=485). The univariate and multivariate analysis of the training set suggested that age, sex, race, primary site, histologic type, grade, stage, M stage, surgery, and tumor size were independent risk factors for elderly patients with MBT. The C-index of the training set and the validation set were 0.779[0.759-0.799] and 0.801[0.772-0.830], respectively. The AUC of the training set and the validation set also showed similar results. The calibration curves of the training set and the validation set both showed that the observed value and the predicted value were highly consistent. DCA suggested that the nomogram had potential clinical value compared with traditional TNM staging.Conclusion: We had established a new nomogram to predict the 1-, 3-, 5-year OS of elderly patients with MBT. This predictive model can help doctors and patients develop treatment plans and follow-up strategies.

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Development and Analysis of a Weighed Prognostic Model in Newly Diagnosed Multiple Myeloma Patients

Blood ◽

10.1182/blood-2020-140464 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 47-48

Author(s):

Xue-Han Mao ◽

Yan Xu ◽

Yuting Yan ◽

Jiahui Liu ◽

Huishou Fan ◽

...

Keyword(s):

Risk Factors ◽

Multiple Myeloma ◽

Multivariate Analysis ◽

Prognostic Factors ◽

High Risk ◽

Prognostic Factor ◽

Prognostic Model ◽

Cytogenetic Abnormalities ◽

Total Score Range ◽

Prognosis Model

Background and Objective: Multiple myeloma (MM) is characterized with significant cytogenetic changes and complex tumor microenvironment, thus patient survival is extremely heterogeneous. Various disease-related or patient-related factors affect the prognosis of patients. This study tried to analyze the prognostic indicators of patients with newly-treated MM, especially explored the prognosis of multiple cytogenetic abnormalities and the ratio of lymphocytes to monocytes (LMR). Additionally, we established a comprehensive prognostic model to help determine the patient prognosis. Methods: After screening, 603 patients of untreated MM from January 2008 to June 2017, with complete baseline indicators were enrolled into the study. By univariate and multivariate Cox analysis, risk factors related to the prognosis of patients were evaluated, and a weighted prognosis model was established to compare the survival differences of patients in each risk stratification. Result: Optimal thresholds of ALC, LWR, NLR and LMR were determined by ROC curve and Youdex index: ALC = 1.415, LWR = 0.325, NLR = 1.935, LMR = 2.95. Survival analysis showed that patients with LMR ≤ 2.95, ALC ≥ 1.415 and LWR ≥ 0.325 had significantly better survival compared with their respective control groups. Cox multivariate analysis showed that among the four indicators, only LMR≤2.95 was an independent adverse prognostic factor for overall survival (OS)(Figure 1A). 17p deletion, 1q21 amplification, t (4; 14) / t (14; 16) were define as high-risk cytogenetic abnormalities (HRA). Of the 603 patients, about 60% were associated with at least one high-risk cytogenetic event. Among them, the occurrence of cumulative 0, 1, 2, and 3 HRA were 39.6% (239/603), 42.5% (256/603), 16.6% (100/603), and 1.3% (8/603), respectively. There was no significant difference in survival among patients with same number of HRAs. The median OS of patients with 0, 1 and ≥ 2 HRA were not reached, 62.1 months (95% CI, 49.3-74.9) and 30.4 months (95% CI, 24.5-36.3), respectively (p <0.001)(Figure 1B).Final Cox regression model showed that age 65 ~ 74 (HR=1.77, 95%CI, 1.24-2.51, p=0.001), age ≥75 (HR=2.46, 95%CI, 1.69-3.58, p < 0.001), LDH≥247 U/L (HR =1.65, 95%CI, 1.07-2.51, p=0.023), ISS stage III (HR=1.76, 95%CI, 1.24-2.50, p=0.002), LMR≤2.95 (HR=1.53, 95%CI, 1.08-2.18, p=0.017), 1 HRA (HR=1.87, 95%CI, 1.27-2.75, p=0.002) and ≥2 HRA (HR=3.48, 95%CI, 2.22-5.45, p<0.001) are independent adverse prognostic factors for OS. Then weighted risk factors were summed to establish a comprehensive prognosis model, with a total score range of 0-6 points. Accordingly, the whole cohort was divided into low risk (0-1 points, 45.4%), intermediate risk (2 points, 27.9%), high risk (3 points, 19.2%) and ultra-high risk (4-6 points, 7.5 %) groups. The median OS of the four risk groups were 85.8 months (67.1-104.5), 49.0 months (44.7-53.3), 35.4 months (31.3-39.5), and 23.2 months (18.8-27.6), respectively (p<0.001). The C-statistics of this prognostic model is 0.68 (95% CI, 0.64-0.71), which is significantly better than the D-S stage (C-statistics = 0.52, 95% CI, 0.50-0.55, p <0.001), ISS (C-statistics = 0.60, 95% CI, 0.57-0.64, p <0.001) and R-ISS stage (C-statistics = 0.60, 95% CI, 0.57-0.63, p <0.001). Bootstrap resampling and calibration curve showed that the model has an accurate predictive effect on both short-term and long-term prognosis of patients(Figure 1C). Conclusion: In our analysis, ALC, LWR, LMR were associated with poor prognosis in NDMM patients, while NLR had no significant prognostic significance. Among the four indicators, LMR≤2.95 was the only independent prognostic factor. In NDMM patients, survival of patients with the same number of high-risk cytogenetic abnormalities were comparable with each other, regardless of whichever combination of HRA. Higher number of high-risk cytogenetic abnormalities were associated with worse prognosis. Cox multivariate analysis showed that, old age (65-74 years old, ≥75 years old), increased LDH (≥247 U/L), decreased LMR (≤2.95), ISS III, 1 HRA and ≥ 2 HRA were independent adverse prognostic factors that affect the OS of MM patients. 4. A comprehensive weighted prognostic model was established with the above factors, which was proved to effectively distinguish different prognosis of patients. Figure 1 Disclosures No relevant conflicts of interest to declare.

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Postoperative PET/CT for detection of early recurrence (ER) after surgery for squamous cell carcinomas (SCC) of the oral cavity (OC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.6060 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 6060-6060

Author(s):

Yao Yu ◽

Heiko Schöder ◽

Jung Kang ◽

Sean Matthew McBride ◽

C. Jillian Tsai ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

High Risk ◽

Postoperative Radiotherapy ◽

Prospective Trial ◽

Disease Free Survival ◽

Distant Metastases ◽

Risk Groups ◽

Free Survival ◽

Pet Ct

6060 Background: Patients with ER after surgery and prior to postoperative radiation (RT) for SCC of the OC have aggressive biology and poor prognosis. After the introduction of a PET/CT simulator in our department, we incorporated post-operative PET/CT as part of RT planning. We hypothesized PET/CT would improve detection of macroscopic disease before postoperative RT. Methods: We reviewed the medical records of patients treated with postoperative radiotherapy between 2005 and 2019 for OC SCC. Clinicopathologic risk factors were recorded. Intermediate risk factors (IRFs) included pT3-4 disease, nodal disease, perineural invasion (PNI), lymphovascular invasion (LVI), and close ( < 5mm) surgical margins (SM); extranodal extension (ENE) and positive SM were considered high-risk factors (HRF). Patients were stratified into risk groups based upon the number and type of risk factors: 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF. Patients were considered to have ER if they had biopsy confirmed recurrence, or if the imaging or exam was sufficiently suspicious, after discussion with the head and neck team, to warrant treatment to definitive doses of RT (70 Gy). Results: Our cohort included 391 patients with SCC of the OCC who were treated with postoperative radiotherapy. 61% of patients were male, 35% had pT3-4 disease, 36% had pN2a-3 disease, 53% had PNI, 20% had LVI, 30% had ENE, and 14% had positive SM. The most common sites were oral tongue (46%), alveolar ridge (18%), and buccal mucosa (13%). 237 (61%) patients underwent postoperative PET/CT planning, and 165 patients (41%) were planned with CT only. Patients screened with post-operative PET/CT were more likely to be diagnosed with ER (46/237, 19.4%) than those simulated with CT only (6/154, 3.9%, p < 0.0001). Among patients simulated with PET/CT, 7%, 9%, 14%, and 35% of patients were diagnosed with ER for patients with 0-1 IRFs, 2 IRFs, ≥3 IRFs, and any HRF, respectively. Median follow-up was 4.1 years (95% CI 3.6 – 4.5). Among 52 patients with ER, 24 (49.0%) had local, 41 (83.7%) had regional, and 5 (10.2%) had distant recurrence. 17 (33%) of ER were biopsy proven. For patients with ER, 3-year freedom from locoregional recurrence, distant-metastasis free survival, and overall survival were 45.2% (95% CI 32% - 64%), 55% (95% CI 42% – 72%), and 43% (95% CI 30% - 61%), respectively. For patients without ER, use of postoperative PET/CT was associated with improved disease-free survival (HR 0.68, 95% CI 0.46 – 0.98, p = 0.041) and overall survival (HR 0.59, 95% CI 0.38 – 0.91, p = 0.019). Conclusions: Postoperative PET/CT may increase detection ER compared to CT simulation alone and improve risk stratification. Patients with ER are at high risk of locoregional failure, distant metastases, and mortality, despite salvage therapy. A prospective trial is underway at our institution to systemically study the role of PET/CT for detection of ER.

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Follicular lymphoma patients with a high FLIPI score and a high tumor burden: A risk stratification model

Vojnosanitetski pregled ◽

10.2298/vsp1501026a ◽

2015 ◽

Vol 72 (1) ◽

pp. 26-32 ◽

Cited By ~ 2

Author(s):

Bosko Andjelic ◽

Milena Todorovic-Balint ◽

Darko Antic ◽

Jelena Bila ◽

Vladislava Djurasinovic ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Prognostic Factors ◽

Follicular Lymphoma ◽

Histological Grade ◽

International Prognostic Index ◽

Prognostic Index ◽

Tumor Burden ◽

Cox Regression Analysis ◽

High Tumor Burden

Background/Aim. The widely accepted Follicular Lymphoma International Prognostic Index (FLIPI) divides patients into three risk groups based on the score of adverse prognostic factors. The estimated 5-year survival in patients with a high FLIPI score is around 50%. The aim of this study was to analyse the prognostic value of clinical and laboratory parameters that are not included in the FLIPI and the New Prognostic Index for Follicular Lymphoma developed by the International Follicular Lymphoma Prognostic Factor Project (FLIPI2) indices, in follicular lymphoma (FL) patients with a high FLIPI score and high tumor burden. Methods. The retrospective analysis included 57 newly diagnosed patients with FL, a high FLIPI score and a high tumor burden. All the patients were diagnosed and treated between April 2000 and June 2007 at the Clinic for Hematology, Clinical Center of Serbia, Belgrade. Results. The patients with a histological grade > 1, erythrocyte sedimentation rate (ESR) ? 45 mm/h and hypoalbuminemia had a significantly worse overall survival (p = 0.015; p = 0.001; p = 0.008, respectively), while there was a tendency toward worse overall survival in the patients with an Eastern Cooperative Oncology Group (ECOG) > 1 (p = 0.075). Multivariate Cox regression analysis identified a histological grade > 1, ESR ? 45 mm/h and hypoalbuminemia as independent risk factors for a poor outcome. Based on a cumulative score of unfavourable prognostic factors, patients who had 0 or 1 unfavourable factors had a significantly better 5-year overall survival compared to patients with 2 or 3 risk factors (75% vs 24.1%, p = 0.000). Conclusion. The obtained results suggest that from the examined prognostic parameters histological grade > 1, ESR ? 45 mm/h and hypoalbuminemia can contribute in defining patients who need more aggressive initial treatment approach, if two or three of these parameters are present on presentation.

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Efficacy and toxicity of postoperative external beam radiotherapy or chemoradiation for early-stage cervical cancer

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2019-001131 ◽

2020 ◽

Vol 30 (12) ◽

pp. 1878-1886

Author(s):

Mick J E van den Akker ◽

Nanda Horeweg ◽

Jogchum Jan Beltman ◽

Carien L Creutzberg ◽

Remi A Nout

Keyword(s):

Risk Factors ◽

Cervical Cancer ◽

Overall Survival ◽

Risk Factor ◽

High Risk ◽

Early Stage ◽

Free Survival ◽

High Risk Factors ◽

Early Stage Cervical Cancer ◽

Risk Factors For Recurrence

ObjectiveThe aim of this study was to assess the impact of the evolving role of the addition of chemotherapy to postoperative radiotherapy on oncological outcomes and toxicity in patients with early-stage cervical cancer after radical hysterectomy.MethodsRetrospective cohort study of patients with stage IB1–IIB FIGO 2009 cervical cancer treated from November 1999 to May 2015 by primary surgery and radiotherapy (46–50.4 Gy in 1.8–2.0 Gy fractions) with or without concurrent cisplatin (40 mg/m2, 5–6 weekly cycles) with or without a brachytherapy boost. Chemotherapy was allocated depending on the risk factors for recurrence. Incidences of all outcomes were calculated using Kaplan–Meier’s methodology and compared by log-rank tests. Risk factors for recurrence and survival were identified using Cox’s proportional hazards models.ResultsA total of 154 patients were included, median follow-up was 9.6 years (IQR: 6.1–12.8). Five-year pelvic recurrence-free survival was 75.3%; 74.7% in patients with high-risk factors treated with radiotherapy; and 77.3% in those treated with chemoradiation (P=0.43). Distant metastasis-free survival at 5 years was 63.4%; 63.6% in high-risk patients after radiotherapy; and 57.1% after chemoradiation (P=0.36). Five-year overall survival was 63.9%: 66.8% and 51.6% after radiotherapy and after chemoradiation in patients with high-risk factors (P=0.37), respectively. Large tumor size was a risk factor for vaginal and pelvic recurrence, ≥2 involved lymph nodes was a significant risk factor for para-aortic recurrence and death. Mild treatment-related late toxicity was observed in 53.9% of the patients. Five-year severe (grade 3–5) late rectal, bladder, bowel, and vaginal toxicities were, respectively, 1.3%, 0%, 3.4%, and 0.9%. Any late severe toxicity was observed in 5.5% of patients treated with radiotherapy and in 15.3% of those treated with chemoradiation (P=0.07).ConclusionPostoperative (chemo)radiation for early-stage cervical cancer patients with risk factors for recurrence yields adequate pelvic tumor control, but overall survival is limited due to distant metastasis.

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Pre-Transplant Variables Affecting the Outcome of Submyeloablative Allogeneic HSCT in Uniformly Treated Patients with Hematologic Malignancies.

Blood ◽

10.1182/blood.v104.11.2324.2324 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2324-2324

Author(s):

Jayesh Mehta ◽

S. Singhal ◽

M. Tallman ◽

S. Williams ◽

J. Winter ◽

...

Keyword(s):

Risk Factors ◽

Overall Survival ◽

Risk Factor ◽

High Risk ◽

Cox Model ◽

Performance Status ◽

Hematologic Malignancies ◽

Current Treatment ◽

Allogeneic Hsct ◽

High Risk Factors

Abstract The outcome of 63 consecutive submyeloablative allografts (27–66 y, median 52) performed for hematologic malignancies after 100 mg/m2 melphalan without (n=21; prior autograft) or with (n=42; no prior autograft) 50 mg/kg cyclophosphamide was analyzed to study the effect of pre-transplant characteristics. GVHD prophylaxis comprised cyclosporine-mycophenolate (n=37; HLA-identical sibling donors) or tacrolimus-mycophenolate (n=26, 1-locus mismatched sibling or 9–10/10 allele-matched unrelated). No growth factors were administered routinely post-transplant and supportive care was uniform. 14 patients experienced transplant-related mortality (TRM), and 32 relapsed. 24 relapsing patients died, and 7 of the other 8 are alive in CR or with declining disease. The following factors were analyzed in a Cox model for their effect on TRM and relapse: chemosensitive (n=25) vs refractory disease (n=38), age ≤55 (n=44) vs >55 (n=19), normal (n=32) vs abnormal (n=31) LDH, HLA match (n=56) vs mismatch (n=7), prior autograft or not, performance status 0–1 (n=47) vs 2–3 (n=16). Outcome Favorable factor RR (95% CI) P TRM Age ≤55 0.20 (0.04–0.86) 0.03 HLA matched 0.21 (0.05–0.89) 0.04 Performance status 0-1 0.25 (0.06–0.99) 0.05 Relape Chemosensitive disease 0.28 (0.11–0.73) 0.01 Fig 1 shows TRM for patients with 0, 1 or 2 high-risk factors for TRM. Fig 1 shows TRM for patients with 0, 1 or 2 high-risk factors for TRM. Fig 2 shows overall survival (OS) for patients with 0 or 1 high-risk factors for TRM by disease chemosensitivity. Fig 2 shows overall survival (OS) for patients with 0 or 1 high-risk factors for TRM by disease chemosensitivity. Table 2 shows the causes of death by risk factors for TRM and disease chemosensitivity. Group (n) Alive TRM Death from disease A: 2 risk factors for TRM (7) 1 (14%) 5 (71%) 1 (14%) B: 1 risk factor for TRM + Refractory (19) 2 (11%) 6 (32%) 11 (58%) C: 1 risk factor for TRM + Sensitive (9) 5 (56%) 1 (11%) 3 (33%) D: 0 risk factor for TRM + Refractory (12) 3 (25%) 1 (8%) 8 (67%) E: 0 risk factor for TRM + Sensitive (16) 13 (81%) 1 (6%) 2 (13%) These data suggest that while the current treatment approach is optimal for patients falling in Group E, modified approaches are needed for other patients. Based on the causes of failure, the following modifications appear to be warranted. Group A: A completely non-ablative regimen to reduce toxicity. Group B: A completely non-ablative regimen to reduce toxicity with augmentation of graft-vs-tumor effects by elective donor leukocyte infusions and/or abbreviated immunosuppression. Group C: Augmentation of graft-vs-tumor effects by elective donor leukocyte infusions and/or abbreviated immunosuppression. Group D: Conventional-intensity rather than reduced-intensity allogeneic HSCT.

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Chronic Lymphocytic Leukemia: Evaluation of Cytogenetic Markers as Prognostic Factors

Blood ◽

10.1182/blood.v116.21.4860.4860 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4860-4860

Author(s):

Jose Carda ◽

Patricia Sousa ◽

Patricia Olim ◽

Emília Magalhães ◽

Luis Rito ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Factors ◽

Retrospective Study ◽

High Risk ◽

Chronic Lymphocytic Leukemia ◽

Progressive Disease ◽

Risk Group ◽

Staging System ◽

Lymphocytic Leukemia ◽

Intermediate Risk

Abstract Abstract 4860 Backgroud: Chronic lymphocytic leukemia (CLL) is one of the most frequent chronic lymphoproliferative disorders in Europe. It is characterized by persistent monoclonal lymphocitosis with localized or generalized lymphadenopathy. Despite the initial clinical presentation, it has a heterogeneous natural history, with the majority of patients living 10–12 years, but with some patients dying rapidly, within 2–3 years of diagnosis. Beside clinical prognostic factors, novel cytogenetic markers are recognized to be useful in predicting disease free and overall survival in CLL. AIMS: In a retrospective study throughout 10 years (1999-2009), we analyzed the clinical and biological presentation and compared the evolution and survival of patients with B-CLL using different cytogenetic markers. METHODS: We identified 112 cases (63 males and 49 females) of B-CLL with cytogenetic study by fluorescence in situ hybridization (FISH). RESULTS: Amongst 112 patients, the male to female (M/F) ratio was 1.3:1 and the median age was 70 (43-96) years. At diagnosis, the median lymphocyte count was 15.5 G/L (5.4-173). Fifty five patients (49%) had lymphadenopathies and seventeen (15%) had splenomegaly and/or hepatomegaly at presentation. By the revised Rai staging system seventy (63%) patients were included in low risk group, thirty (27%) in intermediate risk group and twelve (10%) in high risk group. The expression of ZAP-70 and CD38 by flow citometry was performed in 75 patients and revealed 13 (17%) patients CD38+ and 12 (16%) ZAP70+. The study of chromosomal aberrations with FISH showed thirty six patients (32%) with no abnormality, thirty six (32%) with isolated 13q deletion, fifteen (14%) with 12 trisomy, twelve (11%) with 11q deletion and thirteen (11%) with 17p deletion. Forty (36%) patients showed progressive disease in a median time of sixteen months (0-120), thirteen with 13qdel, seven with 17pdel and five with 12 trisomy. After treatment two patients showed progressive disease, six maintain a stable disease and thirty two obtain a remission, nine in complete remission. The Overall Survival (OS) at ten years was 70%. By the revised Rai staging system the OS at ten years was 80% for low risk, 70% for intermediate risk and all the high risk patients died during follow up. The OS at five years for the del13q-, 12 trisomy, del11q- and del17p- was 90%, 88%, 58% and 60%, respectively. SUMMARY: Chronic lymphocytic leukemia is currently considered a chronic disorder with a favourable outcome, but with a variable evolution to progressive disease. This retrospective study allowed the characterization of patient with CLL in our department and the acknowledgement that our results are quite similar to the published data. Disclosures: No relevant conflicts of interest to declare.

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