scholarly journals Risk-adapted combined therapy with arsenic trioxide and all-trans-retinoic acid for de novo acute promyelocytic leuкaemia

2021 ◽  
Vol 66 (2) ◽  
pp. 168-191
Author(s):  
V. V. Troitskaya ◽  
E. N. Parovichnikova ◽  
A. A. Semenova ◽  
Z. T. Fidarova ◽  
A. N. Sokolov ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
De Novo ◽  
Early Mortality ◽  
Low Risk ◽  
Molecular Remission ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Risk Patients ◽  
High Risk Cohort

Introduction. Non-chemotherapy for acute promyelocytic leukaemia (APL) with a combination of all-trans-retinoic acid (ATRA) and arsenic trioxide (ATO) provides for a high patient survival rate at lesser toxicity as effectively or superior to standard chemotherapy programmes.Aim — assessment of the ATO–ATRA risk-adapted exposure protocol in management of de novo acute promyelocytic leucaemia.Materials and methods. A prospective study included 51 primary APL patients aged 18–76 years. The program included remission induction (ATO 0.15 mg/kg intravenously, ATRA 45 mg/m2 orally) for 30–60 days in a low-risk (until remission) and 60 days — in a high-risk cohort that had idarubicin therapy added on days 2 and 4. Remission consolidation was attained with four (low-risk) or five (high-risk) courses. Minimal residual disease was monitored with real-time PCR at all phases.Results. The high-risk cohort was assigned 15 (29.4 %), the low-risk cohort — 36 (70.6 %) patients. Therapy induction till APL morphological remission was performed in 48/51 (94 %) patients. Molecular APL remission was achieved in 47 (92 %) patients, 100 % in the low-risk and 80 % in high-risk cohort. Early mortality was 6 % (n = 3), death in remission — 2 % (n = 1). Differentiation syndrome (DS) occurred in 16 (31.7 %) patients, more frequently in the high-risk vs. low-risk cohort (53.3 % and 22.2 %, respectively, p = 0.05; odds ratio 4.0 [1.1–14.4]). DS developed on days 1–20 (3 days median) of therapy. DS risk factors: a high-risk status, haemorrhagic syndrome and infection at the disease onset. A median follow-up time in survivors was 12.9 months (2.5–34.3), a six-month overall survival — 92 % (95 % CI: 85–100 %). A six-month overall survival was 100 and 73 % in the low- and high-risk cohorts, respectively (95 % CI: 54–100 %, p = 0.001). APL relapse not registered, 47 (92 %) patients survived and achieved the first molecular remission.Conclusion. A differentiated risk-adapted approach to APL therapy with cytostatic treatment added in high-risk patients only provided for a 100 % molecular remission and relapse-free survival. Therapy failures (early mortality and death in remission) affected high-risk patients due to a severe individual condition at the time of APL diagnosis.

Early Mortality in Acute Promyelocytic Leukemia May Be Higher Than Previously Reported.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1015-1015 ◽  
Author(s):  
Ash A Alizadeh ◽  
James S. McClellan ◽  
Jason R. Gotlib ◽  
Steven Coutre ◽  
Ravindra Majeti ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
High Risk ◽  
Early Death ◽  
Promyelocytic Leukemia ◽  
Early Mortality ◽  
Low Risk ◽  
Intermediate Risk ◽  
Risk Patients

Abstract Abstract 1015 Poster Board I-37 Background: Early mortality, mostly from hemorrhagic complications, occurs in less than 10% of patients currently treated in clinical trials for acute promyelocytic leukemia (APL). However, data about the proportion of patients developing such complications prior to clinical trial enrollment are scarce in the literature (Sanz M, et al Blood 2009). Approximately 5% of newly diagnosed patients with APL have been reported not to be eligible for participation in clinical trials due to very poor clinical condition, and their outcome has never been reported. However, enrollment on clinical trials may be difficult in specific clinical situations, such as after hours/weekend admissions and/or emergent requirement for therapy. This study reports the incidence, time of occurrence and clinical features of APL patients with a focus on early mortality. Methods: 150 consecutive APL patients treated at Stanford University between 8/1986 and 7/2009 were identified. Thirteen patients were excluded for lack of appropriate clinical information. Clinical features of patients with APL were analyzed for factors that might be relate to prognosis, including age, gender, white blood cell count, platelet count, fibrinogen, PTT, and INR. Continuous variables were compared with the t-test and categorical variables by Fisher's exact test or X-square statistic. The Kaplan–Meier method was applied to assess overall survival time. Results: Of the 137 patients included in this analysis, the median age at diagnosis was 45 (1-93) years and 78 (57%) were females. Using the PETHEMA criteria, there were 37, 46 and 20 patients with high-, intermediate- and low-risk disease (34 patients could not be classified based on partial/missing data). With a median follow-up time of 748 (0-6,235) days for the entire cohort, 52 (38%) have died. 19 (14%) and 11 (8%) of these patients died within 7 and 3 days of presentation, respectively. Patients with high-risk features had a 13% and 24% chance of dying with 3 and 7 days of presentation, respectively, with significantly inferior outcomes (p=0.045) when compared to those with intermediate-risk patients (6% and 13%) and low-risk disease (5% and 5%). Patients with unknown risk category faired similarly to low-risk patients. The most common cause of early mortality in these 19 patients was intracranial hemorrhage (n=11). Patients with early death (ED) (either <=3 or <=7 days) tended to be older than APL patients with non-early deaths (>7d), or APL patients alive as of their last follow-up (median age 54 years vs. 50 years vs. 39 years), and were more likely to have higher risk disease, though coagulopathy appeared not significantly different amongst the groups. Median fibrinogen, PTT and INR for each individual group are presented on Table 1. The 3-year overall survival (% +/- SE) of the low, intermediate, and high risk patients was 90+/-7, 74+/-7, and 64+/-8, respectively, though early mortality (death within 7 days) was a major determinant of this stratification (p=0.045). Conclusions: Risk of early death in APL patients appears to be higher than previously reported in clinical trials, where trial registration may exclude patients requiring urgent therapeutic interventions. In this cohort, 25% and 13% patients with high- and intermediate-risk APL died within 7 days of presentation, respectively. Risk group stratification was very predictive of risk of early death. Disclosures: No relevant conflicts of interest to declare.

Use of all-trans retinoic acid plus arsenic trioxide as an alternative to chemotherapy in untreated acute promyelocytic leukemia

Blood ◽  
2006 ◽  
Vol 107 (9) ◽  
pp. 3469-3473 ◽  
Author(s):  
Elihu Estey ◽  
Guillermo Garcia-Manero ◽  
Alessandra Ferrajoli ◽  
Stefan Faderl ◽  
Srdan Verstovsek ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Arsenic Trioxide ◽  
Promyelocytic Leukemia ◽  
Low Risk ◽  
High Risk Patients ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Risk Patients

We examined whether combining all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) might be an alternative to ATRA plus chemotherapy in untreated acute promyelocytic leukemia (APL). Twenty-five low-risk patients (white blood cell [WBC] count less than 10 × 109/L [10 000/μL]) received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily, beginning day 10 of ATRA), and in complete remission (CR) received ATO plus ATRA, without chemotherapy, unless they were reverse transcriptase–polymerase chain reaction (RT-PCR)–positive 3 months from CR date or had molecular relapse. Nineteen high-risk patients were treated identically, but received chemotherapy, generally 9 mg/m2 gemtuzumab ozogamycin (GO) on day 1 of induction. The CR rate was 39 of 44 (24 of 25 in low-risk, 15 of 19 in high-risk). Disease recurred at 9, 9, and 15 months, respectively, in 3 high-risk patients. The median follow-up time from CR date in the 36 patients alive in first CR is 16 months (15 months in low-risk, 20 months in high-risk), with 9 patients followed for at least 24 months. Each of the 36 patients was PCR-negative at last follow-up. Thus, none of the low-risk patients has received chemotherapy, and only 3 high-risk patients (the 3 with relapsed disease) have received chemotherapy past induction. ATRA plus ATO may serve as an alternative to chemotherapy in low-risk untreated APL (eg, in older patients) and, when combined with GO, may improve outcome in high-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.

Incidence, Outcome and Risk Factors of Pseudotumor Cerebri after All- Trans Retinoic Acid and Anthracycline-Based Chemotherapy in Patients with Acute Promyelocytic Leukemia

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2992-2992 ◽  
Author(s):  
Pau Montesinos ◽  
Edo Vellenga ◽  
Aleksandra Holowiecka ◽  
Chelo Rayon ◽  
Gustavo Milone ◽  
...  
Keyword(s):  
Risk Factors ◽  
Retinoic Acid ◽  
Side Effects ◽  
High Risk ◽  
Pseudotumor Cerebri ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Risk Patients

Abstract Background: Pseudotumor cerebri associated with all-trans-retinoic acid (ATRA) treatment in acute promyelocytic leukemia (APL) have been frequently described in pediatric patients. However, the incidence, outcome and risk factors of pseudotumor cerebri in APL are not well-known. We analyze the incidence and risk factors of this complication in a large series of patients with newly diagnosed APL enrolled in three consecutive trials of the PETHEMA Group (LPA96, LPA99 and LPA2005). Mehods: AIDA regimen (ATRA 45 mg/m2/d [25mg/m2/d in patients younger than 20] until CR and idarubicin 12 mg/m2/d on days 2, 4, 6 and 8) was given as induction therapy. Patients in CR received 3 monthly courses of risk-adapted consolidation therapy: idarubicin 5 mg/m2/d × 4 (course #1), mitoxantrone 10 mg/m2/d × 5 (course #2), and idarubicin 12 mg/m2/d × 1 (course #3). Since November 1999 (LPA99 trial), for patients with intermediate or high risk of relapse (Sanz et al, Blood 2000), consolidation was slightly intensified by increasing idarubicin doses in courses #1 and #3, and by simultaneously administering 25 mg/m2 ATRA together with chemotherapy in all three courses. Since July 2005, consolidation therapy in the ongoing LPA 2005 trial included the following modifications: the administration of ATRA for all patients; for low- and intermediate-risk patients, mitoxantrone has been reduced from five to three days in the second course; and for high-risk patients, cytarabine has been added to idarubicin in the first and third course. Maintenance therapy consisted of 50 mg/m2/d mercaptopurine orally, 15 mg/m2/week methotrexate intramuscularly, and 25 mg/m2/d ATRA for 15 days every three months. Diagnosis of pseudotumor cerebri was made in the presence of signs and symptoms of intracranial hypertension without clinical or radiological evidence of infective or space occupying lesions. Results: Of 1034 patients enrolled between November 1996 and July 2008, 32 (3%) experienced pseudotumor cerebri. Headaches without pseudotumor were present in 252 patients (25%). Thirty cases of pseudotumor occurred during induction therapy and 2 cases manifested only during consolidation. In all, 9 of 32 patients (28%) had recurrent pseudotumor cerebri after reinitiating ATRA. All these side effects were transient, reversible, and never a cause of death. CR rates were 96% and 90% in patients with and without pseudotumor cerebri, respectively (p=0.32). The incidence of pseudotumor cerebri among patients younger than 18 years, 18–25 years, 25–50 years and older than 50 years was 13%, 7%, 2% and 0.3%, respectively (p&lt;0.0001). There was a trend toward a correlation between fibrinogen &lt;170 mg/dL and worse general state (ECOG&gt;1) at presentation and development of pseudotumor cerebri (p=0.08 and p=0.06, respectively). We did not found any significant association between pseudotumor cerebri and WBC, platelets, relapse risk-score, hemoglobin, creatinine, PETHEMA trial, gender, morphological subtype, PML/RARA isoform, FLT3 mutations, and surface antigens (CD2, CD11b, CD13, CD15, CD34, CD56, and CD117). Conclusion: This study shows an overall incidence of pseudotumor cerebri of 3% among APL patients treated with ATRA and anthracycline-based regimens, with higher incidences in children and young adults (13% and 7%, respectively). No other prognostic factors could be demonstrated. The development of pseudotumor cerebri was not associated with a worse induction outcome. Side effects were reversible and transient, but roughly a third of patients had recurrent pseudotumor cerebri after reinitiating ATRA

scholarly journals A Novel Four-Gene Signature Associated With Immune Checkpoint for Predicting Prognosis in Lower-Grade Glioma

2020 ◽  
Vol 10 ◽  
Author(s):  
Youchao Xiao ◽  
Gang Cui ◽  
Xingguang Ren ◽  
Jiaqi Hao ◽  
Yu Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Risk Score ◽  
Immune Checkpoint ◽  
Risk Groups ◽  
Gene Signature ◽  
Low Risk ◽  
Lower Grade ◽  
Lower Grade Glioma ◽  
Risk Patients

The overall survival of patients with lower grade glioma (LGG) varies greatly, but the current histopathological classification has limitations in predicting patients’ prognosis. Therefore, this study aims to find potential therapeutic target genes and establish a gene signature for predicting the prognosis of LGG. CD44 is a marker of tumor stem cells and has prognostic value in various tumors, but its role in LGG is unclear. By analyzing three glioma datasets from Gene Expression Omnibus (GEO) database, CD44 was upregulated in LGG. We screened 10 CD44-related genes via protein–protein interaction (PPI) network; function enrichment analysis demonstrated that these genes were associated with biological processes and signaling pathways of the tumor; survival analysis showed that four genes (CD44, HYAL2, SPP1, MMP2) were associated with the overall survival (OS) and disease-free survival (DFS)of LGG; a novel four-gene signature was constructed. The prediction model showed good predictive value over 2-, 5-, 8-, and 10-year survival probability in both the development and validation sets. The risk score effectively divided patients into high- and low- risk groups with a distinct outcome. Multivariate analysis confirmed that the risk score and status of IDH were independent prognostic predictors of LGG. Among three LGG subgroups based on the presence of molecular parameters, IDH-mutant gliomas have a favorable OS, especially if combined with 1p/19q codeletion, which further confirmed the distinct biological pattern between three LGG subgroups, and the gene signature is able to divide LGG patients with the same IDH status into high- and low- risk groups. The high-risk group possessed a higher expression of immune checkpoints and was related to the activation of immunosuppressive pathways. Finally, this study provided a convenient tool for predicting patient survival. In summary, the four prognostic genes may be therapeutic targets and prognostic predictors for LGG; this four-gene signature has good prognostic prediction ability and can effectively distinguish high- and low-risk patients. High-risk patients are associated with higher immune checkpoint expression and activation of the immunosuppressive pathway, providing help for screening immunotherapy-sensitive patients.

Central Nervous System Relapse in Patients with Acute Promyelocytic Leukemia Treated with All-Trans Retinoic Acid and Reinforced Anthracycline Monochemotherapy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 592-592 ◽  
Author(s):  
Pau Montesinos ◽  
Jose D. Gonzalez ◽  
Edo Vellenga ◽  
Chelo Rayon ◽  
Ricardo Parody ◽  
...  
Keyword(s):  
High Risk ◽  
High Dose ◽  
Cns Involvement ◽  
Cns Prophylaxis ◽  
Trans Retinoic Acid ◽  
Cns Relapse ◽  
All Trans Retinoic Acid ◽  
High Dose Cytarabine ◽  
Risk Patients ◽  
First Relapse

Abstract Background: Central nervous system (CNS) relapse can complicate the course of patients with acute promyelocytic leukemia (APL) treated with all-trans retinoic acid (ATRA) and chemotherapy, especially of those with high WBC at diagnosis (≥10 × 109/L). While ATRA and anthracyclines do not crosses the cerebrospinal fluid barrier, some trials for APL includes the use of intratechal prophylaxis or high-dose cytarabine, at least in high-risk patients, to avoid the CNS relapses. However, the convenience of CNS prophylaxis in APL patients is a matter of controversy. Objectives: Analyze the incidence and characteristics of CNS involvement at first relapse, in patients with newly diagnosed APL treated with ATRA and reinforced anthracycline monochemotherapy, without CNS prophylaxis. Methods: From 1999 to 2005, 564 patients (median age 40 years, range 2-83) were included in the PETHEMA LPA99 trial. Induction therapy consisted of ATRA and idarubicin. Patients in CR received 3 monthly courses of risk-adapted consolidation therapy as follows: “low-risk” patients (WBC <10×109/l and platelets >40×109/l), idarubicin 5 mg/m2/d × 4 (course #1), mitoxantrone 10 mg/m2/d × 5 (course #2), and idarubicin 12 mg/m2/d × 1 (course #3); “intermediate-risk “ (WBC <10×109/l and platelet <40×109/l) and “high-risk” (WBC >10×109/l) patients received ATRA (45 mg/m2/d × 15) in combination with reinforced chemotherapy (Idarubicin 7 mg/m2/d in the course #1 and two days instead of one in the course #3). Maintenance therapy consisted of low-dose oral chemotherapy (mercaptopurine and methotrexate with ATRA). We measured the cumulative incidence (CI) of CNS involvement at first relapse during the course of APL patients who achieved the CR. Results: CR was achieved in 511 patients (91%). The median follow-up of the cohort was 57 months (range 20–94 months). Overall, 52 patients relapsed, of whom 5 presented a first relapse in CNS. In all cases, CNS relapses occurred without bone marrow or other extramedullary involvement. CNS relapses occurred after a median of 14 months (range 10–41 months) from the achievement of CR. At the initial diagnosis, APL were classified, according to the Sanz score, as low-, intermediate- and high-risk, in 0, 2, and 3 patients, respectively. The median WBC at diagnosis was 34.5 × 109/L (range 1.9–68.8 × 109/L), and 4 patients showed a Bcr3 PML-RARalpha isoform. Using a competitive-risk method, the overall 5 year CI of CNS relapse was 1.03%. The 5 year CI of CNS relapse in low-, intermediate- and high-risk patients was 0%, 0.77% and 2.71%, respectively (low- vs high-risk and intermediate vs high-risk; p=0.12 and p=0.11, respectively). The 5 year CI of CNS relapse in patients with Bcr3 and Bcr1 PML-RARalpha isoform was 0.45% and 2.44%, respectively (p=0.12). Conclusion: Despite the lack of intratechal prophylaxis or high-dose cytarabine in the therapeutic schedule of the LPA99 trial, the overall 5 year CI of CNS relapse was very low (1%). Our results does not hold up the systematic use of CNS prophylaxis in APL patients treated with ATRA and reinforced anthracycline monochemotherapy.

Treatment with All-Trans Retinoic Acid and Anthracycline Monochemotherapy in Children with Acute Promyelocytic Leukemia: Analysis of Three Sequential Multicenter Trials of the PETHEMA Group

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 137-137
Author(s):  
Luis Madero ◽  
Pau Montesinos ◽  
Pilar Bastida ◽  
Amparo Verdeguer ◽  
Javier De la Serna ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
High Risk ◽  
Maintenance Therapy ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Consolidation Therapy ◽  
Trans Retinoic Acid ◽  
All Trans Retinoic Acid ◽  
Risk Patients ◽  
High Degree

Abstract The combination of all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy has been adopted as the standard treatment for children and adults with acute promyelocytic leukemia (APL). However, information about therapy results in pediatric APL patients is scarce, particularly on long-term outcomes. A previous report of the PETHEMA Group (Ortega et al, JCO 2005) showed that a risk-adapted strategy combining a reduced dose of ATRA (25 mg/m2/d) and anthracycline monochemotherapy for induction and consolidation, followed by ATRA and low dose methotrexate and mercaptopurine for maintenance therapy, produced high antileukemic efficacy, moderate toxicity, and a high degree of compliance. We have now performed an updated analysis of a significantly enlarged cohort of 107 consecutive children (younger than 19 years) with APL who were enrolled in three sequential trials of the PETHEMA Group (LPA96, LPA99 and LPA2005) and followed up for a median of 71 months (range, 3–139). Induction consisted of 25 mg/m2 ATRA daily until CR and 12 mg/m2 idarubicin on days 2, 4, 6 and 8. In the LPA96 trial, patients in CR received three monthly chemotherapy courses: idarubicin 5 mg/m2/d × 4 (course #1), mitoxantrone 10 mg/m2/d × 5 (course #2), and idarubicin 12 mg/m2/d × 1 (course #3). Since November 1999 (LPA99 trial), for patients with intermediate or high risk of relapse (Sanz et al, Blood 2000), consolidation was slightly intensified by increasing idarubicin doses in courses #1 and #3, and by simultaneously administering 25 mg/m2 ATRA together with chemotherapy in all three courses. Since July 2005, consolidation therapy in the ongoing LPA 2005 trial included the following modifications: the administration of ATRA for all patients; for low- and intermediate-risk patients, mitoxantrone has been reduced from five to three days in the second course; and for high-risk patients, cytarabine has been added to idarubicin in the first and third course. Maintenance therapy consisted of 50 mg/m2/d mercaptopurine orally, 15 mg/m2/week methotrexate intramuscularly, and 25 mg/m2/d ATRA for 15 days every three months. Of 1031 patients enrolled in three subsequent PETHEMA trials between November 1996 and July 2008, 107 (10%) from 43 Institutions were aged less than 19 years. WBC counts were &gt;10×09/l and &gt;50×109/l in 36 (34%) and 10 (9%), respectively; morphologically, 22 (22%) cases were hypergranular; PML/RARA isoform type was BCR1 or BCR2 in 47 (57%), and BCR3 in 35 (43%). One-hundred and one patients achieved CR (94%). In general, toxicity was manageable during consolidation and maintenance therapy. One patient died in CR during consolidation due to hepatic failure. At the end of consolidation, only 2 patients of 86 patients tested had molecular persistence (defined by positive RT-PCR of PML/RARA at 10−4 sensitivity). Ten additional relapses were observed, 5 molecular and 5 clinical relapses. Apart from 2 clinical relapses and 2 molecular relapses, all these events occurred among high risk patients. The 5-year Kaplan-Meier estimates of overall, disease-free and relapse-free survival were 89%, 86% and 86%, respectively. These results show a higher incidence of hyperleucocytosis in pediatric patients than in adults with genetically proven APL (p=0.05) and confirm the high antileukemic efficacy, low toxicity and high degree of compliance of three subsequent PETHEMA trials using a risk-adapted strategy with ATRA and anthracycline-based chemotherapy for induction and consolidation therapy.

Renal Cell Carcinoma Recurrence After Nephrectomy for Localized Disease: Predicting Survival From Time of Recurrence

2006 ◽  
Vol 24 (19) ◽  
pp. 3101-3106 ◽  
Author(s):  
Scott E. Eggener ◽  
Ofer Yossepowitch ◽  
Joseph A. Pettus ◽  
Mark E. Snyder ◽  
Robert J. Motzer ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
High Risk ◽  
Renal Cell ◽  
Scoring System ◽  
Median Survival Time ◽  
Low Risk ◽  
Intermediate Risk ◽  
Risk Patients ◽  
Localized Disease

Purpose Prognostic factors for patients with metastatic renal cell carcinoma (RCC) are well established. However, the risk profile is unknown for patients with recurrent RCC after a nephrectomy for localized disease. Patients and Methods From January 1989 to July 2005, we identified patients with localized RCC treated by nephrectomy who subsequently developed recurrent disease. We applied a validated prognostic scoring system previously developed for patients with metastatic RCC. Each patient was given a total risk score of 0 to 5, with one point for each of five prognostic variables (recurrence < 12 months after nephrectomy, serum calcium > 10 mg/dL, hemoglobin < lower limit of normal, lactate dehydrogenase > 1.5× upper limit of normal, and Karnofsky performance status < 80%). Patients were categorized into low- (score = 0), intermediate- (score = 1 to 2), and high-risk subgroups (score = 3 to 5). Results Our final cohort included 118 patients, with a median survival time of 21 months from the time of recurrence. Median follow-up time for survivors was 27 months. Overall survival was strongly associated with risk group category (P < .0001). Low-risk, intermediate-risk, and high-risk criteria were fulfilled in 34%, 50%, and 16% of patients, respectively. Median survival time for low-risk, intermediate-risk, and high-risk patients was 76, 25, and 6 months, respectively. Two-year overall survival rates for low-risk, intermediate-risk, and high-risk patients were 88% (95% CI, 77% to 99%), 51% (95% CI, 37% to 65%), and 11% (95% CI, 0% to 24%), respectively. Conclusion At disease recurrence after nephrectomy for localized disease, a scoring system based on objective clinical and laboratory data provides meaningful risk stratification for both patient counseling and clinical trial entry.

Sign in / Sign up

Export Citation Format

Share Document