Survival Analysis of Additional Chromosomal Aberrations in Philadelphia Chromosome Positive and Negative Cells: A Single Institutional

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2523-2523
Author(s):  
William Bulkeley ◽  
Bijal D. Shah ◽  
Monique A Hartley ◽  
John M. Bennett ◽  
Rami S. Komrokji ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Disease Progression ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Blast Phase ◽  
Clone Group

Abstract Abstract 2523 Background: Chronic myeloid leukemia (CML) is a clonal stem cell malignancy associated with the Philadelphia chromosome, t(9;22)(q34q31)/BCR-ABL gene fusion. Additional cytogenetic abnormalities have been known to emerge in Philadelphia (Ph) positive cells (additional Ph+ clones) or Ph negative cells (Ph- clones) at diagnosis, or during or post tyrosine kinase inhibitor (TKI) therapy. Many studies have elucidated that the presence of some Ph+ clones were frequently associated with disease progression, while presence of Ph- clones were unrelated to disease outcome. A majority of studies have shown a waxing and waning of Ph- clonality in response to therapy. However, there remains no solid data regarding overall survival comparing Ph+ and Ph- clones over a long term period. This study focuses on the observation of clonal evolution in various phases of CML, and the relationship to overall survival, disease resistance, kinase domain mutation (KDM) and progression to accelerated or blast phase in patients with CML. Materials and Methods: Data from 318 patients who were diagnosed with CML was retrieved from Moffitt Cancer Center during January 1990-December 2010. Patients are divided into three groups based on the presence of additional ph+ clone (A), ph- clone (B) and absence of both (C). Clinicopathologic results including initial diagnosis date, nature and frequency of clone, copy of clone at karyotyping, disease status in response to treatment and overall outcome were documented and statistically analyzed. All patients with Ph- and Ph+ clones have been treated with TKIs since 2001. Median overall survival and median disease progression survival were compared between conal ph- and clonal ph+ group by the log-rank test. Survival curves were generated using the Kaplan–Meier method. All reported P values are two-sided. Cox Regression (multivariate analysis) was also performed for time to progression. Results: Of 318 (average age 57, range: 19 to 89, M:F=1:1), 17 carried ph- clones (5.3%) and 41 showed additional ph+ clones (12.9%) and the rest (258) lacked additional ph+ or ph- clones. Additional clonal cytogenetic aberrations were random with the most frequent occurrence of trisomy 8 (7 of 17 ph- and 14 of 41 ph+ clones, respectively) and isochromosome 17q (4 in ph+ clone only). There is a higher rate of transformation to accelerated/blast phase in Ph+ additional clones (36.6%,15 of 41) as compared to Ph- additional clone (17.6%, 3 of 17) and Ph+ without additional clones(11.1%, 29 of 260) (p=0.015). The overall median survival is shorter in patients with ph+ clones (133.4 months) than in those with ph- clones (172 months) (p<0.005). KDM were observed in 27 of 110 tested patients (24.5%), and many of them fell into the Ph+ clone group (10 of 22 tested) and fewer into ph- clone group (3 of 10 tested) (p<0.005). Statistical analysis proved that there is a higher rate of transformation to accelerated/blast phase in the presence of a KDM (p<0.005). Of note, most of those with ph- clones had only one episode (59%) with 41% having more than one occurrence and lasting from 6–58 months (average 21.1 months), while in those 41 patients with Ph+ clone; a subset (18 of 41, 43.9%) showed a long-lasting ph+ clone over months (ranging from 2 months to 70 months, average 14.5 months) and the remaining only occurred one occasion (23 of 41, 56.1%). Multivariate analysis for disease progression demonstrated statistical significance with regards to both the ph+ clone and kinase mutation categories (p=0.003 and 0.034). Conclusion: Most Ph+ or Ph- clones are occasionally observed during the long course of CML, with a minor subset of clones showing persistency, especially in Ph- ones. The presence of an additional Ph+ clone is correlated with disease progression, drug resistance and shorter overall survival in comparison to a Ph- clone. A relatively long overall survival is observed in patients with ph- clones. Ph- clones were often identified during disease remission regardless of frequency of clonal copy or clonal persistence. The outcome of patients with concurrent Ph+ and Ph- clones was dictated by the Ph+ clone. Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-15
Author(s):  
Lin Gui ◽  
Fei Wang ◽  
Jinning Shi ◽  
Baoan Chen
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Survival Time ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Rank Test ◽  
Newly Diagnosed

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: We retrospectively reviewed the data for 60 multiple myeloma patients who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University from August 2011 to March 2020. According to NLR、MLR、PLR, the patients were divided into the low NLR group (NLR&lt;3.61) or high NLR group (NLR≥3.61), low MLR group (MLR&lt;0.33) or high MLR group (MLR ≥0.33), low PLR group (PLR&lt; 129.78) and high PLR group (PLR ≥129.78). Overall survival time (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of onset was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin, lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR≥129.78、HGB&lt;100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR≥129.78、HGB&lt;100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis. Key Wordsmultiple myeloma; overall survival; NLR; PLR; MLR Disclosures No relevant conflicts of interest to declare.

Autoimmunity in Patients (pts) with Chronic Myelomonocytic Leukemia (CMML): A Frequent Finding

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4930-4930 ◽  
Author(s):  
Amer Swedeh ◽  
Mrinal Patnaik ◽  
Dima Alfakara ◽  
Aneel A Ashrani ◽  
Rajiv Pruthi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Mayo Clinic ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Antineutrophil Cytoplasmic Antibodies ◽  
Prognostic Impact ◽  
Autoimmune Antibodies ◽  
Myeloid Neoplasms ◽  
Frequent Finding

Abstract Abstract 4930 Background: Autoimmune disorders have been observed in pts with myeloid neoplasms but their frequency and impact on the natural history of the myeloid neoplasms remains to be defined. Aim: To describe the frequency and prognostic impact of autoimmunity in pts with CMML. Methods: After IRB approval, a retrospective chart review of all pts diagnosed with CMML at Mayo Clinic between 1994 – 2011. Autoimmunity (AI) was defined as positive serologic tests (Anti-nuclear antibodies (ANA), rheumatoid factor (RF), anti –cyclic citrullinate peptide (CCP), and antineutrophil cytoplasmic antibodies (ANCA)), diagnosis of connective tissue disease (Rheumatoid arthritis, RA), vasculitis, or auto-immune thrombocytopenia (ITP). Survival estimates were calculated using Kaplan-Meier estimates and Cox regression model for multivariate analysis for via JMP software v. 9. Results: During the study period, 288 pts with CMML were evaluated at Mayo Clinic, 35% (n=100) were female. Median age at diagnosis was 71yr (20–95). Median hemoglobin was 11 g/dL(6–16), median white blood cell (WBC) 12 x109/L (1–302), and median platelet count 86 x109/L (1–1110). Median peripheral blood (PB) and bone marrow (BM) blasts were 0 and 5 respectively, while median PB and BM monocytes were 20% and 8% respectively. Eight-nine percent of pts had CMML1, while 10% had CMML2 and only 2 pts had CMML transforming into acute myeloid leukemia (-t). Karyotype analysis performed in demonstrated normal (diploid) karyotype in 180 (63%) pts and complex karyotype in 31 pts (11%). JAK2 mutation analysis was performed in 76 pts, 13% (10/76) of which were positive for JAK2V617F mutation. Autoimmunity was found in 46 (16%) of 288 pts. When tested, positive ANA, RF, CCP, and ANCA were found in 28/89 (31%), 8/61 (13%), 1/20 (5%), and 7/25 (28%), respectively. However, RA was reported positive in 6/288 (2%), and vasculitis was reported in only 4 pts. Median overall survival of the 288 patients was 496 days. Pts with evidence of autoimmunity had a median survival of 400 days compared to 527 days to the rest of the group (p 0. 73). On multivariate analysis, autoimmunity was not an independent risk factor for survival (p 0. 15), but age, platelets, WBC and body mass index (BMI) were independent factors. Conclusion: Autoimmunity is a frequent finding in pts with CMML. When tested, autoimmune antibodies were very frequent up to 31% of pts with CMML, but this did not confer into higher frequency of autoimmune diseases. Presence of positive autoimmune antibodies did not affect overall survival adversely. Disclosures: No relevant conflicts of interest to declare.

The Prognostic Significance of the Absolute Lymphocyte to Monocyte Count Ratio (ALC/AMC-dx) at Diagnosis in Hodgkin´s Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2953-2953
Author(s):  
Brenda Lizeth Acosta-Maldonado ◽  
Ana Ramirez-Ibarguen ◽  
Flavio A Grimaldo-Gomez ◽  
Luis Oñate-Ocaña ◽  
Silvia Rivas-Vera
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Conflicts Of Interest ◽  
Independent Predictor ◽  
Prognostic Significance ◽  
Response To Therapy ◽  
Cutoff Point ◽  
Response To Treatment ◽  
Monocyte Count ◽  
Overall Response

Abstract Background. In Classic Hodgkin's lymphoma (cHL), malignant cells constitute only about 1% of the bulk of tumor tissue, the rest constitutes the microenvironment and is made up of a compound of inflammatory cells. Lymphocytopenia and increased CD68+ tumor-associated macrophages (TAMs) are adverse prognostic factors in cHL. TAMs are derived from circulating monocytes and are possibly related to absolute monocyte count (AMC). We have sought to investigate the relationship of circulating lymphocytes and monocytes with response and survival in patients. Recently, Porrata et al. reported that a low absolute lymphocyte count/absolute monocyte count at diagnosis [ALC/AMC-Dx] (<1.1) is an independent prognostic factor in cHL. Subsequent studies used different cutoffs for ALC/AMC (1.5 and 2.9). Currently, there are no studies that evaluate the usefulness of the index relative to the overall response. Aim To determine the prognostic value of ALC /AMC at diagnosis in patients with cHL and its impact on treatment response to therapy, progression and overall survival. Methods: We evaluated 262 consecutive individuals with cHL, referred and treated at the National Cancer Institute in Mexico between 2006 to 2013. The great majority of patients were treated with ABVD with or without radiotherapy, and all had available data for ALC/AMC determined at diagnosis. It was made a multivariate analysis and ROC curves for cutoff point of ALC/AMC. Results: Median age was 35 y (14-89), 59.2% of patients were male, 77% had B-symptoms, 36.3% had stage IV disease, 85% had advanced stage (IB,IIB,III,IV), 51.5% had IPS ≥3, 46.2% nodular sclerosing histology and 45.4% mixed cellularity. The overall response (CR + PR) was obtained in 188 patients (72%) and failure (stable disease or progressive disease) in 73 patients (28%). A new cutoff point, 1.77 in ALC/AMC-Dx ratio with area under the curve of 0.62. Multivariate analysis showed that the ALC/AMC-Dx index was an independent predictor for response to treatment, progression as well as overall survival (Table 1). Additionally the IPS≥3 showed to be an independent factor for response 68.8% vs 41.7% in low and high risk, respectively (p<0.0000). Conclusion: In our population ALC/AMC-Dx index was established with a cutoff of 1.77. The group of patient with < 1.77 had a less overall response and overall survival. It proves that ALM/AMC-Dx is an independent predictor of response, progression and overall survival in patients with classical cHL. That differs of other reviews where the cutoff was lower. Table 1. Multivariate analysis according to ALC/AMC-DX ratio ALC/AMC -Dx index p Low< 1.77 High >1.77 Overall Response 58.1% 79.8% OR 0.25-.0.84p 0.011 Overall Survival8 years 81% 94% p 0.004 Disclosures No relevant conflicts of interest to declare.

Management of renal masses in an octogenarian cohort: Is there a right approach?

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 497-497
Author(s):  
Jude Nawlo ◽  
Dominic H. Tang ◽  
Juan Chipollini ◽  
Scott Michael Gilbert ◽  
Michael Adam Poch ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Creatinine Clearance ◽  
Cox Regression ◽  
Statistical Significance ◽  
Eastern Cooperative Oncology Group ◽  
Cancer Center ◽  
Management Options ◽  
Renal Masses

497 Background: Although several guidelines outline management options for patients with renal masses, few studies describe treatment strategies and outcomes in octogenarians. We sought to review outcomes in this population managed with active surveillance (AS), partial nephrectomy (PN), or radical nephrectomy (RN). Methods: Data were collected on 113 octogenarian patients referred for management of renal masses at Moffitt Cancer Center between 2000 and 2013. Patients were treated with AS, PN, or RN. Univariate and multivariable Cox regression models measured association of management modality and survival. Kaplan-Meier survival analysis was used for overall survival and log-rank tests were used to compare survival curves. Covariates include age, Eastern Cooperative Oncology Group (ECOG) score, clinical and pathologic stage, tumor size, creatinine, creatinine clearance, and overall survival. Results: Out of 113 patients, 27 (22%) underwent AS, 33 (26.8%) underwent PN, and 53 (43%) underwent RN. The mean age was 83 years (range, 80-92). AS patients had a higher mean age (84 years) than PN patients (81.9 years), but not with RN patients (83 years) (p=0.008). At a median follow-up of 30.6 months (IQR 9.9-56), 13 (48%), 10 (30.3%), and 29 (54.7%) patients died from any cause in AS, PN, and RN patients respectively. PN patients tended to have a longer median overall survival at 81 months versus 55.8 and 57 months for AS and RN respectively, but this did not reach statistical significance on univariate (p=0.588) or multivariate analysis (p=0.29). On subgroup analysis of cT1a patients, there was also no difference in overall survival among treatment arms on univariate (p=0.654) and multivariate analysis (p=0.47). At 1 year follow-up, there was no difference in creatinine levels between treatment arms (p=0.331). However, mean creatinine clearance was lower in RN patients (35.8 ml/min) compared to AS (50.7 ml/min) and PN (48.1 ml/min) (p=0.024). Conclusions: Active treatment with PN and RN may not provide a survival advantage among octogenarians. Renal function was inferior in RN patients but comparable between AS and PN patients at 1 year follow-up.

scholarly journals Unicentric Castleman Disease with High Inflammatory State: Surgical Treatment Is a Potential Cure

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 14-15
Author(s):  
Miaoyan Zhang ◽  
Xinxin Cao ◽  
Dao-Bin Zhou ◽  
Lu Zhang ◽  
Jian Li
Keyword(s):  
Overall Survival ◽  
Lymph Node ◽  
Surgical Treatment ◽  
Disease Progression ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Castleman Disease ◽  
Biological Behavior ◽  
First Line ◽  
Inflammatory State

Objective: Castleman disease (CD) is a group of rare lymphoproliferative disorders which are divided into unicentric CD (UCD) and multicentric CD (MCD) according to the number of lymph node regions involved. In the case of UCD, no or only local compressive symptoms are present with normal biochemistry, and prognosis is great after complete surgical resection. However, we have noticed that a small portion of UCD patients presenting with severe constitutional symptoms accompanied by high inflammatory state might resemble MCD in clinical presentations and biochemical features. Since our current understanding of this group of patients is far from enough, we are here to summarize the characteristics, treatments and outcomes of these high inflammatory patients and compare them with other UCD patients to see whether surgery still serves well as first-line treatment, so as to illuminate the biological behavior of these hyper-inflammatory UCD patients. Method: We retrospectively analyzed 123 cases of UCD diagnosed between Jan 2000 and Dec 2019 in Peking Union Medical College Hospital. The patients with high inflammatory state who met the laboratory and clinical criteria for idiopathic MCD (Blood, 2017) were included in the hyper-inflammatory group (Figure 1). We summarized their clinical characteristics, treatments and outcomes. Response criteria of iMCD defined by Castleman Disease Collaborative Network (CDCN) were cited to evaluate treatment response in symptoms and biochemistry. Kaplan-Meier analysis were used to analyze the progress-free survival (PFS) and overall survival (OS), and comparison was made with other UCD patients through Log-rank test. Result: Among 24 UCD patients with high inflammatory state (19.5%), when compared to others without, constitutional symptoms, organomegaly, fluid retention and complication of paraneoplastic pemphigus (PNP) or bronchiolitis obliterans (BO) were more common. ESR or CRP elevation, anemia, abnormal platelet count, albumin decrease, renal function impairment and IgG increase were also more usually discovered (Table 1). Meanwhile, plasmacytic (PC) histopathology was more frequently seen (45.8% vs 14.1%, P=0.001) (Table 2), but no statistical significance was shown on the lymph node region involved. As for first-line treatments (Figure 1), 18 UCD patients with high inflammatory state (75.0%) underwent complete surgical excision alone; there was no recurrence of lymphadenopathy after surgery, and the inflammation resolved completely except 2 cases of disease progression (both complicated by PNP), achieving a response rate of 88.9%. 2 patients (8.3%) received chemotherapy together with surgery, and all disease completely resolved. Among the 3 patients (12.5%) treated only with chemotherapy, 1 experienced symptomatic and biochemical progression of disease. Finally, there was one patient (4.17%), after a watch-and-wait period, experienced progression in symptoms. In contrast, disease progression was not seen in UCD without high inflammatory state. There was no statistical difference between median follow-up time of the two groups. UCD patients without high inflammatory state have a better PFS curve [P&lt;0.001, HR=0.005 (95%CI: 0.001-0.043)], but median PFS was not reached in either group of patients (Figure 2). The overall survival was not significantly different between the two groups [P=0.225, HR=4.722 (95%CI: 0.123-181)]. Conclusion: UCD patients with high inflammatory state are not uncommon. Although they resemble MCD with more PC histopathology, more severe symptoms and abnormal lab results, the good response to surgical treatment suggested that patients with high inflammatory state still shared common biological behavior with other UCD. However, recurrence of symptoms and progression of inflammation might still happen in patients with PNP or unresectable disease, so treatment options other than surgery should be considered in these patients. Figure Disclosures No relevant conflicts of interest to declare.

Clinical Relevance of Circulating Myeloperoxidase (MPO) in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1073-1073 ◽  
Author(s):  
Iman Jilani ◽  
Ted Vincenti ◽  
Homan Faraji ◽  
Francis J. Giles ◽  
Elihu Estey ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cox Regression ◽  
Statistical Significance ◽  
White Cell Count ◽  
Response To Therapy ◽  
Polymorphonuclear Neutrophils ◽  
Leukemic Cells ◽  
Cox Regression Analysis ◽  
Control Subjects ◽  
Cellular Expression

Abstract MPO, a hemoprotein expressed in polymorphonuclear neutrophils and their precursors, is an important component of the antimicrobial activity of phagocytes and is associated with inflammatory response. Cellular expression levels of MPO, assessed by cytochemical staining, are used extensively for the diagnosis and subtyping of various leukemias. However, the association of circulating (plasma or serum) MPO levels with hematologic values and clinical outcomes of AML and MDS has not been reported. We investigated whether MPO, presumably released from leukemic cells, can be detected in the plasma of patients with AML and MDS. We further assessed the association of plasma MPO levels with hematologic characteristics and outcomes. 144 patients with AML, 28 patients with MDS, and 100 control subjects were included in the analysis. Patients with AML (median 19.3, range 1.0–9514.7 ng/mL) and MDS (median 13.6, range 1.0–3021.9 ng/mL) had significantly higher plasma MPO levels than control subjects (median, 4.9; range, 3.5–20.6 ng/mL). Because MPO levels and overall survival did not differ significantly between AML and MDS patients, the 2 groups were considered together in subsequent analyses. MPO levels were inversely correlated with overall survival (Cox regression analysis, P&lt;0.001). In the multivariate model, the inverse correlation between MPO levels and survival was independent of cytogenetics, performance status, anticident hematologic disease (AHD), age, and diagnosis (AML vs MDS). Response to therapy in AML and MDS patients was not associated with plasma MPO levels. However, responders with high MPO levels had shorter remission duration (CRD), although this difference did not reach statistical significance (P = 0.07). As expected, MPO levels correlated with the level of differentiation of leukemic cells (FAB subclassification): patients with M0 and M6 had lower MPO levels than those with M2, M3, or M4 (P = 0.0001). MPO levels also correlated positively with white cell count, beta2-microglobulin, monocyte, LDH, BUN, and creatinine levels. These data indicate that plasma MPO levels are elevated in AML and MDS and may be useful as a prognostic factor. Our findings also raise the question of how the proinflammatory properties of MPO might affect the clinical course of these diseases.

Imatinib mesylate (STI571) therapy for Philadelphia chromosome–positive chronic myelogenous leukemia in blast phase

Blood ◽  
2002 ◽  
Vol 99 (10) ◽  
pp. 3547-3553 ◽  
Author(s):  
Hagop M. Kantarjian ◽  
Jorge Cortes ◽  
Susan O'Brien ◽  
Francis J. Giles ◽  
Maher Albitar ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Chronic Myelogenous Leukemia ◽  
Response Rate ◽  
Philadelphia Chromosome ◽  
Response To Therapy ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
Blast Phase ◽  
Molecular Abnormalities ◽  
Philadelphia Chromosome Positive

Molecular abnormalities caused by the hybrid Bcr-Abl gene are causally associated with the development and progression of Philadelphia chromosome–positive (Ph+) chronic myelogenous leukemia (CML). Imatinib mesylate (STI571), a specific Bcr-Abl tyrosine-kinase signal-transduction inhibitor, has shown encouraging activity in phase I and II studies of CML. Here, we describe the use of imatinib mesylate to treat 75 patients in blast-phase CML (median age, 53 years; 65 with nonlymphoid and 10 with lymphoid blasts), and compare the results with those of a historical control group treated with standard cytarabine-based therapy. Imatinib mesylate was given as oral doses at 300 to 1000 mg per day and was the first salvage therapy for 47 patients. The objective response rate was 52% (39 of 75 patients: 16 had complete and 3 had partial hematologic response; 12 had hematologic improvement; 7 returned to second chronic phase; and 1 had a complete response in extramedullary blastic disease). Response rates were not different between nonlymphoid and lymphoid groups. The cytogenetic response rate was 16% (12 patients: 5 complete, 3 partial [Ph+ below 35%], and 4 minor [Ph+, 34% to 90%]). The estimated median overall survival was 6.5 months; the estimated 1-year survival was 22%. Response to therapy (landmark analysis at 8 weeks) was associated with survival prolongation. Compared with standard cytarabine combinations, imatinib mesylate therapy was less toxic and produced a higher response rate (55% versus 29%, P = .001), longer median survival (7 versus 4 months, P = .04), and lower 4-week induction mortality (4% versus 15%, P = .07). Imatinib mesylate is currently being tested in combination with other drugs to improve the prognosis for blast-phase CML.

Temozolomide Alone or Combined with Capecitabine for the Treatment of Metastatic Neuroendocrine Neoplasia: a “Real World” data analysis

2020 ◽  
Author(s):  
Alberto Bongiovanni ◽  
Chiara Liverani ◽  
Flavia Foca ◽  
Valentina Fausti ◽  
Giandomenico Di Menna ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Real World ◽  
Cox Regression ◽  
Propensity Score Analysis ◽  
Objective Response ◽  
Response To Therapy ◽  
Real World Data ◽  
World Data ◽  
Risk Of Death ◽  
Neuroendocrine Neoplasia

Background: Neuroendocrine neoplasia (NEN) are a rare group of tumors with different prognosis and response to therapy. Their heterogeneity is dependent on the site of origin, morphology and Ki67. Temozolomide (TEM) appears to be active in metastatic NENs (mNENs) but there is limited evidence about its efficacy in gastrointestinal NENs. We analyzed “real-world” data on the use of TEM alone or in association with capecitabine (CAPTEM) in patients with mNENs. Patients and Methods: One hundred consecutive patients with advanced NENs treated with TEM or CAPTEM between 2009 and 2019 were included. A pre-treatment tumor growth rate (TGR0) was calculated. Overall survival (OS), progression-free survival (PFS), tolerance, objective response rate (ORR) and disease control rate (DCR) were analyzed. A propensity score analysis and inverse probability of treatment weights for Cox-regression models were used. Results: TEM-based therapy was administered to 95 patients (26.3% CAPTEM and 83.7% TEM) with a median age of 59 years (range 26-85) years. ECOG performance status was 0-2. Carcinoid syndrome was reported in 12 (12.6%) patients. Twenty (21.1%) patients with grade (G) 3 neuroendocrine carcinoma (NEC) and 9 (9.4%) with G3 neuroendocrine tumors (NET) were included in the analysis. Median PFS of the entire group was 10.4 months (95% confidence interval (CI):6.0-11.5). In multivariate analysis, a higher risk of progression was observed for NEC G3 patients (hazard ratio (HR) 2.70, 95%CI:1.25-5.84) and for a TGR ≥19.55 (HR:2.53, 95%CI:1.45-4.40). Median OS was 23.4 months (95%CI: 17.0-29.0) and was similar in both treatment groups (23.9 vs. 20.5 months for TEM and CAPTEM, respectively, p =0.585). In multivariate analysis, TGR ≥19.55 was associated with a higher risk of death (HR:2.18, 95%CI:1.16-4.11) than TGR<19.55, as was NEC G3 (HR: 2.42, 95%CI:1.04-5.59) with respect to NETs. No differences in terms of mPFS or mOS were seen in relation to the primary site of disease. In the 86 patients evaluable for response, ORR was 44.1% and the DCR was 70.9%. Mild adverse events (grade I-II) included anemia, neutropenia and headache. Rare cases of grade 3 neutropenia and thrombocytopenia were recorded. Conclusions: TEM-based regimens are associated with a high DCR and a relatively tolerable toxicity profile in NEN of pancreatic, intestinal and lung origin. Further investigation of these specific NETs is warranted in prospective clinical trials.

Progression-Free Survival in Children With Optic Pathway Tumors: Dependence on Age and the Quality of the Response to Chemotherapy—Results of the First French Prospective Study for the French Society of Pediatric Oncology

2003 ◽  
Vol 21 (24) ◽  
pp. 4572-4578 ◽  
Author(s):  
Véronique Laithier ◽  
Jacques Grill ◽  
Marie-Cécile Le Deley ◽  
Marie-Madeleine Ruchoux ◽  
Dominique Couanet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Disease Progression ◽  
Objective Response ◽  
Progression Free Survival ◽  
Optic Pathway ◽  
Free Survival ◽  
Factors Associated ◽  
Response To Chemotherapy ◽  
Risk Of Disease

Purpose: To evaluate a strategy aimed at avoiding radiotherapy during first-line treatment of children with progressive optic pathway tumors (OPT), by exclusively administering multiagent chemotherapy during 16 months. Patients and Methods: Between 1990 and 1998, 85 children with progressive OPT were enrolled onto this multicenter nationwide trial. Chemotherapy alternating procarbazine plus carboplatin, etoposide plus cisplatin, and vincristine plus cyclophosphamide was given every 3 weeks. At the time of relapse or progression, second-line chemotherapy was authorized before recourse to radiotherapy. Results: Objective response rate (partial response [PR] + complete response [CR]) to chemotherapy was 42%. Five-year progression-free survival (PFS) and overall survival rates were 34% and 89%, respectively. The 5-year radiotherapy-free survival rate was 61%. In the multivariate analysis of the 85 patients that entered onto the study, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .047) and absence of neurofibromatosis type 1 (P = .035). In the multivariate analysis of the 74 patients that remained on study after the first cycle of chemotherapy, factors associated with the risk of disease progression were age younger than 1 year at diagnosis (P = .0053) and no objective response to chemotherapy (P = .0029). Three-year PFS was 44% in infants ≤ 1 year versus 66% in children older than 1 year. Three-year PFS was 53% in the absence of an objective response to chemotherapy versus 68% after a PR or CR. Conclusion: A significant proportion of children with OPT can avoid radiotherapy after prolonged chemotherapy. Deferring irradiation with chemotherapy protocols did not compromise overall survival of the entire population or visual function.

Post-Treatment FDG-Avid Splenic Lesions in DLBCL: Clinical and Radiographic Characteristics for Risk Assessment

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5358-5358
Author(s):  
Boaz Nachmias ◽  
Geremy Godefroy ◽  
Chezi Ganzel ◽  
Neta Goldschmidt ◽  
Eyal Rozenbach ◽  
...  
Keyword(s):  
False Positive ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Statistical Significance ◽  
B Cell Lymphoma ◽  
Response To Therapy ◽  
Study Cohort ◽  
True Positive ◽  
Discriminative Ability ◽  
Pet Ct

PET-CT has been widely incorporated in the treatment of diffuse large B cell lymphoma (DLBCL) and Hodgkin's lymphoma (HD) both for staging at diagnosis and for evaluation of response to therapy. Residual FDG-avid lesions at the end of treatment (EOT) are often due to infectious or inflammatory process and not due to refractory lymphoma. Nonetheless, such lesions prompt diagnostic and therapeutic interventions. In the present study, we evaluate clinical and radiological characteristics of patients with EOT FDG-avid splenic lesions in hope to provide better tools to discern false from true lesions. The study cohort included patients with DLBCL or HD who had residual EOT FDG-avid splenic lesion with no evidence of active disease in other sites. Patients were concluded as false positive or true positive according to pathological results or long-term follow-up. Clinical and PET-CT characteristics were compared between the two groups. Our cohort included 9 patients with DLBCL and 2 with HD, of which 6 patients were determined to have false positive lesions and 5 true positive. Comparing metabolic volume (MV) ratio between EOT to interim (EOT/interim) tests showed a marked difference between false positive and true positive lesions (0.5 vs 3.6, p= 0.02). Notably, comparing EOT to diagnosis (EOT/Dx) MV showed a similar trend that did not reach statistical significance, highlighting MV EOT/interim ratio as a parameter with higher discriminative ability. EOT SUVmax was also significantly different between false positive and true positive (7 vs. 19, p=0.02). A MV EOT/interim ratio >3 has a 75% sensitivity and 100% specificity for the true positive group. Other clinical and PET-CT characteristics were not found to statistically differ between the groups. To date, this is the first report showing predictive ability of PET-CT characteristics to discern true from false positive residual FDG-avid splenic lesions. Our cohort is of small numbers, nonetheless, EOT/interim MV shows a clear opposite ratio with a decrease in the false positive compared to an increase in the true positive groups. We suggest EOT/interim MV ratio might be a tool to identify patients at low risk of refractory disease allowing non-invasive surveillance. Further larger studies will be needed to validate the role MV EOT/interim ratio as a tool to discriminate residual disease from false positive FDG-avid lesions. Disclosures No relevant conflicts of interest to declare.

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