Primary Parotid MALT Lymphoma: Clinical Characteristics and Treatment – a Single Institution Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1580-1580
Author(s):  
Jason M. Jones ◽  
Thomas M. Habermann ◽  
Kay M. Ristow ◽  
Paul Kurtin ◽  
Ellen McPhail ◽  
...  
Keyword(s):  
Overall Survival ◽  
Malt Lymphoma ◽  
Mayo Clinic ◽  
Clinical Characteristics ◽  
Conflicts Of Interest ◽  
Local Treatment ◽  
Stage I ◽  
Single Institution ◽  
History Of ◽  
The Impact

Abstract Abstract 1580 Background: Extranodal Marginal Zone Lymphomas of Mucosa Associated Lymphoid Tissue (MALT) account for approximately 5% of all non-Hodgkin Lymphoma cases. Specific MALT lymphomas are characterized by distinct clinical features, treatment strategies, and outcome, depending on site of the disease. While previous reports have described clinical course and treatment of gastric and pulmonary MALT lymphomas, a paucity of data exist describing primary parotid MALT lymphoma. This is a single institution experience. Methods: Patients with primary parotid MALT lymphoma were identified from the Mayo Clinic Lymphoma Database since 1986. This database includes all consenting patients with lymphoma seen at Mayo Clinic Rochester. Clinical characteristics, treatment, and outcomes were collected. Pathology was reviewed by a lymphoma pathologist; WHO criteria were used for diagnosis. PFS and OS were assessed using the Kaplan-Meier method and Cox proportional hazard model was used to asses the impact of variables on PFS and OS. Results: Seventy-six consecutive patients with primary parotid MALT lymphoma were evaluated and treated at Mayo Clinic from 1986 to 2010. The median age at diagnosis was 60 years (18–90). 58 (76%) were female. 42 (55.3%) patients had a history of Sjögren's Disease and 51 (67.1%) had a history of autoimmune disorders. 52 (68.4%), 4 (5.3%), and18 (23.7%) had stage I, II, and IV disease, respectively. 2 cases did not have complete staging information. 6 (7.8%) and 2 (2.6 %) had bone marrow and lung involvement, respectively. No patients had GI tract, liver, or CNS involvement. Median estimated OS (overall survival) was 18.3 years and median PFS (progression free survival) was 7.9 years. ALC<0.96 (p=0.0162) were associated with shorter survival. Age, ECOG performance score, stage, LDH, and history of Sjögren's disease were not prognostic for overall survival. The treatment approach and PFS are outlined in the table. For stage I disease, outcomes were excellent with local therapy. The median estimated PFS was 7.9 years with 72% of patients undergoing surgery surviving at 8 years. Patients receiving radiotherapy had an estimated median PFS of 15.7 years and median OS of 18.3 years. In contrast, patients being observed had a median PFS of 5.5 years. The use of systemic therapy with chemotherapy, immunotherapy or in combination was associated with a median PFS of 7.4 years. Summary: Primary parotid MALT lymphoma is strongly associated with Sjögren's disease. This lymphoma is usually limited to the parotid and associated with a favorable prognosis. For limited disease, local treatment with radiation or surgery appears to be an effective treatment options. For extensive disease, both immunotherapy and chemotherapy are efficacious treatments. Further prospective studies and long-term follow up are needed to determine the optimal treatment approaches and efficacy of chemotherapy/immunotherapy regimens. Disclosures: No relevant conflicts of interest to declare.

Primary Pulmonary MALT Lymphoma: Clinical Characteristics and Treatment Outcomes – Single Institution Experience

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4168-4168
Author(s):  
Grzegorz S. Nowakowski ◽  
Kay Ristow ◽  
Paul Kurtin ◽  
Mark S Allen ◽  
Ivana N Micallef ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Outcomes ◽  
Malt Lymphoma ◽  
Mayo Clinic ◽  
Pulmonary Lesion ◽  
Treatment Modalities ◽  
Gastric Malt Lymphoma ◽  
Single Institution ◽  
Pulmonary Malt Lymphoma ◽  
The Impact

Abstract Abstract 4168 Background: Primary Pulmonary MALT lymphoma represents 15–20% of Extranodal Marginal Zone Lymphomas of Mucosa Associated Lymphoid Tissue (MALT). In contrast to the more common gastric MALT lymphoma, natural history, prognosis and treatment outcomes for primary pulmonary MALT lymphoma are not well defined. Herein, we report a single institution experience. Methods: Consecutive patients with primary pulmonary MALT lymphoma registered in the Mayo Clinic Lymphoma Database, which includes all consenting patients with lymphoma seen at Mayo Clinic Rochester, were reviewed for clinical features, treatment outcome progression free survival (PFS) and overall survival (OS). The pathology for all patients was centrally reviewed by hematopathologist and the diagnoses were based on WHO lymphoma classification criteria. PFS and OS were assessed using the Kaplan–Meier method and the Cox proportional hazard model was used to assess the impact of variables on PFS and OS. Results: Between December 1986 and June of 2009, ninety-seven patients with primary pulmonary MALT lymphoma were enrolled. The median age at diagnosis was 63 years (range 31–87). There were 43 (44%) males. The initial presentation was a unilateral pulmonary lesion (n=47, 48%), bilateral pulmonary lesions (n=41, 42%), and pulmonary lesion with intrathoracic lymphadenopathy (n= 4, 4%). Bone marrow involvement and presence of B symptoms were 4, 4% and 5, 5%, respectively. International Prognostic Index (IPI) was 0–1, 2–3 and 4–5 in 69, 25 and 1 patient(s) respectively. The median follow-up was 10.4 years. The estimated median OS was 13. 6 years and the median PFS was 5.5 years (Figure). In a multivariate analysis, age >60 (p=0.02) and ECOG PS>2 (p=0.01) were associated with shortened survival. The IPI and age adjusted IPI were not predictive of overall survival. The treatment outcomes for the most common treatment modalities are summarized in the Table below. The median PFS of the 38% of patients who had a complete surgical resection was excellent at 11.2 years; whereas for observed patients with residual disease after biopsy was 3.2 years. Only 8 patients received single agent rituximan with relatively low response rate. Summary: The prognosis of primary pulmonary MALT lymphoma is favorable, with a median survival of over 13 years. In patients with resectable disease, surgery alone is associated with excellent disease control. Further prospective studies are needed to define the optimal treatment of primary pulmonary MALT lymphoma. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Clinical Characteristics, Immunophenotype and Outcomes of Blastic Plasmacytoid Dendritic Cell Neoplasms in a Peruvian Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 42-43
Author(s):  
Daniela Dueñas ◽  
Elizabeth Cervantes ◽  
Daniel J Enriquez ◽  
Claudio Flores ◽  
Carlos Barrionuevo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Dendritic Cell ◽  
Clinical Characteristics ◽  
Conflicts Of Interest ◽  
Plasmacytoid Dendritic Cell ◽  
Age At Diagnosis ◽  
Bone Marrow Infiltration ◽  
Maturation Stage ◽  
Female Predominance ◽  
The Impact

Background:Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and fatal myeloid malignancy characterized by clonal proliferation of immature plasmacytoid dendritic cells. BDCN has been frequently described in men and age above 60 years, and usually involves the skin and bone marrow. Immunophenotyping is based on CD123+, CD4+ and CD56+ expression and is necessary rule out other myeloid malignancies. Objective: We aimed to describe the clinical characteristics and immunophenotype of BPDCN cases diagnosed at two tertiary Peruvian cancer institutions between 2018-2019. Methods: We retrospectively reviewed medical records of patients diagnosed of BPDCN at two tertiary Peruvian cancer centers (Instituto Nacional de Enfermedades Neoplasicas and Oncosalud-AUNA, Lima-Peru) between 2008 and 2019. Clinical characteristics, treatments, outcomes and immunophenotype by pathology or flow cytometry review, were collected. Patients were classified according to their maturation stage using CD34 and CD117 expression into three subgroups: Immature-Intermediate blastic (IIB-BPDCN; partial expression of CD117 and absence or minimal expression of CD34), mature (M-BPDCN; absence of CD34 and CD117) and unknown(U-BPDCN). Overall survival (OS) and event-free survival (EFS) curves were estimated using the Kaplan-Meier method and compared with the Log-rank test to determine the impact of immunophenotype. Results: Thirty-eight cases were included during the study period. The median age at diagnosis was 38 years (7-82), only six (16%) were older than 65 years, and a notorious female predominance (F/M ratio: 1.7:1) was observed. Twenty-four cases had CD34/117 expression available and were classified according to the maturation stage in IIB-BPDCN (13) and M-BPDCN(11), additionally 14 cases had unknown stage (U-BPDCN). Table 1 summarizes clinical characteristics, treatment and outcomes according to their immunophenotype. Bone marrow infiltration was more frequent in immature phenotypes (92% IIB-BPDCN vs 73% M-BPDCN, p=0.001), as well as skin infiltration was more common in mature phenotype (72% vs 31%, p=0.008). CNS infiltration at diagnosis was 15% and 55% in IIB-BPDCN and M-BPDCN, respectively. Sixteen patients received treatment based on ALL-like protocols, 8 AML-like, 5 CHOP-like and 9 patients only palliative care. At 5 years median follow-up, median EFS and OS was 12 and 16 months, respectively. IIB-BPDCN had the lowest survival (4 months EFS and 6 months OS). Conclusions: We describe a Peruvian cohort of BPDCN patients with younger age at diagnosis and female predominance than reported previously by other series, however further studies in Latino population are required to confirm these results. Immature phenotypes based on CD34 and CD117 expression were associated with high rate of bone marrow infiltration and fatal outcomes. New successful target therapies must be warranted for this rare and fatal condition. Disclosures No relevant conflicts of interest to declare.

Endometrial Cancer Lymphadenectomy Trial (ECLAT) (pelvic and para-aortic lymphadenectomy in patients with stage I or II endometrial cancer with high risk of recurrence; AGO-OP.6)

2021 ◽  
Vol 31 (7) ◽  
pp. 1075-1079
Author(s):  
Günter Emons ◽  
Jae-Weon Kim ◽  
Karin Weide ◽  
Nikolaus de Gregorio ◽  
Pauline Wimberger ◽  
...  
Keyword(s):  
Overall Survival ◽  
Endometrial Cancer ◽  
High Risk ◽  
Controlled Trial ◽  
Left Renal Vein ◽  
Stage I ◽  
Open Label ◽  
Risk Of Recurrence ◽  
Gynecology And Obstetrics ◽  
The Impact

BackgroundThe impact of comprehensive pelvic and para-aortic lymphadenectomy on survival in patients with stage I or II endometrial cancer with a high risk of recurrence is not reliably documented. The side effects of this procedure, including lymphedema and lymph cysts, are evident.Primary ObjectiveEvaluation of the effect of comprehensive pelvic and para-aortic lymphadenectomy in the absence of bulky nodes on 5 year overall survival of patients with endometrial cancer (International Federation of Gynecology and Obstetrics (FIGO) stages I and II) and a high risk of recurrence.Study HypothesisComprehensive pelvic and para-aortic lymphadenectomy will increase 5 year overall survival from 75% (no lymphadenectomy) to 83%, corresponding to a hazard ratio of 0.65.Trial DesignOpen label, randomized, controlled trial. In arm A, a total hysterectomy plus bilateral salpingo-oophorectomy is performed. In arm B, in addition, a systematic pelvic and para-aortic lymphadenectomy up to the level of the left renal vein is performed. For all patients, vaginal brachytherapy and adjuvant chemotherapy (carboplatin/paclitaxel) are recommended.Major Inclusion CriteriaPatients with histologically confirmed endometrial cancer stages pT1b–pT2, all histological subtypes, and pT1a endometrioid G3, serous, clear cell, or carcinosarcomas can be included when bulky nodes are absent. When hysterectomy has already been performed (eg, for presumed low risk endometrial cancer), study participation is also possible.Exclusion CriteriaPatients with pT1a, G1 or 2 of type 1 histology or uterine sarcomas (except for carcinosarcomas), endometrial cancers of FIGO stage III or IV (except for microscopic lymph node metastases) or visual extrauterine disease.Primary EndpointOverall survival calculated from the date of randomization until death.Sample Size640 patients will be enrolled in the study.Estimated Dates for Completing Accrual and Presenting ResultsAt present, 252 patients have been recruited. Based on this, accrual should be completed in 2025. Results should be presented in 2031.Trial RegistrationNCT03438474.

Increased Expression of Macrophage Migration Inhibitory Factor (MIF) Receptor CD74 Is Associated with Inferior Outcome in Younger Patients (Pts) with Cytogenetically Normal Acute Myeloid Leukemia (CN-AML): a Cancer and Leukemia Group B (CALGB) Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1616-1616 ◽  
Author(s):  
Eyal C. Attar ◽  
Kati Maharry ◽  
Krzysztof Mrózek ◽  
Michael D. Radmacher ◽  
Susan P. Whitman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Advanced Pancreatic Cancer ◽  
Disease Free Survival ◽  
Prognostic Impact ◽  
Free Survival ◽  
Expression Levels ◽  
The Impact ◽  
Disease Free

Abstract Abstract 1616 Poster Board I-642 CD74 is a type II integral membrane protein receptor that binds its ligand MIF to induce phosphorylation of the extracellular signal-regulated kinase-1/2 (ERK-1/2) and drive cellular proliferation via nuclear factor-kappa B (NF-kB) activation. CD74 expression has been identified in human solid tumors, and its expression is associated with adverse prognosis in advanced pancreatic cancer. As CD74 is expressed and NF-kB constitutively activated in myeloblasts, we hypothesized that CD74 expression might also be associated with adverse outcome in AML. To investigate the prognostic impact of CD74 expression in the context of other predictive molecular markers in CN-AML, we assessed CD74 expression levels by Affymetrix HG-U133 Plus 2.0 microarray in 102 younger [<60 years (y)] adults with primary CN-AML, treated on the front-line CALGB 19808 trial with an induction regimen containing daunorubicin, cytarabine, etoposide and, in some cases, the inhibitor of multidrug resistance valspodar, and consolidation with autologous stem cell transplantation. Microarray data were analyzed using the Robust Multichip Average method, making use of a GeneAnnot chip definition file, which resulted in a single probe-set measurement for CD74. At diagnosis, CD74 expression, when assessed as a continuous variable, was significantly associated only with extramedullary disease involvement (P=.006) among clinical features, and with none of the molecular prognostic variables tested, including NPM1, WT1, CEBPA, FLT3 (FLT3-ITD and FLT3-TKD) mutations, MLL partial tandem duplication, or differential BAALC and ERG expression levels. Although CD74 expression levels were not associated with achievement of complete remission (CR; 83% vs 81%), higher levels of CD74 were associated with shorter disease-free survival [DFS; P=.046, hazard ratio (HR) 1.85, 95% confidence interval (CI) 1.12-3.08] and with shorter overall survival (OS; P=.02, HR 1.32, CI 1.04-1.67). In multivariable analyses, higher CD74 expression was independently associated with shorter DFS (P=.045, HR 1.98, CI 1.16-3.40), after adjusting for WT1 mutations (P<.001) and FLT3-TKD (P=.04), and shorter OS (P=.01, HR 1.58, CI 1.11-2.25) after adjusting for FLT3-TKD (P=.02), WT1 mutations (P=.007), BAALC expression levels (P=.02), white blood counts (P=.007), and extramedullary involvement (P=.04). As quartiles 2-4 had similar expression levels distinct from the lowest quartile, to display the impact of CD74 expression levels on clinical outcome only, pts were dichotomized into low (the lowest quartile) and high (the top three quartiles) CD74 expressers. The Kaplan-Meier curves for DFS and OS (Figures 1 and 2) are shown below. In conclusion, our study identifies elevated CD74 expression as associated with adverse prognosis in younger CN-AML pts. Since we previously reported that higher CD74 expression was favorably associated with achievement of CR in AML patients receiving chemotherapy plus bortezomib, an inhibitor of the proteasome and NF-kB (Attar et al., Clin Cancer Res, 2008;14:1446-54), it is possible that in future studies elevated CD74 levels can be used not only for prognostication, but also to stratify CN-AML pts to study of bortezomib-containing chemotherapy regimens. Figure 1 Disease free survival Figure 1. Disease free survival Figure 2 Overall survival Figure 2. Overall survival Disclosures No relevant conflicts of interest to declare.

TIMP-1 and TIMP-2 Levels Are Directly Correlated with Neoangiogenesis and Are Prognostic Factors in Multiple Myeloma Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4866-4866
Author(s):  
Luciana Correa Oliveira de Oliveira ◽  
Juliana Alves Uzuelli ◽  
Ana Paula Alencar de Lima Lange ◽  
Barbara Amelia Aparecida Santana-Lemos ◽  
Marcia Sueli Baggio ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Bone Disease ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Newly Diagnosed ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 4866 Background Multiple myeloma (MM) is an incurable malignant disease, characterized by increased angiogenesis in the bone marrow (BM) microenvironment and aberrant BM metabolism. Matrix metalloproteinases (MMP) are a family of zinc-dependent endopeptidases implicated in tumour progression, invasion, metastasis and angiogenesis, via proteolytic degradation of extracellular matrix. MMPs are inhibited by tissue inhibitors of metalloproteinase (TIMP). Although recent studies have implicated MMP 9 in MM bone disease, little is known about the role of the TIMPs. Objectives a) to compare levels of sRANKL, OPG, MMP-2, MMP-9, TIMP-1, TIMP-2, VEGF, bFGF, microvessel density (MVD) between newly diagnosed MM patients and healthy controls; b) to determine the association of these molecules with disease progression, bone disease and neoangiogenesis and c) to evaluate the impact of these variables on survival. Patients and Methods As of July 2009 38 newly diagnosed and untreated multiple myeloma patients were enrolled in the study. The median age was 61years-old (range 39-91) with 24 (63%) males. Patients were diagnosed and categorized according The International Myeloma Working Group criteria and ISS, respectively. Bone involvement was graded according to standard X-ray: patients with no lesions, or with one/ two bones involved or diffuse osteoporosis were classified as low score, whereas patients with lesions in more than two bones or presence of bone fracture were classified as high score. MMP-2 and MMP-9 were determined by PAGE gelatin zymography from plasma as previously described. MMP-9, TIMP-1 and TIMP-2, OPG and sRANKL concentrations were measured by ELISA. The levels of VEGF, bFGF were obtained using cytometric bead array. Ten healthy volunteers were used as controls. Bone marrow MVD measured in hotspots was evaluated in 26 out of 38 patients at diagnosis and 15 patients with Hodgkin Lymphoma stage IA and IIA (used as controls) by staining immunohistochemically for CD34. Comparisons among groups were analyzed by ANOVA and the correlation by the Spearman's correlation coefficient. Cox regression were performed for overall survival (OS) analysis. Results Patients with MM had elevated TIMP-1, TIMP-2 and OPG values compared with controls. No significant difference was found between plasma sRANKL, pro-MMP2, pro-MMP9 and MMP-9 levels. We found that plasma TIMP-1 levels correlated positively with bFGF, VEGF, MVD, beta-2 microglobulin (B2M) and OPG (r: 0.514, p=0,001, r: 0.350, p=0,031; r: 0.610, p<0.0001; r: 0.760, p<0.0001 and r: 0.701, p<0.0001, respectively) and TIMP-2 levels with bFGF, DMV, B2M and OPG (r: 0.512, p=0.002; r: 0.595, p<0.0001; r: 0.587, p<0.0001 and r: 0.552, p<0.0001, respectively). TIMP-1 and TIMP-2 levels correlated with the ISS stage (p<0.0001, p=0.006, respectively). The only variables that correlated with clinical bone disease staging were hemoglobin, B2M and albumin levels, whereas TIMP-1, TIMP-2, bFGF, VEGF and OPG correlated with DMV. On the univariate analyses, age, gender, proMMP2, TIMP-1, TIMP-2, creatinine, B2M and MVD were significantly associated with overall survival. In Cox regression model, TIMP-1, TIMP-2 and B2M levels remained to be significantly associated with OS. In conclusion, our results suggest that TIMP-1 and TIMP-2 levels are strongly associated with neoangiogenesis and are independent prognostic factors in MM. Disclosures No relevant conflicts of interest to declare.

Outcome of Adults with Acute Lymphoblastic Leukemia Treated with a Pediatric-Inspired Therapy: A Single Institution Experience

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4337-4337
Author(s):  
Guillermo J. Ruiz-Delgado ◽  
Julio Macias-Gallardo ◽  
Julia Lutz-Presno ◽  
Maryel Montes-Montiel ◽  
Guillermo J. Ruiz-Arg\)elles
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Single Institution ◽  
B Cell Malignancies ◽  
Secondary Diabetes ◽  
Free Survival ◽  
Results Of Treatment ◽  
Better Than

Abstract Abstract 4337 The results of treatment of adults with ALL remain unsatisfactory. Pediatric-inspired treatments seem to be related with better outcomes. Eighty adult ALL patients were prospectively treated in a single institution in a 16-year period with a schedule based on the St. Jude's TOTAL XI pediatric protocol employing vincristine, prednisone, asparaginase, daunorubicin, etoposide, cytarabine, methotrexate, mercaptopurine and triple intratecal therapy. Median age was 31 years (range 18 – 86); 92% were B-cell malignancies and 14% were Ph1 (+). Ten patients did not complete the first course of chemotherapy and 4 exited early. 44 of 66 patents (67%) achieved a complete remission; relapses presented in 57%. The median probability of overall survival (OS) was 28 months, whereas the 144-month OS was 27%. The median probability of leukemia-free survival (LFS) was 28 months, and the 144-month LFS 35%. Ph1 (+) patients did worse than Ph1-negative and T-cell leukemias did better than B-cell ones. Concerning toxicity, eight patients had toxic deaths (12%), two developed acute pancreatitis and one secondary diabetes. This pediatric-inspired therapy rendered better results than those obtained in similar socioeconomic circumstances using adult-oriented treatments; tolerance was acceptable and costs were low since it employs affordable drugs and can be delivered as outpatients. Disclosures: No relevant conflicts of interest to declare.

Statins Use Improves the Clinical Outcomes of Salvage Therapy in Relapsed/Refractory CLL

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3931-3931
Author(s):  
Long Xuan Trinh ◽  
Young Kwang Chae ◽  
Preetesh Jain ◽  
Ohad Benjamini ◽  
Xuemei Wang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Elderly Patients ◽  
Clinical Outcomes ◽  
Salvage Therapy ◽  
Older Patients ◽  
Conflicts Of Interest ◽  
Young Patients ◽  
The Other ◽  
Concurrent Use ◽  
The Impact

Abstract Abstract 3931 Introduction - Statins are a class of drugs used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase. In addition, statins possess anti-inflammatory, immunomodulatory, antioxidant, and cell growth inhibitory properties. In B- CLL cells, statins induce in-vitro apoptosis (Daphne Chapman-Shimshon et-al), suggesting that statins might possess properties. We noticed a high prevalence of dyslipidemia in patients with chronic lymphocytic leukemia (CLL). However the impact of dyslipidemia and its modulation by statins on clinical outcomes of patients with CLL remains unclear. Therefore, we conducted a retrospective analysis to assess the effect of statins in patients with CLL who received salvage (fludarabine, cyclophosphamide and rituximab) FCR chemotherapy. Methods - We analyzed the clinical outcome of relapsed/refractory patients with CLL (n=284) who underwent FCR salvage therapy at our institution between 1999 and 2012. Patients who were uninterruptedly treated with statins at least one month prior to and during salvage therapy (n=35) were assigned to the statins arm, whereas the other arm consisted of 249 patients who were not treated with statins. The Cox proportional hazards regression model was used to assess the association between patient characteristics and progression-free survival (PFS) and overall survival (OS). Actual survival and PFS were estimated using the method of Kaplan-Meier, and OS and PFS were compared among two groups of patients using log-rank test. Results - All pretreatment characteristics of the patients with concurrent use of statins were similar to those who were not treated with statins except for their age. Patients in the statins arm were older: 21 patients (60%) were older than 65 compared to 74 patients of 249 (30%) in the other group (p<0.05). The median OS and PFS of all 284 patients were 3.9 years (95% CI: 3.4–4.5) and 1.74 years (95% CI: 1.6–2.3), respectively. PFS was significantly longer in patients treated with statins. Fifteen of the 35 statin-treated patients (43%) as opposed to only 36 of 249 (14%) in the non-statins group experience no disease progression. Concurrent use of statins significantly prolonged PFS. The median PFS for statin-treated v/s. untreated was 4.6 and 1.7 years, respectively (p<0.05). This significantly improved PFS was consistent in young and elderly patients. In young patients (age < 65) with statins, the median PFS was not reached whereas in patients who were not treated with statins it was 2 years (p<0.05). In older patients (age ≥ 65), PFS was significant longer with concurrent use of statins than without statins; estimated PFS were 2 and 1.6 years, respectively (p<0.05). With the median follow-up of 5 years, the median overall survival was significantly longer in patients treated with statins, with 17 of 35 (49%) patients of the statins group and 59 (24%) of 249 in patients who were not treated with statins alive at the end of study. Concurrent use of statins significantly prolonged OS with an estimated median OS for the two groups of 6.9 years and 3.9 years, respectively (p<0.05). This significantly improved OS was consistent in young and elderly patients. Young patients (age <65) with statins had a significant prolonged survival with an estimated OS of 8.6 years whereas estimated OS in young patients without statins (p<0.05) was only 4 years. In older patients (age ≥65) the median OS was significantly longer with the concurrent use of statins than without statins; estimated OS in the two subgroups were 6.9 and 2.6 years respectively, (p<0.05). Conclusions - In conclusion, concurrent use of statins significantly improved OS, PFS in relapsed/refractory CLL patients treated with salvage FCR therapy. Further studies to determine the role of statins and mechanism of action in patients with CLL are warranted. Disclosures: No relevant conflicts of interest to declare.

ASXL1 Mutations in AML: Molecular Biomarker for Secondary AML?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2343-2343
Author(s):  
Jingmei Hsu ◽  
Anita J. Kumar ◽  
Martin P. Carroll ◽  
Noelle V. Frey ◽  
Nirav N. Shah ◽  
...  
Keyword(s):  
Overall Survival ◽  
De Novo ◽  
Conflicts Of Interest ◽  
Prognostic Significance ◽  
Myeloproliferative Neoplasm ◽  
Molecular Characteristics ◽  
Intermediate Risk ◽  
Kaplan Meier ◽  
The Impact

Abstract Background: Additional sex combs like transcription factor 1 (ASXL1) is a member of the polycomb group protein. ASXL1 mutation has been implicated in myeloid malignancy transformation. It is hypothesized that mutated ASXL1 leads to the loss of polycomb repressive complex 2 (PRC2) mediated gene repression and subsequent transforming events. Recent studies identify ASXL1 mutation as a poor prognostic marker in patients (pts) with de novo acute myeloid leukemia (AML) who present with intermediate–risk cytogenetic lesions (Patel, NEJM 2012; Schnittger, Leukemia2013). To study the impact of ASXL1 mutations in an unselected AML population, we analyzed clinical and molecular characteristics of patients with untreated AML who express ASXL1 mutation at presentation. Methods: Using next generation sequencing, 254 adult patients with AML seen at the Hospital of the University of Pennsylvania were analyzed for mutations, including ASXL1, using a 33-gene hematologic malignancy panel. Clinical characteristics were obtained from retrospective chart review. Kaplan-Meier estimates were used to calculate overall survival (OS) from time of diagnosis. Living patients were censored at date last seen. Results: ASXL1 mutations were detected in 36/254 (14%) AML pts. There were 29 known pathologic mutations, 1 benign, 1 probable pathologic, and 9 variants of unknown clinical significance (VUS). In 6/36 (16.7%) pts, ASXL1 was the sole mutation identified. Of the 30 pts with additional mutations (Figure 1), 6/30 (20%) pts harbored 2 independent ASXL1 mutations. When the 27 patients with pathologic ASCL mutations were analyzed for co-mutations, TET2 (13/27, 48%) was the most frequent ASXL1 co-mutation. FLT3 (0/27, 0%) and NPM1 (1/27, 3.7%) were notable for their absence. Median age of pts at diagnosis was 69 years (range 23-80). Prior myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) was noted in 9/36 (25%) and 11/36 (30.6%) pts, respectively. Four pts (11.1%) had received chemotherapy and/or radiation therapy for a prior non-myeloid neoplasm. Karyotype was normal in 18/36 (50%) pts, and 7 additional pts had intermediate cytogenetic lesions. There were 7 pts (19.4%) with unfavorable cytogenetics (complex karyotype (3 pts), 7q- (3 pts), and 5q- (1 pt)). Four pts (11.1%) had a favorable karyotype, with t(8;21) in 3 pts and t(15;17) in 1 pt. At presentation, median white blood cell count (WBC) was 6.4x103/uL (1.0 x -103). In pts whose AML transformed from prior MPN, median WBC was 50 X103/uL (3.3-140). Standard induction chemotherapy with an anthracycline and cytarabine was given to 17/36 (47%) pts. An additional 3/36 (8.3%) pts underwent induction therapy with clofarabine. Complete remission (CR) was documented in 14/20 (70%) evaluable pts. Of the remaining pts, 11 received a hypomethylating agent, and 5 received other therapies. Thirty-day treatment mortality for all 36 pts and for 27 pts with known ASXL1 pathologic mutation was 13.4% and 18.5% respectively. Kaplan-Meier estimate showed a median overall survival of 349 days (median follow up of 107 days (range 15-1570)). For the 27 pts with a pathologic ASXL1 mutation, the OS was 276 days (Figure 2, median follow up of 145 days (range 18-1570)). Conclusion: ASXL1 mutations in de novo AML with intermediate-risk cytogenetics is associated with poor clinical outcome in cooperative group trials. Strikingly we demonstrate in a single institution, retrospective analysis that 66.7% of pts who present with ASXL1 mutations in the setting of previously untreated AML had documented MDS, MPN and/or prior chemotherapy/radiation. Further studies are necessary to evaluate if ASXL1 mutation has independent prognostic significance in AML or if it is primarily a marker for secondary leukemia. Figure 1: ASXL1 and co-mutations Figure 1:. ASXL1 and co-mutations Figure 2: Overall survival for AML patients with ASXL1 pathologic mutation Figure 2:. Overall survival for AML patients with ASXL1 pathologic mutation Disclosures No relevant conflicts of interest to declare.

An Analysis of CNS2 Patients with AML: Do They Require Additional Intrathecal Therapy? a Report from Children’s Oncology Group Protocols AAML0531 and 03P1 and St Jude Children’s Research Hospital Protocol AML02

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 277-277 ◽  
Author(s):  
Donna Johnston ◽  
Jeffrey E Rubnitz ◽  
Todd A. Alonzo ◽  
Robert B. Gerbing ◽  
Richard Aplenc ◽  
...  
Keyword(s):  
Overall Survival ◽  
Conflicts Of Interest ◽  
White Blood Cells ◽  
Study Entry ◽  
Intrathecal Therapy ◽  
Oncology Group ◽  
Research Hospital ◽  
Cns Disease ◽  
Cns Relapse ◽  
The Impact

Abstract Introduction: Pediatric patients with acute myeloid leukemia (AML) require central nervous system (CNS) directed chemotherapy to minimize CNS relapse. Patients with AML who have CNS disease at diagnosis, defined as >5 white blood cells (WBC) with positive blast in cytospin, require more intensive CNS directed therapy to clear CNS disease and prevent CNS relapse. Those with <5 WBC but with a positive cytospin are designated as CNS2 disease. Those without any blast (negative cytospin) are designated as CNS1. The need for extra CNS therapy for CNS2 patients varies among treatment protocols, and consensus has not been reached as to the best CNS directed therapy for these patients. We studied the impact of intensive vs. standard management of CNS2 patients by comparing patients treated on the two most recent Children’s Oncology Group (COG) trials to those treated on the St Jude Children’s Research Hospital AML02 trial, where COG trials managed those with CNS2 disease more intensively, similar to CNS3, and AML02 treated such patients similar to CNS1. Both trials used a similar MRC-based chemotherapy backbone. This backbone gave intrathecal (IT) cytarabine at the beginning of each cycle of therapy except Capizzi II therapy, and on the AML02 protocol most patients received IT triple therapy. On both backbones, patients with CNS3 disease, and those on COG trials with CNS2 disease, received twice weekly IT cytarabine until the CSF was clear of blasts plus 2 additional treatments with a minimum of 4 IT treatments given. Thus, this analysis is the first comparison of outcome of CNS2 patients examining the variable of additional CNS directed therapy. Methods: Disease characteristics and clinical outcome for children who were CNS2 treated with intensive or standard intrathecal chemotherapy were compared across COG and SJCRH studies and compared to those who were CNS1 or CNS3. Results: Among the 1361 eligible patients enrolled on AAML03P1 and AAML0531 with available data for CNS status, 247 had CNS2 status. Of the 200 eligible patients enrolled on AML02, 47 patients had CNS2 status. On all protocols, patients with CNS2 status had a significantly higher incidence of Inv(16) compared to CNS1 patients (p<0.001 for both protocols). As well, patients with CNS2 status had a higher incidence of M4 FAB classification compared to CNS1 patients (p<0.001 for COG protocols and p=0.002 for AML02). On both protocols, patients who were CNS2 had similar incidence of Inv(16) compared to patients who were CNS3. In contrast, on the COG protocols the incidence of M4 FAB was similar among CNS2 and CNS3 patients, while on the AML02 protocol the incidence of M4 FAB was significantly higher in CNS2 compared to CNS3. The event free survival (EFS) for patients treated on COG protocols showed significant differences according to CNS status, with CNS1 patients having superior EFS compared to CNS2 and CNS3 patients (p=0.005), while on AML02, the EFS for CNS2 patients was significantly higher than CNS3 patients (p=0.04) and higher, but not significantly, than CNS1 patients (p=0.06). The overall survival (OS) for CNS2 patients treated on COG protocols was not significantly different from that of CNS1 and CNS3 patients (p=0.32), while on AML02, the OS was significantly higher for CNS2 patients compared to CNS1 (p=0.05) and CNS3 patients (p=0.02)(Figures 1 and 2). However, for the AML02 protocol, the Cox analysis showed that CNS status was not independently associated with EFS, OS, or cumulative incidence of relapse On the COG protocols there were 101 patients with relapse involving CNS, of which 34 were CNS1, 32 CNS2 and 34 CNS3 with a 5 year CNS refractory/relapse rate of 4%, 13% and 28% respectively (p<0.001). One patient with CNS relapse was unknown for CNS group. Of the 101 patients who relapsed involving CNS: 34% were CNS1, 32% were CNS2, and 34% were CNS3. Conclusions: Patients with AML who have <5 white cells with blasts present in the cerebrospinal fluid at diagnosis may not require extra IT therapy but may be able to be treated in the same fashion as patients with no blasts in the CSF at diagnosis. Additional analyses will assist in determining which, if any, CNS2 patients require extra IT therapy. Figure 1 Figure 1. – Overall Survival From Study Entry for Patients on COG AAML03P1 and AAML0531 Figure 2 Figure 2. – Overall Survival from Study Entry for Patients on SJCRH AML02 Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document