Transfusion Efficacy of Apheresis Platelet Concentrates (APCs) Irradiated in Advance Is Significantly Lower Compared to Products Irradiated within 24 hours Before Transfusion.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3139-3139
Author(s):  
Friedgard Julmy ◽  
Roland A Ammann ◽  
Behrouz Mansouri Taleghani ◽  
Stefano Fontana ◽  
Andreas Hirt ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Storage Time ◽  
Conflicts Of Interest ◽  
Who Grade ◽  
Significant Difference ◽  
Mixed Regression ◽  
Grade 3 ◽  
The Many ◽  
Gamma Irradiated ◽  
The Impact

Abstract Abstract 3139 Poster Board III-76 Background Several guidelines on gamma irradiation of blood components state that platelets can be irradiated at any stage in their five-day storage and can thereafter be stored up to their normal shelf life of five days after collection. We explored whether the timing of irradiation has an effect on the transfusion efficacy of APCs. Patients and methods Transfusion efficacy of 809 APCs (median 6/child; range 1-68) transfused to 113 children and adolescents (53 girls and 60 boys, age 0.1y-20.0y) with thrombocytopenia due to a reduced platelet production caused by their haematological/oncological disease itself or by the applied chemotherapy was evaluated retrospectively. Transfusions were divided according to 3 APCs-groups: nonirradiated, irradiated within 24 hours before transfusion (≤ 24h), and irradiated in advance (> 24h). Exclusion criteria were: splenomegaly, fever ≥38.5°C, hemorrhage ≥ WHO Grade 3, or discontinuation of transfusion due to transfusion reactions. Transfusion efficacy was measured by the 1-hour PPR, ( PPR1h [%] = (post-transfusion count [109/L] – pre-transfusion count [109/L]) x blood volume [L] / PLT dose [1011/L]). Accounting for the many patients receiving multiple transfusions, linear mixed regression was used for univariate and multivariate analyses. Results Univariate comparison of PPR1h is summarized in the table. We recently have shown that a variety of factors influences transfusion efficacy of APCs (TRANSFUSION 48; 2008, p.442; TRANSFUSION 49; 2009, p.21). Therefore, all these variables were included in the present analysis. Multivariate analysis, corrected for storage time, applied apheresis procedure, apheresis yield, ABO transfusion constellation, body weight of recipients, and platelet count before transfusion, confirmed that transfusion of APCs irradiated in advance was associated with a significantly inferior transfusion efficacy compared to nonirradiated APCs (estimated difference in PPR1h, 4.9%; 95% confidence interval, 1.3 to 8.5; p=0.008), while transfusion efficacy of APCs irradiated within 24 hours before transfusion was not (estimated difference in PPR1h, 2.3%; 95% confidence interval, -1.0 to 5.5; p=0.18). Discussion Interestingly, no significant difference in transfusion efficacy could be observed between nonirradiated and APCs irradiated within 24 hours before transfusion, while transfusions of platelets irradiated in advance were significantly less efficient. Although many studies, including our own, provide evidence that gamma irradiated platelets have a lower transfusion efficacy, there are no data exploring the impact of the timing of the irradiation. Although our retrospective study indicates a reduced transfusion efficacy of APCs irradiated in advance, only a prospective randomized trial can unequivocally answer the question when platelets should be irradiated. Conclusions Our data strongly support that irradiation of APCs should be performed at the latest within 24 hours before transfusion. APCs irradiated in advance are less efficient. Disclosures No relevant conflicts of interest to declare.

scholarly journals Safety and Eficacy of Low Dose- Bortezomib Plus Melphalan/Prednisone (velcadito protocol) in Elderly Patintes Not Eligible to Transplant in Newly Dignosed Multiple Myeloma. Restrospective Study of 26 Patients

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5710-5710
Author(s):  
Breno Moreno Gusmão ◽  
Danielle Isadora Blumenschein ◽  
Ernesto Perez Persona ◽  
Jose Maria Guinea De Castro ◽  
Iracema Esteves Lopes ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Elderly Patients ◽  
Low Dose ◽  
Conflicts Of Interest ◽  
Pharmacoeconomic Analysis ◽  
Albert Einstein ◽  
The Elderly ◽  
High Rate ◽  
Grade 3 ◽  
The Impact

Abstract Introduction: Protocols based on bortezomib have become the standard therapy in the elderly and not eligible for transplantation. The VISTA study showed OR 71%, CR 30%, regardless of adverse factors such as age, renal failure or cytogenetic changes, but the patient had a high rate neuropathy (44%). The Spanish group and the Italian group modified the dose of bortezomib achieving rates of CR 22% and 20%, reducing neurotoxicity 8% and 5% respectively. We present the experience of 26 newly diagnosed patients treated with low-dose bortezomib associdados the melphalan / prednisone (Velcadito protocol). Objective: The aim of this study is to assess the effectiveness and safety of low-dose bortezomib in elderly patients not eligible to transplant. We evaluated according to the criteria IMWG. Results: We evaluated 26 patients treated at the Hospital Universitario de Alava (Spain) and Hospital Israelita Albert Einstein (Brazil) among 2004 to 2016. The patients received 1 cycle with bortezomib 1.3mg/m2 (days 1,4,8,11) associated with melphalan 9 mg/m2 (1- 4 days) and prednisone 60mg/m2 (1- 4 days) 28 days cycle. From the 2nd cycle the patient received low doses of bortezomib (1 mg / m2, days 1 and 4) no change in other drugs and treatment regimen. The mean age was 78 years. 50% men/ 50% women. 2 patients had poor cytogenetics Pronóstico, 1 intermediate and 23 standard. According to the IMWG: ISS1 = 7 (26%) ISS 2 = 10 (38.5%), ISS3 = 6 (23%). 38,4% (n=10) of patientes had neuropathy but only 11,5%(n=3) grade 3-4. 61,5% (n=16) presented as neutropenia toxicity, 19,2% (n=5) with grade 3 (neutrophils <1000). 15,3% (n=4) had thrombocytopenia with grade greater than 3. Response rate was 100%, and if we consider at least PR was 92% (CR 38.5% VGPR 31%). The global survival had median of 80 months (95% confidence interval 57,8 - 102,1%) and the survival free of progression had median of 37 months (95% confidence interval 15 - 58,9%) with follow-up of 91 months. Conclusion: The use of velcadito protocol is safe, very effective and seems to be a good option for elderly patients with newly diagnose MM. A pharmacoeconomic analysis is recommended to assess the impact of the cost of treatment. Being a prospective clinical trial where an analysis of this impact of all patients treated with subcutaneous bortezomib beyond the characteristics of this study. Disclosures No relevant conflicts of interest to declare.

Evaluation of the Impact of Anti-Thymocyte Globulin on Post-Transplant Outcomes in Sickle Cell Anemia Patients Undergoing BMT from HLA-Identical Sibling Donors

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3468-3468 ◽  
Author(s):  
Javid Gaziev ◽  
Antonella Isgro ◽  
Marco Marziali ◽  
Katia Paciaroni ◽  
Gioia De Angelis ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Hemorrhagic Cystitis ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Group Versus ◽  
Disease Free Survival ◽  
Bk Virus ◽  
Significant Difference ◽  
Grade 3 ◽  
The Impact

Abstract Introduction. Anti-thymocyte globulin (ATG) was added to the BuCy conditioning regimen to reduce the risk of rejection in patients undergoing BMT for SCA by the French group. Since then it has been widely used as part of conditioning regimens in SCD patients. However, it remains unknown whether ATG has any effect on survival in these patients. Here we compare outcome of BMT in 17 SCA patients who received Thymoglobulin (rabbit ATG, Genzyme) before transplantation to 33 patients who did not. Methods. Between July 2004 and November 2015, 50 consecutive patients of 1.7-17.1 years of age with SCA received their first BMT from HLA-identical sibling donors. Of these patients, 17 were prepared for transplantation with oral (n=5) or weight-based iv Bu Cy200 ATG 10 (ATG group) and 33 patients with Fludarabine 150 iv Bu Cy200 (non-ATG group). GVHD prophylaxis consisted of CSA/Methylprednisolone/short MTX. The two groups showed similar patient demographics. Sixty five percent of patients in the ATG group versus 6% in the non ATG group (p=0.00002) were on regular chronic blood transfusion. Results. All 50 patients had sustained engraftment. Platelet and neutrophil engraftment kinetics were similar between groups. There was no difference in the incidence of acute or chronic GVHD between the 2 groups. The incidence of grade 2-4 aGVHD in the ATG and non-ATG groups were 35% (95% CI 8-55%) and 33% (95%CI 15-48%), respectively. The incidence of grade 3-4 aGVHD was 0% in the ATG, and 20% (95%CI 4-33%) in the non-ATG group (p=0.07). The incidence of moderate or severe chronic GVHD were 11% (95% CI 0-25%) in the ATG and 22% (95%CI 5-34%) the non-ATG group (p=0.4). At the time of survival analysis, all 17 patients in the ATG group and 27 patients in the non-ATG group were alive, with median follow-up durations of 7.5 years (range, 3.9-12 years) and 3.6 years (range, 0.8-4.5 years), respectively. For all patients the probability of disease-free survival (DFS) was 87% (95% CI 73-94%). DFS was superior in the ATG group (100%) compared with the non-ATG group [79% (95%CI 60-90%)] (P=0.050) (Figure 1). In the non-ATG group 6 patients have died from severe acute or chronic GVHD-related complications. There was no significant difference in the rate of infectious complications between groups, except for a high incidence of BK virus-related hemorrhagic cystitis in the ATG group (Table 1). The incidence of CMV reactivation was high in both groups but none of the patients developed CMV disease. Two patients in the ATG and one in the non-ATG group showed EBV reactivation with low viral load and none of them developed lymphoproliferative disorder. Neurotoxicity related to cyclosporine was similar in both groups (17% vs 15%). At present all patients in the ATG group and 2 patients in the non-ATG group are off immunosuppressive medication. Conclusions. From this single center study, we report excellent DFS in SCA patients who received ATG as part of the conditioning regimen. This is the first reported study comparing outcomes after ATG-based vs non-ATG-based conditioning regimen for SCA. There was a trend, not significant (p=0.07), for less grade 3-4 aGVHD with ATG in the conditioning regimen. This study showed that the addition of fludarabine to the standard BuCy regimen was well tolerated, and successfully prevented graft rejection in SCA patients. Further study, using low dose ATG in the FluBuCy regimen to increase DFS is currently in progress. Disclosures No relevant conflicts of interest to declare.

The impact of pathologic differentiation (well/ poorly) and the degree of Ki-67 index in patients with metastatic WHO grade 3 GEP-NECs.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15686-e15686
Author(s):  
Seung Tae Kim ◽  
Su Jin Lee ◽  
Jeeyun Lee ◽  
Joon Oh Park ◽  
Young Suk Park ◽  
...  
Keyword(s):  
Medical Center ◽  
Unknown Primary ◽  
Ki67 Index ◽  
Who Grade ◽  
Study Results ◽  
Significant Difference ◽  
Poorly Differentiated ◽  
Well Differentiated ◽  
Grade 3 ◽  
The Impact

e15686 Background: Herein, we investigated the impact of pathologic differentiation (well or poorly differentiated) in metastatic grade 3 GEP-NEC patients receiving etoposide and platinum-based therapy. Simultaneously, we evaluated a more exact Ki67 index cut-off point to select patients with grade 3 GEP-NEC who might benefit from etoposide plus platinum (EP)-based therapy. Methods: Among patients pathologically diagnosed with metastatic grade 3 GEP-NECs at Samsung Medical Center between June 2013 and March 2016, 31 GEP-NEC patients receiving etoposide and platinum-based therapy were included in this study. Results: Primary sites included 13 foregut-derived GEP-NECs [stomach (n = 4), duodenum (n = 4), and pancreas (n = 5)] and 2 hindgut-derived GEP-NECs of the rectum. Sixteen unclassified GEP-NECs originated from 7 gall-bladder (GB), 6 liver and 3 unknown primary sites. According to pathologic differentiation, 14 patients had well differentiated and 17 had poorly differentiated grade 3 GEP-NECs. Between well differentiated and poorly differentiated grade 3 GEP-NECs, there was a significant difference in the distribution of Ki67 index. There was no significant difference of treatment efficacy between well and poorly differentiated grade 3 GEP-NECs (RR; 35.7% vs. 41.2%, p = 0.525). Tumor response to EP occurred in 5 of 7 patients with Ki67 > 60% and 7 of 24 with Ki67≤60%, which was significantly different (RR; 71.4% vs. 29.2%, P = 0.043). There was no significant difference in PFS according to pathologic differentiation (well differentiated vs. poorly differentiated) and Ki67 index ( > 60% vs ≤60%). Conclusions: Grade 3 GEP-NECs could be morphologically classified into well and poorly differentiated NETs. Additionally, among grade 3 GEP-NECs, there was a significant difference in ranges of Ki67 index between well and poorly differentiated NECs. Higher levels ( > 60%) of Ki67 index might be a predictive marker for efficacy of EP as a standard regimen in grade 3 GEP-NECs.

scholarly journals PATH-19. MOLECULAR, HISTOLOGIC AND CLINICAL CHARACTERISTICS OF OLIGODENDROGLIOMAS: A MULTI-INSTITUTIONAL RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii168-ii168
Author(s):  
Antonio Dono ◽  
Kristin Alfaro-Munoz ◽  
Yuanqing Yan ◽  
Carlos Lopez-Garcia ◽  
Zaid Soomro ◽  
...  
Keyword(s):  
Health Science ◽  
Cancer Center ◽  
Subtotal Resection ◽  
Adjuvant Radiation ◽  
Science Center ◽  
Who Grade ◽  
Pik3ca Mutations ◽  
Increased Risk ◽  
Significant Difference ◽  
Grade 3

Abstract In the 2016 WHO classification of CNS tumors, oligodendrogliomas are molecularly defined by IDH1 or IDH2 mutations and 1p/19q co-deletion. Some reports suggest that PI3K pathway alterations may confer increased risk of progression and poor prognosis in oligodendroglioma. However, factors that influence prognosis in molecularly defined oligodendroglioma (mOGD) have not been thoroughly studied. Also, the benefits of adjuvant radiation and temozolomide in mOGDs remain to be determined. 107 mOGDs diagnosed between 2008-2018 at the University of Texas Health Science Center at Houston (n= 39) and MD Anderson Cancer Center (n= 68) were included. A retrospective review of the demographic, clinical, histologic, molecular, and outcomes were performed. Median age at diagnosis was 37 years and 61 (57%) patients were male. There were 64 (60%) WHO Grade 2 and 43 (40%) WHO Grade 3 tumors. Ninety-five (88.8%) tumors were IDH1-mutant and 12 (11.2%) were IDH2-mutant. Eighty-two (77%) patients were stratified as high-risk: older than 40-years and/or subtotal resection (RTOG 9802). Gross-total resection was achieved in 47 (45%) patients. Treatment strategies included observation (n= 15), temozolomide (n= 11), radiation (n= 13), radiation with temozolomide (n= 62) and other (n= 6). Our results show a benefit of temozolomide vs. observation in progression-free survival (PFS). However, no benefit in PFS or overall survival (OS) was observed when comparing radiation vs. radiation with temozolomide. PIK3CA mutations were detected in 15 (14%) cases, and patients with PIK3CA-mutant mOGDs showed worse OS (10.7-years vs 15.1-years, p= 0.009). Patients with WHO Grade 3 tumors had shorter PFS but no significant difference in OS was observed compared to grade 2. Our findings suggest that mOGDs harboring PIK3CA mutations have worse OS. Except for an advantage in PFS in temozolomide treated patients, adjuvant treatment with radiation or the combination of both, showed no significant advantage in terms of OS.

Short-term outcomes associated with temozolomide or PCV chemotherapy for 1p/19q-codeleted WHO grade 3 oligodendrogliomas: a national evaluation

2022 ◽  
Author(s):  
Nayan Lamba ◽  
Malia McAvoy ◽  
Vasileios K Kavouridis ◽  
Timothy R Smith ◽  
Mehdi Touat ◽  
...  
Keyword(s):  
Cox Regression ◽  
Extent Of Resection ◽  
First Line ◽  
Short Term ◽  
Who Grade ◽  
Cox Regression Analysis ◽  
Significant Difference ◽  
Pcv Chemotherapy ◽  
Grade 3 ◽  
National Analysis

Abstract Background The optimal chemotherapy regimen between temozolomide and procarbazine, lomustine, and vincristine (PCV) remains uncertain for W.H.O. grade 3 oligodendroglioma (Olig3) patients. We therefore investigated this question using national data. Methods Patients diagnosed with radiotherapy-treated 1p/19q-codeleted Olig3 between 2010-2018 were identified from the National Cancer Database. The OS associated with first-line single-agent temozolomide vs. multi-agent PCV was estimated by Kaplan-Meier techniques and evaluated by multivariable Cox regression. Results 1,596 radiotherapy-treated 1p/19q-codeleted Olig3 patients were identified: 88.6% (n=1,414) treated with temozolomide and 11.4% (n=182) with PCV (from 5.4% in 2010 to 12.0% in 2018) in the first-line setting. The median follow-up was 35.5 months (interquartile range [IQR] 20.7-60.6 months) with 63.3% of patients alive at time of analysis. There was a significant difference in unadjusted OS between temozolomide (5yr-OS 58.9%, 95%CI: 55.6-62.0) and PCV (5yr-OS 65.1%, 95%CI: 54.8-73.5; p=0.04). However, a significant OS difference between temozolomide and PCV was not observed in the Cox regression analysis adjusted by age and extent of resection (PCV vs. temozolomide HR 0.81, 95%CI: 0.59-1.11, p=0.18). PCV was more frequently used for younger Olig3s, but otherwise was not associated with patient’s insurance status or care setting. Conclusions In a national analysis of Olig3s, first-line PCV chemotherapy was associated with a slightly improved unadjusted short-term OS compared to temozolomide; but not following adjustment by patient age and extent of resection. There has been an increase in PCV utilization since 2010. These findings provide preliminary data while we await the definitive results from the CODEL trial.

scholarly journals CTNI-22. RETROSPECTIVE ANALYSIS OF THE COMBINED TREATMENT OF VINCRISTINE, ACNU, CARBOPLATIN AND INTERFERON-β PLUS RADIOTHERAPY (VAC-FERON-R)IN PATIENTS WITH DIFFUSE ASTROCYTOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii47-ii47
Author(s):  
Yoshiki Arakawa ◽  
Yasuhide Makino ◽  
Takeshi Kawauchi ◽  
Masaharu Tanji ◽  
Yohei Mineharu ◽  
...  
Keyword(s):  
Combined Treatment ◽  
Diffuse Astrocytoma ◽  
Wild Type ◽  
Interferon Β ◽  
Mutant Type ◽  
Who Grade ◽  
Integrated Diagnosis ◽  
Significant Difference ◽  
Favorable Clinical Outcome ◽  
The Impact

Abstract OBJECTIVE Diffuse astrocytomas are classified as WHO grade II and its median overall survival (mOS) is 10 to 11 years. The efficacy of chemoradiation in the high-risk feature has been reported. The prognosis is associated with IDH and TERT promoter (TERTp) mutations. Here, we retrospectively analyzed the patients with diffuse astrocytoma treated with vincristine, ACNU, carboplatin and interferon-β plus radiotherapy (VAC-feron-R)in our institute. PATIENTS AND METHODS Between December 2003 to January 2016, 44 patients were diagnosed as diffuse astrocytoma with integrated diagnosis of histological and molecular analysis. The average age was 43.1 years (22–71 years). They received VAC-feron-R as initial treatment in our institute. We analyzed the IDH1/2 and the TERTp mutation using Sangar sequencing and determined the 1p/19q codeletion by the fluorescence in situ hybridization or the multiplex ligation-dependent probe amplification. RESULTS Median follow-up period was 76.5 months, mPFS was 126 months, mOS did not reach, and 10-year survival rate was 60%.IDH status was determined in 29 patients, 9 mutant and 20 wild types. There was no significant difference in PFS and OS between the two groups. TERTp status was determined in 18 patients with IDH wild type, 6 mutant and 12 wild types. mPFS of patients with TERTp wild type did not reach, but that with TERTp mutant type was 34.5 months (p = 0.0356). CONCLUSION Compared with previous clinical studies, VAC-feron-R showed a favorable clinical outcome in diffuse astrocytoma. The impact of TERTp status on prognosis was identified but not IDH status in this cohort.

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.

Association of PML Expression with Chemotherapy-Resistance In Multiple Myeloma Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2959-2959
Author(s):  
Daisuke Ohgiya ◽  
Makoto Onizuka ◽  
Hiromichi Matsushita ◽  
Naoya Nakamura ◽  
Hiroshi Kawada ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cellular Proliferation ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Chemotherapy Resistance ◽  
Nuclear Body ◽  
Rank Test ◽  
Significant Difference ◽  
The Impact

Abstract Abstract 2959 Background: Although several novel agents have improved the prognosis of patients with multiple myeloma (MM), it still remains an incurable disease because of the difficulty to eradicate MM cells by current therapeutic approaches. Recent studies have revealed that a subset of malignant cells, cancer stem cells, contribute to chemotherapy-resistance in cancer treatment. Promyelocytic leukemia gene product (PML), known as a tumor suppressor through a variety of cellular functions in a nuclear macromolecular structure called the PML nuclear body, has been reported to be responsible for the chemotherapy-resistance by regulating cell cycle in chronic myeloid leukemia. We therefore investigated the impact of PML expression on the cellular proliferation status of MM cells and patients' prognoses. Materials/Methods: Bone marrow clot sections from 48 patients with newly diagnosed MM from Jan 1998 to Dec 2009 before any therapy at diagnosis were obtained, and analyzed, according to appropriate procedure approved by IRB at the Tokai University School of Medicine (Kanagawa, Japan) with written informed consent. They were doubly-stained with a combination of anti-PML/anti-CD138 and anti-Ki67/anti-CD138. For evaluation of the relation between PML status and cellular proliferation, the positive rates of PML and Ki67 in CD138 positive cells were compared. For investigation of the impact of PML expression on the prognosis of MM, the patients were divided into 3 groups, according to the PML positive rates in the CD138 positive cells: negative/low (less than 25 percentile: 12 cases), intermediate (from 25 to 75 percentile: 24 cases) and high (more than 75 percentile: 12 cases). Their overall survivals were compared using log-rank test. Furthermore, the PML positive rates between before and after treatments were compared using paired t-test. Results: The median observation period of 48 cases was 915 days. The median age of the patients was 62.5 (38-76) at diagnosis. All the patients were underwent combination chemotherapies containing alkylating agents as initial therapies. Two and nine patients were underwent allogeneic and autologous stem cell transplantation during the clinical courses, respectively. The numbers of patients of international staging system (ISS) stage I, II and III were 17, 14 and 17 cases. The PML positive rates in each case ranged from 0% to 83.8%. They were not correlated with ISS stages (Spearman r = 0.083) and the Ki67 positive rates (Spearman r = -0.13). The PML positive rates in the negative/low, intermediate and the high groups were less than 22.1%, from 22.1 to 56.6% and more than 56.6%, respectively. No significant difference in overall survival was observed among the 3 groups (p>0.05). However, there were significant differences in two year survival rate when the 3 groups were compared (100%, 85.2% and 54.7%; p=0.015) (Fig. 1). In 13 patients whose bone marrow clot sections were sequentially collected, the PML positive rates after treatments were significantly higher than those at diagnosis (p=0.0042) (Fig. 2). Especially, PML positive rates in all the 3 patients from the negative/low group were progressively increased (0.3 to 82.6%, 14.1 to 100%, 19.0 to 37.5%), and 2 of them died due to disease progression. On the other hand, 2 patients whose PML positive rates decreased after treatment were alive more than 5 years without therapies. Conclusion: Our data indicated that the level of the PML expression at diagnosis was a possible prognostic factor for early course of the disease (2 years after diagnosis). Chemotherapies might induce PML expression in MM cells or select PML positive MM cells. These findings suggest that PML expression presumably reflect chemotherapy-resistance in MM cells. The molecular mechanism of the association is now under investigation. Disclosures: No relevant conflicts of interest to declare.

Cytogenetic Evolution (CE) In Patients (pts) with Low and Intermediate Risk Myelodysplastic Syndromes (MDS) Is Associated with Poor Prognosis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2941-2941
Author(s):  
Liunan Li ◽  
Elias Jabbour ◽  
Gautam Borthakur ◽  
Stefan Faderl ◽  
Tapan Kadia ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cytogenetic Analysis ◽  
Conflicts Of Interest ◽  
Myelogenous Leukemia ◽  
Intermediate Risk ◽  
Hematopoietic Stem ◽  
Increased Risk ◽  
Significant Difference ◽  
The Impact ◽  
Cytogenetic Evolution

Abstract Abstract 2941 Introduction: MDS is a spectrum of abnormalities in the proliferation and differentiation of hematopoietic stem cells that result in peripheral cytopenias, bone marrow dysplasia and increased risk of transformation to acute myelogenous leukemia (AML). Cytogenetic abnormalities occur in more than 50% of patients (pts) and have an impact on survival and risk of transformation to AML. CE, or acquisition of additional clonal chromosomal abnormalities, has been reported to occur in 30 to 50% of primary MDS pts. Their impact on prognosis and transformation into AML among pts with low and intermediate risk MDS is not known. In this study, we analyzed the impact of CE on prognosis in lower risk MDS. Methods: we reviewed 722 pts clinic records of low and intermediate risk MDS pts at MD Anderson Cancer Center (MDACC) from 2000–2010 and conducted a retrospective analysis of all MDS pts with at least two consecutive cytogenetic analysis (365 patients, 50.6%) and compared the cytogenetic evolution group (CE group) with the group without cytogenetic changes (no CE group). Cytogenetic analysis was performed in the Cytogenetics Laboratory at MDACC. Results: CE was detected in 200 pts (55%). Characteristics of patients with CE are: median age 65 years (23-91), IPSS int-1 79%, diploid CG 42%, excess blasts 25%. Pts with CE were more frequently female (p=0.005), and had more frequently abnormalities of chromosome 5 and 7 (p<0.001) at baseline. There were no statistically significant difference between these two groups (p>0.05) regarding age, WBC, platelet, hgb, ANC, BM blasts percent, diagnosis (RA or RAEB), and IPSS score. There were more chr.-5/-7, insufficient metaphases, and other abnormalities, but less diploid cases in CE group compared with no CE group (p<0.001). History of malignancy (p=0.001) and prior chemotherapy exposure were also associated with CE (p=0.001), but this was not as strong for radiation exposure (p=0.066). Also, more CE patients required therapy for MDS compared to no CE patients (p=0.039). Progression free survival was significantly extended in no CE patients (p=0.02). Overall survival was a longer in no CE (34.1months), compared with CE group (26.2 months), although this was not statistically significant. Conclusion: CE is more commonly observed among pts with high-risk features, and is usually associated with disease progression and resistance. Also, prior malignancy and chemotherapy exposure were associated with CE in this study. This data indicates that genomic instability has a role in disease progression in MDS. Further analysis of CE in MDS is needed. Disclosures: No relevant conflicts of interest to declare.

Release of Procoagulant and Proinflammatory Cell-Derived Microparticles (MP) During Blood Storage: Effects of Storage Time, Leukoreduction, and Residual Platelets,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3373-3373
Author(s):  
Wenche Jy ◽  
Sherry Shariatmadar ◽  
Marco Ricci ◽  
Orlando Gomez-Marin ◽  
Carlos Bidot ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Storage Time ◽  
Time Course ◽  
Conflicts Of Interest ◽  
Annexin V ◽  
Bioactive Substances ◽  
Platelet Counts ◽  
The Impact ◽  
Stored Blood ◽  
Over Time

Abstract Abstract 3373 Introduction Several studies have indicated that transfusion with older blood carries more risk of adverse reactions than transfusion with younger blood, but this remains controversial. It is not clear why older blood may carry increased risks, or what the “safe age” of stored blood is. It is known that multiple bioactive substances are generated from blood during storage, and one or more of these substances may be involved in transfusion-related complications. Among them, MP are a recognized marker of the storage lesion, and their involvement in transfusion-related complications has been postulated. However, questions such as MP species, quantity, biological activity, and factors affecting their release are not well elucidated. The purpose of this study was to quantify MP species and their activity in stored RBC as a function of storage time, and to evaluate the impact of leukoreduction and residual platelets on MP release. Methods (I) MP generation and functional activity Thirty-four bags of packed RBC (16 non-leukoreduced, 18 leukoreduced) of known blood types (A+, B+, AB+, O+) were obtained from the blood bank within 2–4 days of drawing, and then stored at 4°C. Time of receipt was defined as day 0. At days 0, 10, 20, 30, and 40, 40 mL samples were centrifuged at 1000xg for 20 min to remove cells. The supernatants were then assayed for: (1) subtypes of MP by flow cytometry comprising (a) red cell MP (RMP) assessed by CD235a, (b) leukocyte MP (LMP) by CD45, (c) platelet MP (PMP) by CD41, (d) endothelial MP (EMP) by CD144, and (e) generic MP by Ulex Europaeus (Ulex) or Annexin V (AnV); (2) MP-mediated thrombin generation assay (TGA); (3) MP-mediated inflammatory activity by CD 11b expression in neutrophils following incubation with MP. (II) Reconstitution of increasing platelet counts in leukoreduced RBC. To investigate the effect of residual platelets on RMP generation, we mixed a constant amount of RBC with increasing amounts of type-matched platelets (0 to 250,000/μL f.c.) in standard storage bags and measured time-dependent MP release. Results (A) Time-course of MP generation (i) Non-leukoreduced. RMP, PMP and LMP all increased with time, but with different patterns. RMP increased little to day 10 but then rose exponentially, and by day 40 they were 4–6 fold higher than at day 0. PMP counts rose steadily from day 0 and peaked at day 20, being 2–3 fold higher than at day 0. LMP showed no significant change until day 20 when they started to increase, and then increased sharply after day 30, and by day 40 were 1.5–2 fold higher than at day 0. Levels of PMP (days 0 to 20) and RMP (days 20 to 40) correlated with increasing MP-mediated procoagulant and inflammatory markers. (ii) Leukoreduced. Pre-storage leukoreduction decreased RMP generation by 20–40%, completely suppressed PMP and LMP generation, and reduced total MP-mediated procoagulant and inflammatory markers by 40–60%. CBC showed that leukoreduction not only removed >99% WBC but also reduced residual platelets by >95% (from 90 ±30 ×103/μL to 3.5 ±1.3 ×103/μL). This suggests that residual leukocytes and platelets potentiate RMP generation. (B) Effects of residual platelets on RMP generation. To further study the effects of platelets on RMP generation, we mixed known counts of platelets with leukoreduced RBC, and then evaluated RMP generation over time. We found that RMP levels released were proportional to the platelet counts, as were the procoagulant and inflammatory markers. These results show that platelets in stored RBC play a key role in RMP generation. Conclusion Multiple MP types (PMP, LMP, RMP) are released during storage, and their levels increase over time but their patterns of change are different. Procoagulant and inflammatory markers increase in parallel with PMP and RMP. Our data support the hypothesis that age of stored blood could be important in transfusion-related complications, via MP production. Leukoreduction sharply reduces MP generation and procoagulant and inflammatory markers, suggesting that known benefits of leukoreduction may be attributable to reduced MP production. The finding that residual platelets in stored RBC can potentiate RMP generation suggests that minimizing platelets in non-leukoreduced packed cells could reduce the risk of transfusion-related complications. (Supported by NIH grant 1R01HL098031). Disclosures: No relevant conflicts of interest to declare.

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