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  • 1
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    Chronic myeloid leukemia after treatment of lymphoid malignancies: Response to imatinib mesylate and favorable outcomes in three patients
    Elsevier BV ; 2006
    In:  Leukemia Research Vol. 30, No. 6 ( 2006-6), p. 701-705
    Details
    In: Leukemia Research, Elsevier BV, Vol. 30, No. 6 ( 2006-6), p. 701-705
    Type of Medium: Online Resource
    ISSN: 0145-2126
    URL: Article
    DOI: 10.1016/j.leukres.2005.10.015
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2006
    detail.hit.zdb_id: 2008028-1
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  • 2
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    Pro-apoptotic therapy with the oligonucleotide Genasense TM (oblimersen sodium) targeting Bcl-2 protein expression enhances the biological anti-tumour activity of rituximab : Bcl-2 Antisense Oligonucleotide Enhances mAb-based Therapy
    Wiley ; 2004
    In:  British Journal of Haematology Vol. 127, No. 5 ( 2004-12), p. 519-530
    Details
    In: British Journal of Haematology, Wiley, Vol. 127, No. 5 ( 2004-12), p. 519-530
    Type of Medium: Online Resource
    ISSN: 0007-1048
    URL: Issue
    URL: Article
    DOI: 10.1111/bjh.2004.127.issue-5
    DOI: 10.1111/j.1365-2141.2004.05239.x
    RVK:
    XA 34100
    Language: English
    Publisher: Wiley
    Publication Date: 2004
    detail.hit.zdb_id: 1475751-5
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  • 3
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    Efficacy and Safety of Rituximab in Post Transplant Lymphoproliferative Disorders (PTLD): Pooled Analysis and Review of Literature.
    American Society of Hematology ; 2007
    In:  Blood Vol. 110, No. 11 ( 2007-11-16), p. 1084-1084
    Details
    In: Blood, American Society of Hematology, Vol. 110, No. 11 ( 2007-11-16), p. 1084-1084
    Abstract: PTLD are heterogeneous monoclonal or polyclonal neoplasm usually of B-cell origin with a variable incidence in allogenic bone marrow and solid organ transplant recipients. Due to immunosuppresion in transplant patients, PTLD follows an aggressive course with enhanced treatment-associated toxicity, leading to a overall poor clinical outcome and mortality. Rituximab is a chimeric monoclonal anti-CD20 antibody with known activity in B-cell PTLD and minimal toxicity. A few anecdotal uncontrolled studies and case reports have evaluated the use of rituximab-based therapy for PTLD. In order to define the efficacy and safety of rituximab single agent in the treatment of patients with PTLD we conducted a review of the current available literature and performed a pooled-analysis. We conducted a MEDLINE literature search using Pub med, Ovid software for the key words rituximab, anti-CD20 antibody, PTLD, hematopoetic stem cell transplant (HSCT), solid organ transplant (SOT) and lymphoproliferative disorders on all available published literature analyzed to date (January 1998 to June 30, 2007). Studies involving children ( 〈 18 years), individual case reports with less than 5 patients, patients who were treated with chemo-immunotherapy combination were excluded and our search was limited to those PTLD patients treated with rituximab single agent after failure to respond to withdrawal of immunosuppressants. References of each article were also reviewed for additional literature. Studies were also analyzed for duration of PTLD from time of transplantation, rituximab toxicity, and characteristics of responders. A total of 164 peer-reviewed publications were identified after the electronic search using the above keywords. After excluding patients based on above criteria, the pooled-analysis consisted of 308 patients described in 17 reports. Diagnosis of PTLD cases was based on histological examination and World Health Organization classification. Among the 17 reports, 3 studies included HSCT patients with n=24; the rest consisted of SOT patients. The mean age of the patients was 57; PTLD classified as late onset ( 〉 1 year) in most patients (∼70%). Rituximab was used as first line therapy after failure of immunosuppression withdrawal, and patients were initially treated with four weekly doses of rituximab at 375mg/m2. Rituximab was continued as maintenance therapy in responding patients in few studies. The complete response rate (International Workshop Criteria) was 58% (29%–78%), among SOT patients and 70% (66%–83%) among HSCT patients. Side effects were minimal and no treatment related deaths were attributed to rituximab. Long term follow up from 2 prospective studies demonstrate a durable remission in 30%–37% SOT patients at 5 years. Limited evidence exists for optimal treatment approach in PTLD. Clinical heterogeneity among small number of patients diagnosed makes it difficult to conduct randomized prospective studies in this disorder. Our study is the first pooled analysis evaluating the role of rituximab in PTLD. Minimal toxicity with good efficacy favors rituximab’s use among patients with less aggressive PTLD who fail or unable to tolerate withdrawal of immunosuppression.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V110.11.1084.1084
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2007
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  • 4
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    In Vivo Downregulation of Bcl-2 by G3139 (G) Enhances Rituximab (R) Anti-Tumor Activity: Effect of Sequential Versus Concurrent G3139 Administration on Survival in a Lymphoma-Bearing SCID Mouse Model.
    American Society of Hematology ; 2004
    In:  Blood Vol. 104, No. 11 ( 2004-11-16), p. 1398-1398
    Details
    In: Blood, American Society of Hematology, Vol. 104, No. 11 ( 2004-11-16), p. 1398-1398
    Abstract: Bcl-2 over expression has been associated with poor prognosis and chemoresistance in various hematologic and solid tumor malignancies. G, an antisense oligonucleotide (ASO) targeting Bcl-2, downregulates Bcl-2 expression favoring apoptosis in cancer cells. Previously, we have demonstrated that G enhances R anti-tumor activity in various lymphoma pre-clinical models. Clinical trials are being conducted to evaluate the safety and efficacy of G3139 combined with R in relapsed/refractory NHL patients. However, the optimal sequence of administration of G and R is unknown. Our main objective was to determine the optimal anti-tumor schedule to administer G in combination with R. Six 8-week old SCID mice were inoculated via tail vein injection with Raji cells (1 x 106 on day 0). After five days, to allow for tumor engraftment, mice were assigned to receive placebo [P] , G, R, R followed by G [R→G], G followed by R [G→R] or G preceding each dose of R [G+R]. In addition, other control groups consisted of lymphoma-bearing mice treated with G3622 (ASO control) [reverse sequence, RS] , trastuzumab (isotype) [I] and R in combination with G3622 [R+RS] . Antibodies were administered vial tail vein injection at a dose of 10mg/kg/dose x 4 doses and ASO were administered intraperitoneally at 5mg/kg/dose x 8 doses. The end-point of the study was survival. Survival analysis was performed by Kaplan-Meier curves and p values calculated using log rank test. Differences in survival of lymphoma-bearing SCID mice were noted according to the schedule of G/R administration. Synergistic activity was observed in animals treated with [G+R]. A modest improvement in the mean survival was noted in animals treated with [G] (26 days) or [G→R] (28 days) when compared to control mice (20 days) (P 〈 0.001). Anti-tumor activity was observed in SCID mice treated with R (mean survival 34 days) and was improved by the sequential addition of G [R→G] (median survival 48 days, P = 0.038). Concomitant administration of G and R resulted in the highest anti-tumor activity as measured by the longest survival (mean 80 days, P 〈 0.001). Our data demonstrates differences in R/G anti-tumor activity depending on the schedule of administration of G and R. Sequential administration of R followed by G resulted in a better disease control than G followed by R. However, concurrent G and R administration was shown to be superior to sequential strategies in improving survival of lymphoma-bearing SCID mice. Our pre-clinical data suggest the importance of a concurrent administration of these agents in clinical trials whereby, down-regulation of Bcl-2 by G allows enhancement of rituximab-associated anti-tumor activity.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V104.11.1398.1398
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2004
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    detail.hit.zdb_id: 80069-7
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  • 5
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    Effect of Renin Angiotensin System (RAS) Blockade on Hematological Parameters in Patients with Secondary Polycythemia (SP) Associated with Chronic Obstructive Pulmonary Disease (COPD) and Sleep Apnea (SA).
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 3759-3759
    Details
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 3759-3759
    Abstract: Introduction: Erythrocytosis secondary to hypoxia is an erythropoeitin (EPO) driven physiologic mechanism to sustain tissue oxygenation. Phlebotomy is indicated to relief symptoms of hyperviscosity that occur at very high hemoglobin (Hb)/hematocrit (Hct) levels. Recent evidence suggests a causal relationship between RAS and hematopoesis in SP through either EPO related or non-EPO-related mechanisms. On that premise, angiotensin converting enzyme inhibitors (ACEI) used to treat post-transplant erythrocytosis in kidney recipients may have a beneficial effect in lowering hct levels in SP patients. Objective: To study the effect of RAS blockade with ACEIs on Hb, Hct and EPO levels in patients with SP due to COPD/SA. Material and methods: We retrospectively identified patients with SP or erythocytosis treated at our Institutions using the ICD code system. Search involved patients evaluated/treated between 1999 and 2006. Only patients with documented hypoxemia (diagnosis of COPD or sleep apnea), normal to elevated EPO levels, absent splenomegaly and elevated red cell mass in nuclear studies when available were included in the analysis. Demographic characteristics, pulmonary function tests results, baseline, peak Hb, Hct, serum creatinine (Cr), EPO levels at initial diagnoses and history of ACE inhibitors use were obtained. Subsequently, patients were divided into two groups based on whether or not they were on ACE inhibition for at least 2–3 months prior to the peak HgB/Hct values. Patients without documented hypoxemia were excluded as well as those with features suggestive of myeloproliferative disorder or relative polycythemia. Chi-square test was used to evaluate differences in Hct levels between groups before and after ACEI or placebo. Results: A total of 44 patients were identified with median age 60.5 years. There were 22 patients who had received ACEIs for other co-morbid conditions, for at least 3 months prior to peak hematocrit/hemoglobin values. Serum creatinine (median 1.0 mg/dl) levels were equally balanced between two groups. About half of patients in each group had moderate to severe COPD/SA base on PFTs and sleep studies. The median peak Hct and HgB in patients receiving ACEI were 57.45% and 18.65 gr/dl (Mean peak values 56.92% and 18.96 grs/dl; range 51.3–66.9% and 17–20.8 gr/dl) respectively. Patients not on ACEIs had a median peak Hct/HgB of 56.6% and 18.95 gr/dl (Mean peak values 56.54% and 19.2 gr/dl; range 53.0–61.1% and 17.4–21.8 grs/dl). EPO levels were available in 12/44 patients at the time of initial diagnosis with mean values 13.47 MIU/ml (range 5.9–22.3 MIU/ml) without any difference between two groups. Higher percentage of patients achieved decrease in Hct levels ( 〉 /=2.5%) from baseline after starting ACEI compared to placebo p=0.017. Discussion: Our results suggest that the use of ACEI decrease Hct levels from baseline in patients with hypoxemia induced SP. It is unclear if this decline is beneficial therapeutically in patients with chronic pulmonary disease. Further studies are warranted to determine if ACEI can decrease frequency of phlebotomies in SP due to hypoxemia.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V108.11.3759.3759
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 6
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    Tumor Necrosis Factor Alpha (TNF-a) Blockade and Risk of Lymphoma: Systematic Review and Analysis of Literature
    American Society of Hematology ; 2008
    In:  Blood Vol. 112, No. 11 ( 2008-11-16), p. 5278-5278
    Details
    In: Blood, American Society of Hematology, Vol. 112, No. 11 ( 2008-11-16), p. 5278-5278
    Abstract: BACKGROUND: TNF-α plays a critical role in the regulation of cytokine mediated cancer immunosurveillance. Evidence suggests that depletion of TNF-α may result in abrogated anti-tumor immunity and increase in the risk of malignancies. Anti-TNF-α therapy (infliximab, adalimumab and etanercept) is known to halt the progression of certain inflammatory disorders and has been approved for the treatment of at least five autoimmune/inflammatory conditions. Given the widespread use of these biological agents, it is vital to explore the associated increased risk of malignancies especially lymphoma. OBJECTIVE: Risk of lymphoma associated with anti-TNF-α therapy is controversial in rheumatoid arthritis (RA) and has not been extensively studied in other inflammatory disorders. With the expanding role of anti-TNF-α therapy, we evaluated the risk of lymphoma among all approved indications for which they are currently in use. METHODOLOGY: We conducted a systematic electronic search of MEDLINE using the terms TNF-α, infliximab, adalimumab, etanercept, rheumatoid, psoriasis, arthritis, inflammatory bowel disease, ankylosing spondylitis from January 1998 to December 2007. Studies analyzed were restricted to those in English language, full text published articles, randomized controlled trials (RCT), meta-analysis (MT), review articles, extension studies, reports from national databases (ND) and postmarketing surveillance studies. Risk of lymphoma from ND was obtained as odds ratio with 95% confidence interval. Incidence of lymphoma reported from RCT was analyzed as percentage fraction of the total number of patients enrolled in the study and follow up. RESULTS: Overall 51 studies (2 MT, n=10,370; 4 ND, n=29,099 and 45 RCT, n=54,637) that included anti-TNF-α therapy in inflammatory disorders were analyzed. Treatment/follow up period were variable from 12 weeks to 8 years. Ten patients (0.09%) from MT treated with anti-TNF-α therapy developed lymphoma vs 0 in the non-anti-TNF-α group. Report from one of the 3 ND showed an increased risk (11.5 RR 95% CI 3.7–26.9) of lymphoma among the anti-TN-α exposed group. Among the RCT, 16 patients (0.02%) in the anti-TNF-α group developed lymphoma vs 3 (0.005%) in the control group. CONCLUSION: Existing data suggests that anti-TNF-α therapy in rheumatoid arthritis is associated with an increased risk of lymphoma but this may be attributed to the severity of the disease itself. Among other inflammatory disorders, a rise in lymphoma risk could not be established. Whether anti-TNF-α therapy in the long term can in fact decrease the incidence of lymphoma by altering the disease severity remains to be determined.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V112.11.5278.5278
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2008
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 7
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    Efficacy and Safety of Rituximab in the Treatment of Refractory/Relapsed Idiopathic Thrombocytopenic Purpura (ITP): Results of a Meta-Analysis of 299 Patients.
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 1076-1076
    Details
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 1076-1076
    Abstract: Background: Rituximab is a chimeric monoclonal antibody (mAb) targeting CD20 antigen on neoplastic and normal B cells. In addition to its role in the treatment CD20-positive B-cell malignancies, rituximab has been approved for symptom management of rheumatoid arthritis. Expanding the use of rituximab in other autoimmune diseases remains investigational. The treatment of auto-antibody mediated platelet destruction in refractory ITP is challenging. Although a good response is seen in the majority of patients treated with steroids and/or splenectomy, relapses occur in half of the patients. A few uncontrolled studies have evaluated the use of rituximab for therapy of relapsed/refractory ITP. Objective: In order to define the efficacy and safety of rituximab in the treatment of patients with refractory/relapsed ITP we conducted a review of the current available literature and performed a meta-analysis. Materials and Methods: We conducted a MEDLINE literature search using Pub med, Ovid software for the key words rituximab, ITP and immune thrombocytopenia on all available published literature analyzed to date (Jan 2001 to June 30, 2006). Studies involving children ( & lt;18 years) were excluded and our search was limited to reports in English. References of each article were also searched for additional literature. Individual case reports with less than 5 patients were excluded. In addition, studies were analyzed for disease duration, rituximab toxicity, and characteristics of responders. Results: A total of 34 peer reviewed publications were identified after the electronic search that identified a total of 324 patients. Five abstracts and 14 full-length manuscripts were excluded from the analysis as they included & lt; 5 patients/report. Thus, the meta-analysis consisted of 299 patients described in 15 reports. The mean age of the patients was 50 (39–49 years); about half (52%) had failed splenectomy; mean duration of ITP was 54.4 months. All patients received four weekly doses of rituximab at 375mg/m2. The overall response rate was 55%, of which 38% of the patients achieved a complete response (CR) that was defined as a platelet count of at least 100,000–150,000. In addition, 17% of the patients achieved a partial response (PR) (i.e. platelet count & gt;50,000 and & lt; 100,000). The median duration of response in CR patients was 74 weeks (24–120) and in PR patients was 55 weeks (12–160). Of 12 patients re-treated with rituximab: 7 had 2nd CR (duration 6 m to 4 yrs). CR in splenectomized patients (available from 5 studies, n=126) was higher (62%) than non-splenectomized patients. Initial rise in platelet count in early responders was seen as early as 7–14 days from initiation of therapy. Discussion: Treatment of relapsed or refractory ITP is based on retrospective studies and no specific guidelines exist. Rituximab-associated depletion of antibody producing B-cells and/or Fc receptor blockade by mAb results in objective responses in over half (55%) of the patients treated. Re-treatment is effective in a similar percentage of patients with durable response. Minimal toxicity with equivalent results to other immunosuppressants favors rituximab’s use in patients with symptomatic refractory ITP. Prospective trials should further validate these results and potentially identify ITP patient characteristics prognostic for responsiveness to rituximab immunotherapy.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V108.11.1076.1076
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
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    Individualized Dosing of Fludarabine (FLU) for Low Grade Lymphoproliferative Disorders Results in Administration of Less Medication with Fewer Infections and Equivalent Survival.
    American Society of Hematology ; 2006
    In:  Blood Vol. 108, No. 11 ( 2006-11-16), p. 4977-4977
    Details
    In: Blood, American Society of Hematology, Vol. 108, No. 11 ( 2006-11-16), p. 4977-4977
    Abstract: When used in the treatment of low-grade lymphoproliferative disorders, common practice is to administer 6 monthly cycles of FLU 25-mg/m2 daily × 5. This practice is reported to cause infections (including opportunistic such as PCP and Listeria) in over 50% of patients. It has been our practice to individualize the number of monthly cycles of FLU per treatment course based on response in general administering 1 cycle of therapy when rapid and substantial response is obtained, or 1 cycle past best response. Our objective is to describe our experience with this dosing schema - incidence of infections in relation to the number of cycles of FLU administered per treatment course and overall survival. We conducted a retrospective chart review of medical records of all patients who received FLU at the Stratton VA Medical Center. We defined one treatment course as the number of five day monthly FLU doses received. Any time interval of 3 or more months between FLU was considered to indicate a new treatment course. All infectious episodes of NCI grades 3 or higher that occurred within 6 months of the last FLU treatment course were attributed to that prior treatment course. Survival was estimated by Kaplan-Meier analysis from date of diagnosis to death or last known alive. There were 15 patients treated for CLL, 9 for low-grade lymphoma, and 4 for macroglobulinemia. Three individuals treated with FLAG for ANLL were excluded. These 28 patients received a total of 44 treatment courses (each treatment course with 1 to 6 monthly cycles) of FLU. Fifty-four (54) percent of the treatment courses were with ≤2 cycles. Mean ± SD age of the patients was 65 ± 11 years. Number of FLU cycles per treatment course Number of treatment courses with infection Number of treatment courses without infection % treatment courses with infection 1 3 12 20 2 1 8 11 3 6 3 67 4 3 1 75 5 3 1 75 6 2 1 67 The overall incidence of NCI grade 3 or higher infections was significantly increased with increased numbers of FLU cycles per treatment course (complex Chi-square = 0.0193). Treatment cycles with ≤2 compared with 3 or more cycles per treatment course (Chi-square with Yate’s correction = 0.0008) had significantly fewer infections. Median overall survival was 158 months with 78 ± 44 months of follow-up. Our data indicates that individualized dosing of FLU based on response results in using lower numbers of monthly cycles per treatment course, lower incidence of severe infections, and equivalent (based on historical controls) overall survival.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    URL: Article
    DOI: 10.1182/blood.V108.11.4977.4977
    RVK:
    XA 33000
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2006
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
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    Targeted treatment of chronic myeloid leukemia: role of imatinib
    Informa UK Limited ; 2009
    In:  OncoTargets and Therapy
    Details
    In: OncoTargets and Therapy, Informa UK Limited
    Type of Medium: Online Resource
    ISSN: 1178-6930
    URL: Journal
    URL: Article
    DOI: 10.2147/OTT
    DOI: 10.2147/OTT.S3993
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2009
    detail.hit.zdb_id: 2495130-4
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  • 10
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    PI CME driven interventions in an outpatient oncology practice to improve awareness and utilization of advanced care directives.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e20508-e20508
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e20508-e20508
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.e20508
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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