Clinical Lymphoma and Myeloma最新文献

{"title":"Serum Levels of Total-RANKL in Multiple Myeloma","authors":"Christian Jakob ,&nbsp;Andrea Goerke ,&nbsp;Evangelos Terpos ,&nbsp;Jan Sterz ,&nbsp;Ulrike Heider ,&nbsp;Dagmar Kühnhardt ,&nbsp;Susanne Ziefle ,&nbsp;Lorenz Kleeberg ,&nbsp;Maren Mieth ,&nbsp;Ivana von Metzler ,&nbsp;Christian Müller ,&nbsp;Orhan Sezer","doi":"10.3816/CLM.2009.n.085","DOIUrl":"10.3816/CLM.2009.n.085","url":null,"abstract":"<div><h3>Background</h3><p>Receptor activator of nuclear factor-κB ligand (RANKL) plays a key role in osteoclast activation in myeloma bone disease. The increased expression of RANKL in the bone marrow microenvironment was demonstrated in several studies, but there are only rare data on circulating RANKL levels in patients with multiple myeloma (MM).</p></div><div><h3>Patients and Methods</h3><p>In the current study, we investigated the clinical significance of serum RANKL levels, using an enzyme-linked immunosorbent assay test that detects both free and osteoprotegerin (OPG)-bound RANKL (total-RANKL, tRANKL) in patients with newly diagnosed MM (n = 93) and monoclonal gammopathy of undetermined significance (MGUS; n = 20) compared with healthy controls (n = 20).</p></div><div><h3>Results</h3><p>Circulating serum tRANKL was significantly elevated in patients with MM compared with controls (<em>P</em> &lt; .001) or MGUS (<em>P</em> &lt; .001). Furthermore, tRANKL levels were higher in smoldering MM versus MGUS (<em>P</em> = .031) and in symptomatic versus smoldering MM (<em>P</em> &lt; .001). Serum tRANKL increased parallel to International Staging System stages I to III (<em>P</em> = .004) and correlated with the presence of lytic bone lesions (<em>P</em> &lt; .001). Total-RANKL was a prognostic factor for overall survival in symptomatic MM (<em>P</em> = .043). A significantly longer progression-free survival was observed in patients with a &gt; 50% decrease in tRANKL levels after 3 months of combined chemotherapy and bisphosphonate treatment.</p></div><div><h3>Conclusion</h3><p>Our study demonstrates for the first time that serum tRANKL reflects advanced disease, lytic bone destruction, and poor prognosis in MM.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.085","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28540763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metronomic Cyclophosphamide and Vinblastine in Refractory Lymphoma","authors":"Filip Geurs,&nbsp;Luc Derveaux,&nbsp;Jelke Verwimp","doi":"10.3816/CLM.2009.n.095","DOIUrl":"10.3816/CLM.2009.n.095","url":null,"abstract":"<div><h3>Introduction</h3><p>A recent phase I report drew attention to the effectiveness of metronomic (daily low-dose oral) CPA and I.V. vinblastine in refractory Hodgkin disease.¹ We used this combination in a patient with Hodgkin lymphoma and extensive prior treatment. The regimen was adapted to include rituximab for another patient who was unfit for R-CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone plus rituximab) therapy due to prior myocardial infarction.</p></div><div><h3>Case 1</h3><p>A 56-year-old patient had first-line chemotherapy for Hodgkin lymphoma stage IVB in 2004, treated with ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine). A year later a recurrence was treated with stem cell transplantation. He presented in February 2008 with extensive bone metastases, for which 45 Gy radiotherapy was given, also with curative intent. In April 2008 we started with metronomic chemotherapy (cyclophosphamide 50 mg + methylprednisolone 32 mg per day orally, vinblastine 3 mg/m² intravenously [I.V.] 1 × per week) for retroperitoneal lymph node recurrence. This treatment was well tolerated. After 9 months of treatment, there were no lymph nodes detectable on computed tomography scan. Complete remission now lasts &gt; 3 months.</p></div><div><h3>Case 2</h3><p>An 81-year-old farmer had a myocardial infarction 40 years ago. He presented with cutaneous involvement and axillary lymph node. Biopsy showed a cutaneous involvement by B-cell diffuse large-cell lymphoma. International Prognostic Index score was low. Ejection fraction was 42%. The same chemotherapy was applied (cyclophosphamide 50 mg/d and methylprednisolone 32 mg per day, vinblastine I.V. days 1, 8, 15), but on day 22 of the 28-day cycle, we applied rituximab 375 mg/m². The patient had a complete remission after 4 months of treatment.</p></div><div><h3>Conclusion</h3><p>These data confirm the effectiveness of this well-tolerated regimen in refractory lymphoma as well as in a lymphoma patient unfit for anthracyclines.</p></div><div><h3>Reference</h3><p>Young S, Whissell M, Noble JC. Phase II clinical results involving treatment with low-dose daily oral cyclophosphamide, weekly vinblastine, and rofecoxib in patients with advanced solid tumors. <em>Clin Cancer Res</em> 2006; 12; 3092-9.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.095","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"96795714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behçet's Disease in a Patient With Myelodysplastic Syndrome","authors":"Erzsebet Kovacs ,&nbsp;Hajnalka Nemeth ,&nbsp;Bela Telek ,&nbsp;Aniko Ujfalusi ,&nbsp;Erzsebet Balogh ,&nbsp;Eva Pasztor ,&nbsp;Gyorgy Pfliegler","doi":"10.3816/CLM.2009.n.090","DOIUrl":"10.3816/CLM.2009.n.090","url":null,"abstract":"<div><p>A 75-year-old man presented with painful oral and groin ulcers. The lack of any infections and the location of the ulcers suggested Behçet's disease. Subsequently, pancytopenia developed and bone marrow examination revealed myelodysplastic syndrome. Cytogenetic examination revealed 7q— and 20q— but not 8+. Immunosuppressive therapy with cyclosporine and corticosteroid resulted in a dramatic improvement in both clinical signs and hematologic abnormalities.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.090","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28540110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Platelet Aggregation a Useful Investigation in Assessing the Risk of Thrombosis in Patients With JAK-Positive Chronic Myeloproliferative Disorders? Brief Report: A Study on 14 Patients","authors":"V.M. Popov ,&nbsp;A.M. Vladareanu ,&nbsp;H. Bumbea ,&nbsp;D. Casleanu ,&nbsp;A. Ilea ,&nbsp;M. Onisai ,&nbsp;A. Nicolescu ,&nbsp;C. Marinescu ,&nbsp;C. Ciufu ,&nbsp;I. Voican ,&nbsp;M. Begu ,&nbsp;A.M. Vintilescu ,&nbsp;C. Dobrea ,&nbsp;E. Kovacs ,&nbsp;T. Savopol","doi":"10.3816/CLM.2009.n.106","DOIUrl":"10.3816/CLM.2009.n.106","url":null,"abstract":"<div><p>Patients with chronic myeloproliferative disorders have frequently thrombosis, especially for JAK2-positive patients. The aim of this study is to identify and correlate abnormalities of platelet aggregation for 14 JAK-positive patients, with thrombosis incidence. Thromboses were present more frequently in the JAK-positive group than the JAK-negative group. Patients with JAK2 genotype have more diminished platelet response for ADP, epinephrine, and collagen than the JAK-negative group and normal response for ristocetin, but these results do not have statistical significance to correlate with a higher risk of thrombosis</p></div><div><h3>Full Abstract</h3><p></p></div><div><h3>Background</h3><p>Patients with chronic myeloproliferative disorders (CMPD) have a variety of structural and functional abnormalities of platelets. JAK2, which is constitutively activated in most patients with CMPD, might be involved in signal transduction for thrombopoietin-induced aggregation of platelets in these disorders. The patients with JAK2-positive CMPD have a higher incidence of venous thrombosis compared with noncarriers; these are more frequent in patients with the wild-type JAK2 genotype.</p></div><div><h3>Aim</h3><p>We aim to identify abnormalities of platelet aggregation for CMPD patients with JAK present and to correlate these findings with increased risk of thrombosis.</p></div><div><h3>Materials and Methods</h3><p>We present a retrospective study on 14 cases with JAK2-positive CMPD compared with 6 cases with JAK2-negative CMPD admitted in University Emergency Hospital Bucharest. We analyzed the clinical and laboratory parameters for both groups. Platelet function was investigated by platelet aggregation on Chrono-log aggregometer. As stimuli, we used ADP, collagen, epinephrine, and ristocetin.</p></div><div><h3>Results and Discussion</h3><p>We studied 14 JAK2-positive patients (5 patients, ET; 6, PV; 1, IMF; and 2, unclassifiable CMPD), 9 men and 5 women, with a median age of 58.35 years; and 6 JAK2-negative patients (1 patient, ET; 2, PV; 3, IMF), 4 men and 2 women, with a median age of 67.16 years. Thrombosis was present in 69.12% of the JAK2-positive patients. Of these, 3 patients presented with portal vein thrombosis as the first clinical manifestation; all 3 patients were young (median age, 33 years). Ischemic stroke was presented in 5 patients (median age, 74.75 years), arterial or venal thrombosis in 2 patients. Patients who were JAK negative rarely presented with thrombosis (1 patient in our study). Platelet aggregation studies showed decreased response to ADP (49.75 vs. 50.92), epinephrine (23.05 vs. 11.53), and collagen (42.93 vs. 66.51). For ristocetin, we obtained normal value for JAK2-positive patients (60.67 vs. 44). We also obtained higher duration of collagen lag phase for JAK2-positive patients (153.97 vs. 61.57) and no differences for amplitude or duration of ADP lag phase (4.27 vs. 5.1; 8.14 vs. 9.46) or amplitude of collagen lag ","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.106","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76843198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Complex Immunophenotypic Changes as Prognosis Panel in Chronic Lymphocytic Leukemia","authors":"Horia Bumbea ,&nbsp;Sanziana Radesi ,&nbsp;Ana-Maria Vladareanu ,&nbsp;Viviana Roman ,&nbsp;Anamaria Vintilescu","doi":"10.3816/CLM.2009.n.099","DOIUrl":"10.3816/CLM.2009.n.099","url":null,"abstract":"<div><p>The present study proposes to asses the prognosis with consecrated markers CD38 and the new ZAP-70 related to the various patterns of CLL complex immunophenotype: cyclin D1, CD38, CD20, FMC7, CD23. This particular combination could be used as a prognosis panel in CLL.</p></div><div><h3>Brief Abstract</h3><p></p></div><div><h3>Background</h3><p>Chronic lymphocytic leukemia (CLL) has many other prognostic markers established in the past years related to disease and to the patient status, and the most important seem to now be immunophenotypical, genetic, and molecular. CD38 and ZAP-70 are now used in a strong prognosis panel of markers for CLL.</p></div><div><h3>Aims</h3><p>The present study proposes to assess the prognosis with consecrated markers CD38 and the new ZAP-70 related to the various patterns of CLL immunophenotype.</p></div><div><h3>Patients and Methods</h3><p>We have analyzed 187 patients diagnosed with CLL in order to find correlations between clinical stage, immunophenotype, and outcome.</p></div><div><h3>Results</h3><p>We found correlations between expression of CD38 related to clinical outcome, (dr: 0.541; <em>P</em> &lt; .05.), and between ZAP-70 and CD38 (dr: 0.666; <em>P</em> = .018). The expression of BCL-2 was correlated to outcome (dr: 0.533; <em>P</em> &lt; .01) and response to treatment (dr: 0.420; <em>P</em> &lt; .01). Cyclin D1 expression was found in correlation with outcome (<em>P</em> = .014) and BCL-2 expression (<em>P</em> = .034). Lower expression CD23 was associated with poor outcome and expression of CD38 and ZAP-70 (<em>P</em> value &lt; .05; dr: —0.117). We found in patients with cyclin D1 positive comparative to those cyclin D1 negative the association of high intensity CD20⁺ (28% vs. 3%), FMC7⁺ (33% vs. 8%), and lower CD23 (30%-60% vs. &gt; 60%). Also, CD38 was positive in 44% vs. 10% and ZAP-70 in 66% versus 5%. This association defines a “lymphoma”-like immunophenotype for cyclin D1—positive cases. Treatment was chlorambucil, fludarabine/cyclophosphamide (FC), or FC + rituximab (FCR).</p></div><div><h3>Conclusion</h3><p>Flow cytometry is the most practical method used in CLL for diagnosis and prognosis evaluation. The immunophenotypical markers surrogate for IgVH mutation status, as CD38 and ZAP-70 have a strong correlation with outcome in CLL, and our results found that analysis by flow cytometry of both CD38 and ZAP-70 could be used in the evaluation of patients with CLL as strong prognosis markers. The complex immunophenotype in CLL could be used to define 2 main prognosis patterns: (1) cyclin D1—positive, CD38 positive, CD20 high, FMC7 positive, CD23 weak with poor prognosis; and (2) cyclin D1—negative, CD38 negative, CD20 low, FMC7 negative, CD23 high with good prognosis. These patterns have strong association with expression of ZAP-70 and could be used as prognosis assessment of patients with CLL.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.099","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82158590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ofatumumab, a Novel CD20 Monoclonal Antibody, Is Active in Patients With Fludarabine- and Alemtuzumab-Refractory or Bulky Fludarabine-Refractory Chronic Lymphocytic Leukemia Irrespective of Prior Rituximab","authors":"William Wierda ,&nbsp;Thomas Kipps ,&nbsp;Jiří Mayer ,&nbsp;Stephan Stilgenbauer ,&nbsp;Cathy D. Williams ,&nbsp;Andrzej Hellmann ,&nbsp;Tadeusz Robak ,&nbsp;Richard R. Furman ,&nbsp;Peter Hillmen ,&nbsp;Marek Trneny ,&nbsp;Martin J.S. Dyer ,&nbsp;Swami Padmanabhan ,&nbsp;Magdalena Piotrowska ,&nbsp;Tomas Kozak ,&nbsp;Geoffrey Chan ,&nbsp;Randy Davis ,&nbsp;Nedjad Losic ,&nbsp;Joris Wilms ,&nbsp;Charlotte Russell ,&nbsp;Anders Österborg","doi":"10.3816/CLM.2009.n.098","DOIUrl":"10.3816/CLM.2009.n.098","url":null,"abstract":"<div><p>Ofatumumab, a novel CD20 monoclonal antibody, produces high response rates regardless of prior rituximab exposure in patients with fludarabine- and alemtuzumab-refractory or bulky fludarabine-refractory chronic lymphocytic leukemia.</p></div><div><h3>Full Abstract</h3><p></p></div><div><h3>Background</h3><p>Patients with CLL refractory to fludarabine and alemtuzumab (FA-ref) or refractory to fludarabine with bulky (&gt; 5 cm) lymphadenopathy (BF-ref) have poor outcomes with current salvage therapy (overall response rate [ORR], 23%; overall survival [OS], 9 months). Ofatumumab is a human monoclonal antibody that binds a distinct membrane-proximal epitope on the CD20 molecule and elicits more efficient in vitro complement-dependent cytotoxicity of B-cell lines and primary tumor cells versus rituximab. We assessed whether prior rituximab exposure impacted outcomes with ofatumumab in patients with FA-ref or BF-ref CLL enrolled in an international, pivotal trial.</p></div><div><h3>Patients and Methods</h3><p>Patients received 8 weekly ofatumumab infusions followed by 4 monthly infusions (infusion, 1300 mg; infusions 2–12, 2000 mg). The primary endpoint was ORR (1996 NCI-WG criteria) assessed by an Independent Endpoint Review Committee over 24 weeks. Secondary efficacy endpoints included progression-free survival (PFS) and OS.</p></div><div><h3>Results</h3><p>In the 59 FA-ref and 79 BF-ref patients at the planned interim analysis, ORR was 58% (95% CI, 40%–74%) and 47% (95% CI, 32%-62%), respectively. Median PFS was 5.7 months (95% CI, 4.5–8.0 months) and 5.9 months (95% CI, 4.9–6.4 months), and median OS was 13.7 months (95% CI, 9.4-[not yet reached] months) and 15.4 months (95% CI, 10.2-20.2 months), respectively. In the subgroup of FA-ref (n = 35) and BF-ref (n = 43) patients who previously received a rituximab-containing regimen, ORR was 54% and 44%, and median PFS was 5.5 months (95% CI, 3.7–8.0 months) and 5.5 months (95% CI, 3.8–6.4 months), respectively. In FA-ref and BF-ref patients refractory to fludarabine in combination with rituximab and cyclophosphamide (n = 16 in each group), ORR was 50% and 44%, and median PFS was 4.6 months (95% CI, 2.3–6.4 months) and 5.6 months (95% CI, 2.1–6.6 months), respectively.</p></div><div><h3>Conclusion</h3><p>Single-agent ofatumumab is active in patients with FA-ref and BF-ref CLL, irrespective of prior anti-CD20 monoclonal antibody therapy with rituximab, including refractoriness to fludarabine-based regimens containing rituximab.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.098","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85839847","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Outcomes of Autologous Transplantation in Multiple Myeloma: Significant Survival Benefit of Novel Drugs in Post-Transplantation Relapse","authors":"Marta Krejci ,&nbsp;Vlastimil Scudla ,&nbsp;Elen Tothova ,&nbsp;Miroslava Schutzova ,&nbsp;Vladimir Koza ,&nbsp;Zdenek Adam ,&nbsp;Andrea Krivanova ,&nbsp;Ludek Pour ,&nbsp;Tomas Buchler ,&nbsp;Viera Sandecka ,&nbsp;Dana Kralova ,&nbsp;Lenka Zahradova ,&nbsp;Jiri Vorlicek ,&nbsp;Jiri Mayer ,&nbsp;Roman Hajek","doi":"10.3816/CLM.2009.n.086","DOIUrl":"10.3816/CLM.2009.n.086","url":null,"abstract":"<div><h3>Background</h3><p>Autologous stem cell transplantation (autoSCT) has an important role in the treatment of patients with symptomatic multiple myeloma (MM). Treatment options for myeloma have expanded in the past decade, and it seems that patients who are treated with novel drugs such as thalidomide and bortezomib for relapse after autoSCT have longer overall survival (OS).</p></div><div><h3>Patients and Methods</h3><p>Herein, we describe the long-term outcome of a cohort of 185 patients with newly diagnosed MM treated with autoSCT. We have analyzed factors that might predict for long-term survival.</p></div><div><h3>Results</h3><p>Following autoSCT, the overall response rate was 94% (173 of 185 patients); 29% (53 of 185 patients) were in complete remission (CR). Median time to progression (TTP) and OS from start of therapy were 39.8 months and 77.9 months, respectively. The median follow-up was 103.8 months (range, 60.8-144.8 months); 23% of the patients are alive and disease free, 21% of the patients are alive with relapse, and 56% of the patients have died. On multivariate analysis, factors associated with significantly better OS were International Staging System (ISS) disease stage &lt; III (hazard ratio [HR], 2.6; <em>P</em> &lt; .001), achievement of CR after autoSCT (HR, 2.8; <em>P</em> &lt; .001) and use of thalidomide (HR, 4.3; <em>P</em> &lt; .001) and/or bortezomib (HR, 7.3; <em>P</em> &lt; .001) in posttransplantation relapse treatment. The patients' age, renal impairment, disease status before autoSCT and maintenance therapy with interferon-α (IFN-α) or IFN-α and dexamethasone did not significantly affect TTP and OS after transplantation.</p></div><div><h3>Conclusion</h3><p>According to our results, the achievement of CR after transplantation, ISS stage other than III, and administration of thalidomide or bortezomib in posttransplantation relapse were significant parameters favoring long-term posttransplantation survival.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.086","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28540764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Next Generation of Therapies for Chronic Myeloid Leukemia","authors":"Alfonso Quintás-Cardama ,&nbsp;Jorge E. Cortés","doi":"10.3816/CLM.2009.s.040","DOIUrl":"10.3816/CLM.2009.s.040","url":null,"abstract":"<div><p>Therapy with the tyrosine kinase inhibitor (TKI) represents the current standard first-line therapy for the management of patients with chronic myeloid leukemia (CML). Although most patients respond satisfactorily to imatinib, a subset of patients develops resistance mainly because of the acquisition of mutations within the kinase domain of <em>BCR-ABL1</em> that impair the ability of TKIs to block the activity of the enzyme. Moreover, <em>BCR-ABL1</em> transcripts can be detected in most patients by molecular techniques, underscoring the limitations of imatinib to eradicate minimal residual disease. Although the resistance conferred by most <em>BCR-ABL1</em> mutations can be overcome with the use of second-generation TKIs such as nilotinib, dasastinib, bosutinib, or bafetinib, the T315I mutation, which represents a common resistance pathway in CML, remains unassailable to TKI therapy. We herein discuss current research efforts in 2 areas of vital importance in CML research, the management of patients with imatinib-resistant mutations, with particular emphasis on those carrying T315I, and the eradication of residual disease.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.s.040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10647843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Effect of Zoledronic Acid on the Prevention of Bone Loss in Lymphoma Patients Receiving First-line Therapy","authors":"Jason Westin ,&nbsp;Fredrick Hagemeister ,&nbsp;Michael A. Thompson ,&nbsp;Vince D. Cataldo ,&nbsp;Bela B. Toth ,&nbsp;Perpetua Sanjorjo ,&nbsp;Scott Bourgeois ,&nbsp;Camilo Jimenez ,&nbsp;William A. Murphy ,&nbsp;Michelle Fanale ,&nbsp;Luis Fayad ,&nbsp;Nathan Fowler ,&nbsp;Larry Kwak ,&nbsp;Peter McLaughlin ,&nbsp;Sattva Neelapu ,&nbsp;Barbara Pro ,&nbsp;Alma Rodriguez ,&nbsp;Jatin Shah","doi":"10.3816/CLM.2009.n.092","DOIUrl":"10.3816/CLM.2009.n.092","url":null,"abstract":"<div><p>Patients with lymphoma are at high risk of osteoporosis. The majority have osteopenia at baseline, and the risk increases when treated with alkylating agents or corticosteroids. We conducted a randomized phase III trial to evaluate the effect of zoledronic acid on bone mineral density (BMD) in patients with lymphoma undergoing chemotherapy.</p></div><div><h3>Full Abstract</h3><p></p></div><div><h3>Introduction</h3><p>Osteoporotic bone cannot easily be restored to normal levels of strength; thus, the prevention of bone loss is crucial. Pamidronate can reduce the risk of bone loss and vertebral fractures in patients with lymphoma receiving chemotherapy. Zoledronic acid, a bisphosphonate approximately 100-fold more potent than pamidronate, has not been evaluated in lymphoma patients to date. We conducted a prospective trial to determine whether zoledronic acid reduces the risk of developing osteoporosis in this patient population.</p></div><div><h3>Patients and Methods</h3><p>All patients with newly diagnosed lymphoma seen at our institution from 2005 to 2009 were evaluated for protocol eligibility. Exclusion criteria included bone fractures, bone mineral density (BMD) T-scores poorer than −2.0, creatinine clearance &lt; 60 mL/min, dental problems, and recent steroid or bisphosphonate use. Patients on study were stratified according to sex and menopausal status. Accrued patients received randomized therapy of either: (1) oral calcium and vitamin D (Ca + D), or (2) Ca + D and 4 mg zoledronic acid intravenously (I.V.) at baseline and at 6 months.</p></div><div><h3>Results</h3><p>To date, 33 patients have completed the study and have evaluable data. Patient characteristics included 17 men; 4 pre-menopausal women; 12 post-menopausal women; and median age, 62 years (range, 33–80 years). Seventeen patients had mild osteopenia upon enrollment. Patients who received zoledronic acid had stable median T-scores at all locations during the 12-month observation, whereas the T-scores of the control group decreased at every location evaluated (location: L1-4, <em>P</em> = .004; L neck, <em>P</em> = .001; L hip, <em>P</em> = .118; R neck, <em>P</em> = .009; R hip, <em>P</em> = .04).</p></div><div><h3>Conclusion</h3><p>Treatment with zoledronic acid in patients with newly diagnosed lymphoma prevents the BMD loss commonly seen in this population. Bone mass loss is difficult to restore, thus necessitating effective prevention strategies; additional studies should be conducted to confirm these findings.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.092","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80834272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Concomitant or Sequential Chronic Lymphocytic Leukemia (CLL) and Chronic Myeloid Leukemia (CML): A Molecular and Clinical Survey","authors":"Carla Said ,&nbsp;P. Heimann ,&nbsp;B. Dessars ,&nbsp;Dinh Phong ,&nbsp;B. Cantiniaux ,&nbsp;N. Meuleman ,&nbsp;D. Bron","doi":"10.3816/CLM.2009.n.096","DOIUrl":"10.3816/CLM.2009.n.096","url":null,"abstract":"<div><p>A 75-year-old man presented with B-CLL followed by a CML. We retrospectively analyzed the frozen BM and PB lymphocytes that evidenced 2 distinct clonal proliferations: one is a B CD5⁺/CD19⁺ lymphocyte population, without BCR-ABL fusion; the other is the CD19⁺ mononuclear cell population expressing traces of BCR-ABL, 3 years before the occurrence of CML. We suggest that (1) the emergence of the Ph⁺ clone after the treatment of CLL is probably related to RFC-induced immunosuppression, and (2) the long DFS of CLL might be due to the current TK inhibitor treatment</p></div><div><h3>Full Abstract</h3><p></p></div><div><h3>Introduction</h3><p>The coexistence of B-cell chronic lymphocytic leukemia (B-CLL) and chronic myeloid leukemia (CML) is a rare event. This coexistence has led to speculation of the clonal origin of these neoplasms. In some cases, 2 independent clones were demonstrated.</p></div><div><h3>Patients and Methods</h3><p>A 75-year-old man presented with splenomegaly and enlarged lymph nodes. Immunophenotype (kappa, CD19⁺, CD5⁺, CD23⁺) was compatible with B-CLL. Bone marrow examination showed infiltration by small lymphocytes next to a myeloid and megakaryocytic hyperplasia. Cytogenetic analysis of the marrow showed 46XY, del(16q). Philadelphia chromosome (Ph) was negative. The patient was diagnosed with B-CLL and treated by 6 RFC (rituximab/fludarabine/cyclophosphamide). He reached a molecular remission (MCR), but 3 years after the treatment for CLL, he developed hyperleukocytosis (26000/μL), mainly myeloid cells. Bone marrow smear demonstrated a myeloid hyperplasia with predominance of immature progenitors. The Ph was clearly evidenced, and CML was confirmed. The patient thus received thus imatinib 400 mg/day orally with hematologic but only partial molecular remission at 18 months. A Y25.3H mutation was detected, and the patient was switched to dasatinib with a successful evolution. The CLL remained in MCR during this 5-year period.</p></div><div><h3>Results</h3><p>To know whether CML is a secondary event induced by RFC treatment or the emergence of a latent CML clone, we analyzed retrospectively the frozen BM and PBL lymphocytes. The results were consistent with the view that there are 2 distinct clonal proliferations: one is a clonal B CD5⁺/CD19⁺ lymphocyte population, without BCR-ABL fusion; the other is the CD19⁺ mononuclear cell population expressing traces of BCR-ABL, 3 years before the occurrence of CML.</p></div><div><h3>Conclusion</h3><p>Our data provide evidence for a separate clonal origin for each disorder, raising the hypothesis that (1) the emergence of the Ph⁺ clone after the treatment of CLL is probably related to RFC-induced immunosuppression, and (2) the long disease-free survival of CLL might be due to the current tyrosine kinase inhibitor treatment.</p></div>","PeriodicalId":100272,"journal":{"name":"Clinical Lymphoma and Myeloma","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2009-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3816/CLM.2009.n.096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89839795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}