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• W4250930990 abstract "International Journal of Hematologic OncologyVol. 1, No. 2 News & ViewsFree AccessJournal Watch: Our panel of experts highlight the most important research articles across the spectrum of topics relevant to the field of hematologic oncologyStefano Molica & Simon J HarrisonStefano MolicaGeneral Hospital “Pugliese–Ciaccio”, Catanzaro, ItalySearch for more papers by this author & Simon J HarrisonPeter MacCallum Cancer Centre, VIC, AustraliaSearch for more papers by this authorPublished Online:18 Dec 2012https://doi.org/10.2217/ijh.12.23AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareShare onFacebookTwitterLinkedInRedditEmail Toor AA, Payne KK, Chung HM et al. Epigenetic induction of adaptive immune response in multiple myeloma: sequential azacitidine and lenalidomide generate cancer testis antigen-specific cellular immunity. Br. J. Haematol. 158(6), 700–701 (2012).The use of cell-based immune therapy is gaining increased traction, with striking efficacy shown in studies such as those in chronic lymphoid leukemia by June and coworkers [1].Toor and coworkers hypothesized that as cancer testis antigen (CTA) expression is modified by methylation of CpG islands, and azacytidine (Aza) may increase CTA expression in tumor models, Aza therapy may induce CTA-specifc T-cell responses, and these responses may be boosted in vivo using the stimulatory effects of lenalidomide on natural killer and T cells. They designed a clinical trial to collect autologous lymphocytes on day 21 of the second and third cycles of Aza 75 mg/m2 subcutaneous injection days 1–5 and lenalidomide 10 mg days 6–21.Autologous lymphocytes (dose of cells infused: 2.0 ± 1.0 × 108 CD3+ cells/kg) were reinfused between days 30–60 following a high-dose melphalan stem cell transplant during which GM-CSF (sargramostim 5 µg/kg/day) was administered from day 4 post-transplant for hematopoietic engraftment and to augment dendritic cell function. Fourteen patients have been enrolled following a median of two prior regimens.There are a large number of CTA and this study examined the expression of a number of these within the context of the study. An increase in CTA-reactive T-cell responses was seen in three out of three patients tested.This study supports the hypothesis that it is feasible to induce in vivo antitumor immune responses in patients with refractory multiple myeloma, although the induction regimen had modest antitumor efficacy.– Written by Simon HarrisonNgoma T, Adde M, Durosinmi M et al. Treatment of Burkitt lymphoma in equatorial Africa using a simple three-drug combination followed by a salvage regimen for patients with persistent or recurrent disease. Br. J. Haematol. 158(6), 749–762 (2012).The treatment of endemic Burkitt lymphoma in equatorial Africa has previously resulted in dismal outcomes with survival in the range of 10–20%. Although combination chemotherapeutic regimens, such as CODOX-M/IVAC, as used in Europe and the USA, induce high rates of remission, they are not suitable in this context due to the high cost and toxicity. The authors devised a low-cost regimen consisting of cyclophosphamide, methotrexate, vincristine and intrathecal therapy, and a noncross-resistant second-line (salvage) regimen using ifosfamide, mesna, etoposide and cytarabine when patients failed to achieve a complete response to first-line therapy or relapsed early. Patients ranged in age from 2 to 59 years, with a median age of 7 years. Overall survival rates of 67 and 62% were observed at 1 and 2 years, respectively (relapse is rare after 1 year of remission). These striking results show that, with careful modifications to regimens, modern combination therapy may be delivered in this population and improve outcomes cost-effectively.– Written by Simon HarrisonSiegel DS, Martin T, Wang M et al. A Phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood 120(14), 2817–2825 (2012).In a recent issue of Blood, Siegel and coworkers report the results of a large Phase II trial of the new proteasome inhibitor carfilzomib in patients with progressive multiple myeloma previously treated with different effective agents including bortezomib. Carfilzomib is a proteasome inhibitor that irreversibly binds to the proteasome, primarily inhibiting the chymotrypsin-like activity of this enzyme. Results of this trial demonstrated that carfilzomib used as a single agent provided an overall response rate of 23.7%. Progression-free survival was relatively short at 3.7 months; however, the duration of response for patients judged at least in partial remission was 7.8 months and did not reflect response to previous therapies. As a matter of fact, results in terms of response were also consistent in patients who were previously treated with either bortezomib or lenalidomide, which accounted for 80% of the entire series. The median survival of the entire group was also promising, at 15.6 months. Interestingly, patients with double-refractory disease (i.e., refractory to both bortezomib and lenalidomide) experienced an overall survival of approximately 1 year.In conclusion, results of this Phase II trial led authors to argue that durable responses and an acceptable tolerability profile in this heavily pretreated population qualify carfilzomib as a reliable therapeutic option for double refractory multiple myeloma patients.– Written by Stefano MolicaSolal-Céligny P, Bellei M, Marcheselli L et al. Watchful waiting in low-tumor burden follicular lymphoma in the rituximab era: results of an F2-study database. J. Clin. Oncol. 30(31), 3848–3853 (2012).A prospective collection of clinical, pathologic, biologic and therapeutic parameters of patients with follicular lymphoma (FL) was launched in 2003 by the International Follicular Lymphoma Prognostic Factor Project. The project, known as the F2-study, was aimed to prospectively validate the Follicular Lymphoma International Prognostic Index to propose an accurate and up-to-date index for progression-free survival.The present subset analysis of F2-study addresses the clinical impact of a ‘watch and wait’ policy in the rituximab era. For this purpose 107 patients selected from the 1093 treatment-naive patients with FL in the F2-study cohort were considered suitable for the analysis.After a median follow-up time of 64 months, 54 patients (50%) needed therapy. Variables predictive of a shorter time to first treatment were in univariate analysis, involvement of more than four nodal areas (hazard ratio [HR]: 2.26) and serum albumin less than 3.5 g/dl (HR: 3.51). Only involvement of more than four nodal areas retained its significance in multivariate analysis (HR: 2.32). Interestingly, the 4-year freedom from treatment failure rate of watch and wait patients was not inferior to that of a subgroup of 242 patients from the F2-study cohort with good prognosis characteristics, who were initially treated with a rituximab-based regimen (p = 0.103).This study provides relevant information on the management of patients with FL, therefore suggesting that observation remains the gold standard when dealing with asymptomatic patients with low-tumor-burden FL.– Written by Stefano MolicaMoreira J, Rabe KG, Cerhan JR et al. Infectious complications among individuals with clinical monoclonal B-cell lymphocytosis (MBL): a cohort study of newly diagnosed cases compared to controls. Leukemia doi:10.1038/leu.2012.187 (2012) (Epub ahead of print).For individuals with clinical monoclonal B-cell lymphocytosis (MBL) the risk of progression to chronic lymphocytic leukemia (CLL) has been evaluated in several well-conducted studies. However, it is unknown whether other complications generally associated with CLL, such as increased risk of infection, also occur in individuals with MBL. In this study investigators at the Mayo Clinic evaluated 154 newly diagnosed MBL and 174 newly diagnosed CLL patients who resided within 50 miles of the Mayo Clinic. A cohort of 689 adult patients seen for a general medical examination, who resided within 50 miles of Mayo clinic and who were enrolled in a case–control study of non-Hodgkin’s lymphoma, was used as a comparison cohort. Individuals with newly diagnosed clinical MBL had a 6.5-fold risk of hospitalization for infection in comparison to the control cohort. MBL was an independent risk factor for hospitalization for infection after controlling for age and sex. These results suggest that the risk of developing serious infection in subjects with clinical MBL is consistently high and should be seriously considered during the follow-up. In addition, physicians should provide individuals with clinical MBL with complete information on the potential infectious risk.– Written by Stefano Molicavon Grünigen I, Raschle J, Rüsges-Wolter I, Taleghani BM, Mueller BU, Pabst T. The relapse risk of AML patients undergoing autologous transplantation correlates with the stem cell mobilizing potential. Leuk. Res. 36(11), 1325–1329 (2012); Schuurhuis GJ, Zweegman S, Ossenkoppele GJ. The adverse prognosis for acute myeloid leukemia patients with superior autologous stem cell mobilization. Leuk. Res. 36(11), 1323–1324 (2012).The debate about stem cell dose and stem cell source for use in autologous stem cell transplantation for acute myeloid leukemia has been running since the advent of these techniques. It seems to be clear that patients who are supermobilizers (i.e., mobilize in excess of 60 CD34+ cells per µl) have a poorer outcome in terms of overall survival and time to progression because the grafts contain increased numbers of leukemic stem cells. The question is, why? There are two possible explanations. Patients who mobilize high numbers of cd34+ cells proportionately mobilize more leukemic cells that contaminate the graft and contribute to higher risk of relapse. The alternate theory is that patients mobilize more CD34+ cells because they have different pharmacokinetics, resulting in less impact on the normal and leukemic stem cell pools; therefore, they mobilize greater numbers of normal and leukemic cells. This suggests that we may be able to predict outcome using both the level of minimal residual disease and the peak number of CD34+ cells mobilized in the blood and ‘more’ is definitely not ‘better’ in this context.– Written by Simon HarrisonFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.Reference1 Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N. Engl. J. Med.365(8),725–733 (2011).Crossref, Medline, CAS, Google ScholarFiguresReferencesRelatedDetails Vol. 1, No. 2 Follow us on social media for the latest updates Metrics Downloaded 178 times History Published online 18 December 2012 Published in print December 2012 Information© Future Medicine LtdFinancial & competing interests disclosureThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.No writing assistance was utilized in the production of this manuscript.PDF download" @default.
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