International Journal of Hematologic Oncology最新文献

{"title":"Chronic lymphocytic leukemia paradigm continues to be refined: news from the American Society of Hematology 2018 annual meeting","authors":"S. Molica","doi":"10.2217/ijh-2019-0001","DOIUrl":"https://doi.org/10.2217/ijh-2019-0001","url":null,"abstract":"There were a number of important updates and advances presented at the 2018 Annual American Society of Hematology meeting. With respect to the treatment of chronic lymphocytic leukemia, the American Society of Hematology 2018 was notable for an improved understanding of ibrutinib-based therapies. In fact, three prospective Phase III trials presented at the meeting indicate, in turn, that ibrutinib alone, ibrutinib plus rituximab, or ibrutinib plus obinutuzumab, should be the new standard of care for chronic lymphocytic leukemia. However, additional clinical trials comparing chemo-immunotherapy with ibrutinib alone or in association with an anti-CD20 monoclonal antibody remain a reasonable avenue to complete results of these large studies.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2019-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42924937","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":"Zebrafish MYC-induced leukemia models: unique <i>in vivo</i> systems to study B and T cell acute lymphoblastic leukemia.","authors":"Chiara Borga,&nbsp;John Kimble Frazer","doi":"10.2217/ijh-2018-0013","DOIUrl":"https://doi.org/10.2217/ijh-2018-0013","url":null,"abstract":"Over the past two decades, zebrafish (Danio rerio) has become an increasingly powerful in vivo oncology model system. Technical and practical advantages, such as their low cost, high fecundity and optical translucency, together with the ease of building transgenic zebrafish, all make D. rerio excellent for studying pathways altered in cancer and also facilitate their use in high-throughput anticarcinogenic chemical library/drug screens. In particular, both genetically and functionally, oncogenic and developmental hematopoietic pathways are highly conserved between teleost (bony) fish and mammals. These features have allowed the creation of zebrafish models mimicking several human hematopoietic malignancies, such as acute myeloid leukemia (AML) and T-cell lymphoblastic lymphoma (T-LBL) and acute lymphoblastic leukemia (T-ALL) [1,2]. Surprisingly, zebrafish B cell malignancy models lagged behind, with only a single 2006 report of pre-B-cell ALL (pre-B ALL) in a transgenic line expressing human ETV6-RUNX1 [3]. No subsequent publications using this line exist, likely because it exhibited low incidence and long latency, making it challenging to study. Recently, the scarcity of zebrafish B-cell leukemia models was addressed by the related but distinct discoveries [4,5] that B-ALL occurs in fish expressing either transgenic murine or human c-MYC (mMyc and hMYC, respectively), controlled by a zebrafish rag2 promoter, which is active in immature B and T lymphoblasts. Previously, these lines were thought to exclusively develop T-ALL [6,7], although a logical explanation for this exclusivity was lacking. As noted, in zebrafish and in mammals, rag2 is expressed by both B and T cell progenitors and MYC is known to drive B cell cancers like Burkitt lymphoma and B-ALL [8,9]. These recent papers proved that mMyc/hMYC-induced B-ALL occurs, but was apparently overlooked until now. In the paper by Garcia et al. [4], RNA-seq analysis of a cohort of 12 rag2:mMyc-induced monoclonal tumors [10] revealed the presence of B-ALL. Specifically, the authors found nine T-ALL, two pro-B ALL and one bi-phenotypic ALL that expressed both T and B lineage markers. In contrast, Borga et al. [5] used double-transgenic rag2:hMYC;lck:GFP fish, where differential lck expression drives distinct levels of GFP in Band Tcells, with B cells expressing less GFP than T cells. This study reported data from >50 hMYC-driven ALL, proving the existence of highly penetrant B-ALL that resembled human pre-B-ALL. Of note, the authors also found several instances of ’mixed’ ALL that was not the bi-phenotypic ALL described by Garcia et al., but rather simultaneous cases of Band T-ALL arising in the same animal. Notably, mMyc/hMYC zebrafish are the first animal models described to develop both T-ALL and B-ALL. This highlights MYC’s potency as an oncogene in both lymphocyte lineages, but MYC may use distinct molecular mechanisms and activate unique oncogenic pathways in Tversus B-ALL; these models provide","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":" ","pages":"IJH12"},"PeriodicalIF":0.0,"publicationDate":"2019-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2018-0013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37050360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Welcome to Volume 8 of the <i>International Journal of Hematologic Oncology</i>.","authors":"Jennifer Straiton","doi":"10.2217/ijh-2018-0012","DOIUrl":"https://doi.org/10.2217/ijh-2018-0012","url":null,"abstract":"As the new Editor for the International Journal of Hematologic Oncology, it is with great excitement that I introduce the first issue of Volume 8. The year 2019 has lots of interesting things to be excited about; new projects, new ideas and, of course, more excellent content from all of our authors. The return of our Journal Watch series will help to broaden the range of topics we are able to publish, increasing our coverage of the latest information in the field. However, before we start this new period I would like to look back over the past year and our highlights from 2018. The year 2018 was a year of change for the editorial team at International Journal of Hematologic Oncology with new faces starting and the journal gaining recognition. Our presence on PubMed Central has been a huge help in widening our audience and increasing the reach of the articles we publish.","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":" ","pages":"IJH11"},"PeriodicalIF":0.0,"publicationDate":"2019-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2018-0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37050359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methods for reducing delays in the diagnosis of multiple myeloma.","authors":"Constantinos Koshiaris","doi":"10.2217/ijh-2018-0014","DOIUrl":"https://doi.org/10.2217/ijh-2018-0014","url":null,"abstract":"Multiple myeloma & diagnostic delays Myeloma is a hematological malignancy that starts in the bone marrow and mainly affects the elderly population with a median diagnosis age of 70 years old [1]. A systematic review has shown that patients with multiple myeloma experience long diagnostic intervals, with 50% of patients having waiting times longer than 3 months [2]. Myeloma patients also experience many consultations as 50% visit their primary care physician more than three times before they get referred to specialist services [3]. Longer time to diagnosis has been associated with more complications and worse disease-free survival [4]. Approximately 30% of myeloma patients are being diagnosed through emergency services and these patients have worse survival compared with patients being diagnosed through other routes [5,6]. More timely diagnosis could have a positive impact on myeloma patients both in terms of treatment options and subsequent survival and quality of life. Myeloma has been classified as one of the hardest cancers to diagnose and no single reason is responsible for the delays observed in diagnosis [7]. It is usually a combination of multiple factors which together form a very complex diagnostic picture. One of them is the rarity of the disease; in the UK, the yearly incidence is approximately nine per 100,000 population and it accounts for 2% of all cancer cases diagnosed every year [8]. A full-time primary care practitioner in the UK will diagnose on average one myeloma case every 5 years. The other main factor is the nonspecific nature of the symptoms that can include back pain, bone pain, fatigue and repeated infections [9]. These symptoms are also common in many other conditions of varying severity that makes it difficult to suspect myeloma as the underlying cause. Patients with comorbidities are also more likely to experience diagnostic delays as multiple comorbidities can mask myeloma-related symptoms [10].","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":" ","pages":"IJH13"},"PeriodicalIF":0.0,"publicationDate":"2019-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2018-0014","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37050361","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Checkpoint inhibition of PD-L1 and CTLA-4 in a child with refractory acute leukemia.","authors":"Larisa Broglie, Jill Gershan, Michael J Burke","doi":"10.2217/ijh-2018-0009","DOIUrl":"10.2217/ijh-2018-0009","url":null,"abstract":"<p><p>Children with multiple relapsed or refractory leukemia have dismal survival. Research has identified engagement of immune checkpoint receptors (e.g., PD-1, PD-L1 and CTLA-4) as a mechanism for treatment resistance. For adult cancer, inhibitors of PD-1 (nivolumab) and CTLA-4 (ipilimumab) have shown promise with response rates ranging from 7 to 40%. <i>In vitro</i> studies using acute myeloid leukemia cell lines have shown that acute myeloid leukemia blasts may similarly utilize the PD-1/PD-L1 axis to evade an anticancer immune response. We report the first case of a pediatric patient with multiple relapsed/refractory leukemia treated with nivolumab, ipilimumab and 5-azacytidine who tolerated therapy with brief improvement of symptoms.</p>","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":"8 1","pages":"IJH10"},"PeriodicalIF":0.0,"publicationDate":"2019-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/23/4b/ijh-08-10.PMC6410023.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10543324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current trends in the management of Richter's syndrome.","authors":"John N Allan,&nbsp;Richard R Furman","doi":"10.2217/ijh-2018-0010","DOIUrl":"https://doi.org/10.2217/ijh-2018-0010","url":null,"abstract":"<p><p>Richter's syndrome (RS) is a life-threatening complication of chronic lymphocytic leukemia (CLL). While previous research has increased our knowledge on the distinct evolutionary patterns of RS and provided a deeper understanding of the risk factors and molecular events predisposing to transformation, there remain few targetable aberrations and treatment is largely ineffective. The ability to obtain deeper remissions, without selecting for deletion 17p, by using novel B-cell receptor (BCR) antagonists and bcl2 inhibition might lead to a decrease in the incidence of RS, but these agents have done little to significantly change outcomes when incorporated into treatment regimens for RS. In this review we highlight the current landscape of molecular lesions specific to RS, review the data on historical treatment options, and look to the horizon for potential opportunities in the future.</p>","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":"7 4","pages":"IJH09"},"PeriodicalIF":0.0,"publicationDate":"2019-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2018-0010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36860564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"First Italian birth after cryopreserved ovarian tissue transplantation in a patient affected by non-Hodgkin's lymphoma.","authors":"Raffaella Fabbri,&nbsp;Maria Macciocca,&nbsp;Rossella Vicenti,&nbsp;Roberto Paradisi,&nbsp;Stefani Rossi,&nbsp;Elena Sabattini,&nbsp;Anna Gazzola,&nbsp;Renato Seracchioli","doi":"10.2217/ijh-2018-0011","DOIUrl":"https://doi.org/10.2217/ijh-2018-0011","url":null,"abstract":"<p><p>This case report describes the first Italian live birth obtained by cryopreserved ovarian tissue transplantation in a woman affected by non-Hodgkin's lymphoma. Before anticancer treatments, several fertility preservation options were proposed. At 29 years the patient underwent laparoscopy for ovarian tissue cryopreservation. After treatments she experienced premature ovarian failure (POF) and asked for cryopreserved ovarian tissue transplantation. Before transplantation, ovarian samples were analyzed to assess neoplastic contamination and tissue quality. Two subsequent ovarian tissue transplantations were performed 4 and 7 years after cryopreservation. The follicle-stimulating hormone and luteinizing hormone reduction, estradiol increase and first menstrual cycle appeared 2 months after the second transplantation. The woman conceived spontaneously 5 months after the second transplantation. After 39 weeks of uneventful gestation, a healthy male baby was born. Ovarian tissue cryopreservation, thawing and transplantation successfully restored ovarian function and fertility after tissue storage.</p>","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":"7 4","pages":"IJH08"},"PeriodicalIF":0.0,"publicationDate":"2018-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2018-0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36860563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nuclear transport inhibition in acute myeloid leukemia: recent advances and future perspectives.","authors":"Chetasi Talati,&nbsp;Kendra L Sweet","doi":"10.2217/ijh-2018-0001","DOIUrl":"10.2217/ijh-2018-0001","url":null,"abstract":"<p><p>Selective inhibitors of nuclear export (SINE) are emerging as a potentially efficacious therapeutic strategy for overcoming resistance to conventional chemotherapy for acute myeloid leukemia. SINE specifically block the protein Exportin 1, also known as chromosomal region maintenance 1, leading to nuclear retention of cargo proteins, including several tumor suppressor proteins. Selinexor, a first generation SINE, is currently in early phase clinical studies in various combinations with promising antileukemic and pro-apoptotic activity. Here we discuss the mechanism of action of SINEs and further elaborate on the clinical data available from the various trials in acute myeloid leukemia.</p>","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":"7 3","pages":"IJH04"},"PeriodicalIF":0.0,"publicationDate":"2018-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2018-0001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36657455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The transformative journey of chronic myeloid leukemia.","authors":"Pratap Neelakantan,&nbsp;Adam Mead","doi":"10.2217/ijh-2018-0008","DOIUrl":"https://doi.org/10.2217/ijh-2018-0008","url":null,"abstract":"Five thousand years after the ancient physicians began conceiving treatment methodologies for cancers in the form of arsenic, the publication of the results of the pivotal IRIS trial with imatinib for chronic myeloid leukemia (CML) in 2003 was a remarkable landmark [1]. Imatinib, one of the first examples of a so called ‘magic-bullet’ therapy, transformed the outlook of a cancer which, up to that point, had a median survival of 3–5 years from diagnosis [2]. Indeed, since CML was first described in 1845 by JH Bennett in Edinburgh, and the causative genetic lesion of CML, the Philadelphia (Ph) chromosome, was discovered 140 years later by J Rowley, this disease has been at the forefront of advances in diagnosis and treatment of cancer. Most patients between the years 1970–2000 needed bone marrow transplantation to offer any realistic hope of long-term survival and this was a procedure restricted to a minority of patients and also associated with significant toxicity. The discovery of the Ph chromosome fast tracked the pace of discoveries in the field, to the extent that the first targeted therapy for this disease was being tested in first-in-man trials during the late 1990s, culminating in the remarkable results of the IRIS trial [1]. For the first time, patients were achieving extremely high rates of sustained cytogenetic remissions [1]. Fast forward 10 years and newer ‘2nd generation’ tyrosine kinase inhibitors (TKI) were further transforming the outlook for patients with CML. These newer 2nd generation TKIs were able to induce faster and deeper responses and also offered the minority of patients who fail imatinib an alternative treatment [3]. Indeed, such is the success of the current therapeutic armamentarium, that recent studies have shown that the life expectancy for CML patients is now approaching that of the normal population, a remarkable turnaround over a relatively short period of time [2]. The goals of therapy in CML have consequently been completely rewritten and are now focused on the achievement of faster and deeper molecular responses which correlate with better outcomes for patients. Although TKIs are highly-effective treatments, until recently the conventional wisdom was that therapy needed to be ‘lifelong’, an important consideration as TKIs are not without side effects. The next chapter in the CML story started with publication of the French STIM study, which suggested that it was possible to successfully stop TKI therapy without disease recurrence in approximately half the patients who achieve deep molecular responses [4]. Subsequently, large prospective clinical trials of the 2nd generation TKI nilotinib have confirmed these findings, leading to this drug receiving the first licence for ‘treatment-free remission’ [5,6]. Today, it is hard to believe that one of the key goals of therapy is now to achieve deep molecular remission so that treatment-free remission and ‘cure’ might become a reality for many patients in routine clini","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":"7 1","pages":"IJH07"},"PeriodicalIF":0.0,"publicationDate":"2018-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2018-0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36558605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An observational study of Chinese adults with relapsed/refractory Philadelphia-negative acute lymphoblastic leukemia.","authors":"Jun Ma,&nbsp;Ting Liu,&nbsp;Jie Jin,&nbsp;Jianda Hu,&nbsp;Qifa Liu,&nbsp;Jianxiang Wang,&nbsp;Zhixiang Shen,&nbsp;Xin Du,&nbsp;Bin Jiang,&nbsp;Xianhua Meng","doi":"10.2217/ijh-2018-0006","DOIUrl":"https://doi.org/10.2217/ijh-2018-0006","url":null,"abstract":"<p><strong>Aim: </strong>Chinese adults with relapsed/refractory Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (Ph- ALL) have poor outcomes.</p><p><strong>Patients & methods: </strong>We conducted a nationwide, retrospective, observational study to assess outcomes in this patient population.</p><p><strong>Results: </strong>Of the 270 enrolled patients, 31% of patients at last salvage achieved complete remission (CR) or CR with partial hematologic recovery (CRh), with median time to CR/CRh of 30 days and median CR/CRh duration of 2.7 months. The CR/CRh rate was more favorable with earlier versus later lines of salvage (41, 24 and 17% at first, second and third or later salvages, respectively).</p><p><strong>Conclusion: </strong>This dataset serves as an important reference of real-world outcomes using currently available chemotherapy regimens for high-risk Chinese adults with relapsed/refractory Ph- ALL.</p>","PeriodicalId":14166,"journal":{"name":"International Journal of Hematologic Oncology","volume":"7 2","pages":"IJH06"},"PeriodicalIF":0.0,"publicationDate":"2018-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2217/ijh-2018-0006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36657454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}