Journal of Hematology & Oncology

http://www.jhoonline.org/

List of Papers (Total 755)

Correlation between deletion of the CDKN2 gene and tyrosine kinase inhibitor resistance in adult Philadelphia chromosome-positive acute lymphoblastic leukemia

Background Frequency relapses are common in Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL) following tyrosine kinase inhibitors (TKIs). CDKN2A/B is believed to contribute to this chemotherapy resistance. Methods To further investigate the association between CDKN2 status and TKI resistance, the prevalence of CDKN2 deletions and its correlation ...

l-asparaginase-based regimens followed by allogeneic hematopoietic stem cell transplantation improve outcomes in aggressive natural killer cell leukemia

Aggressive nature killer cell leukemia (ANKL) is a mature NK-T cell lymphoma with worse prognosis, but optimal treatment is unclear. Therefore, we analyzed the efficacy of l-asparaginase-based regimens for ANKL patients. Twenty-one patients who received dexamethasone, methotrexate, ifosfamide, l-asparaginase, and etoposide (SMILE) or etoposide, ifosfamide, dexamethasone, and ...

Azacitidine front-line in 339 patients with myelodysplastic syndromes and acute myeloid leukaemia: comparison of French-American-British and World Health Organization classifications

Background The MDS-IWG and NCCN currently endorse both FAB and WHO classifications of MDS and AML, thus allowing patients with 20–30 % bone marrow blasts (AML20–30, formerly MDS-RAEB-t) to be categorised and treated as either MDS or AML. In addition, an artificial distinction between AML20–30 and AML30+ was made by regulatory agencies by initially restricting approval of ...

How do we choose the best donor for T-cell-replete, HLA-haploidentical transplantation?

In haploidentical stem cell transplantations (haplo-SCT), nearly all patients have more than one donor. A key issue in the haplo-SCT setting is the search for the best donor, because donor selection can significantly impact the incidences of acute and chronic graft-versus-host disease, transplant-related mortality, and relapse, in addition to overall survival. In this review, we ...

Rheb1 promotes tumor progression through mTORC1 in MLL-AF9-initiated murine acute myeloid leukemia

Background The constitutive hyper-activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways has frequently been associated with acute myeloid leukemia (AML). While many inhibitors targeting these pathways have been developed, the anti-leukemic effect was not as robust as expected. As part of the molecular link ...

A phase II study on the role of gemcitabine plus romidepsin (GEMRO regimen) in the treatment of relapsed/refractory peripheral T-cell lymphoma patients

Background There is no consensus regarding optimal treatment for peripheral T-cell lymphomas (PTCL), especially in relapsed or refractory cases, which have very poor prognosis and a dismal outcome, with 5-year overall survival of 30 %. Methods A multicenter prospective phase II trial was conducted to investigate the role of the combination of gemcitabine plus romidepsin (GEMRO ...

Third-generation inhibitors targeting EGFR T790M mutation in advanced non-small cell lung cancer

The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are widely used in patients with non-small cell lung cancer (NSCLC). However, EGFR T790M mutation leads to resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation have been in active clinical development. These agents include osimertinib, ...

Therapeutic options in peripheral T cell lymphoma

Peripheral T cell lymphoma (PTCL) is a rare and heterogeneous group of non-Hodgkin lymphomas with a very poor prognosis. The standard first-line treatments have resulted in unsatisfactory patient outcomes. With the exception of low-risk anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL), the majority of patients relapse rapidly; the current 5-year ...

PML-RAR alpha induces the downmodulation of HHEX: a key event responsible for the induction of an angiogenetic response

Background Recent studies indicate that angiogenesis is important in the pathogenesis of acute myeloid leukemias (AMLs). Among the various AMLs, the bone marrow angiogenetic response is particularly pronounced in acute promyelocytic leukemia (APL). However, the molecular mechanisms responsible for this angiogenetic response are largely unknown. In the present study, we have ...

Functional and genetic screening of acute myeloid leukemia associated with mediastinal germ cell tumor identifies MEK inhibitor as an active clinical agent

Background Hematologic malignancies arising in the setting of established germ cell tumors have been previously described and have a dismal prognosis. Identification of targetable mutations and pathway dysregulation through massively parallel sequencing and functional assays provides new approaches to disease management. Case Presentation Herein, we report the case of a 23-year-old ...

Molecular alterations in the TCR signaling pathway in patients with aplastic anemia

Background A previous study has demonstrated a significantly increased CD3ζ gene expression level in aplastic anemia (AA). However, the mechanism underlying the upregulated CD3ζ mRNA expression level and that of T cell activation signaling molecules in AA patients remains unclear. Thus, we investigated the expression levels of the CD3ζ, CD28, CTLA-4, and Cbl-b genes, the SNP ...

Discovery and characterization of a novel CCND1/MRCK gene fusion in mantle cell lymphoma

The t(11;14) translocation resulting in constitutive cyclin D1 expression is an early event in mantle cell lymphoma (MCL) transformation. Patients with a highly proliferative phenotype produce cyclin D1 transcripts with truncated 3′UTRs that evade miRNA regulation. Here, we report the recurrence of a novel gene fusion in MCL cell lines and MCL patient isolates that consists of the ...

Case report: mismatch repair proficiency and microsatellite stability in gastric cancer may not predict programmed death-1 blockade resistance

Background Anti-programmed death-1 therapy has poor efficacy in mismatch repair-proficient (pMMR) colorectal cancers; however, its efficacy in pMMR gastric cancers remains undetermined. Here, we report the case of a patient with pMMR and microsatellite-stable gastric cancer who exhibited a partial response to salvage anti-programmed death-1 therapy with pembrolizumab. Case ...

Trends in survival of chronic lymphocytic leukemia patients in Germany and the USA in the first decade of the twenty-first century

Background Recent population-based studies in the United States of America (USA) and other countries have shown improvements in survival for patients with chronic lymphocytic leukemia (CLL) diagnosed in the early twenty-first century. Here, we examine the survival for patients diagnosed with CLL in Germany in 1997–2011. Methods Data were extracted from 12 cancer registries in ...

Anti-proliferative effects of T cells expressing a ligand-based chimeric antigen receptor against CD116 on CD34 + cells of juvenile myelomonocytic leukemia

Background Juvenile myelomonocytic leukemia (JMML) is a fatal, myelodysplastic/myeloproliferative neoplasm of early childhood. Patients with JMML have mutually exclusive genetic abnormalities in granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor (GMR, CD116) signaling pathway. Allogeneic hematopoietic stem cell transplantation is currently the only curative ...

The favorable role of homozygosity for killer immunoglobulin-like receptor (KIR) A haplotype in patients with advanced-stage classic Hodgkin lymphoma

Background Interim positron emission tomography after 2 cycles of ABVD (iPET-2) is a good predictor of outcome in advanced-stage classic Hodgkin lymphoma. So far, there are no other prognostic biomarkers capable of identifying chemotherapy refractory patients with comparable accuracy. Despite the considerable amount of evidence suggesting that antitumor immune surveillance is ...

Impact of conditioning intensity in T-replete haplo-identical stem cell transplantation for acute leukemia: a report from the acute leukemia working party of the EBMT

Background Increasing numbers of patients are receiving haplo-identical stem cell transplantation (haplo-SCT) for treatment of acute leukemia with reduced intensity (RIC) or myeloablative (MAC) conditioning regimens. The impact of conditioning intensity in haplo-SCT is unknown. Methods We performed a retrospective registry-based study comparing outcomes after T-replete haplo-SCT ...

Pharmacological inhibition of LSD1 for the treatment of MLL-rearranged leukemia

Background Mixed lineage leukemia (MLL) gene translocations are found in ~75 % infant and 10 % adult acute leukemia, showing a poor prognosis. Lysine-specific demethylase 1 (LSD1) has recently been implicated to be a drug target for this subtype of leukemia. More studies using potent LSD1 inhibitors against MLL-rearranged leukemia are needed. Methods LSD1 inhibitors were examined ...

Romidepsin for the treatment of relapsed/refractory peripheral T cell lymphoma: prolonged stable disease provides clinical benefits for patients in the pivotal trial

Background Achievement of durable responses in patients with relapsed/refractory peripheral T cell lymphoma (PTCL) is challenging with current therapies, and there are few data regarding the potential benefits of continuing treatment in patients with the best response of stable disease (SD). Histone deacetylase inhibitors are a novel class of drugs with activity in T cell ...

First-in-human, open-label dose-escalation and dose-expansion study of the safety, pharmacokinetics, and antitumor effects of an oral ALK inhibitor ASP3026 in patients with advanced solid tumors

Background ASP3026 is a second-generation anaplastic lymphoma kinase (ALK) inhibitor that has potent in vitro activity against crizotinib-resistant ALK-positive tumors. This open-label, multicenter, first-in-human phase I study (NCT01284192) assessed the safety, pharmacokinetic profile, and antitumor activity of ASP3026. Methods Advanced solid tumor patients received oral ASP3026 ...

Acalabrutinib (ACP-196): a selective second-generation BTK inhibitor

More and more targeted agents become available for B cell malignancies with increasing precision and potency. The first-in-class Bruton’s tyrosine kinase (BTK) inhibitor, ibrutinib, has been in clinical use for the treatment of chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenstrom’s macroglobulinemia. More selective BTK inhibitors (ACP-196, ONO/GS-4059, BGB-3111, ...

Metformin sensitizes sorafenib to inhibit postoperative recurrence and metastasis of hepatocellular carcinoma in orthotopic mouse models

Background Sorafenib is recognized as a standard treatment for advanced hepatocellular carcinoma (HCC). However, many patients have to adopt dose reduction or terminate the use of sorafenib because of side effects. In addition, a large number of patients are resistant to sorafenib. Thus, it is essential to investigate the underlying mechanisms of the resistance to sorafenib and ...

Second- and third-generation ALK inhibitors for non-small cell lung cancer

Crizotinib as the first-generation ALK inhibitor has shown significant activity in ALK-mutated non-small cell lung cancer (NSCLC). Second- and third-generation ALK inhibitors are entering clinical applications for ALK+ NSCLC. In addition, a third-generation ALK inhibitor, lorlatinib (PF-06463922), was reported to resensitize NSCLC to crizotinib. This review provided a summary of ...

Bleeding, thrombosis, and anticoagulation in myeloproliferative neoplasms (MPN): analysis from the German SAL-MPN-registry

Background Patients with Ph-negative myeloproliferative neoplasms (MPN), such as polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), are at increased risk for thrombosis/thromboembolism and major bleeding. Due to the morbidity and mortality of these events, antiplatelet and/or anticoagulant agents are commonly employed as primary and/or ...

Journal of Hematology & Oncology reviewer acknowledgement 2015

Contributing reviewers The Editor-in-Chief of Journal of Hematology & Oncology would like to thank all our reviewers who have contributed to the journal in Volume 8 (2015).