Impact of p53-associated acute myeloid leukemia hallmarks on metabolism and the immune environment.

Acute myeloid leukemia AML), an aggressive malignancy of hematopoietic stem cells, is characterized by the blockade of cell differentiation, uncontrolled proliferation, and cell expansion that impairs healthy hematopoiesis and results in pancytopenia and susceptibility to infections. Several genetic and chromosomal aberrations play a role in AML and influence patient outcomes. is a key tumor suppressor gene involved in a variety of cell features, such as cell-cycle regulation, genome stability, proliferation, differentiation, stem-cell homeostasis, apoptosis, metabolism, senescence, and the repair of DNA damage in response to cellular stress.

Therapeutic options for chronic myeloid leukemia following the failure of second-generation tyrosine kinase inhibitor therapy.

The management of chronic myeloid leukemia in the chronic phase (CML-CP) has witnessed significant advancements since the identification of a common chromosomal translocation anomaly involving chromosomes 9 and 22, which results in the formation of the Philadelphia chromosome driven by the BCR-ABL1 fusion protein. This discovery paved the way for the development of tyrosine kinase inhibitors (TKIs) that target the adenosine triphosphate (ATP) binding site of ABL1 through the BCR-ABL-1 fusion protein. Following the approval of Imatinib by the Food and Drug Administration (FDA) as the first TKI for CML treatment in 2001, the median overall survival (OS) for chronic phase CML (CML-CP) has significantly improved, approaching that of the general population.

Long-term outcomes in patients with chronic lymphocytic leukemia treated with ibrutinib: Focus on hypertension and cardiovascular toxicity.

Background: Continuous ibrutinib administration is needed to maintain efficacy in patients with chronic lymphocytic leukemia (CLL) and, as such, long-term toxicity is a concern. The authors report the 5-year follow-up of patients with CLL who received treatment with ibrutinib with a focus on hypertension and cardiovascular toxicities.

Methods: Patient characteristics were assessed, including blood pressure, cardiovascular disease, disease progression, and death.

Therapy-related core binding factor acute myeloid leukemia.

Therapy-related acute myeloid leukemia (t-AML) usually stems from exposure of the bone marrow to cytotoxic chemotherapy and/or radiation therapy. t-AML is usually associated with poor overall survival, but occasionally t-AML can involve favorable-risk cytogenetics, including core binding factor AML (CBF-AML), which shows a recurrent chromosomal rearrangement with t(8;21) (q22;22) and 'inv(16) (p13.1;q22)/t(16;16)(p13.

Current Management of Chronic Myeloid Leukemia Myeloid Blast Phase.

Despite the major advancements in the management of chronic phase (CP) chronic myeloid leukemia (CML), blast crisis (BC) remains a major therapeutic challenge. BC can be myeloid, lymphoid, or mixed lineage with myeloid BC being the most common type. BC in CML is mediated by aberrant tyrosine kinase activity of the fusion protein.

Therapeutic Management of Chronic Lymphocytic Leukemia Presenting with Recurrent Massive Ascites.

Chronic lymphocytic leukemia (CLL) is a lymphoproliferative malignancy that is categorized by the production and accumulation of CD5+ monoclonal B cell lymphocytes, commonly in the spleen, bone marrow, and peripheral blood; these are morphologically mature lymphocytes with abnormal immune function. Ascites, although common in solid organ malignancies such as ovarian, breast, and gastrointestinal, is a rare clinical manifestation in hematological malignancies. The case presented herein describes an elderly male patient with CLL who presented with transudative ascites 7 years after the completion of chemotherapy.

B-Lymphoid Blast Phase-Chronic Myeloid Leukemia: Current Therapeutics.

Blast crisis (BC) is one of the most dreaded complications of chronic myeloid leukemia (CML). Fortunately, the incidence of BC has diminished markedly in the tyrosine kinase inhibitor (TKI) era. The primary objective of initial treatment in BC is to achieve a second chronic phase (CP) and to proceed to an allogeneic stem cell transplantation (SCT) in eligible patients.

Primary Bone Marrow HIV-Associated Hodgkin Lymphoma Complicated by Hemophagocytic Lymphohistiocytosis.

The presentation of human immunodeficiency virus (HIV)-associated Hodgkin lymphoma can differ from that of the general population. More specifically, primary bone marrow Hodgkin lymphoma is an uncommon presentation that is more often reported in patients with HIV. Given the many overlapping symptoms of Hodgkin lymphoma and HIV as well as HIV-associated infections, diagnosis can be difficult and delayed.

Mixed-Phenotype Acute Leukemia: Clinical Diagnosis and Therapeutic Strategies.

Mixed-phenotype acute leukemia (MPAL) comprises a heterogenous group of leukemias that are genetically, immunophenotypically, and clinically, diverse. Given the rarity of the disease, the diagnosis and treatment of MPAL is extremely challenging. Recent collaborative efforts have made significant progress in understanding the complex genomic landscape of MPAL.

in Acute Myeloid Leukemia: Molecular Aspects and Patterns of Mutation.

Mutation of the tumor suppressor gene, , is associated with abysmal survival outcomes in acute myeloid leukemia (AML). Although it is the most commonly mutated gene in cancer, its occurrence is observed in only 5-10% of de novo AML, and in 30% of therapy related AML (t-AML). mutation serves as a prognostic marker of poor response to standard-of-care chemotherapy, particularly in t-AML and AML with complex cytogenetics.

A prospective analysis of symptom burden for patients with chronic myeloid leukemia in chronic phase treated with frontline second- and third-generation tyrosine kinase inhibitors.

Background: Treatment with tyrosine kinase inhibitors (TKIs) for patients with chronic myeloid leukemia (CML) is effective but needs to continue for several years, possibly indefinitely. Although generally safe, TKI may have hitherto poorly recognized effects in the quality of life (QoL) of such patients.

Methods: We prospectively measured the symptom burden of patients with chronic phase CML enrolled on frontline TKI trials with dasatinib, nilotinib, or ponatinib.

The Addition of Bevacizumab to Oxaliplatin-Based Chemotherapy: Impact Upon Hepatic Sinusoidal Injury and Thrombocytopenia.

Background: Oxaliplatin-based chemotherapy can cause hepatic sinusoidal injury (HSI), portal hypertension, and splenic sequestration of platelets. Evidence suggests that bevacizumab may protect against HSI.

Methods: Two cohorts of metastatic colorectal cancer (CRC) were analyzed: a nonrandomized exploratory cohort of 184 patients treated at a single institution from 2003 to 2010 and a confirmatory cohort of 200 patients from a multi-institutional randomized trial (NO16966).

Role of inotuzumab ozogamicin in the treatment of relapsed/refractory acute lymphoblastic leukemia.

Inotuzumab ozogamicin is a humanized anti-CD22 monoclonal antibody bound to a toxic natural calicheamicin, which is under investigation for the treatment of relapsed/refractory acute lymphoblastic leukemia. CD22 is commonly expressed in 90-100% of malignant mature B-lymphocyte lineage. The first Phase II study with inotuzumab ozogamicin conducted by Kantarjian et al.

Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib.

Ibrutinib is a Bruton tyrosine kinase inhibitor approved for the treatment of patients with relapsed refractory chronic lymphocytic leukemia (RR-CLL). We describe the characteristics, causes of discontinuation, and outcomes in patients who discontinued treatment with ibrutinib. One hundred twenty-seven patients were enrolled in various clinical trials of ibrutinib, with or without rituximab, at our center.

The addition of erlotinib to gemcitabine and cisplatin does not appear to improve median survival in metastatic pancreatic cancer.

Metastatic pancreatic cancer carries a poor prognosis, with median survival on the order of several months. There is evidence that combining gemcitabine with either erlotinib or cisplatin may be superior to single agent gemcitabine in patients with good performance (PS 0-1). We retrospectively compared outcomes of patients treated with either the three drug regimen of gemcitabine, cisplatin, and erlotinib (GCE) or the doublet of gemcitabine and cisplatin (GC) in order to assess the potential benefit of erlotinib.