Clinical Leukemia最新文献

Clinical presentation of acute myelogenous leukemia (AML) in infants as an ovarian tumor is extremely rare, although AML is well reported in older children and adults. Granulocytic sarcoma or chloroma is an extramedullary tumor seen in AML and myeloid and myeloproliferative disorders. We report a case of a 5-month-old female infant who presented with bilateral ovarian masses. Based on a left oophorectomy and bone marrow evaluation, the patient was diagnosed with bilateral ovarian granulocytic sarcoma and erythroleukemia (French-American-British type M6 AML). Our patient has unusual cytogenetics involving rearrangements of chromosomes 1, 11, and 16. The patient has received chemotherapy and is alive at 2 years from the diagnosis.

The clinical staging systems developed by Rai and Binet have remained the mainstay for clinical decision-making in patients with chronic lymphocytic leukemia (CLL). However, there is substantial heterogeneity in the course of the disease. In recent years, molecular and cellular markers have helped to predict the prognosis of patients with CLL. Genomic aberrations subdivide CLL into distinct clinical subgroups. Fluorescence in situ hybridization (FISH) can identify genomic aberrations in approximately 80% of CLL cases. Furthermore, innovations in chromosome banding analyses, novel genome-wide approaches (ie, array– comparative genomic hybridization, single nucleotide polymorphism–chip), and sensitive mutation analyses have helped to characterize the critical aberrations and identify candidate genes for further refinement of genomic profiling. The most frequent aberrations are deletions in 13q, 11q, or 17p, and trisomy 12. Apart from providing insights into the pathogenesis of the disease, genomic aberrations identify subgroups of patients with distinct clinical pictures (lymphadenopathy [11q deletion] or resistance to chemotherapy [17p deletion]). Deletions in 11q and particularly 17p are associated with rapid disease progression or inferior survival, and patients with these genetic abnormalities might be candidates for clinical trials investigating alternative treatments and stem cell transplantation.

The advent of imatinib, a potent and selective inhibitor of the Bcr-Abl tyrosine kinase whose deregulated expression drives Philadelphia chromosome-positive leukemias, has revolutionized outcome and quality of life of patients. However, resistance can develop through a variety of mechanisms, including point mutations in the Abl kinase domain, which are capable of abrogating inhibitor binding. The problem of resistance-associated mutations has fostered intensive research over the past 5 years. Herein, we review the current knowledge on the clinical significance of Abl kinase domain mutations in various settings. We discuss the contribution of mutations to imatinib resistance, and we hypothesize how the advent of novel tyrosine kinase inhibitors could change this scenario. We also warn against a systematic screening for Abl kinase domain mutations of imatinib-naive patients and patients who exhibit and maintain a complete cytogenetic response, because the practical relevance of finding rare mutated cells in these settings still needs to be confirmed.

Acute promyelocytic leukemia is recognized to occur infrequently during pregnancy. The prognosis is good for acute promyelocytic leukemia with modern therapy including treatment with all-trans-retinoic acid that specifically targets the causative retinoic acid receptor (PML-RAR)α oncoprotein; however, the management of this disease in pregnancy is complex. This is because there are a number of possible treatment strategies that have varying implications for the mother and fetus. We describe a recent experience relating to 3 consecutive cases arising in the United Kingdom that demonstrates the different therapeutic decisions that can be taken and the various outcomes that can occur during pregnancy. In each case, treatment response was subject to stringent monitoring by real-time quantitative polymerase chain reaction for the PML-RARA fusion transcript. We have reviewed the available literature and, when possible, we have outlined the treatment strategies available for each stage of pregnancy.

Monoclonal antibodies offer a focused therapeutic approach for solid and hematologic malignancies. Alemtuzumab is a chimeric monoclonal antibody that targets the CD52 antigen on normal and malignant lymphoid cells and is approved for the treatment of patients with relapsed chronic lymphocytic leukemia. Its main mechanistic cell-killing effects include complement-dependent cytoxicity, antibody-dependent cell-mediated cytotoxicity, and apoptosis. Ongoing investigation into the relative importance of these cytotoxic pathways is necessary for improved understanding of the mechanisms of action by which alemtuzumab and other monoclonal antibodies exert their beneficial antitumor activity in vivo.

Chronic lymphocytic leukemia (CLL) rarely involves the meninges. There are few cases published in the literature. In this report, we describe a 59-year-old man with an 8-year history of CLL who presented with bone marrow involvement and cytopenias; received therapy with rituximab, fludarabine, pentostatin, and cyclophosphamide; and later went on to receive alemtuzumab. He developed leptomeningeal infiltration presenting as diplopia. The cerebrospinal fluid revealed a white blood cell count of 51/mm³; all of them were mononuclear, and the diagnosis was confirmed to be CLL by flow cytometry. A gadolinium magnetic resonance imaging scan of the head showed abnormal enhancement extending from the choroids in the left ventricle into the right ventricle, as well as changes in intensity in the splenium of the corpus callosum and left cerebellar peduncle. Whole-brain irradiation (2500 cGy) and 5 cycles of intrathecal cytarabine were administered. After this, a diffuse large B-cell lymphoma of the right testicle was discovered. An orchiectomy was performed, followed by radiation to the testicular bed. Persistent leptomeningeal involvement was treated with intrathecal methotrexate, resulting in a remission. A matched, unrelated donor bone marrow transplantation was performed.