Treatment of Acute Lymphoblastic Leukemia in Adults: Applying Lessons Learned in Children.

Although pediatric acute lymphoblastic leukemia (ALL) has cure rates of over 90%, adult ALL remains a challenging disease to treat, with cure rates roughly half those seen in children. The inferior outcomes in adults can be attributed mainly to adverse genetic features, as well as the inability-particularly of older adults-to tolerate chemotherapy. Modest improvements have been seen in outcomes for adolescents and young adults; these can largely be attributed to the use of pediatric-type combination chemotherapy regimens in patients aged 50 years or younger. In patients with Philadelphia chromosome-positive ALL, once a very-high-risk group, outcomes have markedly improved as a result of the use of tyrosine kinase inhibitors in combination with chemotherapy. The persistence of minimal residual disease has emerged as the single most important prognostic factor for ALL and is increasingly being used to help make decisions regarding allogeneic hematopoietic stem cell transplantation or novel salvage therapies. Relapsed/refractory ALL has had a dismal prognosis. In recent years, novel immune-based therapies have been developed that have shown impressive results and that have the potential to improve the outcome of relapsed ALL. These include antibody-drug conjugates, the bispecific T-cell-engaging antibody blinatumomab, and chimeric antigen receptor-modified T cells.

Outcome disparities in multiple myeloma: a SEER-based comparative analysis of ethnic subgroups.

Studies of ethnic disparities in malignancies have revealed variation in clinical outcomes. In multiple myeloma (MM), previous literature has focused only on patients of Caucasian and African-American (AA) descent. We present a Surveillance Epidemiology and End Results (SEER)-based outcome analysis of MM patients from a broader range of ethnicities, representing current United States demographics. The SEER 17 Registry data was utilized to analyse adult MM patients diagnosed since 1992 (n = 37,963), as patients of other ethnicities were not well represented prior to that. Overall survival (OS) and myeloma-specific survival (MSS) were compared across different ethnicities stratified by year of diagnosis, registry identification, age, sex and marital-status. Hispanics had the youngest median age at diagnosis (65 years) and Whites had the oldest (71 years) (P < 0·001). Increased age at diagnosis was an independent predictor of decreased OS and MSS. Asians had the best median OS (2·7 years) and MSS (4·1 years), while Hispanics had the worst median OS (2·4 years). These trends were more pronounced in patients ≥ 75 years. Cumulative survival benefit over successive years was largest among Whites (1·3 years) and smallest among Asians (0·5 years). These disparities may be secondary to multifactorial causes that need to be explored and should be considered for optimal triaging of healthcare resources.

Seliciclib in malignancies.

Cyclins and cyclin-dependent kinases (CDK) form a key part of the regulatory proteins that govern the cell cycle. Aberrancy in their function can lead to uncontrolled growth and proliferation of the cells which forms the basis of many human diseases, especially cancers. Seliciclib (CYC202, R-roscovitine) is a second-generation CDK inhibitor that competes for ATP binding sites on these kinases, reducing tumor growth and inducing cell death. It is a direct inhibitor of cyclin E/CDK2 and also has inhibitory effects on cyclin H/CDK7 and cyclin T/CDK9. Seliciclib leads to growth arrest and apoptosis of cell lines through activation of the p53 gene, inhibition of RNA processing and blockage of the RNA polymerase II-dependent transcription, and reduction of anti-apoptotic proteins. Seliciclib has good oral bioavailability, although its absorption is slowed by food. It is distributed rapidly to the body tissues and metabolized rapidly to a carboxylated derivative that is excreted by the kidneys. The major adverse effects of seliciclib are electrolyte disturbances (hypokalemia, hyponatremia), gastrointestinal side effects (nausea, emesis, anorexia), fatigue, transient hyperglycemia, elevation of liver enzymes and reversible elevation of serum creatinine. At present, it is in Phase II trials for non-small cell lung cancer and nasopharyngeal carcinoma.

Chilaiditi syndrome complicated by cecal perforation.

Chilaiditi sign is a radiological finding which describes the interposition of a part of the bowel between the diaphragm and the liver, a finding that can be misinterpreted as pneumoperitonium. Chilaiditi syndrome refers to a clinically symptomatic patient in the presence of the classical radiographic findings. It is a very rare syndrome which usually follows a benign course. Here we report the first documented case of Chiliaditi syndrome complicated by cecal perforation.

Cetuximab in hemodialysis: a case report.

BACKGROUND: Concurrent chemoradiotherapy with cisplatin is the standard therapy for patients with unresectable locally advanced head and neck squamous cell carcinoma. However, cisplatin administration in patients on hemodialysis is complicated by the need to perform hemodialysis immediately after the infusion. Concurrent chemoradiation with cetuximab has been approved in definitive treatment of locally advanced head and neck cancer. Although cetuximab is not excreted via the kidneys, its use in patients on hemodialysis has not been reported. METHODS AND RESULTS: We present the case of a 65-year-old man undergoing hemodialysis, with stage IVA squamous cell carcinoma of the hypopharynx. Given the logistics of performing hemodialysis immediately postcisplatin, he received concurrent chemoradiotherapy with cetuximab. He tolerated treatment well with minor side effects. CONCLUSION: Cetuximab can be safely used in patients with renal impairment. This is the first reported case of the use of cetuximab in a patient undergoing hemodialysis.

The role of bendamustine in the treatment of indolent non-Hodgkin lymphoma.

There is no consensus on recommendations for the treatment of relapsed and refractory indolent non-Hodgkin lymphoma (NHL). Bendamustine hydrochloride (bendamustine) has recently been approved for treatment of these patients. Bendamustine is a uniquely structured alkylating agent that lacks cross-resistance with other alkylators. This agent has a high degree of activity against a variety of tumor cell lines. Clinically, bendamustine has demonstrated activity against indolent NHL, chronic lymphocytic lymphoma, multiple myeloma and mantle cell lymphoma. Moreover, studies have validated its activity in patients with indolent NHL who are resistant to purine analogs and rituximab. The cytotoxic activity of bendamustine has been shown to be synergistic with rituximab in hematological malignancies. The incidence of alopecia is significantly less than with other alkylating agents. Myelosuppression is the major toxicity associated with bendamustine.

Targeted therapy for squamous cell carcinoma of the head and neck.

Targeted agents have emerged as novel drugs in the oncology field based on our understanding of the biology of individual malignancies, and have had a promising impact in several tumors. Squamous cell carcinoma of the head and neck (SCCHN) is a common disease with little progress made in survival over the past few decades. SCCHN is characterized by overexpression of the epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF), both of which appear to have a prognostic value. Hence these receptors and their downstream pathways make attractive therapeutic targets. This review discusses targeted therapies currently being evaluated for their role in squamous cell carcinoma of the head and neck.

Adult Burkitt lymphoma: advances in diagnosis and treatment.

Burkitt lymphoma is a unique B-cell malignancy with a high proliferation rate and characteristic genetic changes involving the c-myc oncogene. Burkitt lymphoma is common in children but also occurs in adults, where distinction from diffuse large B-cell lymphoma may pose a problem. The development of brief, very intensive chemotherapy regimens has led to a very high cure rate in children with Burkitt lymphoma. The use of these regimens in adults, often in combination with the antibody rituximab (Rituxan), has also made the cure of a majority of adults possible. Burkitt lymphoma in adults cannot be treated effectively with the common regimens used for diffuse large B-cell lymphoma such as CHOP-R (cyclophosphamide, doxorubicin HCl, vincristine [Oncovin], prednisone, rituximab). Prompt diagnosis and initiation of appropriate therapy with attention to the possibility of tumor lysis syndrome are necessary for optimal results.