Hematologic Oncology

Results of a Phase I study of the novel Poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) in solid tumors and lymphoma have just been published in Cancer Research (doi:10.1158/0008-5472.CAN-11-1227).

Researchers at the University of Chicago and colleagues have identified two variants on chromosome 6q21 that are associated with second malignant neoplasms (SMNs) in survivors of pediatric Hodgkin’s lymphoma. The SMNs are linked to radiation therapy used to treat the pediatric cancer.

There has been dramatic progress in the management of acute promyelocytic leukemia during the past three decades. Important insights into the pathogenesis of the disease have come to light and effective treatment has been developed.

Our ability to stratify patients with CLL into high-risk and low-risk categories has advanced dramatically over the past two decades. However, which test or tests are most reliable remains to be seen.

A rarely noted aspect of the era of novel agents and explosive new knowledge in the clonal plasma cell diseases is how short the half-life of relevant information has become, and how this churning has challenged clinical thinking.

In less than a decade, the resources available to treat light chain (AL) amyloidosis have increased impressively.

This review of the various available options for the treatment of systemic amyloidosis is designed to help the clinician determine which patients are candidates for stem cell transplantation and which should be treated with conventional chemotherapy.

Observation is the standard of care. However, clinical trials are ongoing to determine whether early therapy with newer agents can prolong the time to progression-and most importantly, prolong survival.

In this video interview, Joseph Connors gives an overview of the results presented here at ASCO of the phase II trial of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma, and discusses the most intriguing work currently being done with novel agents used to treat relapsed or refractory Hodgkin lymphoma.

Myelodysplastic syndromes, also referred to collectively as MDS, have significant biological and clinical heterogeneity, a highly variable natural history, and a complex pathobiology that is not clearly understood.

The myelodysplastic syndromes (MDS) are a heterogeneous spectrum of clonal hematopoietic diseases characterized by bone marrow hypercellularity, dysplasia of cellular elements, and consequent inadequate hematopoiesis, with resultant peripheral blood cytopenias.

The review by Dr. Akhtari outlines the diagnosis, prognosis, and treatment options for patients with myelodysplastic syndromes (MDS), and touches on the current challenges in treating patients suffering from MDS.

This review will cover the key elements of modern acute lymphoblastic leukemia treatment regimens, focusing primarily on front-line treatment and concluding with a brief discussion of the management of relapsed disease.

We have witnessed remarkable gains in the biological understanding and treatment of acute lymphoblastic leukemia (ALL) over the past decade.

About 35 years ago, I encountered several children and adolescents with acute lymphoblastic leukemia or widespread non-Hodgkin lymphoma who presented with or who developed, upon initiation of therapy, severe renal and metabolic derangements.

Computerized registry couldbe easily adopted in the U.S.,according to Italian developers. Developing a web-based registry amongcommunity oncologists may be usefulfor collecting significant informationabout febrile events in patients withhematologic malignancies.

The accurate and in-depth documentation of learning gaps is a fundamental aspect of developing continuing education activities. To obtain a better understanding of community-based medical oncology practice patterns, 43 oncologists within the United States were recruited to complete a traditional clinical case–based questionnaire and to contribute specific anonymous demographic and treatment information derived from their actual patients. This information was used to create a cross-sectional case database on two types of cancer in which major clinical advances have been reported in recent years - multiple myeloma and follicular lymphoma. These diseases also are similar in that most patients experience clinically meaningful benefits from systemic treatment but are unlikely to be cured by therapy. As further described in this and the subsequent two articles, this case-based series documents that (a) clinical research advances are being quickly implemented in daily patient care and that (b) although therapeutic strategies vary based on patient age, the short-term outcomes in terms of response to and tolerance of treatment are similar in younger and older patients.

A number of recent treatment advances in the management of follicular lymphoma (FL), including the introduction of the anti-CD20 monoclonal antibody rituximab, have effectively shifted the primary therapeutic goal away from palliation and avoidance of toxicity toward the more proactive objective of extending survival. This paper reviews recent practice patterns in the broad context of the published findings from major phase III randomized trials; it documents potential gaps between trial results and actual practice, and the implications of these for continuing education of oncologists. Forty-three US-based community oncologists participated in a cross-sectional case survey during which 40 documented their management of 186 patients with newly diagnosed FL and 133 patients with relapsed FL, all of whom were treated after January 1, 2008. The findings from this initiative indicate that the majority of these patients did not have any major symptoms at presentation. Additionally, tolerance of and response to treatment, regardless of the regimen employed, were similar across the different age groups studied (<65, 65-74, ≥75 years). Therapies selected by the physicians surveyed in both the up-front and the relapsed settings broadly corresponded to the evidence-based published literature and were supported by treatment guidelines. In addition, a change in the proportional use of bendamustine/rituximab (BR) in the up-front treatment of FL from 2008 to 2010 was observed, suggesting that community oncologists are rapidly incorporating pivotal clinical trial results when deciding on individual patient management strategies.

The management of multiple myeloma (MM) has undergone rapid change with the recent emergence of several effective novel agents that have added complexity to individualized treatment decision-making. This paper reviews the initial management of 276 patients with MM diagnosed and treated by 43 US-based community oncologists since January 1, 2008. The case survey data obtained are evaluated within the broad context of published findings from major phase III randomized trials and as such reveal potential education gaps and implications for oncology CME. Overall, the results reveal that most patients were symptomatic at diagnosis and were risk-stratified by fluorescene in situ hybridization (FISH) and/or cytogenetics. When analyzed by age, the overall symptomatology and biomarker-defined risk profiles appeared similar in the three age groups studied (

The effectiveness of RT in the palliative setting is sometimes overlooked; however, RT can provide excellent palliation for patients whose disease becomes refractory to other modalities.

Canadian researchers also find that patients are not having recommended cancer screening studies done on a regular basis.

Here we present the case of a 3-year-old girl with generalized lymphadenopathy and fever, in whom the cause of the symptoms was initially thought to be infectious. Ultimately, however, anaplastic large cell lymphoma (ALCL) was diagnosed. Using this case as a backdrop, we discuss the wide range of systemic illnesses that the differential diagnosis of generalized lymphadenopathy encompasses.

Combined with first-line chemotherapy, intravenous delivery therapy also confers a survival benefit over oral bisphosphonates. Gareth J. Morgan, MD, PhD, lead investigator of the Medical Research Council Myeloma IX study, will share additional trial results at ASH 2010.

Imatinib (Gleevec), the first-line standard of care in chronic myeloid leukemia, will become a generic drug in 2015, so the race is on to find a second generation of tyrosine kinase inhibitors (TKIs) that can do the job just as well.

Eighteen-month follow up supports lower-dose nilotinib as the new standard of care for newly diagnosed chronic myeloid leukemia. The ENESTnd trial (Evaluating Nilotinib Efficacy and Safety in Clinical Trials of Newly Diagnosed Ph+CML Patients) enrolled 846 patients at 217 sites in 35 countries. Timothy P. Hughes, MD, MBBS, will present an update to the ENESTnd trial at ASH 2010.