Hematologic Oncology

Research presented at the 51st Annual ASH Meeting explored optimal induction therapies for managing multiple myeloma and a potential first-line therapy for patients with non-Hodgkin lymphoma (NHL).

Adult T-cell leukemia/lymphoma (ATL) is defined as a histologically or cytologically proven peripheral T-cell malignancy associated with a retrovirus, human T-cell lymphotropic virus type I (HTLV-1).[1] Southwestern Japan is the district with the highest prevalence of HTLV-1 infection and the highest incidence of ATL in the world. A high prevalence of HTLV-1 infection is also found in the Caribbean islands, tropical Africa, South America, and northern Oceania.

Eltrombopag (Promacta) is the first orally absorbed, small-molecule, thrombopoietin receptor (TPO-R) agonist, approved (on November 20, 2008) by the US Food and Drug Administration (FDA) for the treatment of chronic immune thrombocytopenia (ITP) in patients who have relapsed following treatment with corticosteroids, immunoglobulins, and/or splenectomy.

The purpose of this review is to familiarize oncologists with the clinical and pathologic features of this relatively rare disease spectrum. This should enable appropriate clinical management and reassurance of patients concerned about their prognosis.

One of the greatest challenges facing the physician caring for patients with chronic lymphocytic leukemia (CLL) is the heterogeneity of this disease. Over the past decade, there have been major advances in understanding the pathophysiology of CLL, and in the identification of biomarkers that are helpful to predict the clinical course for individual patients. Over the same period, the available therapeutic options have developed dramatically, exemplified by the introduction of combination therapy with purine analogs and monoclonal antibodies, resulting in significant opportunities to induce complete remission (CR) in CLL patients.

Chronic lymphocytic leukemia (CLL) is a heterogeneous disease with an extremely variable course. Survival after diagnosis can range from months to decades. As the pathogenesis of the disease is increasingly understood, we begin to unfold the molecular patterns that define the different prognostic subgroups and to develop strategies to predict the clinical course.

Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western hemisphere. Both the Rai and Binet staging systems have been important clinical tools for predicting outcomes of this heterogeneous disease.

Lymphoblastic lymphoma (LBL) is a rare disease, comprising about 2% of all non-Hodgkin lymphomas (NHLs) in adults.[1] It is a highly aggressive subtype of lymphoma, most commonly of precursor T-cell origin, occurring most frequently in adolescents and young adults, with male predominance and frequent mediastinal, bone marrow, and central nervous system (CNS) involvement.

Lymphoblastic lymphoma (LBL) is a rare disease, most commonly of T-cell origin, that shares biologic features with acute lymphoblastic leukemia (ALL). Indeed, LBL and ALL are considered a single entity (lymphoblastic leukemia/lymphoma, T and B types) in the World Health Organization (WHO) classification of precursor lymphoid neoplasms.

A large, population-based study of the association between venous thromboembolism and mortality in hematologic malignancies found an increased risk of death in patients with acute lymphoblastic leukemia, but not in those with acute myelogenous leukemia. The authors had no explanation for the differential association between the two types of acute leukemia.

In their Areas of Confusion article, “Management of Relapsed Mantle Cell Lymphoma: Still a Treatment Challenge,” Ruan et al attempt to make the case that the relative merits of different upfront approaches for mantle cell lymphoma (MCL) are difficult to appreciate due to the differences in eligible patient populations and limited randomized data.

Dr. Ruan and colleagues provide an excellent summary of available treatment options, as well as new drugs on the horizon, for the management of relapsed mantle cell lymphoma (MCL). As the authors emphasize, treatment of relapsed MCL is strongly influenced by the patient’s first-line therapy and needs to be individualized based on both patient and disease characteristics.

Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin lymphoma that occurs most commonly in older patients with advanced-stage disease.

On August 22, 2008, the US Food and Drug Administration (FDA) granted marketing approval (licensure) to romiplostim (Nplate, Amgen Inc) for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

Romiplostim (Nplate) was the first thrombopoietin (TPO) receptor agonist to receive regulatory approval by the US Food and Drug Administration (FDA) for treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic purpura (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy.

The introduction of mandatory risk evaluation and mitigation strategy (REMS) programs, in which patients must participate in order to receive a new therapy, provides an opportunity to examine an issue affecting ethical oversight and publication of scientific study results.

Drs. Hernandez-Ilizaliturri and Czuczman should be complimented on their comprehensive review of management options for patients with relapsed and refractory diffuse large B-cell lymphoma (DLBCL).

According to published statistics, in 2008 approximately 66,120 new cases of non-Hodgkin lymphoma (NHL) were diagnosed and 19,160 lymphoma patients died from their disease despite currently available treatment.[1] Diffuse large B-cell lymphoma (DLBCL), the most common type of B-cell NHL, has an aggressive clinical course and, as demonstrated by gene-profiling studies, can be further divided into subgroups with distinct biologic characteristics and prognoses.[2]

Cephalon, Inc, announced that the US Food and Drug Administration (FDA) has approved injectable bendamustine hydrochloride (Treanda) for the treatment of patients with indolent B-cell non-Hodgkin lymphoma (NHL) that has progressed during or within 6 months of treatment with rituximab (Rituxan) or a rituximab-containing regimen. The data supporting the FDA approval show that bendamustine is effective, has a tolerable side effect profile in patients with indolent NHL, and that treatment results in a high durable response rate. In March of this year, bendamustine received approval for the treatment of patients with chronic lymphocytic leukemia, the most common form of leukemia in the United States.

The results of an international randomized trial found that the use of dexamethasone in the induction phase of combination chemotherapy led to a one-third reduction in the risk of relapse as compared with the standard corticosteroid, prednisone, translating into a significant benefit in terms of event-free survival in children with acute lymphoblastic leukemia.

Hodgkin lymphoma (HL) is one of the most curable malignancies in adults. However, survival rates for elderly patients with HL (often defined as ≥ 60 years of age) are inferior to those achieved by younger populations.

Myelodysplastic syndromes (MDS) are a heterogeneous collection of hematopoietic disorders that are thought to be clonal and are characterized by low blood counts and a tendency to progress to acute myeloid leukemia (AML).

In this issue of ONCOLOGY, Evens et al present a thoughtful and compelling argument that Hodgkin lymphoma in elderly patients deserves to be a focus for clinical research.

As the authors have correctly pointed out, Hodgkin lymphoma (HL) in elderly patients is an orphan disease that has been the subject of very few specific studies, particularly regarding treatment.

Since the topic of risk-stratified management of patients with myelodysplastic syndromes (MDS) was last reviewed in ONCOLOGY in 2007,[1] a few additional clinically relevant studies have emerged that can help inform decision-making in the consultation room.

Drs. Scott and Estey provide an excellent, concise review of current diagnostic and therapeutic approaches for patients with myelodysplastic syndromes (MDS). Both physicians are recognized world leaders in this area.

Socioeconomic factors and the type of treatment received have an impact on a non-Hodgkin lymphoma (NHL) patient’s risk of dying.

This supplement to ONCOLOGY provides a comprehensive look at state-of-the-art management of three of the most prevalent hematological malignancies in the US today.

Consider the following case study, which illustrates the complex physical and psychosocial care required for the patient developing graft-versus-host disease (GVHD) following an allogeneic hematopoietic stem cell transplantation (HSCT): Mr. SR is a 38-year-old male with a diagnosis of anaplastic large cell non-Hodgkin’s lymphoma (NHL).

Prophylaxis and management of graft-versus-host disease (GVHD) following a related or unrelated allogeneic hematopoietic stem cell transplant (HSCT) is very complex. The review article written by Barton-Burke and colleagues discusses all of the major components of the clinical manifestations, prophylaxis, and treatment of GVHD.