Lymphoma

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.

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.

Researchers are exploring ways to manipulate rituximab (Rituxan) when added to the current standard therapy for diffuse large B-cell lymphoma, specifically shortening the number of treatment days. Preliminary results of a phase III trial showed that rituximab plus CHOP over a 14-day cycle achieved similar response rates and comparable toxicity compared to CHOP on a 21-day cycle in newly diagnosed patients.

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.

After almost a decade of research and two trials of a follicular lymphoma vaccine with negative results, a study of a personalized idiotype vaccine has achieved positive results. BiovaxID prolonged median disease-free survival by more than a year in a subset of patients who maintained complete remission after one year of chemotherapy and then received the vaccine.

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.

An 8-year randomized, controlled phase III clinical study has shown that a patient-specific therapeutic vaccine, BiovaxID, significantly prolongs disease-free survival in follicular non-Hodgkin’s lymphoma. The study, featured in ASCO’s plenary session, found that patients who received the vaccine experienced a median disease-free survival of approximately 44 months compared to approximately 30 months for those who received a control vaccine-an increase of 47% (abstract P2).

The addition of rituximab (Rituxan) to systemic chemotherapy has improved the response rates, progression-free survival, and overall survival of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) compared to chemotherapy alone. In the front-line setting, the use of rituximab is changing the biology and clinical behavior in DLBCL patients who fail to respond or relapse following chemoimmunotherapy.

Chemoimmunotherapy has been the most significant step in recent years to improving overall survival (OS) and progression-free survival (PFS) rates in patients with diffuse large B-cell lymphoma ­(DLBCL).[1] Despite this major therapeutic advance, a significant proportion of patients will relapse or remain refractory to initial chemoimmunotherapy. The pivotal PARMA trial confirmed the place of high-dose chemotherapy and autologous stem cell transplant (ASCT) as the optimum salvage treatment.

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]

Sargramostim (Leukine) paired with a patient-specific immunotherapy mitumprotimut-T (Specifid), failed to reduce time to remission in patients with CD20+ follicular lymphoma following therapy with rituximab (Rituxan), according to the highly anticipated results of a phase III clinical trial.

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.

Results of the first clinical study examining the use of fostamatinib disodium, an investigational treatment that targets a protein called SYK (spleen tyrosine kinase), showed that the new agent represents a safe and novel therapeutic approach that should be further developed for the treatment of B-cell non-Hodgkin lymphoma.

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.

Burkitt lymphoma (BL) is a unique B-cell lymphoma characterized by a high proliferation rate and cytogenetic changes related to c-myc proto-oncogene overexpression. Burkitt lymphoma is a highly aggressive B-cell lymphoma that is most frequently seen in children and young adults in endemic areas.

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.

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.

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.

CHICAGO-Increasing the dose density of rituximab in the R-CHOP-14 regimen yields better rituximab (Rituxan) pharmacokinetics and improved clinical outcomes among older adults with high-risk diffuse large B-cell lymphoma (DLBCL), reported lead investigator Michael G.M. Pfreundschuh, MD.

The investigational tyrosine kinase inhibitor bosutinib has an acceptable safety profile and appears to be efficacious among patients with chronic-phase chronic myelogenous leukemia who have intolerance or resistance to other TKIs, according to new data presented at ASCO 2008 (abstract 7001).

An analysis of 2,459 mantle cell lymphoma patients diagnosed from 1992 (when the disease was first recognized as a separate type of lymphoma) to 2004 showed that men were more than twice as likely to be diagnosed as women, Caucasians had the highest risk of all ethnic groups, and people aged 70 to 79 were more likely to be diagnosed than all other age groups (Cancer, published online July 7, 2008, DOI: 10.1002/cncr.23608).

CHICAGO-Ongoing trials are still clarifying the optimal approach to management after induction therapy for non-Hodgkin’s follicular lymphoma. In the meantime, patients and physicians are left to ponder whether maintenance rituximab (Rituxan) should be used routinely in all cases. Leading researchers in hematology debated this topic in an education session at ASCO 2008.