Lymphoma

With improved prognosis for patients with Hodgkin's lymphoma (HL), interest has increasingly focused on high-risk groups such as elderly patients. Advanced age at presentation is still one of the strongest negative risk factors. Many different factors influence the prognosis in elderly patients. These include biologic differences such as more aggressive histology, different distribution of disease, more frequent diagnosis of advanced stage, and shorter history of disease. In addition, however, aging itself and associated factors such as comorbidity, reduced tolerability of conventional therapy, more severe toxicity and treatment-related deaths, failure to maintain dose intensity, shorter survival after relapse, and death due to other causes contribute to the poorer outcome in elderly patients. Besides the evaluation of specific causes and risk factors, this review highlights recent and ongoing studies for elderly patients with HL as well as international approaches and recommendations for this age group.

With improved prognosis for patients with Hodgkin's lymphoma (HL), interest has increasingly focused on high-risk groups such as elderly patients. Advanced age at presentation is still one of the strongest negative risk factors. Many different factors influence the prognosis in elderly patients. These include biologic differences such as more aggressive histology, different distribution of disease, more frequent diagnosis of advanced stage, and shorter history of disease. In addition, however, aging itself and associated factors such as comorbidity, reduced tolerability of conventional therapy, more severe toxicity and treatment-related deaths, failure to maintain dose intensity, shorter survival after relapse, and death due to other causes contribute to the poorer outcome in elderly patients. Besides the evaluation of specific causes and risk factors, this review highlights recent and ongoing studies for elderly patients with HL as well as international approaches and recommendations for this age group.

Adding the anti-CD20 monoclonal antibody rituximab (Rituxan) to chemotherapy (R-chemo) achieved better overall survival rates than chemotherapy alone for patients with advanced indolent or mantle cell lymphoma, according to a recent meta-analysis.

The spectrum of CD30+ lymphoproliferative diseases of the skin includes CD30+ cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, as well as borderline cases. These entities constitute the second most common group of cutaneous lymphomas according to the newly revised World Health Organization and European Organisation for Research and Treatment of Cancer consensus classification. Recent progress in immune and molecular biology, and identification of therapeutic targets have increased our understanding of these diseases and have led to novel treatment approaches. This review will provide an update on recent findings of immunologic, molecular, cytogenetic features and treatment strategies for patients with CD30+ lympho-proliferative diseases.

The spectrum of CD30+ lymphoproliferative diseases of the skin includes CD30+ cutaneous anaplastic large cell lymphoma, lymphomatoid papulosis, as well as borderline cases. These entities constitute the second most common group of cutaneous lymphomas according to the newly revised World Health Organization and European Organisation for Research and Treatment of Cancer consensus classification. Recent progress in immune and molecular biology, and identification of therapeutic targets have increased our understanding of these diseases and have led to novel treatment approaches. This review will provide an update on recent findings of immunologic, molecular, cytogenetic features and treatment strategies for patients with CD30+ lympho-proliferative diseases.

In chronic myelogenous leukemia (CML) patients who have failed two tyrosine kinase inhibitor therapies—imatinib (Gleevec) and dasatinib (Sprycel)—the investigational agent nilotinib (Tasigna) has significant clinical activity

Despite significant improvements in the treatment of Hodgkin's lymphoma over the past 2 decades, physicians continue to face dilemmas in therapy for the disease, and many cured patients live with complications of treatment. Newer therapeutic options are still needed for the disease, to minimize complications and to improve the treatment of patients in relapse. This review considers the treatment of Hodgkin's lymphoma in younger patients, addressing such issues as which patients with early-stage disease may require radiotherapy, what prognostic factors provide information that can affect treatment choices in patients with advanced disease, and what we have learned about treatment complications in this setting.

Despite significant improvements in the treatment of Hodgkin's lymphoma over the past 2 decades, physicians continue to face dilemmas in therapy for the disease, and many cured patients live with complications of treatment. Newer therapeutic options are still needed for the disease, to minimize complications and to improve the treatment of patients in relapse. This review considers the treatment of Hodgkin's lymphoma in younger patients, addressing such issues as which patients with early-stage disease may require radiotherapy, what prognostic factors provide information that can affect treatment choices in patients with advanced disease, and what we have learned about treatment complications in this setting.

Despite significant improvements in the treatment of Hodgkin's lymphoma over the past 2 decades, physicians continue to face dilemmas in therapy for the disease, and many cured patients live with complications of treatment. Newer therapeutic options are still needed for the disease, to minimize complications and to improve the treatment of patients in relapse. This review considers the treatment of Hodgkin's lymphoma in younger patients, addressing such issues as which patients with early-stage disease may require radiotherapy, what prognostic factors provide information that can affect treatment choices in patients with advanced disease, and what we have learned about treatment complications in this setting.

Two clinical studies with a total of 1,202 patients have found posaconazole (Noxafil) significantly more effective than two other antifungal agents in preventing fatal invasive fungal infections in acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) patients who develop neutropenia as a result of chemotherapy

Tositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.

Hana Biosciences, a biopharmaceutical company focused on advancing cancer care, recently announced that the US Food and Drug Administration (FDA) has granted orphan drug designation for vincristine sulfate liposomes injection (Marqibo) in the treatment of adult patients with acute lymphoblastic leukemia (ALL).

Tositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.

Tositumomab/iodine-131 tositumomab (Bexxar) and ibritumomab tiuxetan (Zevalin) are radioimmunoconjugates targeting the CD20 antigen. Both agents are approved in the United States for use in relapsed or refractory, indolent or transformed, B-cell lymphoma. These agents are well tolerated and have the highest levels of single-agent activity observed in these histologies. This review will summarize the key trials that led to approval of both I-131 tositumomab and ibritumomab tiuxetan, and then focus on four novel therapeutic concepts in radioimmunotherapy: retreatment, therapy of de novo indolent lymphoma, therapy of aggressive histologies, and incorporation in high-dose therapy programs utilizing autologous stem cell support.

The diagnosis of cutaneous T-cell lymphoma (CTCL) requires accurate histopathology, including immunocytochemistry, as well as careful clinical appraisal and analysis for T-cell clonality. This paper reviews the key histologic features of mycosis fungoides (MF) and its variants, and of lymphomatoid papulosis (LyP). Mycosis fungoides is an epidermotropic CTCL that evolves through distinct disease stages of patch, plaque, and tumor, often leading to transformation in the final stages. Disease staging is made clinically, and diagnosis may be difficult during the early stages because several common dermatologic conditions share features with MF. Therefore, clinical appraisal plus the presence of characteristic histopathologic features are needed to ensure accurate diagnosis. Clinical information is particularly important in the diagnosis of LyP, as the disease appears malignant histologically, but has a benign clinical course. Several other T-cell lymphomas were defined in a recent classification of these cutaneous lymphomas, and some key features of these disorders are also briefly reviewed.

The role of autologous and allogeneic stem-cell transplantation (SCT) in the treatment of cutaneous T-cell lymphoma (CTCL) is reviewed. Patients most likely to benefit are those with advanced-stage disease, multiple relapses, and short remissions; chemosensitive disease is also a prerequisite for these treatments. Autologous SCT produces high response rates in patients with peripheral T-cell lymphoma, but these are generally of short duration. This therapy is relatively safe to administer, with little transplant-related mortality. In contrast, allogeneic SCT may be highly toxic and result in transplant-related mortality, but it has the potential to produce long-lasting responses. Prospective studies of these treatments in patients with CTCL are required. Nevertheless, selected patients could be considered for allogeneic SCT, preferably early in their disease when their performance status is still good.

The investigational agent nilotinib (Tasigna) has shown significant clinical activity and an acceptable safety and tolerability profile in the treatment of imatinib (Gleevec) resistant or intolerant, chronic phase chronic myelogenous leukemia (CP-CML)

The FDA has granted approval to Velcade (bortezomib for injection, Millennium) for the treatment of mantle cell lymphoma (MCL) in patients who have received at least one prior treatment.

Acute myeloid leukemia (AML) is a disease of the elderly, with the majority of patients diagnosed in their 6th and 7th decade of life. Older patients with AML are less likely to achieve complete remission after induction chemotherapy, and they suffer from higher rates of leukemia relapse compared to younger cohorts. Suboptimal outcomes are the result of adverse biologic characteristics of leukemia in the elderly, as well as the presence of medical comorbidities and patient or physician preferences as to initiating treatment. In addition, there is a distinct lack of randomized, prospective data to guide management decisions for the treatment of AML in the elderly. Patients who are over age 75, with poor performance status, multiple comorbidities, or poor prognostic features, should be considered for a clinical trial or palliative therapy. Elderly patients who are candidates for standard induction chemotherapy and achieve complete remission are unlikely to benefit from intensive postremission therapy and should be referred to a clinical trial when possible. Further prospective trials are needed to identify a tolerable, effective treatment regimen for older patients with AML.

Patients with advanced follicular non-Hodgkin's lymphoma who received a new combination of chemotherapy and targeted radiation (radioimmunotherapy) lived significantly longer than patients treated with standard chemotherapy alone on previous trials. Five-year follow-up data from the phase II trial was published in the September 1 issue of the Journal of Clinical Oncology.

Hana Biosciences recently announced the initiation of a multicenter phase II clinical trial of vincristine sulfate liposomal injection (Marqibo) in patients with relapsed or refractory acute lymphoblastic leukemia (ALL).

The FDA has granted accelerated approval to Bristol-Myers Squibb's Sprycel (dasatinib) Tablets for the treatment of adults in all phases of chronic myeloid leukemia (CML) (chronic, accelerated, or myeloid or lymphoid blast phase) with resistance or intolerance to prior therapy, including imatinib (Gleevec). Sprycel also received regular FDA approval for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.

A phase I study of AMN107 (Novartis) in Philadelphia-positive (Ph+) chronic myelogenous leukemia (CML) and acute lymphocytic leukemia (ALL) shows the new agent induces responses in patients with imatinib (Gleevec)-resistant Bcr-Abl mutations, according to a presentation at the 47th Annual Meeting of the American Society of Hematology (abstract 37).

The FDA has granted priority review to dasatinib (BMS-354825), developed by Bristol-Myers Squibb, for treatment of imatinib (Gleevec)-resistant or refractory chronic myelogenous leukemia (CML) in adults.

Concomitant administration of rituximab (Rituxan) and chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP) appears effective in patients with stage III-IV follicular non-Hodgkin's lymphoma (NHL).