ATLCAR.CD30 cells for Lymphoproliferative Disorders

The cause of lymphoproliferative diseases is still not clear. It was usually thought that cancer originated in a certain organ, but evidence shows that cancer may arise in many organs. It is likely that many different factors, including environmental factors, predispose a person to developing the diseases. Tissue damage may also be a precipitating factor. The overall aim of diagnostic and therapeutic efforts should be to make the disease less likely to occur.

About 10,000 children and 7,000 adults were diagnosed with lymphoproliferative disorders in the United States in 2001. The most common disorders are non-Hodgkin's lymphomas and Mature B-Cell Lymphomas. There is no significant difference in diagnostic age groups at diagnosis, although diagnosis rates increased from 1995 to 2001 in children with non-Hodgkin's and mantle cell lymphomas. The five year OS rate was 77% for the pediatric group and 73% for the adult group. Survival for NHLs was comparable between pediatric and adult patients.

It is difficult to formulate a one-word answer to the myriad of potential treatment regimens for lymphoproliferative disorders. Treatment involves the combination of agents that are effective in treating each individual condition, and a combination of treatments that are effective against systemic relapse. The agents most often used include chemotherapy, radiotherapy and biologic therapy. The most common first-line treatment is R-CHOP, followed by EBRT and then chemotherapy alone. For patients with high-risk conditions (e.g., bone marrow, central nervous system involvement, liver lesions, or pulmonary disease), treatment with allopurinol or azathioprine/IMiC are often used in combination with chemotherapy.

The signs of lymphoproliferative disorders include symptoms of lymphadenopathy; enlarged, tender and painful lymph nodes in the neck or under the arm (a finding referred to as 'Barr-Lees-Engelberg nodes'); high levels of the white blood cell count (thrombocytosis) and an elevated gamma glutamyl transpeptidase (GGT), an enzyme produced in the liver that can be elevated in many conditions. B symptoms, including fever, night sweats, loss of appetite and weight loss, can also be present.

Lymphoproliferative disorders can be cured only if the lymphoproliferative disorder is a clonal LPD, as shown by histology, with no recurrences for several years and no metastases at presentation.

Nodal disease is not a rare occurrence in both Hodgkin's disease and anaplastic large cell lymphomas. Clinically, these disorders, especially Hodgkin's disease and ALCL, behave very differently, and their management differs considerably. Nodal staging may help diagnose both diseases early.

Results from a recent clinical trial provides novel evidence to suggest an unexpected benefit of CD30-directed cell therapy for HL/CLL patients. At a time where effective treatments are scarce, this novel approach holds a great potential for translational application against CD30-overexpressing B-cell neoplasms.

The data in this report support current recommendations to use CD30-positive cells for allogeneic stem cell transplantation due to safety, in the absence of evidence of harm.

Atlcell CD30 (CD30) cells are a distinct subset of primary CD30+ HL cells with multiple translocations in the t(11;14)(q13;q32). Atlcell CD30 cells are in part HL-like; however, they have other characteristics that set them apart from HL, including cell division in a lytic manner and a more aggressive gene expression profile. Findings from a recent study are important as they raise the possibility of a novel and distinct disorder.

Although some patients with lymphoproliferative disorders, such as T-cell (mycosis fungoides) and B-cell (lymphoma) cancers and ALK-rearranged non-small cell lung cancer, may be eligible for clinical trials, the clinical usefulness of these studies is debated. Future research evaluating the inclusion and exclusion criteria may assist clinicians in managing these patients.

The primary cause of lymphoproliferative disorders is unknown. Because both the diagnosis and characterization of lymphoproliferative disorders are complicated, there are difficulties in developing efficient diagnostic strategies for lymphoproliferative disorders.