Adult T-Cell Lymphoma/Leukaemia Recurrent
Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive blood cancer linked to a viral infection. When the disease returns after treatment or does not respond to initial therapy, patients face particularly challenging circumstances that require specialized approaches and careful consideration of available options.
Table of contents
- What is adult T-cell leukemia/lymphoma?
- Cause and transmission
- Types of adult T-cell leukemia/lymphoma
- When the disease returns
- Treatment approaches for recurrent disease
- Outlook for relapsed disease
What is adult T-cell leukemia/lymphoma?
Adult T-cell leukemia/lymphoma (ATLL) is a rare type of blood cancer that affects special white blood cells called T-cells, which normally help your body fight infections[1]. The disease can appear in the blood (when it is called leukemia), in the lymph nodes (groups of small organs that are part of the body’s defense system), in the skin, or in multiple other areas of the body[1].
ATLL is considered a form of non-Hodgkin lymphoma, which is one of the two main categories of lymphoma. More specifically, it falls under a group called peripheral T-cell lymphomas[1][6].
Cause and transmission
ATLL is strongly linked to infection with the human T-cell lymphotropic virus type 1 (HTLV-1), a virus that infects T-cells. However, only about 5% of people infected with HTLV-1 will eventually develop ATLL[1][2]. Doctors currently have no way to predict which infected individuals will develop the disease.
The HTLV-1 virus is most common in southwestern Japan, the Caribbean region, parts of Central and South America, Africa, and some areas of the Middle East[1][2]. The virus can be passed through sexual contact or contact with infected blood, but it is most often transmitted from mother to child through the placenta, during childbirth, and through breastfeeding[1][2]. In most cases, HTLV-1 infection does not cause any symptoms[1].
Types of adult T-cell leukemia/lymphoma
ATLL is divided into four distinct types based on how the disease behaves and what symptoms it causes[1][2]:
- Acute: This aggressive type of ATLL may develop rapidly and cause symptoms including fatigue, skin rash, and enlarged lymph nodes in the neck, underarm, or groin[1].
- Lymphomatous: This aggressive type is found primarily in the lymph nodes but may also cause high white blood cell counts[1].
- Chronic: This slow-growing type can result in elevated lymphocytes (a type of white blood cell) in the blood, enlarged lymph nodes, skin rash, or fatigue[1].
- Smoldering: This slow-growing type is associated with very mild symptoms, such as a few skin lesions[1].
The disease subtypes are not completely separate conditions but occur on a spectrum. About one-quarter of people with chronic or smoldering ATLL may develop the more aggressive acute subtype over time[6].
When the disease returns
ATLL that returns after treatment is called relapsed disease. Disease that does not respond to initial treatment is called refractory disease. The aggressive forms of ATLL (acute, lymphoma, and higher-risk chronic types) carry some of the poorest outlooks of any non-Hodgkin lymphomas[6][9].
Most patients with aggressive ATLL are not curable with current chemotherapy treatments alone[6]. In a large analysis, patients with ATL had 5-year failure-free and overall survival of only 12% and 14%, respectively[6]. Many patients experience disease return shortly after or even during initial treatment[2].
The outlook for relapsed disease remains particularly difficult due to the cancer cells’ resistance to chemotherapy and the severe weakening of the immune system that often occurs[2][11].
Treatment approaches for recurrent disease
For patients with relapsed or refractory ATLL, several treatment options may be considered[9][10]:
Clinical trials: Enrollment in a study testing new treatments is strongly recommended when available. Because ATLL is rare, large-scale clinical trials have been challenging to perform, and treatment recommendations are based on limited evidence[9][11].
Stem cell transplantation: Allogeneic stem cell transplantation (using stem cells from a donor) is considered the only potentially curative approach for aggressive ATLL. For patients who respond to initial chemotherapy, doctors may consider whether this treatment is suitable[6][9]. The procedure involves intensive chemotherapy followed by transplantation as a consolidation strategy[6].
Newer targeted medications: Several newer drugs have shown promise in treating relapsed ATLL. Mogamulizumab, an antibody that targets a protein called CCR4 on the surface of cancer cells, was approved in Japan for relapsed ATLL based on clinical studies[10]. Lenalidomide, another medication, has also shown promise in treating this disease[6].
In some cases, doctors have reported success with medications originally developed for other blood cancers. Case reports describe patients with relapsed ATLL achieving complete response to venetoclax, a drug that blocks a protein called Bcl-2 that helps cancer cells survive[13].
Chemotherapy regimens: When clinical trials are not available or patients are not eligible, intensive chemotherapy combinations used for aggressive lymphomas may be tried[10].
Outlook for relapsed disease
The outlook for patients with relapsed or refractory ATLL remains difficult. The aggressive subtypes have median overall survival typically measured in months in the absence of allogeneic stem cell transplantation[9]. Patients who have rapidly progressive disease carry a poor outlook due to the resistance of cancer cells to treatment and severe weakening of the immune system[2].
However, ongoing research into the biology of ATLL and development of new treatments offers hope. Scientists are working to better understand the genetic changes that drive this disease, with the goal of developing more effective targeted therapies[6][9].
Once treatment is completed and the disease is in remission (a period when the cancer cannot be detected), doctors will continue to monitor patients during follow-up care. Regular visits with a physician familiar with the patient’s medical history and treatments are important. Some treatments can cause long-term or late effects that vary based on the duration and frequency of treatments, age, gender, and overall health at the time of treatment[14].
