Adult T-cell leukemia/lymphoma (ATLL)

ATLL is diagnosed by pairing a virus test with tests on blood or tissue. A blood test looks for antibodies to HTLV-1, and a second, different test confirms a positive result. Under the microscope, ATLL cells in the blood often have a nucleus shaped like a flower, so they are called flower cells. Marker tests usually show T cells that carry CD4 and CD25. A biopsy of a lymph node or other tissue can show the lymphoma.

When possible, a lab test also checks whether one family of virus-infected cells has multiplied (monoclonal HTLV-1 integration). Blood calcium, a blood enzyme called LDH and scans show how active the disease is and where it is. Doctors then sort ATLL into one of four types: acute, lymphoma, chronic or smoldering. The type guides whether to treat right away or watch closely.

International experts advise an HTLV-1 blood test for people found to have certain T-cell lymphomas, especially in regions where the virus is common. That test helps tell ATLL apart from other T-cell cancers. U.S. researchers note that in the United States, ATLL is rarely found before it causes life-threatening problems. Barriers to care in the communities most affected are part of the reason.

Treatment depends on the clinical subtype, risk features and where care is delivered. Some slower-growing forms may be monitored or treated with antiviral-based approaches. One exception is ATLL that shows up only as tumors in the skin: experts say it should not simply be watched, because it often behaves like aggressive disease. Aggressive disease usually needs prompt systemic treatment. Chemotherapy, zidovudine with interferon in appropriate settings, targeted medicines and clinical trials may be considered.

Allogeneic transplantation can offer durable remission and a chance of cure for eligible people with aggressive ATLL, often after initial disease control. Early referral and donor planning help preserve that option.

Mogamulizumab can be useful in ATLL in some regions and settings, but prior exposure can affect graft-versus-host disease risk after transplant. For that reason, international experts suggest chemotherapy without mogamulizumab when a transplant is planned soon after first treatment, and a gap of at least 50 days after the last dose when it is used before a later transplant. No single treatment sequence applies across every ATLL subtype.

When a transplant from a donor is planned, the team usually tests brothers and sisters first. Each full sibling has about a one in four chance of being a full match.

Most patients do not have a matched relative. In the words of NMDP, the U.S. registry, “75% of patients don’t have a fully matched donor in their own family.” The team then searches registries of volunteer donors around the world and banks of donated cord blood. In some transplants, a half-matched parent, child or sibling can also be the donor.

Matching depends on inherited tissue markers called HLA, so a patient is most likely to match someone who shares their ancestry. Every person who joins makes the search a little more likely to succeed, especially for patients from groups that are underrepresented on registries.

The outlook for ATLL depends most on its type. Smoldering ATLL and chronic ATLL without certain warning signs in blood tests tend to move slowly. In Japan, care teams usually watch these forms closely without treatment until they change. In many other countries, antiviral medicines are often used. The acute and lymphoma types, and chronic ATLL with those warning signs, are aggressive and need prompt treatment.

A nationwide study in Japan followed 770 people diagnosed in 2010 and 2011. Four years later, about 1 in 6 people with the acute type were alive. About 6 in 10 people with the smoldering type or the slower chronic type were alive. Japanese experts note that even the slower types often do poorly over the long term.

For aggressive ATLL, a donor stem cell transplant can give some people long-term remission. The donor's immune cells can attack the leukemia. International experts advise early referral to a transplant center and prefer donors who do not carry HTLV-1. These figures describe groups in one country. They cannot predict how any one person will do.