Stage 3 Cancer: Definition, Diagnosis, Treatment, Prognosis

Understanding Leukemia -- Diagnosis And Treatment

Because many types of leukemia show no obvious symptoms early in the disease, leukemia may be diagnosed incidentally during a physical exam or as a result of routine blood testing. If a person appears pale, has enlarged lymph nodes, swollen gums, an enlarged liver or spleen, significant bruising, bleeding, fever, persistent infections, fatigue, or a small pinpoint rash, the doctor should suspect leukemia. A blood test showing an abnormal white cell count may suggest the diagnosis. To confirm the diagnosis and identify the specific type of leukemia, a needle biopsy and aspiration of bone marrow from a pelvic bone will need to be done to test for leukemic cells, DNA markers, and chromosome changes in the bone marrow.

Important factors in leukemia include the age of the patient, the type of leukemia, and the chromosomal abnormalities found in leukemia cells and bone marrow.

While the reported incidence of leukemia has not changed much since the 1950s, more people are surviving longer thanks mainly to advances in chemotherapy. Childhood leukemia (3 out of 4 cases in children is ALL), for example, represents one of the most dramatic success stories of cancer treatment. The five-year survival rate for children with ALL has risen to about 85% today.

For acute leukemia, the immediate goal of treatment is remission. The patient undergoes chemotherapy in a hospital and stays in a private room to reduce the chance of infection. Since acute leukemia patients have extremely low counts of healthy blood cells, they are given blood and platelet transfusions to help prevent or stop bleeding. They receive antibiotics to prevent or treat infection. Medications to control treatment-related side effects are given as well.

People with acute leukemia are likely to attain remission when chemotherapy is used as the primary treatment. To keep the disease under control, they will then receive consolidation chemotherapy for 1-4 months to get rid of any remaining malignant cells.

Patients with ALL will receive intermittent treatment usually for up to two years.

After obtaining a complete remission, some patients with acute myeloid leukemia (AML) may require an allogeneic stem cell transplant. This requires a willing donor with compatible tissue type and genetic characteristics -- preferably a family member. Other donor sources could include a matched unrelated donor or umbilical blood.

A stem cell transplant has three stages: induction, conditioning, and transplantation. First, the individual's white blood cell count is brought under control by chemotherapy. Then a single dose of chemotherapy may be given followed by a conditioning regimen of high dose chemotherapy. This will destroy the individual's bone marrow and any residual leukemia cells that may be present. Then the donor cells will be infused.

Until the donor marrow cells start producing new blood, the individual is left with virtually no blood cells -- white cells, red cells, or platelets. This makes death by infection or bleeding a strong possibility. Once the donor stem cells grow sufficiently into the marrow, usually in two to six weeks, long-term remission becomes a strong possibility. In addition to chemotherapy, the person will receive medication to prevent and treat graft versus host disease. With this disease, donor cells attack the person's normal tissue cells. Medication is also given to prevent rejection of the donor stem cells.

Allogeneic stem cell transplantation is both expensive and risky, but it offers the best chance for long-term remission for high risk AML and certain cases of ALL.

If these treatments don't work for kids and young adults that have B-cell type ALL, or the cancer comes back, their doctor may want to try a new kind of gene therapy. Using CAR T-cell therapy, certain immune cells can be "reprogrammed" to attack the cancer. Because there can be severe side effects, only certified hospitals and clinics can do this treatment.

Chronic lymphocytic leukemia (CLL), a form of leukemia that usually affects older persons, typically progresses slowly. Therefore, treatment may be conservative. Not all patients require immediate treatment. Patients experiencing symptoms requiring treatment include the so-called 'B' symptoms of fevers, night sweats for 14 consecutive days, or 10% unintentional body weight loss over 6 months. Other symptoms, such as painful swollen lymph glands, painful swollen liver or spleen, or evidence of bone marrow failure, also require treatment.

Oral chemotherapy can effectively control symptoms of CML for several years. In the past, most cases of CML eventually advanced to an acute phase despite treatment, so doctors advised bone marrow transplantation during the chronic phase. Allogeneic stem cell transplantation for CML is still a treatment option for diseases resistant to treatment or for persons whose disease is in the acute phase.

The drug imatinib (Gleevec) has radically changed treatment for CML. Known as a molecular targeting drug, it attacks the genetic alterations that cause white blood cells to grow out of control. Gleevec doesn't cure CML, but it can result in long-term remission and survival of CML. This drug was shown to be superior to prior therapies such as busulfan, hydroxyurea, and interferon alpha. There are now five other drugs - asciminib (Scemblix), bosutinib (Bosulif), dasatinib (Sprycel), nilotinib (Tasigna), and ponatinib (Iclusig), that can be used in CML if the leukemia becomes resistant to Gleevec. 

Nilotinib (Tasigna) has FDA approval for CML in the chronic phase. Dasatinib (Sprycel) is FDA-approved for first-line therapy of chronic phase CML. Bosutinib  (Bosulif) and ponatinib (Iclusig) can be used during any phase of CML if a person is resistant to or cannot tolerate the other drugs. Still another drug, omacetaxine mepesuccinate (Synribo), is approved for those whose CML has progressed after treatment with two or more of the previous medications. Asciminib (Scemblix) can also be used after two or more of the previous medications have already been tried or if the person's cancer cells have a T315I mutation. 

New Way Found To Treat Early Relapse In Leukemia

Researchers at Peter Mac have found a new way to treat a form of leukemia that stops the disease in its tracks to prolong remission.

The research, published in the Journal of Clinical Oncology, has shown how a new combination of a molecular technology called measurable residual disease (MRD), medication and low-dose chemotherapy is helping patients live longer with acute myeloid leukemia (AML).

Despite the best treatment, many patients with AML have recurrent disease within the first two years. This MRD test provides advanced warning that the disease is returning several months before the leukemia is visible under the microscope or the patient develops abnormal blood counts.

As soon as MRD was detected to rise, patients were treated with a pill called venetoclax combined with low-dose, under-the-skin injection of chemotherapy that stopped the leukemia in its tracks in the majority of patients.

Dr. Ing-Soo Tiong, hematologist and researcher at Peter Mac, said with the previous approach to treatment, the median survival after first relapse is only 6–8 months. Results of this clinical trial shows 50–70% of AML patients are still alive after two years.

"Prior to this discovery, patients and clinicians face the uncertainty of disease relapse, and the only treatment option then was an even stronger dose of salvage chemotherapy requiring at least a month of stay in hospital associated with a very high risk of infection," he said.

"In this new study we measured a patient's MRD as soon as they finished chemotherapy with the aim of the data telling us which patients were most likely to relapse."

Professor Andrew Wei, co-lead of the AML program at Peter Mac and Royal Melbourne Hospital, explained this option meant patients could be treated as an outpatient or by hospital in the home with results comparable to intensive chemotherapy.

"This is a paradigm-changing clinical trial that utilizes molecular technologies to enable patients to receive their interventional therapy much earlier than normal and with less toxicity," he said.

"The response to treatment was fast and durable, enabling patients to receive a subsequent stem cell transplant with much lower levels of disease burden and enhanced fitness.

"This is the first ever prospective trial using a pre-emptive MRD targeted approach. It has led to the development of a new national trial called INTERCEPT, coordinated by the Australasian Leukemia and Lymphoma Group."

The INTERCEPT trial is currently recruiting patients at Peter Mac and approximately 15 sites nationwide. AML is a type of blood cancer that affects the blood and bone marrow. It is a rare cancer with 1,218 people diagnosed in Australia in 2019.

More information: Ing Soo Tiong et al, Targeting Molecular Measurable Residual Disease and Low-Blast Relapse in AML With Venetoclax and Low-Dose Cytarabine: A Prospective Phase II Study (VALDAC), Journal of Clinical Oncology (2024). DOI: 10.1200/JCO.23.01599

Citation: New way found to treat early relapse in leukemia (2024, April 15) retrieved 24 April 2024 from https://medicalxpress.Com/news/2024-04-early-relapse-leukemia.Html

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Mayo Clinic Q&A: Treatment-free Remission For Chronic Myeloid Leukemia

DEAR MAYO CLINIC: My 32-year-old daughter was recently diagnosed with chronic myeloid leukemia. It's a lot to take in. We've heard about treatment-free remission. That sounds hopeful. What does that mean? How is it achieved?

ANSWER: It is a lot to take in. Some background information may help you and your daughter understand this diagnosis and potential treatment.

Leukemias are cancers of the blood cells. Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the bone marrow, which produces blood cells. "Myelogenous" refers to the type of blood cells this leukemia affects. "Chronic" means this cancer is more slowly progressing than other severe forms of leukemia.

CML is a genetic problem that causes overproduction of a protein that allows some blood cells to grow out of control. But the gene change that causes CML is not hereditary. Parents do not pass the gene to their children.

According to the American Cancer Society, nearly 9,000 people are diagnosed with CML each year in the U.S. This type of leukemia typically affects older adult males, but both men and women can be diagnosed with CML. It is rarely seen in children.

Some people with CML may experience symptoms such as bone pain, bleeding easily and feeling full after eating a small amount. But many people do not have symptoms until later stages. It is diagnosed with a blood test.

People first diagnosed with CML likely will begin targeted treatment to eliminate blood cells that are overproducing a protein called tyrosine kinase. Medications called tyrosine kinase inhibitors (TKIs) are first-line treatments. Each medication has its own side effects, such as swelling or nausea, that differ for each patient and are discussed in the early stages of choosing treatment. At later stages, other treatments may include chemotherapy or a bone marrow transplant.

Patients we consider for treatment-free remission include those in a low-risk category who take one kind of medication during their treatment course and are in what's called "molecular remission" for at least two years. Molecular remission means the gene that causes CML cannot be found in the patient's blood or bone marrow.

During and after treatment, regular tests are necessary to monitor the patient's blood. When no leukemia is detected, patients may be able to end treatment. Even patients in treatment-free remission must be monitored regularly, for life, and work closely with a hematologist or oncologist. That means testing monthly, progressing to every other month, then every three months, to every six months.

If a patient were to relapse, the disease would be discovered early, and treatment using the same kind of medication would be resumed. Studies over the last 10 to 15 years have shown when restarting medication early, the chance of achieving remission is almost 100%.

There are certain criteria before stopping TKI treatments. This is important as it affects women and family planning. Managing CML, pregnancy and childbirth is challenging but possible with the help of the health care team.

At Mayo, we started this treatment-free remission approach in 2015. Many patients have been off treatment for years. For more information, visit the CML Patient Education website. — Kebede Begna, M.D., Hematology, Mayo Clinic, Rochester

Mayo Clinic Q&A is an educational resource and doesn't replace regular medical care. Email a question to MayoClinicQ&A@mayo.Edu. For more information, visit www.Mayoclinic.Org .

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