P站视频

In recent years, doctors have begun to use more intensive treatments, which has led to more leukemias going into remission. But this is also more likely to cause side effects, such as low white blood cell counts. People may need to get other drugs to help prevent or treat these side effects.

Treatment of ALL typically takes place in 3 phases:

• Induction (remission induction)
• Consolidation (intensification)
• Maintenance

The total treatment usually takes about 2 years, with the maintenance phase taking up most of this time. Treatment may be more or less intense, depending on the subtype of ALL and other prognostic factors.

ALL can spread to the area around the brain and spinal cord. Sometimes this has already occurred by the time ALL is first diagnosed. This spread is found when the doctor does a lumbar puncture (spinal tap) and leukemia cells are found in the cerebrospinal fluid (CSF), the liquid that surrounds the brain and spinal cord. The treatment of this is discussed below.

Even if leukemia cells aren't found in the CSF at diagnosis, it's possible that they might spread there later on. This is why an important part of treatment for ALL is central nervous system (CNS) prophylaxis – treatment that lowers the risk of the leukemia spreading to the area around the brain or spinal cord. This is also described in more detail below.

Induction

The goal of induction chemo is to get the leukemia into remission (complete remission). This means that leukemia cells are no longer found in bone marrow samples (on a bone marrow biopsy), the normal marrow cells return, and the blood counts return to normal levels. But a remission is not necessarily a cure, as leukemia cells may still be hiding somewhere in the body.

Induction chemo usually lasts for a month or so. Different combinations of chemo drugs might be used, but they typically include:

• Vincristine
• Dexamethasone or prednisone
• An anthracycline drug such as doxorubicin (Adriamycin) or daunorubicin

Based on a person’s prognostic factors, some regimens may also include other drugs such as cyclophosphamide, L-asparaginase (or pegaspargase), and/or high doses of methotrexate or cytarabine (ara-C) as part of the induction phase.

For people with ALL whose leukemia cells have the Philadelphia chromosome, a targeted drug such as imatinib (Gleevec) or dasatinib (Sprycel) is often included as well.

For people who are older (typically over 65) or who have other serious health conditions, many of the same drugs are used for induction, although the doses of the drugs might need to be reduced.

This first month of treatment is intensive and requires frequent visits to the doctor. You may spend some or much of this time in the hospital, because serious infections or other complications can occur. It's very important to take all medicines as prescribed. Sometimes complications can be serious enough to be life-threatening, but with recent advances in supportive care (nursing care, nutrition, antibiotics, growth factors, red blood cell and platelet transfusions as needed, etc.), these are much less common than in the past.

Most often, leukemia goes into remission with induction chemotherapy. But because leukemia cells may still be hiding somewhere in the body, further treatment is needed.

CNS treatment or prophylaxis: Treatment needs to be given either to keep the leukemia cells from spreading to the CNS (CNS prophylaxis), or to treat the leukemia if it has already spread to the CNS. This is often started during induction and continued through the other phases of treatment. It may include one or more of the following:

• Chemo injected directly into the CSF (called intrathecal chemotherapy). The drug used most often is methotrexate, but sometimes cytarabine or a steroid such as prednisone may be used as well. Intrathecal chemo can be given during a lumbar puncture (spinal tap) or through an Ommaya reservoir (as discussed in the surgery section).
• High-dose IV methotrexate, cytarabine, or other chemo drugs
• Radiation therapy to the brain and spinal cord

Consolidation (intensification)

If the leukemia goes into remission, the next phase often consists of another fairly short course of chemo, using many of the same drugs that were used for induction therapy. This typically lasts for a few months. Usually the drugs are given in high doses so that the treatment is still fairly intense. CNS prophylaxis/treatment is typically continued at this time.

A targeted drug like imatinib is also continued for people whose leukemia cells have the Philadelphia chromosome.

For some people with ALL, the immunotherapy drug blinatumomab (Blincyto) might be part of the consolidation phase as well.

Some people in remission, such as those who have certain subtypes of ALL or other poor prognostic factors, are still at high risk for the leukemia relapsing (coming back). Instead of standard chemo, doctors may suggest an allogeneic stem cell transplant (SCT) at this time, especially for those who have a brother or sister who would be a good donor match. An autologous SCT may be another option. The pros and cons of a stem cell transplant need to be weighed carefully for each person, as it’s not clear that they are helpful for everyone. People considering this procedure should think about having it done at a center that has done a lot of stem cell transplants.

Maintenance

After consolidation, people generally get maintenance chemotherapy with methotrexate and 6-mercaptopurine (6-MP). In some cases, this may be combined with other drugs such as vincristine and prednisone.

For people with ALL whose leukemia cells have the Philadelphia chromosome, a targeted drug like imatinib is often included as well.

Maintenance usually lasts for about 2 years. CNS prophylaxis/treatment is typically continued at this time.

Response rates to ALL treatment

In general, about 80% to 90% of adults will have complete remissions at some point during these treatments. This means leukemia cells can no longer be seen in their bone marrow. Unfortunately, about half of these patients relapse, so the overall cure rate is in the range of 40%. Again, these rates can vary a lot, depending on the subtype of ALL and other prognostic factors. For example, cure rates tend to be higher in younger patients.

If the leukemia doesn’t respond or if it comes back after treatment

If the leukemia is refractory – that is, if it doesn’t go away with the first treatment (which happens in about 10% to 20% of people with ALL) – then newer or more intensive doses of chemo drugs may be tried, although they are less likely to work. Immunotherapy (monoclonal antibodies or CAR T-cell therapy) may be an option for patients with B-cell ALL. A stem cell transplant may be tried if the leukemia can be put into at least partial remission. Clinical trials of new treatment approaches may also be considered.

If leukemia goes into remission with the initial treatment but then comes back (relapses or recurs), it will most often do so in the bone marrow and blood. Occasionally, the brain or spinal fluid will be the first place it recurs.

It is sometimes possible to put the leukemia into remission again with more chemotherapy (chemo), although this remission tends to be shorter than the first one.

The approach to treatment may depend on how soon the leukemia returns after the first treatment. If the relapse occurs after a long time, the same or similar treatment may be used to try for a second remission. If the time to relapse is shorter, more aggressive chemo with other drugs may be needed.

Immunotherapy might be another option for some people. For example, a monoclonal antibody or CAR T-cell therapy might be an option for some people with B-cell ALL.

People with ALL that has the Philadelphia chromosome who were taking a targeted drug like imatinib are often switched to a different targeted drug.

If the leukemia cells have a KTM2A gene mutation, treatment with a targeted drug called a menin inhibitor, such as revumenib (Revuforj), might be an option.

For patients with T-cell ALL, the chemo drug nelarabine (Arranon) may be helpful.

If a second remission can be achieved, most doctors will advise some type of stem cell transplant if possible.

If the leukemia doesn’t go away or keeps coming back, eventually treatment with more chemo is unlikely to be helpful. If a stem cell transplant is not an option, a clinical trial testing newer treatments might still be an option for some people.

Palliative treatment

At some point, it may become clear that further treatment, even in clinical trials, is extremely unlikely to cure the leukemia. At this time, the focus of treatment may shift to controlling the leukemia and its symptoms for as long as possible, rather than trying to cure it. This may be called palliative treatment or supportive care. For example, the doctor may advise less intensive chemo to try to slow the leukemia growth instead of trying to cure it.

As the leukemia grows in the bone marrow it may cause pain. It's important that you be as comfortable as possible. Treatments that may be helpful include radiation and appropriate pain-relieving medicines. If medicines such as aspirin and ibuprofen don’t help with the pain, stronger opioid medicines such as morphine are likely to be helpful.

Other common symptoms from leukemia are low blood counts and fatigue. Medicines or blood transfusions may be needed to help with these problems. Nausea and loss of appetite can be treated with medicines and high-calorie food supplements. Infections that occur may be treated with antibiotics.