ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Patient education: Acute lymphoblastic leukemia (ALL) treatment in adults (Beyond the Basics)

Patient education: Acute lymphoblastic leukemia (ALL) treatment in adults (Beyond the Basics)
Literature review current through: Jan 2024.
This topic last updated: Nov 01, 2022.

ACUTE LYMPHOBLASTIC LEUKEMIA OVERVIEW — Acute lymphoblastic leukemia (also called ALL) is a cancer of blood cells. It affects a type of white blood cell called a lymphocyte. ALL is also known as lymphoblastic lymphoma when the disease primarily involves lymph nodes rather than the blood and bone marrow. "Acute" means that it develops and advances quickly, and requires urgent treatment. ALL is the most common malignant disease in children, but it is less common in adults.

Normally, lymphocytes and other blood cells are produced in the bone marrow (the spongy area in the middle of bones) in a controlled fashion. In someone with ALL, this process is abnormal. Large numbers of immature and abnormal lymphocytes (called lymphoblasts) are produced and released into the bloodstream. In their immature state, these cells cannot perform their usual functions. The overgrowth of these cells leads to an inadequate number of normal, healthy blood cells, including white blood cells, red blood cells, and platelets. This can result in:

Neutropenia (low numbers of neutrophils) – Neutrophils are a type of white blood cells that help to fight infection. People with neutropenia are more likely to get infections.

Anemia (low numbers of red blood cells) – Red blood cells carry oxygen to our tissues. People without enough red cells may be pale and are often tired and short of breath.

Thrombocytopenia (low numbers of platelets) – Platelets help to prevent and stop bleeding. People with low platelets have bleeding and spontaneous bruising.

There are several types of ALL. The three main subtypes are B cell ALL, T cell ALL, and Philadelphia chromosome positive ALL (also called Ph+ ALL). B cell ALL is the most common type. Ph+ ALL is a subtype of B cell ALL that accounts for about one-third of all adult ALL, but is uncommon in children. While the general principles are the same, the specifics of treatment differ according to subtype. As an example, treatment of patients with Ph+ ALL includes specific drugs that target the gene product of the Philadelphia chromosome.

More detailed information about ALL, written for healthcare providers, is available by subscription. (See 'Professional level information' below.)

CANCER CARE DURING THE COVID-19 PANDEMIC — COVID-19 stands for "coronavirus disease 2019." It is an infection caused by a virus called SARS-CoV-2. The virus first appeared in late 2019 and has since spread throughout the world. Getting vaccinated lowers the risk of severe illness; experts recommend COVID-19 vaccination for anyone with cancer or a history of cancer.

In some cases, if you live in an area with a lot of cases of COVID-19, your doctor might suggest rescheduling or delaying medical appointments. But this decision must be balanced against the importance of getting care to screen for, monitor, and treat cancer. Your doctor can talk to you about whether to make any changes to your appointment schedule. They can also advise you on what to do if you test positive or were exposed to the virus.

GENERAL INFORMATION ABOUT ALL TREATMENT — A number of medications, or chemotherapy agents, are known to be effective against ALL. However, the best combination of medicines or the best treatment schedule is still not known. Because there are many different medicines, dosing schedules, and combinations, it has been difficult to study any one component of treatment thoroughly.

However, general principles of treatment have emerged and are followed in most cancer treatment centers. The exact regimens may vary from one center to another. Regimens can also vary based upon individual characteristics such as your ALL subtype, whether there are ALL cells in the spinal fluid that surrounds your brain and spinal cord, your age, and your general health.

Treatment side effects — Side effects of treatment will depend on the actual medicines being used, the schedule of treatment, and other factors. Many of the chemotherapy medicines used to treat ALL share common side effects, such as temporary hair loss, nausea and vomiting, mouth sores, diarrhea or constipation, numbness of fingertips and toes, need for transfusions, and an increased risk of infections and bleeding. Treatment to minimize these side effects is available.

Phases of treatment — The usual treatment for ALL can be divided into three phases: induction of remission, post-remission consolidation/intensification of therapy, and remission maintenance (also called continuation therapy). Each of these phases is important for destroying the cancer cells and preventing recurrence.

Induction of remission – In this phase, several medications are given with the goal of destroying as many cancer cells as possible to achieve a remission, meaning there are no detectable lymphoblasts in the blood or bone marrow and the normal blood cells have returned. This phase of treatment usually lasts four to six weeks and most of the time is spent in the hospital. Sometimes several courses of induction therapy are needed to achieve remission.

Consolidation/intensification therapy – This phase happens after remission has been achieved, and involves more chemotherapy, other medications, and/or stem cell transplantation to prevent a relapse. It is designed to eliminate residual leukemia cells even if they cannot be detected using a microscope to examine blood samples. Chemotherapy is usually given in monthly cycles that last for four to six months, while stem cell transplantation is more intensive but shorter.

Remission maintenance (or continuation) therapy – This treatment is intended to prevent relapse and involves alternating chemotherapy sessions with oral medications (pills), usually over two to three years. Most people are able to return to their normal activities during their maintenance treatment period.

INDUCTION OF REMISSION — Induction of remission takes about four weeks and is almost always performed while the patient remains in the hospital. Treatment usually includes vincristine and a steroid hormone (such as prednisone or dexamethasone) and may include an anthracycline (such as daunorubicin or doxorubicin). An enzyme called asparaginase is often given intravenously to starve malignant lymphoblasts of the essential amino acid asparagine in the plasma. Patients with Philadelphia chromosome-positive ALL require the addition of a BCR-ABL1 tyrosine kinase inhibitor (called a TKI), such as imatinib, dasatinib, or ponatinib. For induction therapy, the TKI may be used in combination with conventional chemotherapy or it may be given together with dexamethasone alone. Treatment with a TKI is generally continued for several years. Patients with CD20-positive ALL (in which a protein called CD20 is found on the surface of leukemia cells) may also be treated with a monoclonal antibody directed against CD20, called rituximab.

Vincristine and the anthracycline drugs are anti-cancer chemotherapy drugs. Chemotherapy refers to the use of medicines to stop or slow the growth and proliferation of cancer cells. Chemotherapy targets growing cells, interfering with their ability to divide or multiply. Because most of an adult's normal cells are not actively growing, they are not as affected by chemotherapy as the cancer cells. However, the cells in the bone marrow (where normal blood cells are produced), the hair follicles, and the lining of the gastrointestinal (GI) tract are all growing. Effects of chemotherapy on these and other normal tissues cause side effects during treatment, including hair loss, nausea, anemia (lowered red blood cell count), an increased risk of infection (lowered white blood cell count), and bleeding (lowered platelet count).

Vincristine and the anthracycline drugs are given through an intravenous (IV) line. Prednisone or dexamethasone can be given either by mouth or IV. Other medicines such as cyclophosphamide (Cytoxan, given IV) or pegylated asparaginase (given as a subcutaneous, intramuscular or IV injection) may also be given.

More than 80 percent of newly diagnosed adults with ALL enter complete remission after the initial treatment. This means that there are no detectable lymphoblasts in the blood or bone marrow and that the bone marrow is functioning normally. However, such remissions are usually short-lived unless additional chemotherapy is given (see 'Consolidation/intensification therapy' below).

Very sensitive pathology tests (flow cytometry and molecular methods) may be able to detect tumor cells that cannot be identified using routine examination of the blood or bone marrow. Tumor cells detected by these tests are called measurable residual disease (MRD; also called minimal residual disease). Detection of MRD at the end of induction might change the treatment plan since even small numbers of ALL cells can lead to relapse.

CONSOLIDATION/INTENSIFICATION THERAPY — Once remission is achieved, additional therapy is needed to avoid relapse. Relapse occurs because cancer cells are still present, even though these cells cannot be detected by routine examination of the blood or bone marrow. The intensity of consolidation therapy will depend upon the anticipated risk of relapse and the risks associated with treatment.

This phase of treatment generally involves either consolidation chemotherapy or stem cell transplantation:

For patients with a standard risk of relapse, consolidation chemotherapy is usually preferred, because there is no clear survival advantage to stem cell transplantation (rather than consolidation chemotherapy) for standard risk patients in their first complete remission.

Stem cell transplantation is usually reserved for ALL in first remission that has a higher risk of relapse, and for patients who have already relapsed and achieved a second remission (see 'Stem cell transplantation' below).

Consolidation chemotherapy — Some of the same medicines given during induction are also used during post-remission consolidation therapy, which may last for several months. Most of this treatment can take place as an outpatient during the day, without the need to remain in the hospital overnight.

In addition to scheduled doses of chemotherapy, many treatment programs call for preventive treatment of the central nervous system (the brain and spinal cord). Abnormal lymphoblasts in the brain often do not respond to chemotherapy given only into a vein, but must be treated directly with injection of chemotherapy, such as methotrexate, into the cerebrospinal fluid (CSF) surrounding the spinal cord and brain through a lumbar puncture (also called a spinal tap). For some patients, radiation therapy to the head may be used instead.

Patients with ALL in remission, but who have measurable residual disease by flow cytometry of molecular assays, may receive targeted antibody therapy such as blinatumomab or inotuzumab. These synthetic antibodies bind to specific proteins that are present on the surface of leukemia cells (CD19 and CD22, respectively). These antibodies are infused into a vein either as an inpatient or as an outpatient.

Stem cell transplantation — Stem cell transplantation, also called bone marrow transplantation or hematopoietic stem cell transplantation, is a treatment in which the patient's normal source of blood cells (the bone marrow) is replaced by healthy bone marrow cells (called stem cells) from a healthy genetically well-matched donor. (See "Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)".)

In preparation for stem cell transplantation, patients with ALL are usually given very high doses of chemotherapy or total body irradiation (TBI), called myeloablative conditioning. This kills cancer cells but also destroys all normal cells developing in the bone marrow. This means that the body's normal source of blood cells (the bone marrow) is no longer functional. The transplanted cells quickly re-establish the blood cell production process in the bone marrow.

Reduced-intensity conditioning and nonmyeloablative conditioning are less intensive treatments that can prepare the bone marrow for transplantation and are being studied in older patients and others who are not candidates for myeloablative treatment.

Allogeneic transplantation uses stem cells from a donor other than the patient, ideally a sibling with a similar genetic makeup (called a matched related donor). If the patient does not have a sibling with similar genetic characteristics, an unrelated person with a similar genetic makeup may be used (called a matched unrelated donor). Another donor possibility is a sibling with partially similar genetic characteristics, although this is not as well studied (sometimes called a partially matched family member donor). Family members who share 50 percent of the genetic identity with the patient are called haploidentical donors. Umbilical cord blood can also provide a source of unrelated stem cells.

Allogeneic transplantation treats ALL in two ways. First, high doses of chemotherapy or total body irradiation are given immediately before the transplant, which aggressively attacks and kills the leukemia cells in the blood and bone marrow. Second, when cells from another person are transplanted, some of the donor stem cells mature into immune cells, and these donor immune cells can help to destroy any remaining leukemia cells. This is called the "graft-versus-leukemia" or "graft-versus-tumor" effect. Unfortunately, this response is closely associated with a complication called "graft-versus-host disease" in which the immune response includes an attack on some of the patient's own healthy organs. Symptoms can include severe skin rash, diarrhea, liver damage, and other problems.

Autologous transplantation, which uses the patient's own stem cells collected while the patient is in complete remission, is generally not recommended for adults with most subtypes of ALL, because it is of no greater benefit than consolidation chemotherapy. However, autologous transplantation may have a role for patients with Philadelphia chromosome positive (Ph+) ALL who achieve a complete molecular remission.

MAINTENANCE THERAPY — Remission maintenance therapy or remission continuation therapy is a standard part of ALL treatment, although research studies have not clearly shown its benefit for adults. It is also unclear how long therapy should continue. Depending upon the program chosen, treatment is often continued for two to three years.

During maintenance treatment, oral medications (pills) are taken on certain days of the month and intravenous (IV) chemotherapy may be given into a vein once per month. Side effects during this phase of treatment are less frequent and less severe than those experienced during earlier stages of treatment. Most people are able to return to their normal activities during their maintenance treatment period.

RESIDUAL DISEASE AND RELAPSE RISK — Following the standard two to three years of treatment, patients in complete clinical remission should be monitored closely for evidence of early relapse. This involves checking blood counts and bone marrow aspiration and biopsy to look for lymphoblasts. This allows for early detection and treatment if relapse were to occur. Patients with ALL who maintain complete, continuous remission for four to five years are considered cured and no longer need routine bone marrow examination. However, relapses of ALL as long as 21 years after diagnosis have been reported.

Unfortunately, up to 25 percent of adults with ALL have disease that is resistant to the initial induction of remission. In addition, many adults with ALL who do attain an initial complete remission will ultimately suffer a relapse. Although a second remission can often be achieved, re-treatment of such patients is generally unsuccessful in the long run, and most will die of their disease or of complications of treatment. Allogeneic stem cell transplantation is generally recommended for patients who attain a second remission.

Treatment of relapsed or resistant disease — A second remission may be attained using a similar induction regimen if the relapse occurs more than two years following initial treatment. However, this approach is not recommended if a patient has primary resistant disease (complete remission was never attained) or for those who relapse while still receiving induction or maintenance therapy.

Several novel anti-leukemia treatments have been approved for specific subtypes of ALL. Immune-based (non-chemotherapy) treatments have been developed and are becoming more widely available. Some of these are synthetic antibodies that bind to the surface of ALL cells in the bloodstream or bone marrow and kill them. Another approach uses genetic engineering of the patient's own immune cells to create chimeric antigen receptor (CAR) T cells which, when reinfused back into the patient, can destroy chemotherapy-resistant ALL cells.

Salvage regimens, also called rescue treatments, are used after standard frontline treatments have failed. These regimens are designed to reduce symptoms and prolong survival, but may not be able to cure the disease. Optimally, patients should enroll onto a clinical trial specifically designed for treatment of resistant or relapsed ALL so they can get access to new agents given either alone or in combination.

Allogeneic stem cell transplantation is a reasonable option for selected patients with resistant or relapsed disease. All eligible patients who achieve a second complete remission should consider allogeneic stem cell transplantation.

CLINICAL TRIALS — Many patients with leukemia will be asked to enroll on a clinical research trial. Clinical research trials have advanced our knowledge and been crucial in the development of modern ALL therapy. Agents that are useful for relapsed disease are now being tested for patients with newly diagnosed ALL.

A clinical trial is a controlled way to study the effectiveness of new treatments or new combinations of known therapies. They are carefully designed and reviewed by experts in the field to provide state-of-the-art care for individual patients as well as to improve the outcomes of patients overall. Additional information concerning clinical trials for ALL can be obtained from the treatment team or the following websites:

www.cancer.gov/about-cancer/treatment/clinical-trials

https://clinicaltrials.gov/

Videos addressing common questions about clinical trials are available from the American Society of Clinical Oncology (www.cancer.net/research-and-advocacy/clinical-trials/welcome-pre-act).

WHERE TO GET MORE INFORMATION — Your healthcare provider is the best source of information for questions and concerns related to your medical problem.

This article will be updated as needed on our web site (www.uptodate.com/patients). Related topics for patients, as well as selected articles written for healthcare professionals, are also available. Some of the most relevant are listed below.

Patient level information — UpToDate offers two types of patient education materials.

The Basics — The Basics patient education pieces answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials.

Patient education: Acute lymphoblastic leukemia (ALL) (The Basics)
Patient education: Leukemia in adults (The Basics)
Patient education: Neutropenia and fever in people being treated for cancer (The Basics)

Beyond the Basics — Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are best for patients who want in-depth information and are comfortable with some medical jargon.

Patient education: Hematopoietic cell transplantation (bone marrow transplantation) (Beyond the Basics)

Professional level information — Professional level articles are designed to keep doctors and other health professionals up-to-date on the latest medical findings. These articles are thorough, long, and complex, and they contain multiple references to the research on which they are based. Professional level articles are best for people who are comfortable with a lot of medical terminology and who want to read the same materials their doctors are reading.

Clinical manifestations, pathologic features, and diagnosis of B cell acute lymphoblastic leukemia/lymphoma
Clinical manifestations, pathologic features, and diagnosis of precursor T cell acute lymphoblastic leukemia/lymphoma
Classification, cytogenetics, and molecular genetics of acute lymphoblastic leukemia/lymphoma
Hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) in adults
Treatment of relapsed or refractory acute lymphoblastic leukemia in adults
Induction therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults
Post-remission therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults
Induction therapy for Philadelphia chromosome positive acute lymphoblastic leukemia in adults
Post-remission therapy for Philadelphia chromosome positive acute lymphoblastic leukemia in adults

The following organizations also provide reliable health information.

National Library of Medicine

(https://medlineplus.gov/healthtopics.html)

National Cancer Institute

(https://www.cancer.gov/about-cancer)

American Cancer Society

(www.cancer.org)

The Leukemia & Lymphoma Society

(www.lls.org)

The American Society of Hematology

(www.hematology.org)

National Marrow Donor Program

(https://bethematch.org/)

The American Society of Clinical Oncology

(www.cancer.net/cancer-types/leukemia-acute-lymphocytic-all)

[1-12]

  1. Hunger SP, Mullighan CG. Redefining ALL classification: toward detecting high-risk ALL and implementing precision medicine. Blood 2015; 125:3977.
  2. Moriyama T, Relling MV, Yang JJ. Inherited genetic variation in childhood acute lymphoblastic leukemia. Blood 2015; 125:3988.
  3. van Dongen JJ, van der Velden VH, Brüggemann M, Orfao A. Minimal residual disease diagnostics in acute lymphoblastic leukemia: need for sensitive, fast, and standardized technologies. Blood 2015; 125:3996.
  4. Jabbour E, O'Brien S, Ravandi F, Kantarjian H. Monoclonal antibodies in acute lymphoblastic leukemia. Blood 2015; 125:4010.
  5. Maude SL, Teachey DT, Porter DL, Grupp SA. CD19-targeted chimeric antigen receptor T-cell therapy for acute lymphoblastic leukemia. Blood 2015; 125:4017.
  6. Curran E, Stock W. How I treat acute lymphoblastic leukemia in older adolescents and young adults. Blood 2015; 125:3702.
  7. Gökbuget N. How I treat older patients with ALL. Blood 2013; 122:1366.
  8. Larson RA. Managing CNS disease in adults with acute lymphoblastic leukemia. Leuk Lymphoma 2018; 59:3.
  9. Stock W, Luger SM, Advani AS, et al. A pediatric regimen for older adolescents and young adults with acute lymphoblastic leukemia: results of CALGB 10403. Blood 2019; 133:1548.
  10. DeFilipp Z, Advani AS, Bachanova V, et al. Hematopoietic Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Updated 2019 Evidence-Based Review from the American Society for Transplantation and Cellular Therapy. Biol Blood Marrow Transplant 2019; 25:2113.
  11. Advani AS, Moseley A, O'Dwyer KM, et al. SWOG 1318: A Phase II Trial of Blinatumomab Followed by POMP Maintenance in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia. J Clin Oncol 2022; 40:1574.
  12. Grover P, Veilleux O, Tian L, et al. Chimeric antigen receptor T-cell therapy in adults with B-cell acute lymphoblastic leukemia. Blood Adv 2022; 6:1608.
Disclaimer: This generalized information is a limited summary of diagnosis, treatment, and/or medication information. It is not meant to be comprehensive and should be used as a tool to help the user understand and/or assess potential diagnostic and treatment options. It does NOT include all information about conditions, treatments, medications, side effects, or risks that may apply to a specific patient. It is not intended to be medical advice or a substitute for the medical advice, diagnosis, or treatment of a health care provider based on the health care provider's examination and assessment of a patient's specific and unique circumstances. Patients must speak with a health care provider for complete information about their health, medical questions, and treatment options, including any risks or benefits regarding use of medications. This information does not endorse any treatments or medications as safe, effective, or approved for treating a specific patient. UpToDate, Inc. and its affiliates disclaim any warranty or liability relating to this information or the use thereof. The use of this information is governed by the Terms of Use, available at https://www.wolterskluwer.com/en/know/clinical-effectiveness-terms. 2024© UpToDate, Inc. and its affiliates and/or licensors. All rights reserved.
Topic 685 Version 28.0

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟