Patient information: Acute lymphoblastic leukemia (ALL) treatment in adults (Beyond the Basics)
ACUTE LYMPHOBLASTIC LEUKEMIA OVERVIEW
Acute
lymphoblastic leukemia (ALL) is a cancer of blood cells. ALL is also
known as lymphoblastic lymphoma when the disease primarily involves
lymph nodes rather than the blood and bone marrow. ALL involves a type
of white blood cell called a lymphocyte. Acute means that it develops
and advances quickly, and requires immediate treatment.Normally, lymphocytes and other blood cells are produced by 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 (lymphoblasts) are produced and released into the blood stream. In their immature state, these cells cannot perform their usual functions, leaving the person vulnerable to anemia, infection, and bleeding.
The overproduction of lymphoblasts prevents the bone marrow from producing other important blood cells, including red blood cells, other types of white blood cells (especially neutrophils, sometimes called "polys"), and platelets. The lymphoblasts can collect in certain areas of the body, such as the brain, spinal cord, and lymph nodes (glands).
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 so 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 age, the total number of white blood cells, or characteristics of the genetic changes. (See "Cytogenetics in acute lymphoblastic leukemia".)
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 hair loss
(which is temporary), nausea and vomiting, mouth sores, diarrhea or
constipation, 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, consolidation/intensification of therapy, and remission
maintenance (also called continuation therapy). A summary of one
regimen’s entire treatment process is available in the table (table 1).
Treatment of high-risk disease — Patients
with high risk disease, including those with Philadelphia chromosome
positive (Ph+) acute lymphoblastic leukemia and Burkitt
leukemia/lymphoma, require special treatment programs that use different
medications and doses from those used in patients with standard risk
ALL. In addition, allogeneic stem cell transplantation is more
frequently recommended in those patients with Ph+ ALL.
INDUCTION OF REMISSION
Induction
of remission takes about four weeks and is almost always performed
while the patient remains in the hospital. Treatment includes:
vincristine (Oncovin) and an anthracycline (such as daunorubicin or
doxorubicin) along with prednisone, dexamethasone, or another steroid
hormone (table 1).
Patients with Philadelphia chromosome positive ALL require the addition
of a BCR-ABL tyrosine kinase inhibitor, such as imatinib or dasatinib.
(See "Induction therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults".)Vincristine and the anthracycline drugs are anti-cancer chemotherapy drugs. These drugs work by interfering with the ability of rapidly growing cells (such as cancer cells) to divide or reproduce themselves. Because most of an adult's normal cells are not actively growing, they are less affected by chemotherapy, with the exception of bone marrow (where the blood cells are produced), the hair, and the cells lining the gastrointestinal tract.
Effects of chemotherapy on these and other normal tissues cause side effects during treatment, including 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 L-asparaginase (Elspar, given as a subcutaneous, intramuscular or IV injection) may also be given.
Approximately 80 percent of newly diagnosed adults with ALL enter complete remission after the initial treatment, meaning 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).
CONSOLIDATION/INTENSIFICATION THERAPY
Once
remission is achieved, additional therapy is needed to avoid relapse.
Relapse probably occurs because abnormal cells are still present, even
though these cells cannot be detected by routine examination of the
blood or bone marrow. (See "Post-remission therapy for Philadelphia chromosome negative acute lymphoblastic leukemia in adults".)
Chemotherapy — Some
of the same medicines given during induction are also used during
remission consolidation therapy, which may last for several months. Most
of this treatment can take place during the day, without the need to
remain in the hospital overnight (table 1).
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 radiation to the head and/or injection of chemotherapy,
such as methotrexate, into the fluid surrounding the spinal cord and
brain through a lumbar puncture (also called a spinal tap).
Stem cell transplantation — Stem
cell transplantation, also called bone marrow transplantation or
hematopoietic stem cell transplantation, is a treatment in which the
patient is given very high doses of chemotherapy or total body
irradiation (TBI), called myeloablative treatment. 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. (See "General principles of hematopoietic cell transplantation for acute lymphoblastic leukemia in adults".)
After
the treatment, the patient requires a supply of healthy young blood
cells (called stem cells) to be reintroduced, or transplanted. This is
done by a transfusion of blood stem cells from a healthy well-matched
donor. The transplanted cells re-establish the blood cell production
process in the bone marrow. (See "Patient information: Bone marrow transplantation (stem cell transplantation) (Beyond the Basics)".)Current data indicate that there is no clear advantage to stem cell transplantation as compared with chemotherapy during consolidation therapy for standard risk patients in their first complete remission, although it may shorten the overall treatment course. However, allogeneic stem cell transplantation is recommended, if necessary, following a relapse when patients are in a second complete remission, and for subsets of patients with more aggressive forms of ALL in first remission.
- 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, or MRD).
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, or MUD). Another possibility
is to use a sibling with partially similar genetic characteristics,
although this is not as well studied (sometimes called a partially
matched family member donor). 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 present in the blood and bone marrow. Second, when cells from another person are transfused, some of the donor stem cells mature into immune cells, and these donor immune cells can cause an immune response that helps 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. Still, allogeneic transplantation is preferred over autologous transplantation in patients with ALL. - Autologous transplantation, which uses the patient's own stem cells collected while the patient is in complete remission, is of no greater benefit than chemotherapy for adults with ALL. Thus, it is generally not recommended.
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 three years (table 1).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 full activity 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 have a bone marrow aspiration and biopsy
repeated every three to six months for at least the next two years. 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 transplantation is generally recommended for patients who attain a second remission.
Treatment of relapse 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 receiving induction or maintenance therapy. (See "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults".)
Salvage
regimens are also called rescue treatments and 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 also 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. 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:
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 information: Acute lymphoblastic leukemia (ALL) (The Basics)Patient information: Leukemia (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 information: Bone marrow transplantation (stem cell 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 precursor B-cell acute lymphoblastic leukemia/lymphomaClinical manifestations, pathologic features, and diagnosis of precursor T-cell acute lymphoblastic leukemia/lymphoma
Cytogenetics in acute lymphoblastic leukemia
General principles of hematopoietic cell transplantation for acute lymphoblastic leukemia 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
(www.nlm.nih.gov/medlineplus/healthtopics.html) - National Cancer Institute
(www.cancer.gov/cancertopics) - American Cancer Society
(www.cancer.org) - The Leukemia & Lymphoma Society
(www.leukemia-lymphoma.org/hm_lls) - National Marrow Donor Program
(www.marrow.org) - The American Society of Clinical Oncology
(www.cancer.net/portal/site/patient)
Literature review current through: 20.4:
feb 2012
This topic last updated: feb 2, 2012
This topic last updated: feb 2, 2012
The content on the UpToDate website is not intended nor recommended as a substitute
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References
- Gökbuget N, Hoelzer D. Treatment of adult acute lymphoblastic leukemia. Semin Hematol 2009; 46:64.
- Khaled SK, Thomas SH, Forman SJ. Allogeneic hematopoietic cell transplantation for acute lymphoblastic leukemia in adults. Curr Opin Oncol 2012; 24:182.
- Fielding AK. Current treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia. Hematology Am Soc Hematol Educ Program 2011; 2011:231.
- Fielding AK. Current therapeutic strategies in adult acute lymphoblastic leukemia. Hematol Oncol Clin North Am 2011; 25:1255.
GRAPHICS
Cancer and Leukemia Group B (CALGB) study 8811 chemotherapy regimen for acute lymphoblastic leukemia in adults
Course I: Induction (4 weeks) | |||
For patients <60 years old: | |||
Cyclophosphamide | IV | 1200 mg/m2 | Day 1 |
Daunorubicin | IV | 45 mg/m2/day | Days 1-3 |
Vincristine | IV | 2 mg | Days 1, 8, 15, 22 |
Prednisone | PO | 60 mg/m2/day | Days 1-21 |
Asparaginase (E. coli) | SC/IM | 6000 units/m2 | Days 5, 8, 11, 15, 18, 22 |
For patients ≥60 years old: | |||
Cyclophosphamide | IV | 800 mg/m2 | Day 1 |
Daunorubicin | IV | 30 mg/m2/day | Days 1-3 |
Vincristine | IV | 2 mg | Days 1, 8, 15, 22 |
Prednisone | PO | 60 mg/m2/day | Days 1-7 |
Asparaginase (E. coli) | SC/IM | 6000 units/m2 | Days 5, 8, 11, 15, 18, 22 |
All patients receive filgrastim (G-CSF) 5 mcg/kg subcutaneously once per day starting on day 4 and continuing until the ANC is >1000/microL on two consecutive determinations >24 hours apart. | |||
Course IIA: Early intensification (4 weeks; repeat once for Course IIB) | |||
Intrathecal methotrexate | IT | 15 mg | Day 1 |
Cyclophosphamide | IV | 1000 mg/m2 | Day 1 |
Mercaptopurine | PO | 60 mg/m2/day | Days 1-14 |
Cytarabine | SC | 75 mg/m2/day | Days 1-4, 8-11 |
Vincristine | IV | 2 mg | Days 15, 22 |
Asparaginase (E. coli) | SC/IM | 6000 units/m2 | Days 15, 18, 22, 25 |
Course III: CNS prophylaxis and interim maintenance (12 weeks) | |||
Cranial irradiation | 2400 cGy | Days 1-12 | |
Intrathecal methotrexate | IT | 15 mg | Days 1, 8, 15, 22, 29 |
Mercaptopurine | PO | 60 mg/m2/day | Days 1-70 |
Methotrexate | PO | 20 mg/m2 | Days 36, 43, 50, 57, 64 |
Course IV: Late intensification (8 weeks) | |||
Doxorubicin | IV | 30 mg/m2 | Days 1, 8, 15 |
Vincristine | IV | 2 mg | Days 1, 8, 15 |
Dexamethasone | PO | 10 mg/m2/day | Days 1-14 |
Cyclophosphamide | IV | 1000 mg/m2 | Day 29 |
Thioguanine | PO | 60 mg/m2/day | Days 29-42 |
Cytarabine | SC | 75 mg/m2/day | Days 29-32, 36-39 |
Course V: Prolonged maintenance (until 24 months from diagnosis) | |||
Vincristine | IV | 2 mg | Day 1 of every 4 weeks |
Prednisone | PO | 60 mg/m2/day | Days 1-5 of every 4 weeks |
Mercaptopurine | PO | 60 mg/m2/day | Days 1-28 |
Methotrexate | PO | 20 mg/m2 | Days 1, 8, 15, 22 |
ANC: absolute neutrophil count; IT: intrathecal; IV: intravenous; IM: intramuscular; PO: oral; SC: subcutaneous.
Data from: Acute Leukemias VI: Prognostic
factors and treatment strategies, Buchner T, Hiddeman W, Wormann B
(Eds), Springer-Verlag, Berlin 1997. p.677; Larson RA, Dodge RK, Burns
CP, Blood 1995; 85:2025; and Larson RA, Dodge RK, Linker CA, et al.
Blood 1998; 92:1556-1564.
Acute Lymphocytic Leukemia
Also called: ALL
open here please ►
Leukemia
is cancer of the white blood cells. White blood cells help your body
fight infection. Your blood cells form in your bone marrow. In leukemia,
however, the bone marrow produces abnormal white blood cells. These
cells crowd out the healthy blood cells, making it hard for blood to do
its work. In acute lymphocytic leukemia (ALL), there are too many of
specific types of white blood cells called lymphocytes or lymphoblasts.
ALL is the most common type of cancer in children.
Possible risk factors for ALL include being male, being white, previous chemotherapy treatment, exposure to radiation, and for adults, being older than 70.
Symptoms of ALL include:
Possible risk factors for ALL include being male, being white, previous chemotherapy treatment, exposure to radiation, and for adults, being older than 70.
Symptoms of ALL include:
- Weakness or feeling tired
- Fever
- Easy bruising or bleeding
- Bleeding under the skin
- Shortness of breath
- Weight loss or loss of appetite
- Pain in the bones or stomach
- Pain or a feeling of fullness below the ribs
- Painless lumps in the neck, underarm, stomach, or groin
NIH: National Cancer Institute
MEDICAL ENCYCLOPEDIA
National Institutes of Health
- The primary NIH organization for research on Acute Lymphocytic Leukemia is the National Cancer Institute
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