City of Hope

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City of Hope

1500 East Duarte Road
Duarte, California 91010

626-256-HOPE (4673)

Leukemia

City of Hope is recognized internationally for its breakthrough research discoveries and clinical treatments for leukemia, lymphoma, myeloma and blood disorders.

A pioneer in the field of hematopoietic cell transplantation (HCT), we have performed more than 8,500 bone marrow and stem cell transplants to date and operate one of the largest, most successful programs of its kind in the world, with many patients experiencing long-lasting remissions and even cures.

We conduct clinical trials using innovative combination chemotherapy protocols which have produced impressive results in a variety of leukemias and lymphomas.

Our team of specialists is renowned for its collaborative and compassionate approach, combining highly advanced technologies, aggressive therapies and an extensive support network to give patients the best outcomes possible.

Leukemia Treatment Options

Patients with acute leukemia usually require urgent treatment to reduce symptoms and return blood counts to normal. This is called complete remission. Once a remission is achieved, additional treatment is given to help prevent recurrence of the disease.

Patients with chronic types of leukemia may receive treatment or it may be decided to wait until symptoms appear before taking action.

Chemotherapy
Chemotherapy is the main treatment for all forms of leukemia. Because leukemia is a cancer of the blood, surgery is not an option as it is with solid tumors. Chemotherapy uses powerful drugs to kill leukemic cells. The drugs target fast-dividing cells by disrupting critical parts of the cell cycle. Since cancer cells divide faster than normal cells, more cancer cells than normal cells are killed. Of course, a significant number of normal cells are damaged, which causes the many familiar side effects of chemotherapy. Chemotherapy may be given by mouth (pills), intravenously through an IV or catheter, or into the cerebrospinal fluid (intrathecally). Most often, combinations of chemotherapy drugs are used to achieve the optimal therapeutic outcome.

City of Hope’s New Drug Development Program is actively developing and testing novel drugs and drug combinations designed to improve outcomes for all types of leukemia. Chemotherapy is usually given in cycles, sometimes starting with intensive induction treatment, which takes several days. This is followed by a few weeks without treatment, allowing the patient to recover from side effects, mostly related to lower blood counts. The sequence is then repeated. Patients who achieve initial remission require additional treatment, usually given over a period of months (in chronic lymphocytic leukemia and acute myeloid leukemia) or years (in acute lymphoblastic leukemia and chronic myelogenous leukemia) in order to prevent recurrence.

Chemotherapy for Acute Leukemia Treatment for acute leukemia is intensive and usually requires hospitalization. Treatment for acute leukemia is intensive and usually requires hospitalization.

Chemotherapy for Acute Lymphocytic Leukemia (ALL) Chemotherapy for ALL usually involves a number of agents. The following is a common combination protocol:

* L-asparaginase (Elspar) or PEG-L-asparaginase (pegaspargase, Oncaspar)
* daunorubicin ,also known as daunomycin (Cerubidine)
* vincristine (Oncovin)
* prednisone (numerous brand names)

Other drugs that may be used include:
* doxorubicin (Adriamycin)
* cytarabine, also known as cytosine arabinoside or ara-C (Cytosar)
* etoposide (VePesid, others)
* teniposide (Vumon)
* 6-mercaptopurine (Purinethol)
* methotrexate
* cyclophosphamide (Cytoxan)
* dexamethasone (Decadron, others)

Chemotherapy for Acute Myelogenous Leukemia (AML) Chemotherapy for AML usually involves a combination of two or three different anticancer drugs. One often-used combination is the following:

* daunorubicin, also known as daunomycin (Cerubidine) or idarubicin (Idamycin)
* cytarabine, also known as cytosine arabinoside or ara-C (Cytosar)

Currently under investigation at City of Hope

* vorinostat with decitabine
* clofaribine with melphalan

Other drugs that may be used include:

* mitoxantrone (Novantrone)
* 6-thioguanine, also known as 6-TG
* 6-mercaptopurine, also known as 6-MP (Purinethol)
* fludarabine (Fludara)
* vincristine (Oncovin)
* etoposide (VePesid, others)
* prednisone (numerous brand names)

Chemotherapy for Chronic Leukemia For patients with chronic leukemia such as chronic myeloid leukemia (CML) or chronic lymphocytic leukemia (CLL), oral or intravenous drugs may often be given in an outpatient setting.

Chemotherapy for CML First-line treatment for CML is the orally-administered drug imatinib mesylate (Gleevec). Gleevec works by targeting tyrosine kinase, the protein produced by a gene on the abnormal Philadelphia chromosome, which is a hallmark of CML. Gleevec has demonstrated tremendous success in treating CML, producing significant and sustained remissions. The success of Gleevec is a testament to the strategy of molecularly-targeted drug therapy. The second choice is hydroxyurea (Hydrea).

Chemotherapy for CLL Chemotherapy in CLL is used when the course of the disease appears aggressive rather than indolent, based on factors such as blood counts, cytogenetics/FISH testing and symptoms.

Conventional chemotherapy

* Single Agent Therapy For CLL, the most frequently used single agent is chlorambucil (Leukeran). Chlorambucil is frequently combined with oral prednisone.
* Combination Therapy Various drug combinations have been used in CLL, mostly in patients with advanced-stage disease. The most frequently employed combinations have been cyclophosphamide, vincristine (Oncovin), and prednisone, and these three drugs plus doxorubicin (CHOP).
* Nucleoside Analogs Fludarabine (Fludara) is the most effective single agent for the treatment of CLL.

New Approaches
New approaches to chronic lymphocytic leukemia (CLL) include:

* Fludarabine combinations, primarily with cyclophosphamide. Combinations of fludarabine with mitoxantrone (Novantrone) or anthracyclines (such as doxorubicin) may also be effective.
* Monoclonal antibody-targeted therapy monoclonal antibodies are increasingly being used in the treatment of CLL, including Campath, Rituximab (Rituxan), and a combination of fludarabine, cyclophosphamide and rituximab (FCR).

City of Hope Treatment Recommendations

* Early Stage As discussed above, most patients with early stage CLL do not require immediate treatment. Many patients with early stage CLL enjoy long survival and do not suffer reduced longevity as a result of having the disease.
* First-line Treatment Chlorambucil, with or without prednisone, or single agent fludarabine are both appropriate standard treatments for patients with CLL who require treatment.
* Second-line Treatment Combinations such CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone), fludarabine and cyclophosphamide (FC) and fludarabine, cyclophosphosphamide and rituximab (FCR) or treatment with Campath monoclonal antibody therapy. Some of these newer combinations are associated with increased potential for side effects, and may require close monitoring at a tertiary care center specializing in the treatment of leukemia. In some clinical situations, FC and FCR combinations may be used as first-line therapy, especially if a rapid response is needed for amelioration of symptoms.

Beyond Chemotherapy: Advances in Treating Leukemia
City of Hope utilizes stem cell transplantation and pioneering approaches such as radioimmunotherapy and adoptive T cell therapy in treating leukemia patients. These methods augment the effectiveness of chemotherapy. In fact, for many patients, a stem cell transplant offers a real chance at curing leukemia rather than just achieving remission.

City of Hope’s acclaimed leadership in stem cell transplantation assures patients receive the latest treatment protocols designed to maximize successful transplant engraftment while minimizing rejection and debilitating side effects. Our many patients who have been cured of various types of leukemia provide a continued testament to the expertise of City of Hope physicians.

Stem Cell Transplantation
Hematopoietic cell transplantation (HCT) and peripheral blood stem cell transplantation are therapeutic treatments that use stem cells (immature blood cells) to treat a patient's malignancy, or to repair diseased or defective bone marrow. Transplants are sometimes performed early in the course of treatment to improve outcomes. In some patients, they are utilized when other treatments are not working.

These transplant procedures include intensive chemotherapy with or without radiation therapy to destroy the cancerous cells. This is followed by an infusion of healthy new stem cells, which have the ability to grow back into the bone marrow and begin making normal blood cells again.

If a patient receives stem cells from a matched donor (using related, unrelated or cord blood), the transplant is called allogeneic. Like other tissue transplants, allogeneic stem cell transplants require a genetic match between the donor and recipient.

In allogeneic transplants, the donor is preferably a sibling. Alternatively, a matched unrelated donor who has a similar genetic type may be used. In fact, 45 percent of all allogeneic transplants at City of Hope come from volunteer donors who are unrelated to the patient.

In some cases, a patient’s own stem cells may be used. This is called an autologous (self) transplant. First, stem cells are removed from the blood or bone marrow of the patient and stored. When the intensive chemotherapy and/or radiation are completed, the stem cells are then infused back into the patient. As these new stem cells grow, they restore the body's own blood cells.

In the transplant process, intensive chemotherapy also causes weakening of the immune system (immunosuppression). This helps to prevent rejection of the newly transplanted stem cells from a related or unrelated donor. In contrast, with autologous transplants there is little risk of rejection of a patient's own stem cells.

Non-myeloablative HCT
A new transplant procedure has been developed to treat patients with leukemia and myelodysplasia who are older or have underlying medical problems. Non-myeloablative HCT, also called “mini-HCT or “mini transplant,” involves less intensive chemotherapy and radiation treatments.

Researchers now understand that the immune cells created by the transplanted donor stem cells may recognize any remaining cancer cells in the patient as “foreign,” and kill them – thus helping to fight the cancer. This mini-HCT strategy is showing great promise for leukemia and many other cancers, and is being used to treat patients into their 80s. Chronic lymphocytic leukemia (CLL), as an example, cannot be cured without a successful stem cell transplant. Because CLL patients are often over age 70, mini-HCT has provided a viable and powerful treatment option in patients with aggressive or late-stage disease.

Radioimmunotherapy
City of Hope has developed novel ways of delivering radiation utilizing monoclonal antibodies. These antibodies (part of the immune system) can be combined with small amounts of radioactive substances. When given to the patient, they specifically seek out sites of cancer, and deliver high-dose radiation directly, while minimizing damage to normal tissues and toxicity to the patient.

Adoptive T Cell Therapy
T cells are a powerful part of the immune system. A new approach being studied at City of Hope involves redirecting T cells to recognize leukemia cells and destroy them. By targeting microscopic traces of disease, treatment with adoptive T cells may help prevent a relapse. Trials are ongoing at City of Hope with T cells to treat acute lymphoblastic leukemia.

Radiation Therapy
Radiation therapy uses high-energy X-rays or other types of radiation to kill cancer cells. Our Division of Radiation Oncology was the first in the western United States to offer the Helical TomoTherapy Hi-Art System, one of the first radiation therapy systems of its kind to incorporate not only radiation therapy, but also tumor imaging capabilities comparable to a diagnostic computed tomography (CT) scan.
Two types of technology are integrated – spiral CT scanning and intensity modulated radiation therapy, or IMRT – thus producing hundreds of pencil beams of radiation (each varying in intensity) that rotate spirally around a tumor. The high-dose region of radiation can be shaped or sculpted to fit the exact shape of each patient’s tumor, resulting in more effective and potentially curative doses to the cancer. This also reduces damage to normal tissues and results in fewer complications.

© 2009 City of Hope.