When parents are told their child has a form of cancer called acute lymphoblastic leukemia (ALL), but that it can be treated and cured with therapy that involves injections of preservative-free methotrexate, families can feel some relief and hope. But when they are told this life-saving drug is running out, their hope can turn to panic.

Children with ALL need preservative-free methotrexate

Acute lymphoblastic leukemia, also known as acute lymphocytic leukemia or acute lymphoid leukemia, is the most common leukemia in children. Approximately 4,000 new cases of ALL are diagnosed in the United States each year, according to the National Marrow Donor Program. Two-thirds of those cases involve children, and the majority of children with ALL are younger than age 10.

ALL progresses rapidly, and so prompt treatment is critical. That’s where the chemotherapy drug methotrexate comes in, and it can be a life-saver: the overall survival rate after chemotherapy is nearly 80%. Here’s why methotrexate is so important.

The bone marrow produces unformed cells called blasts that are supposed to develop into white blood cells called lymphocytes, which fight infections. In people who have acute lymphoblastic leukemia, however, the blasts are abnormal and do not develop into lymphocytes.

This means leukemia cells have an opportunity to grow and spread quickly, crowding out not only lymphocytes but also red blood cells and platelets the body needs to function properly. The disease typically spreads to the lining of the brain and spine, but treatment with large doses of methotrexate, injected directly into the spinal fluid, can prevent this, because it slows the growth of cancer cells.

Not just any methotrexate will do, however: it must be preservative-free because the preservative can cause paralysis when it is injected into the spinal column.

The problem now is that the five pharmaceutical companies that make the injectable preservative-free methotrexate have either slowed or ceased production of the drug, according to the Food and Drug Administration. One of the largest producers of the drug, Ben Venue Laboratories (Bedford Labs), voluntarily ceased production in November 2011 because of concerns over quality and production.


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This manufacturing shut-down, along with production delays or higher than anticipated demand at the other companies (APP, Hospira Inc., Mylan Institutional, Sandoz), have placed parents of children with ALL as well as hospitals and physicians on alert.

The longer this shortage continues, the greater the number of children who will be at risk of not receiving the chemotherapy drug they need to help them stay alive. In an ABC News report, Dr. Michael Link, who is a pediatric oncologist and also president of the American Society of Clinical Oncology, noted that some hospital pharmacies have only enough preservative-free methotrexate for a few weeks.

Other treatments for ALL

All patients who have ALL receive some form of chemotherapy as part of their treatment program. Chemotherapy may be divided into three stages:

Induction chemotherapy is the first stage, and it is designed to reduce the number of cancer cells

Consolidation chemotherapy enhances the effect of induction treatment, with the goal of reaching complete remission

Maintenance chemotherapy may be administered to prevent cancer relapse

In some cases, children receive radiation therapy to the brain if they have signs the disease has spread to the brain and spinal cord or if they are at high risk of this occurring. A bone marrow or cord blood transplant is usually reserved for patients who have the least chance of achieving remission with chemotherapy alone.

Methotrexate and rheumatoid arthritis

Methotrexate is also used to treat rheumatoid arthritis. For this disease, it can be taken either by mouth or by injection. Methotrexate is considered to be a disease-modifying antirheumatic drug (DMARD), as it helps reduce inflammation caused by rheumatoid arthritis and also helps slow progression of the disease.

The two main issues concerning oral or injectable methotrexate for rheumatoid arthritis patients are convenience and effectiveness. A January 2008 study found methotrexate injections were significantly more effective than the oral form of the drug when given at the same dosage. However, some patients prefer taking weekly oral doses rather than getting an injection once a week.

It is uncertain how long the methotrexate shortage will last or what the final impact will be on ALL patients. Parents need to discuss their questions and concerns with their physician so the best course of action can be taken.

SOURCES:

ABC News report

Braun et al. Comparison of the clinical efficacy and safety of subcutaneous versus oral administration of methotrexate in patients with active rheumatoid arthritis. Arthritis & Rheumatism 2008 Jan; 58(1): 73-81

Food and Drug Administration

National Marrow Donor Program

Image: Courtesy Wikimedia Commons/National Cancer Institute