Results of a study at St. Jude show why imatinib (Gleevec) is unable to prevent the relapse of an aggressive form of acute lymphoblastic leukemia (ALL). Imatinib has improved the treatment of chronic myelogenous leukemia (CML) dramatically.

CML and an aggressive form of ALL share the same mutation, the Philadelphia chromosome (Ph). Ph-postiive cells produce a growth-promoting enzyme BCR-ABL. However, in some aggressive cases of ALL, Ph-positive cells lack a tumor suppressor gene called Arf, which is present in CML cells, say the researchers.

The paper's first author, Richard T. Williams, says that doctors might be able to identify those people with ALL who lack Arf.

In the January issue of Blood, a study shows that in rare cases of chronic myelogenous leukemia (CML), treatment with Gleevec can be discontinued.

The researchers think that some patients treated with Gleevec (imatinib mesylate) that go into extended remissions can stop the drug. They add that patients continue strict monitoring for relapse.

Twelve patients were put into remission with Gleevec for over two years. Six of these patients experienced a relapse within five months after being taken off the drug. When Gleevec was restarted, residual disease again declined.

The other six patients remain in remission after nine to twenty four months follow up.

Despite these results the researchers say 'we do not widely recommend imatinib discontinuation at the present time".

I do have a few questions myself that the article did not address:

Does Gleevec have severe side effects that warrants stopping it at all?

Do they think that Gleevec can potentially cure the patient and some might be able to stop treatment all together?

Sprycel is an oral agent that has recently been approved by the FDA. It works by stopping the production of proteins involved in cancer growth.

The American Society of Hematology presented results that stated that treatment with Sprycel (dasatinib) provides better outcomes compared to giving higher doses of Gleevec (imatinib), in patients with chronic myeloid leukemia (CML), who have stopped responding to standard doses of Gleevec.

In the clinical trial the patients were either treated with Sprycel or increased doses of Gleevec to see who had the better response.

Study results indicated:

• Patients who had achieved a major anticancer response with the standard dose of Gleevec initially, achieved a 35 percent complete response to Sprycel, compared with only 7 percent of those treated with the increased doses of Gleevec.
• Patients who did not receive a major anticancer response with the standard dose of Gleevec initially, achieved a 44 percent major anticancer response to Sprycel, compared to only 7 percent of those treated with the increased doses of Gleevec.
• The main side effect of Sprycel was low levels of blood cells, which may be partly corrected with the use of Neulasta.

The research has concluded that Sprycel provides superior responses to increased-doses of Gleevec among patients with chronic-phase CML who have stopped responding to prior Gleevec therapy.

Nilotinib is an investigational drug that targets the same protein as Gleevec, but through a different mechanism. Nilotinib, according to results recently presented at the 2006 meeting of the American Society of Hematology, is effective and well tolerated in patients with chronic-phase myeloid leukemia (CML) who do not respond to or cannot tolerate Gleevec.

In the past the only curative treatment for CML was a stem cell transplant. Researchers are focused on finding curative therapies that do not involve so much of a mortality risk and are more easily tolerated. A study was conducted to further evaluate the treatment with nilotinib in patients with CML who have stopped responding to Gleevec. Results of the study indicate that nilotinib was effective.

At one time, patients with blood cancers were treated with harsh drugs, like interferon or hydroxyurea, yet only two to three percent would ever achieve any sort of remission. Many would suffer such extreme side effects from these drugs they would stop taking the medication early, decreasing even further their potential odds for survival.

The fate of these patients is changing. And the proof is in print -- in today's issue of the New England Journal of Medicine.

It all began with the study of a highly targeted molecular therapy called STI571 -- designed to block the genetic aberration that gives rise to chronic myeloid leukemia (CML), a disease that affects about 6,000 Americans every year. A clinical trial followed, and a compound marketed by the drug company Novartis emerged. Today, this compound is know as Gleevec.

In the clinical trial of Gleevec, 1,106 CML patients were randomly chosen to receive either Gleevec or Interferon. Early results were so encouraging that all but three percent of the participants using Interferon switched to Gleevec. Five-year survival rates were 89 percent. And 93 percent of patients saw no progression to the acute phase of the disease. Many patients witnessed their blood counts return to normal, and a large number experienced a reverse in the gene mutation that causes CML. Virtually no one reported side effects while using the drug.

Despite a rare reaction that can cause heart failure, Gleevec has now been approved by the FDA for the treatment of six other rare, life-threatening disorders. And other drugs similar in nature to Gleevec are hitting the scene. Some believe long-term suppression of CML will come from a cocktail of these types of drugs.

For now, Gleevec -- on its own -- is a success story.

Glamour editor and leukemia cancer survivor Erin Zammett Ruddy blogs Life with Cancer and is the author of My (So-Called) Normal Life. Five years ago, at the age of 23, Erin was diagnosed with chronic myelogenous leukemia (CML). Immediately after her cancer diagnosis, Erin began chronicling her life with cancer in a monthly Life with Cancer column for Glamour magazine. Recently, she has launched a blog after the same name as her column.

"I am excited to be starting my blog for Glamour. I am going to be talking about whatever it is I am feeling about that particular day.

I hope to hear from readers that instead of being a patient or a victim -- it's something like I have this disease, what can I do with it -- how can I help other people.

Do I wish I didn't have cancer? Yes, but I wouldn't trade my life right now for anything and that life includes cancer."

While Erin is new to blogging, she is not new to writing, and she is an excellent writer. Frank, serious, open, vulnerable, and bouyant with a delightful sense of humor, her writing makes for a blog that is difficult to leave until you have read every post. Erin takes Gleevac, and in order to have a baby she will need to stop taking the drug that keeps her in cancer remission. She is very honest in sharing the anxiety and anticipation of making this choice.

From the blog, you can access the monthly column Erin writes for Glamour magazine. One of the most recent features an interview with MTV's Real World/Road Rules Challenge: Fresh Meat Diem Brown, a 25-year-old woman currently battling ovarian cancer. After hearing about Diem, and watching her on the reality show, Erin was intrigued to meet her. As a result of the time the two spent together, and sharing stories with Diem, Erin was inspired to stay positive in the midst of uncertainty.

Erin Zammett Ruddy is a phenomenal woman with a terrific attitude, and a blog we are glad she keeps.

A review was done by an international panel of experts of literature concerning chronic myeloid leukemia (CML) for the recommendation of treatment options. The panel included ten members that reviewed 194 papers on CML written since 1998.

The article was recently published in the journal Blood. Gleevec (imatinib mesylate) has become a standard treatment for Philadelphia chromosome-positive CML. Specific guidelines for the use of Gleevec in the treatment of CML have recently been compiled.

• All newly diagnosed patients should be treated with 400 mg of Gleevec per day.
• Patients who do not respond to Gleevec should be treated with higher doses, an allogeneic stem cell transplantation, or experimental therapy. This experimental therapy could include agents designed to over come resistance to Gleevec.

Responses to treatment can be determined by several laboratory tests. Talk to your physician about specific details regarding responses to Gleevec.

Gleevec, one of the first targeted cancer drugs, has proven to be effective after five years. Speaking to a group at a American Society of Clinical Oncology meeting, Brian J. Druker, M.D., of Oregon Health and Science University, said that for 75 percent of chronic myeloid leukemia, CML, patients, "Five years ago we could only say that we hoped the response would last. Now we can say with assurance that we are offering real hope for CML patients." Dr. Druker indicates he believes the ten-year outcome might be just as promising.

Gleevec doesn't cure cancer, but makes cancer a chronic condition. CML cancer survivors take two pills a day, and so far, it seems to be working in three-fourths of the patients on the targeted drug therapy.

According to the news story, Dr. Druker is upfront about who was behind the original study in revealing that he was paid a consulting fee by Novartis. However, he also points out that in the last four years, he have received no consulting income from Novartis. I respect him for his honesty. Gleevec is proving that targeted drugs work, and might work well. As noted in a previous post, I am a proponent of targeted cancer drugs and the elimination of the scorched earth chemotherapy regimens.