Genetic Profiling Could Help Doctors Make More-Accurate Leukemia Prognoses

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By Jim Stallard

Pictured: Ross Levine

Physician-scientist Ross Levine

A study led by Memorial Sloan Kettering researchers has identified a set of genetic abnormalities that can be used to make more-accurate prognoses in people with acute myelogenous leukemia (AML). This information could help clinicians determine which treatments are most likely to benefit patients with this type of leukemia.

“Our study shows that genetic profiling makes it possible to categorize leukemia patients more precisely in terms of whether their disease will return after treatment,” says medical oncologist Ross L. Levine, the lead author of the study reported in the March 22 issue of the New England Journal of Medicine. Dr. Levine is a member of Memorial Sloan Kettering’s Leukemia Service and the Human Oncology and Pathogenesis Program.

“We also want to use existing therapies more intelligently,” Dr. Levine adds. “It helps a great deal to know which subset of patients will actually benefit from intensive therapies, such as a higher chemotherapy dose or a bone marrow transplant.”

Calculating Risk Based on Genes

At present, clinicians rely on a handful of known genetic biomarkers (markers of disease) to predict outcome in leukemia patients, and these biomarkers provide useful information for only a subset of patients. For most people diagnosed with AML, it is difficult to predict the chance of a cure.

The method used in the study incorporates information from an array of genes and could enable nearly two-thirds of patients to be categorized into clearly defined prognostic groups. “Our goal was not to ask whether a certain gene or two raised or lowered risk, but to determine whether an amalgam of information from a set of genes made it possible to precisely stratify patients by risk,” Dr. Levine says.

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Linking Gene Mutations to Treatment Response

In the study, the researchers analyzed blood or bone marrow samples from 502 patients with AML who were participating in a clinical trial. Such samples are routinely taken for research purposes during trials with patient consent. Led by Martin S. Tallman, Chief of Memorial Sloan Kettering’s Leukemia Service, the clinical trial investigated whether increasing the standard dose of chemotherapy in AML patients under age 60 would improve survival.

The team that performed the genetic analysis, which included investigators from Memorial Sloan Kettering, Weill Cornell Medical College, and other institutions, examined the samples for mutations within 18 genes known to have abnormalities in people with AML. The researchers noted the relationship between the mutations present in each patient and how that patient ultimately fared with the disease under either the standard or increased chemotherapy dose.

The analysis enabled the researchers to determine specific risk levels for a variety of gene-mutation combinations. They also were able to establish that the higher chemotherapy dose used in the trial benefited only some of the patients.

The researchers took into account variables such as patient age and gender, and validated the results in a separate group of patients — ensuring that the profiling approach could be generally applied beyond the current trial.

“We want to show this approach can be used not just at Memorial Sloan Kettering but throughout the leukemia community,” Dr. Levine explains.

Dr. Levine and his Memorial Sloan Kettering colleagues are working to translate the results from the study into clinical use. “We’ve already developed genetic tests for this set of mutations in patients, and we’re in the process of making sure they work well in practice,” he says.

“We have preliminary evidence that they do, and we’re hoping to have a pilot study soon as a step toward getting it into the clinic.”

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Comments

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Phyllis Blaunstein

Mar 23, 2013 • 12:42 AM

My sister's husband has just been diagnosed with Acute Myeloid Leukemia and I am interested in learning about clinical trials for which he might be eligible.

Phyllis Blaunstein

Mar 23, 2013 • 12:59 AM

A close relative has just been diagnosed with acute myeloid leukemia. He is very weak and has been hospitalized for nearly 2 weeks as he was running an undiagnosed high fever. A bone marrow biopsy just identified AML as the cause of this fever and weakness. Will his condition preclude his beginning treatment?

Roberta Ellen

Mar 29, 2013 • 5:12 PM

My husband has been recently diagnosed with AML. Will all of the current research be shared with the National Cancer Institute or should we make an appointment at Sloan Kettering? He is currently under the care of a medical oncologist at Robert Wood Johnson, Cancer Institute.

Memorial Sloan Kettering

Mar 29, 2013 • 10:09 PM

Hi, Roberta. We spoke with Dr. Levine, who said, “Our research has been shared with leukemia experts all over the world, both so that others are aware of our findings and to compare results between different institutions. If your husband and you would like to see one of our AML experts to discuss diagnostic and treatment options, please call the physician referral service and they will refer him to our AML treatment team.” You can reach our physician referral service at 800-525-2225. Thanks for your comment.

Roberta Ellen

Mar 29, 2013 • 7:57 PM

i RECEIVED A REPLY VIA EMAIL. HOWEVER, THERE WAS NO RESPONSE TO MY QUESTION.

Memorial Sloan Kettering

Mar 29, 2013 • 10:10 PM

Roberta, the response to your original question has been reposted. Sorry for the confusion!

Linda Hoyer

Jul 13, 2013 • 1:32 PM

I have two questions:
1) Why at 69 and very healthy can't I be (if otherwise qualified) a marrow transfer for my cousin? I have some arthritis no other diseases. No donors can be found.
2) If a possible inherited disease, could a person, who in his 60's gets AML leukemia had, in his 20's, been a marrow doner to a sister, 29 with AML leukemia, who died from the donation, have died from a (perhaps exact) gene carried by the doner at the time of donation? ie:would having a related or exact gene react in a recipient with the same disease cause a recipient death?

Memorial Sloan Kettering

Jul 13, 2013 • 2:38 PM

Linda, thank you for your comment. We are looking into your questions and will get back to you as soon as we can.

Memorial Sloan Kettering

Jul 16, 2013 • 2:01 PM

Linda, we consulted with Dr. Ross Levine, one of the authors of the study mentioned in the story you commented on. This is his response to your questions:

1. The decision of who to use as a bone marrow donor involves many factors, including age, other illnesses, and other factors. In addition it is critical for the donor to be matched to the recipient. Your cousin’s doctors are assessing every possibility and if they have questions can consult with the MSKCC transplant doctors.

2. There are very rare cases described (fewer than 10) in which a bone marrow recipient has gotten a blood cancer which is derived from the donor’s cells. I am not aware of any cases where the same leukemia occurred in both the donor and in the recipient; this is technically possible but very unlikely. In addition it is very, very unlikely that this would happen in this case, as a 40 year duration would be unusually long for a leukemia to remain dormant in the donor and then manifest 40 years after it did in their sister.

Eleanor O'Connell

Oct 18, 2013 • 1:10 PM

My son, age 40, was diagnosed with AML in 2011 and died at MSKCC in Jan 2013. He had all the treatment that was available. Family history includes breast cancer and ovarian cancer among blood relatives. I am worried about my grandchildren. Research seems to suggest that genetics plays a part in identifying the disease. Is it possible? will it be possible? that your research might be used to identify potential victims of the disease.

Memorial Sloan Kettering

Oct 20, 2013 • 11:06 PM

Eleanor, we consulted with Dr. Levine about your question and he responded: We are sorry for your loss. Unlike other cancers such as breast cancer, most cases of AML are sporadic, and are not associated with a family history or a risk of AML in other members of the family. Although very rare families have been identified with multiple cases of AML within a single family, this is exceedingly rare and not so common that we advise screening if only one family member is affected.

G Paige

Oct 27, 2013 • 11:29 AM

My sister of 66 has just undergone her second treatment and it has been unsuccessful she is now doing MEG. She has Aml. The problem chromosome is number eight and she has been differentiated blast. If this treatment does not put her into remission can she still come to your hospital to be treated. She is in For help and has tolerated treatment very well. excellent condition and has tolerated the treatments well.

Andy Rodriguez

Nov 11, 2013 • 6:45 AM

Hi, my wife was diagnosed with AML a few months ago, it's M2. She is 40 yrs old , she works as a NP, she is very healthy but at night she gets these strong headaches, every night, I would like to know why? She is not getting treatment because she just became directer of a insurance CO. What will happen untreated ? Thank you

Memorial Sloan Kettering

Nov 11, 2013 • 7:29 AM

We are sorry to hear about your wife’s diagnosis. We are not able to answer specific medical questions on the blog. It’s best that she consult with her physician. If she would like to make an appointment with one of our specialists, please call 800-525-2225. Here is a link with more information about making an appointment: http://www.mskcc.org/cancer-care/appointment Also, here is more information about leukemia, and treatment for AML: http://www.mskcc.org/cancer-care/adult/leukemias
Thank you for your comment.

WALTER WESOLOWSKI

Jan 23, 2014 • 2:48 PM

I am a 77 year old male with AML diagnosed initially in August, 2012, went through the 7/3 induction chemo treatment locally in Norfolk, VA. Consolidation treatment has consisted of Vidaza on a 4 week cycle (7 days of 3 shots, followed by a Nulasta shot). All bone marrow tests show me to be in remission, latest being in Dec. 2013. Last summer I saw Dr Douer at MSKCC for a second opinion on my treatment. I have two questions:
1. Based upon my excellent response to treatment, can you give me an estimated prognosis? I feel I am in excellent health at present. Walk daily, play golf, etc.
2. I am also wondering if my Vidaza shot routine could be changed from 7 days to five as my body really takes a beating by days 6 and 7.
Thank you,
Walter Wesolowski
LCDR, USN (RET)

Memorial Sloan Kettering

Jan 23, 2014 • 3:17 PM

Dear Mr. Wesolowski, unfortunately, we are unable to answer personal medical questions on the blog. We suggest you call Dr. Douer’s office directly to discuss your concerns. His number is 212-639-2471. Thanks for your comment.

Carol A. Preece

Nov 13, 2014 • 12:04 AM

My father died of multiple myeloma. A cousin died of AML. My daughter has been diagnosed with MGUS and told she cannot be in crowds or work with children or elderly. Her doctor says she may develop MM or AML. He says there is nothing to stop it. Is this true?

Memorial Sloan Kettering

Nov 13, 2014 • 9:49 AM

Dear Carol, our deepest condolences for your losses, and we are sorry to hear about your daughter’s MGUS diagnosis. We sent your inquiry to Dr. Levine, and he responded:

“The testing we have helped developed is used for patients who already have
a diagnosis of a blood cancer. It cannot currently be used to predict who
is at risk for a new diagnosis. For your daughter, if she would like, she
can be seen by one of our myeloma experts, who do see patients with MGUS and can advise on the best course of action.”

To make an appointment with one of our specialists, please call our Referral Service at 800-525-2225. FYI, here is a bit more information about MGUS from our website: http://www.mskcc.org/cancer-care/adult/multiple-myeloma/monoclonal-gamm…

Thank you for reaching out to us.

Carol A. Preece

Nov 13, 2014 • 12:13 AM

I just finished a question about genetics in my family which has had MM and AML. I forgot to mention that my cousin with AML had an "extra chromosome" He was in his 50s and a successful businessman so it wasn't Down's syndrome. Could this be significant?

Mia

Jun 11, 2015 • 2:13 PM

I am a 51 year old woman and was diagnosed with MGUS about a year ago. I am anxious to see a specialist at Sloan Kettering. Can you please tell me who deals specifically with this precursor to MM at Sloan Kettering? Thank you!