When you start taking a TKI to control your CML, there are important milestones along the way that indicate that you’re responding well to the medication. Reaching these milestones is important to your prognosis – how well you’re likely to do in the years ago. Conversely, if these milestones aren’t reached, or you start to wholesale mlb jerseys lose some of the gains you’ve made, it indicates that the medication .tk域名启用 isn’t working for you and it’s probably best to start another treatment.
There are two sets of guidelines for CML treatments that are widely used. One is produced by the European LeukemiaNet (ELN) group (Baccarani and colleagues. Blood 2013;122:872-884). The second is produced by the National Comprehensive Cancer Network (NCCN) in the U.S. (O’Brien and colleagues. J Natl Compr Canc Netw 2011;9 Suppl 2:S1-25; updated as version 2.2014 in November 2013). Free full-text versions are available in the CML-IQ Library.
In most people, CML is caused by a mutation that results in the BCR-ABL cancer gene. When you first begin treatment, testing is done to look for this abnormal gene inside ASH cells (called cytogenetics). (For more on this process, see Tests &Procedures: What do they do?) The gene is located on chromosome 22, which is detectable because the chromosome has a shorter arm. Hematologists call this the Philadelphia chromosome (abbreviated as Ph+), which is found in most people with CML (as well as in some people with other blood cancers).
When you start a medication, the effectiveness of the drug is determined every three months and each of these time points has its own measure of success. At the three-month mark, blood counts should have normalized (called a hematologic response). In addition, the number of Ph+ cells in the bone marrow (where blood cells are produced) should now wholesale nfl jerseys be less then they were before (called a cytogenetic response). The target is for this number to have gone down by by two-thirds (to less than 35% of the original). This is called a major cytogenetic response (MCyR).
By six months, Ph+ cells should no longer be detectable (some are still there, but they are so few that they aren’t detectable in a given sample). This is called a complete cytogenetic response (CCyR).
As your response becomes more profound, it becomes harder to see the changes that are occurring so more sensitive methods have to be used. The BCR-ABL gene produces signalling molecules (called transcripts) that stimulate Rüstungsindustrie white blood cells to proliferate. This proliferation is the problem seen in CML.
Since TKIs block the cancer signals, it’s possible to determine just how effective the treatment is by looking at the amount of signalling molecules (transcripts) that are still present. Decreases are measured in log reductions (i.e. a factor of 10) compared to an international standard. So if your transcript number is decreased by 1/10th, this is of a 1-log reduction; by cheap mlb jerseys 1/100th, this is a 2-log reduction; by 1/1000th, this is a 3-log reduction; and so on.
The ideal scenario is to achieve a 3-log reduction within six months of starting a TKI. After one year, the hope is that you’ll have The better than a 3-log reduction. This is called a major molecular response (MMR). A more rapid response, or a deeper response (i.e. a 4-log reduction or better) further improve your chances that your CML will not progress because these profound responses indicate that your disease is very susceptible to the medication.
The tests used to determine the log reduction in BCR-ABL transcripts aren’t sensitive enough Northumberland to detect changes beyond a 4.5-log or 5-log reduction (depending on the lab). So at the moment, a 4-log or 4.5-log reduction is considered a deep molecular response. Anything more (either a 4.5-log or a 5-log reduction) was once called a complete molecular response (CMR) but is now called molecularly undetectable leukemia. This doesn’t necessarily mean that your body is free of leukemia (although it may mean that), but that our laboratory techniques are not sensitive enough to detect any leukemia. One of the issues now being explored is whether people with a deep molecular response still need to take their medication, or will leukemia come back if the drug is stopped.
Are these treatment goals achievable?
For most people – yes!
According to the ELN review of drug studies, about 18-58% of people taking Gleevec (depending on the study) can achieve a major molecular response at one year. This means that up to 94% will not have disease progression (to accelerated-phase or blast-crisis CML), and about 97% of people will be alive 5-6 years later. With higher doses of Gleevec, 54% Major of people had a confirmed deep molecular response (4.5-log reduction) after 9 years of treatment in the CML-Study IV (Hehlmann and colleagues. J Clin Oncol 2014;32:415-423).
Many people now start with a second-generation TKI, such as Tasigna or Sprycel, and here the success rates are even better. In the ENESTnd study of Tasigna, 50% achieved MMR at one year and 73% had reached the mark after three years. One-third reached a 4.5-log reduction after three years. In the DACISION study of Sprycel, 46% achieved MMR at one year and 68% had reached the mark after three years. Twenty-two percent attained a wholesale nfl jerseys 4.5-log reduction. In the BELA trial of Bosulif, 41% reached MMR by the end of the first year.
Over the past decade, we’ve seen more medications being approved for CML, which means that you can still achieve these important milestones even if your first medication doesn’t hit the mark. If Gleevec isn’t enough, you can switch to Tasigna, Sprycel or Bosulif (depending on wholesale nfl jerseys the availability of individual drugs in your country and your insurance coverage). If you don’t respond to one second-generation drug (Tasigna, Sprycel and Bosulif), you may respond to another one. After that, there’s still Iclusig, Synribo or a bone-marrow transplant. There are many ways to reach the goal of achieving a profound suppression of CML.