Trey's CML Leukemia Blog: SPECIAL TOPICS ON CML

Special Topics Related to CML:

The special topics covered in order below are:

1. Information for the CML Newly Diagnosed

2. Genetics of CML Leukemia: An Overview

3. CML Testing Explained: Introduction and Basics of CML Leukemia Testing

4. Bone Marrow Transplant Overview

Information for the CML Newly Diagnosed:

We all remember how helpless we felt when newly diagnosed with CML. If you have just been diagnosed with CML, the overall probability of surviving CML is now about 95%, so we can generally expect a normal lifespan. This compares with numbers that were very poor prior to the introduction of Gleevec in 2001. In general, the outlook for CML has changed significantly for the better since 2001 when Gleevec was approved for treatment. This drug changed CML from a deadly disease into one that is now highly survivable for most people, with less impact on our quality of life. Additional CML drugs (Sprycel,Tasigna, Bosulif, & Iclusig) have been approved, and more are being developed.

The information below covers a variety of subjects, starting with general information, and going to more specific information about CML. When getting started it helps to know where to find just a very few of the more useful resources regarding CML. This information may also help avoid the numerous out-of-date (and needlessly scary) websites that would only cause undue anxiety, which is what most people find when initially searching the internet for information about CML leukemia, especially related to survival, prognosis, life span, and other important issues. Such information is also useful to help family and friends understand what the newly diagnosed CML patient is facing. And the news is generally positive, since the outlook for CML has greatly improved over the past decade.

Below is a summary article that shows the dramatic changes in treating and surviving CML as a result of the drugs that have been approved since 2001. The article says that “In a study of patients with chronic myeloid leukemia, some 95 percent have survived the cancer after five years due to treatment with Gleevec...”
http://www.scienceda...61207160526.htm
A recent article declared that CML patients have achieved a life expectancy similar to the normal overall population because of these drugs:
http://www.drugs.com...rate-30274.html
Dr Brian Druker, a leading CML specialist who was instrumental in the development of Gleevec, said "we assume that most CML patients will now live a normal lifespan". Because Gleevec was only approved in 2001, CML experts had previously hesitated to put a time-frame on expected survival due to lack of data, even though they often said it could be significant. In 2010 Dr Druker said "Today, more than 100,000 lives have been saved by Gleevec. In May of 2001, Gleevec was approved by the FDA in record time. Now, the five-year survival rate is 95% for this previously fatal leukemia. People diagnosed with this leukemia were once told they had five years to live, or less; now we are projecting 30." This should be very encouraging, and especially encouraging to young people with CML, since lifespan estimates appear to be close to "normal" as more data is accumulated and more drugs are developed.
In 2012 a leading CML expert, Dr Neil Shah, stated: "it appears that the likelihood of dying of CML is approximately equivalent to the likelihood of dying of other causes, and it is hoped that with longer follow-up and more access to effective next-generation TKIs, the majority of chronic-phase CML patients, in stark contrast to historical experience, will die of causes unrelated to CML or its treatment."
http://www.cancernet...e/10165/2107596
News articles about how CML has become a very survivable disease:
http://jnci.oxfordjo...nci.djr127.full
http://www.nytimes.c...ner=rss&emc=rss
It is important for patients, family, and friends to know the following: 1) CML has changed from a poor prognosis to a very good prognosis due to our three drugs – the survival rate is around 95%; much internet information is very out-of-date on this issue because of the recent advances in CML drug therapy; 2) bone marrow transplant has become a very rare event for those with CML, where in the past it was a primary therapy; 3) CML is probably the most likely leukemia to have a cure discovered in the reasonable future, according to CML experts. This information does not mean every person will respond the same way to drug therapy, and there is still a small percentage chance of not surviving CML, but the overall news is very positive.

The Leukemia & Lymphoma Society (L&LS) Online Overview provide information for the newly diagnosed:
http://www.lls.org/#/resourcecenter/freeeducationmaterials/leukemia/cml

Information from leading CML specialist Dr Brian Druker:
http://www.ohsu.edu/...Is Within Reach
(NOTE: In link above start about 1/4 way through to skip the intro stuff)

Video Presentations on CML and Treatment:
http://www.leukemia-...?item_id=161418 http://www.lls.org/#...grams/leukemia/
Here is an article which outlines the history of how Gleevec changed the treatment of CML (somewhat long but a good read):
http://www.smithsoni...html?c=y&page=1
Information on Managing CML:http://cmlinfo.org/CMLmonitoring.html
http://bloodjournal....full/110/8/2828
http://community.lls...ecttype[thread]
Time Magazine article from when Gleevec was first approved in 2001:
http://www.time.com/...?internalid=ACA
The Leukemia & Lymphoma Society has a live person help line available to answer questions about CML: 1-800-955-4572
If you wish, before you call the L&LS CML Helpline, you can also search our support group website using the search button in the upper right part of the web page. You can search for discussions we have had regarding many subjects such as drug side effects, understanding test results, and many other subjects. Or just join our support group and start posting questions.
http://community.lls.org/forum/27-chronic-myeloid-leukemia/
Here is information that might be useful right away regarding CML by popular topics:
http://ubb-lls.leuke...TML/000868.html http://community.lls...?view=documents
Here is a blog I have put together discussing numerous CML related subjects listed A - Z:
http://treyscml.blogspot.com/
This information is trying to fill a need to help the CML Newbie get started, and to help eliminate the unnecessary shock of sorting through outdated information about CML on the internet that will needlessly scare you, your family, and friends. So much has changed in such a short time due to the new CML drugs. As a result, you will very likely live a long and mostly normal life, and without requiring a marrow transplant. A few will still not be so fortunate, but research continues to make advances, and new drugs are coming along to help those who are not currently doing as well. There is much to be hopeful about, and much to be grateful for. We are here if you need us, so please join in and learn along with us about living with CML leukemia.

Genetics of CML Leukemia: An Overview

This overview is an attempt to help CML leukemia patients understand the genetic basis of the disease. In order to keep it somewhat simple, there is much that will not be covered. This is a complicated subject, so it is not possible to make it easily understandable, just somewhat understandable. So the hope is to make a few issues a little more clear.

Leukemia is a group of diseases of the blood cells where certain cells become abnormal and also take on a greatly enhanced capability to reproduce. It is this combination of cell mutation and out-of-control reproduction that makes leukemia so hazardous. The word leukemia is from the Greek meaning “white blood”, because the blood can take on a whitish color in the latter stages of the disease due to the extremely large numbers of white blood cells in the bloodstream.

Leukemia is divided into myeloid and lymphoid types, and within each of these two categories are two sub-types, namely acute and chronic sub-types. When leukemia affects lymph system white blood cells (T-Cells, B-Cells, etc) it is called lymphocytic leukemia. When bone marrow white blood cells are primarily affected (neutrophils, basophils, eosinophils) the disease is called myeloid or myelogenous leukemia, as in CML.

So the 4 main types of leukemia are divided into Lymphoid and Myeloid cell lines, each with Acute and Chronic sub-types:

Lymphoid: Acute Lymphocytic Leukemia (ALL), and Chronic Lymphocytic Leukemia (CLL)

Myeloid: Acute Myeloid Leukemia (AML), and Chronic Myeloid Leukemia (CML)

Although these 4 types of leukemia are somewhat related, the treatments are very different for each one. This is because they are actually very different at the genetic level, although they all affect the blood through cell mutations and overproduction.

The blood is made up of fluid (plasma) and three main types of blood cells – white, red and platelets, each with special functions. Two different types of white blood cells (WBCs) fight infection and disease by killing bacteria, viruses and other invaders in the bloodstream. Those two WBC types are lymph cells and myeloid (marrow) cells. These two types of WBCs have overlapping functions of protecting the body from infection and disease, but they accomplish the tasks in different ways. Generally speaking, the lymph cells “shoot and kill” their targets, while the myeloid cells “eat and digest” the invaders. Red blood cells (RBCs or erythrocytes) carry oxygen from the lungs to the body's tissues and take carbon dioxide from the tissues back to the lungs. Platelets (also called thrombocytes) are not technically cells, but rather pieces of cells that have broken into fragments, and these jagged fragments form clots at wound sites to control bleeding. Blood cells are normally produced in an orderly, controlled manner by a complex series of genetic and chemical signals as the body needs them, but in leukemia and other cancers that process gets out of control because new genetic/chemical signals are created by mutations inside the cells, specifically on the chromosomes. These new signals are often stronger and more aggressive than the normal ones, which means they dominate the blood cell forming process.

Chronic myeloid (or myelogenous or myelocytic or granulocytic) leukemia (CML) is characterized by the overproduction of the myeloid (marrow) type white blood cells (WBCs), namely the neutrophils, eosinophils, and basophils. CML develops when a genetic mix-up occurs, called a chromosome translocation. CML starts when a piece of chromosome 22 and a piece of chromosome 9 each break off simultaneously inside a single blood producing stem cell, and those pieces exchange places by re-attaching at the wrong chromosomes (the piece of 9 joins with the main body of 22, and the piece of 22 joins with the main body of 9). The new chromosome 22 (called the Philadelphia Chromosome) causes CML by combining two previously unrelated genes that were not intended to be in contact with each other. The combination of the BCR gene from chromosome 22, and the ABL gene from chromosome 9, create a new cancerous gene called BCR-ABL when they come together in this unnatural form. Since this mutation occurs in a blood producing stem cell, that leukemic stem cell can then reproduce and ultimately produce trillions of leukemic cells over a period of time, possibly years. It is this combination of too many cells, along with their poor function, that causes CML’s symptoms and harmful effects on the body. The BCR-ABL gene on the Philadelphia Chromosome sends out a BCR-ABL messenger RNA, which in turn creates a new type of BCR-ABL signal enzyme called a tyrosine kinase, which causes the new WBCs to become leukemic, and also greatly speeds up their production. So when we discuss BCR-ABL, there are actually 3 levels of BCR-ABL, which can be the source of confusion. Those 3 types are 1) BCR-ABL gene on the Philadelphia Chromosome, 2) BCR-ABL messenger RNA, and 3) BCR-ABL tyrosine kinase. Our CML drugs inhibit this last BCR-ABL tyrosine kinase, stopping the chain of events that creates new leukemic blood cells.

Explanation of the CML translocation and formation of the BCR-ABL gene:

http://www.cclocator.com/en/video/?v=zxXY19fQxf8&lang=en

The Philadelphia Chromosome (Ph+) can be one of several types, defined by where the pieces broke off from their original locations on chromosomes 9 and 22. There are two main types of Ph+ called e13a2 (b2a2) and e14a2 (b3a2), which make up approximately 95% of all CML cases. Others such as e1a2, e8a2, e6a2, etc are more rare. Some people can have more than one type.

This BCR-ABL signaling process causes leukemic WBCs to greatly overproduce, and also the leukemic cells live longer than they normally should; additionally, these cells do not function as well as normal WBCs. At the same time, the body senses that there are far too many WBCs in the blood, so it tries to decrease the level of WBCs and stops the signalling process that creates new good cells. So it shuts down only the good WBC production, since the non-leukemic WBCs are the only ones that will respond to demands to slow down blood cell production. But the leukemic cells ignore the signals to stop producing more cells. If the CML is not controlled, the leukemic WBCs eventually crowd out the normal cells including the WBCs, red blood cells and platelets. This robs the body of oxygen and reduces resistance to infection and disease.

So leukemia is primarily a disease of the white blood cells (WBCs), because the leukemic mutations described above are found in the nucleus of a cell where the chromosomes are located. Since red blood cells and platelets do not have a nucleus or chromosomes, they cannot truly be considered leukemic cells (although the precursor cells that manufactured them can be leukemic cells). However, red cells and platelets can have a reduced level of effectiveness because they were produced by the same mutant (leukemic) ancestors that produce the leukemic WBCs. So the emphasis in CML is on monitoring WBC issues. A BMB only looks at white blood cells capable of producing other WBCs, both the FISH and PCR tests only look at the BCR-ABL in the WBCs, the CBC is mainly focused on the WBC count, and so on.

Our CML drugs (Gleevec, Sprycel, Tasigna, Bosulif, Ponatinib) are called tyrosine kinase inhibitors (TKI). They are bio-engineered to “park” in a chemical slot on the leukemic BCR-ABL tyrosine kinase (discussed above), which prevents the tyrosine kinase from sending the message to produce leukemic blood cells. When the signals stop, the production line stops -- somewhat like running out of the right parts on an assembly line, shutting down the whole process. A side benefit is that when the leukemic cell signaling process is shut down, the leukemic white blood cells become confused and self-destruct. Unfortunately, the TKI drugs cannot shut down the originating leukemic blood stem cell(s). As a result, the leukemic stem cells keep functioning, so the TKI drugs must be continued indefinitely to keep killing off the children of those stem cells. But the TKI drugs also accomplish a second important function, which is to keep the leukemic cells from further mutations that would lead to accelerated or blast phase CML. So the TKI drugs work by 1) shutting off the signals needed to produce new leukemic blood cells, 2) causing the leukemic cells to become confused and self-destruct, and 3) reducing the genetic instability of the remaining leukemic cells. This essentially creates a continuous status of low level chronic phase CML, also called Minimum Residual Disease level. That is the current goal of our CML drugs, meaning we are not cured, but can live with the disease in a form that does not harm us.

Blood cell production has a complex hierarchy with many levels. In a simplified sense, it starts with “ancient” (pluripotent) blood stem cells, which in turn produce long-term stem cells, which in turn produce short-term stem cells, which produce progenitor cells, which eventually produce the final level of blood cells (which cannot reproduce). CML begins with a translocation of genetic material in a very high level blood stem cell. Stem cells are those cells which are the "mother cells" for all others. There are many levels of dividing blood cells, including high level "pluripotent" blood stem cells, progenitor cells, committed precursor cells, and so on, to name only a few in the chain. The "working level" blood cells cannot divide, so although they contain the leukemic genes, they cannot perpetuate the CML. So CML must be continued by the dividing blood cells in the hierarchy. Some leukemias start at lower level "stem" cells, but CML starts at the highest level blood stem cells. This is known because all blood cells are affected by CML, including white, red, and platelets. Other types of leukemias generally affect only portions of the blood cell chain.

In CML, the original leukemic cell that had the original translocation is near the top of the blood making hierarchy, which means any cure would require killing off ancient stems cells. But these ancient stem cells have extraordinary means of survival through multiple paths, including BCR-ABL signaling, but also using other signaling methods that can get around the CML drug impact on BCR-ABL signaling. That is why our CML drugs do not directly cure CML, since the originating leukemic cell or cells can out-smart the drugs. They also escape by going dormant for long periods of time (quiescence), by finding alternate signaling pathways to reproduce, by hiding deep in the bone marrow next to the bone where immune system cannot find them, and by using other self-survival mechanisms. So a cure for CML will need to find a way to defeat these very smart leukemic stems cells.

We do not all have the same type of CML. 95% have either b2a2 (e13a2) or b3a2 (e14a2) or both. A few have e1a2, and some have very rare other breakpoint types. Some patients have a der 9 deletion (ASS deletion) (maybe 10%). Some have three or four way translocations of the Philadelphia Chromosome, or other secondary chromosome mutations (trisomy 8, monosomy 7, or others) or even secondary translocations (all of these can only be found by a BMB).

So not all CML is the same. Some leukemic cells have alternate splicing. Most CML has a rather “normal” Philadelphia Chromosome rearrangement whereby the chromosomes 9 and 22 break at the normal spots and then rearrange in the expected fashion on the new chromosome 22. Although the b2a2 (e13a2) and b3a2 (e14a2) are the most common, statistically the b2a2 responds more quickly than b3a2. Also, within both b2a2 and b3a2 there can be alternate splicing whereby certain micro-genetic material is deleted during the translocation, changing the nature of their BCR-ABL signals slightly. While the Philadelphia Chromosome (chromosome 22) is the cause of the BCR-ABL signals which cause CML, the chromosome 9 called der(9) may form in a way which puts out its own signals, although for most the der(9) is benign. But this is less of an issue than it was in the days before TKI drugs.

Some patients can have an amplified Philadelphia Chromosome, meaning it puts out stronger signalling. This is because there are two copies of the BCR-ABL gene on the Philadelphia Chromosome, so it sends out twice the BCR-ABL signals. Whether this can be seen during a BMB I am not sure, but it would be somewhat longer than the standard Philadelphia Chromosome.

There is much more that could be covered, but this introduction to CML genetics might help clear up some of the mystery surrounding this disease.

CML Testing Explained: Introduction and Basics of CML Leukemia Testing:

This is designed as a general overview to provide a basic layman's understanding of testing and CML. I will avoid the jargon and keep this somewhat short, so this will not cover everything in detail. For more details, Google the phrase and also ask your doctor/Oncologist.
There are tests to diagnose CML, evaluate response to drug therapy, assess the levels of the disease, and to check for specific problems. Among these are Complete Blood Count (CBC), Bone Marrow Biopsy (BMB), Bone Marrow Aspiration (BMA), Cytogenetics Testing, Fluorescence In Situ Hybridization (FISH) testing, Polymerase Chain Reaction (PCR) testing, Comprehensive Metabolic Panel (CMP) testing, Kinase Domain Mutation testing, Gleevec Blood Level testing, and miscellaneous other tests.

When a person is suspected of having CML, testing is done to confirm the diagnosis. A Complete Blood Count (CBC) test will usually show a very high white blood cell (WBC) count, and may also show high platelets (PLT) and other abnormalities. But this does not confirm that a person has CML. The confirmation of CML is usually done by Cytogenetics Testing (cell testing) on white blood cells taken during a Bone Marrow Biopsy (BMB) process. During a BMB, a core sample is taken from the hip bone using a hollow needle, and marrow cells are collected that cling to that bone sample. While that hole is open in the hip bone, fluid from the hip marrow is also taken out by a syringe, and this second part is called a Bone Marrow Aspiration (BMA). So the BMA aspirate or fluid is extracted through the hole created during the BMB. Cytogenetics Testing is done on the core sample and aspirate fluid, whereby approximately 20 marrow cells are thoroughly examined in the lab for abnormalities, including the leukemic Philadelphia Chromosome (Ph+ chromosome), which is the indicator of CML, and a diagnosis can be made. The sample is also checked for other abnormalities, including secondary chromosome mutations, high blast count (immature WBCs), and other abnormalities such as marrow fibrosis, abnormal cell morphology (shapes and sizes),etc. So a BMB at diagnosis is critical to a proper diagnosis. The aspirate fluid may also be tested by FISH or PCR testing to determine the relative amount of leukemic cells in the body (see later explanations). A follow-up BMB might be done again at six months post-diagnosis, and then every 12-18 months after that, or sooner if other tests show a suspected problem such as loss of response to drug therapy. BMBs are likely to be decreased in frequency or stopped altogether if the person has a 3 log response or reaches undetectable levels by PCR. When therapy reduces the levels of CML disease to where the Cytogenetics Testing (BMB or FISH) can no longer detect any Ph+ chromosome cells, that person has achieved a Complete Cytogenetic Response (CCR or CCyR).
After diagnosis, it is important to continually monitor response to therapy with regular tests. The most basic of these tests is the Complete Blood Count test, which assesses overall blood health. When a CBC test shows that blood counts have returned to normal levels, and especially the WBC and platelet counts, the person has achieved a Complete Hematological Response (CHR). After that, the CBCs should still be continued, but the frequency is often reduced. CML patients can often have certain blood counts become too low, especially white and red blood cell levels and platelet levels, so continued CBC monitoring is important. Also, a rapidly rising WBC count could indicate the need for more testing and possibly a change in drug therapy, since it might indicate a loss of response.
The BMA fluid taken during the BMB process can also be used to perform a FISH or PCR test. (FISH is fluorescence in situ hybridization and PCR is polymerase chain reaction). Or circulating (peripheral) blood can also be used to perform a FISH or PCR. Both FISH and PCR show the levels of CML disease, and are used to monitor progress, or detect setbacks or loss of response to therapy. A FISH test checks approximately 200 – 500 WBC cells, and counts the number of cells that have the Ph+ chromosome (technically it looks for the BCR-ABL gene in the WBC cells, which resides on the Ph+ chromosome). FISH is done by a machine which uses a dye process, isolates approx 200 - 500 cells, and counts the leukemic WBC cells. The result is given as a percentage of leukemic cells to good cells, so the person can say that X% of their WBC cells are leukemic. The limitation of FISH is that it can only count a small sample of cells, so if the level of disease is only a few percent, the FISH report will likely be zero (a zero FISH is also CCR response, same as a zero BMB Test). So FISH is generally not used once the level of leukemia drops below approximately 5%. At that point only PCR testing is used to monitor CML patients in this Minimal Residual Disease (MRD) status, since PCR is far more sensitive than FISH. A trend among Oncologists is to start doing PCRs early instead of FISH, including at diagnosis, since PCRs are more sensitive and can be used to track log reductions in disease levels, and FISH cannot track log reductions (discussed later).
There are two types of PCR tests. One is called a Qualitative PCR, which is a simple “yes/no” test that says it either detected BCR-ABL (leukemic cells) or did not detect them, but no number is provided – this is generally only useful to help diagnose CML since it helps distinguish between CML and other types of leukemia. The other type of PCR, the Quantitative PCR, counts the number of BCR-ABL (Ph+ chromosome cells) and reports it as a percentage number, so this is the type of PCR that is useful to track treatment progress, especially in Minimal Residual Disease (MRD) status where the levels of Ph+ chromosome cells are low and harder to detect. Some Oncologists will do a baseline Quantitative PCR at or near diagnosis to establish a baseline from which to evaluate progress, especially toward a 3 log reduction in disease levels.
PCR tests a sample of blood or marrow fluid, and can detect approximately 1 leukemic cell out of 100,000 or possibly 1 million cells in the sample, so the test is very useful for long term monitoring of disease levels and showing treatment progress. PCR testing can be done using either blood or BMA fluid. During a PCR test, the BCR-ABL in leukemic cells is counted and the result of the test is given as a percentage ratio of BCR-ABL (leukemic cells) to another gene in the cells (called a control gene). So PCR results are not a ratio of leukemic cells to good cells as we might think, which technically means that a PCR result is not actually a total percentage of leukemic cells in the body. This is one reason why PCR results from one person to another, and one lab to another, are not equivalent, due to lack of standardization among labs regarding equipment and which control genes are used (there are several different control genes used for CML PCRs). That is a reason for sticking with the same lab, so the results will be directly comparable for each PCR done, and trends can be watched. It is important when switching labs that the first PCR from the new lab be used to set a new baseline, since it may not directly compare to the previous PCRs from the other lab. A number of labs in Europe, Australia, and other countries use an International Scale for PCR reporting in an attempt to standardize the test results among labs. In early 2009 some U.S labs started this conversion, so watch for changes in the PCR numbers (possibly a significant jump in the PCR number) due simply to a change in reporting methods.
PCR results are very useful for showing trends, whether progress or retrogression. The hope for PCR results is to see progress toward a 3 logarithmic (3 log) reduction from the level of disease that existed at the time of diagnosis. This 3 log reduction is called a Major Molecular Response (MMR). A recent advance in PCR testing is that many (but not all) labs now give the log reduction along with the percentage number. So if your lab provides the log number, then use that to track log reduction progress. But if the lab does not provide this information, it makes the 3 log reduction goal more difficult to track, since many do not know where they started at diagnosis. The International Scale conversion is an attempt to standardize PCR results, but it is only used at certain US labs. Because Gleevec, Tasigna and Sprycel can rapidly reduce the levels of leukemic cells, if the first PCR is not done before starting drug therapy, the individual baseline for calculating a 3 log reduction will not be available. Otherwise, the lab may provide your log reduction number based on average results for that lab. The International Scale uses .1% as a 3 log reduction and uses conversion factors for each lab. Or a very rough estimate for U.S. labs will sometimes use .01% as the 3 log reduction goal. If someone has a baseline PCR value done at diagnosis, progress toward the 3 log goal can be calculated by taking the baseline PCR number and moving the decimal point 3 places to the left. For example, if the PCR at diagnosis was 10.0%, then moving the decimal point one place to the left is 1.0% (1 log), two decimal places is .1% (2 log), and three decimal places is .01%, which is a 3 log reduction. So 3 log/MMR for that person at that lab would be .01%.
If a 3 log reduction is achieved, the next goal becomes maintaining the 3 log reduction or even continued reduction toward a negative/undetectable PCR (PCRU). PCRU is the point where the PCR is not sensitive enough to detect any leukemic cells in the sample. This PCRU is called Complete Molecular Response (CMR), which is the deepest level of response currently measurable. In PCRU status, the leukemic cells are most likely still there, although fewer than 1 in a million. But research indicates there would likely still remain over 1 million leukemic cells in the body at the point of initial PCRU. This initial PCRU is roughly equivalent to a 5 – 6 log reduction in leukemic cells, depending on the lab. The patient can continue to drive down the number of leukemic cells after the initial PCRU is attained, but no current monitoring techniques can assess the progress. There is no test to determine if a person with CML is actually cured (usually associated with a stem cell/marrow transplant). The current indicator is 5 years without therapy coupled with continuous PCRU. Normally, the goal of CML drug therapy is to drive the number of leukemic cells to the lowest level possible, with the combined effect of stopping the advance of the disease, putting the CML patient into permanent, low level chronic phase CML.
FISH numbers do not correlate to log reductions, so only PCR can be used for log reduction measurements. Also, FISH percentages do not relate to PCR percentage numbers. For instance, at diagnosis I had both a FISH and PCR done. The FISH was 100% and the PCR was 7%.
It is not true that a low FISH means a low PCR. A FISH is like measuring the weight of something with your hand, and a PCR is like measuring with a surgical scale. Also, the FISH has an error rate of approx 1 - 5%, so your FISH could read 5% but actually be zero. When the FISH result gets below approx 5%, you should rely on PCRs from then on. A recent trend is to perform PCRs from the start.
If any of the tests, such as CBC, Cytogenetics, FISH or PCR, show the patient may be losing response to drug therapy, additional tests may be ordered. A Kinase Domain Mutation Test is one test that may show whether a certain drug, especially Gleevec, can no longer work.. The results will show if a mutation in the BCR-ABL has occurred that prevents the drug from working, and an alternate drug can usually be used. Sprycel and Tasigna work against most mutations, but both do not work equally well against certain mutations, so this test can also help with alternative drug selection. (Just an added note on the word mutation, a kinase domain mutation is not the same as a secondary chromosome mutation such as Trisomy 8, Monosomy 7, etc). Below is one lab’s description of this test:
http://www.aruplab.com/Testing-Information/resources/TechnicalBulletins/BCR-ABL1%20Kinase%20Domain%20Mutation%20Jan%202007.pdf
Another CML related test is the Gleevec Blood Level Test. This test can show how much Gleevec is being absorbed into the bloodstream, since we all absorb and process drugs at different rates. So this test can show whether a person needs to take a higher dosage of Gleevec to ensure adequate levels of drug in the bloodstream. This test is currently available free through Novartis (maker of Gleevec) under a program they call CML Alliance:
https://www.bloodleveltesting.com/index.aspx
http://www.cmlalliance.com/health-care-professional/cml-blood-level-tests.jsp?site=google&irmasrc=none&source=01030&campaign=CML-900127
There are other tests that are used for monitoring CML patients. A Comprehensive Metabolic Panel (CMP) test should be performed regularly (probably at the same time PCR is done). This checks a range of issues such as liver function, kidney function, metabolite levels, etc.
http://www.labtestsonline.org/understanding/analytes/cmp/glance.html
Examples of some other relevant tests: CAT Scans or physical checks for enlarged spleen (left side pain), physical checks for enlarged lymph nodes, complete or partial physical exams. There are also other tests to check for other specific problems when suspected, such as thyroid function, iron levels, heart issues, colonoscopy, bone density, skin problems, etc.
A sample CML testing schedule might look like the following (assuming no complications) -- your Onc should determine your specific schedule:
Diagnosis: BMB/BMA, FISH and/or PCR; CMP; abdominal (spleen) CAT scan; physical
First several months: CBC weekly
3 months: FISH and/or PCR; CMP
CBC now every 2 weeks
6 months: BMB/BMA; FISH and/or PCR; CMP
CBC now every 2 – 4 weeks
9 months: PCR; CMP
12 months: BMB/BMA, PCR; CMP
After 1 year: PCR and CMP every 3 months, CBC every 4 – 6 weeks; BMB every 18 months
After 3 log response or PCRU: Possibly longer intervals – consult your Onc, but PCR monitoring is still required at “regular” intervals, and CMP to watch liver, kidney and other ongoing items.
Your Onc should be following the National Comprehensive Cancer Network Guidelines for CML monitoring and treatment:
http://www.nccn.org/professionals/physician_gls/PDF/cml.pdf
http://www.cmlsupport.com/practicalmanagementjourclinonc0303.pdf
Other thoughts: Get copies of every lab report – you will need them for reference. Also, your Onc will not normally take time to cover every issue with you during your office visit. Read all of your lab reports thoroughly. You must be your own health care advocate.
If loss of Gleevec response occurs (possibly a 1 log or greater rise in PCR results), a Kinase Mutation Test would be used to check for mutations that interfere with Gleevec's functioning. Here is one lab's description of the test:
http://www.aruplab.com/TestDirectory/resources/TechnicalBulletins/BCR-ABL1%20Kinase%20Domain%20Mutation%20Jan%202007.pdf
Other testing info:
The color of the stopper on the specimen tube the blood or marrow fluid is drawn into: Green top is for BMB and FISH. Lavender top is PCR. See the link below, page two (all labs use the same color coding):
http://www.genzymegenetics.com/pdf/CML_physician_brochure.pdf
Here are some links to help:
http://www.cmlsupport.com/practicalmanagementjourclinonc0303.pdf
http://hep.uchicago.edu/~seturner/druk.pdf
BMB article:
http://www.forpath.org/0011/introduction.htm
CBC overview:
http://www.labtestsonline.org/understanding/analytes/cbc/test.html
Comprehensive Metabolic Panel (CMP) test info:.
http://www.webmd.com/a-to-z-guides/comprehensive-metabolic-panel-topic-overview
If testing reveals issues, you may want to discuss the following with your Onc:
If a PCR test suddenly shows a sharp increase (greater than 1 log – one decimal place):
1) Reaccomplish the PCR right away to assure it is accurate (sometimes things go wrong, such as contamination, lab errors, etc). We would hope that this is the problem, but you cannot count on that.
2) If the PCR result is confirmed, or at the same time as the PCR if you wish, have both a Bone Marrow Biopsy and a Kinase Domain Mutation test done. The latter tests for drug resistance, which is a primary cause of lack of response -- see link below for one lab's explanation of the test:
http://www.aruplab.com/TestDirectory/resources_testDirectory/Technica...
3) Depending on what the drug resistance test shows, possibly increase Gleevec dosage if not resistant (but possibly assess Gleevec levels in the blood with a Gleevec Blood Level Test), or switch to another drug if you are Gleevec resistant.
Here is some info on Gleevec resistance:
http://jci.org/articles/view/30890
4) Kinase Domain mutations are not the only reason for drug resistence. Researchers have found that an over-expression of the LYN Kinase can also cause drug resistence:
http://www.sciencedaily.com/releases/2008/06/080624174903.htm
5) If in the meantime you wanted to increase Gleevec dosage, I would discuss that with your Onc. If the PCR increases by 1 or 2 logs, it likely would mean Gleevec has stopped working and a drug change would be required. But an interim increase in dosage is an option.
6) Leading CML specialists are recommending faster switching to Sprycel or Tasigna when issues occur.

Bone Marrow Transplant (BMT) Overview:

A Bone Marrow Transplant (BMT) is one of the potential treatments for any leukemia patient. This overview is designed to be a layman’s approach to help leukemia patients get started understanding the difficult issues involved with a BMT, also known as a Stem Cell Transplant (SCT). Of course, only your Oncologist can assess individual needs, requirements, and treatment approach, but it helps to have some basic information so you can understand the Oncologist’s language, and to help formulate questions.
A BMT replaces the blood making system of a person who has a serious blood disease. It is much the same as an organ transplant, with many similar issues. So in this regard the blood may be viewed as a “fluid organ”. As with any transplant, the old must be taken out before the new is put in. But a BMT cannot remove the diseased blood, so the blood cells must be destroyed – all of them, both good and bad ones, and then the new blood cells can start with a clean slate. The blood making (hematopoietic) system is a very complex system made up of many layers of blood-making cells, starting with blood stem cells and ending with “worker bee” blood cells (white cells, red cells, platelets). The higher level stem cells survive for long periods, possibly a lifetime, and the worker bee cells may only live for several days. So the blood is constantly renewing itself, making billions of new cells every single day during the life of the person. http://en.wikipedia....transplantation
Before considering a BMT, other acceptable options should be ruled out. A BMT is often a “last resort” option. Determine that there is no other reasonable option except a BMT. A BMT will be neither fun nor risk-free, and it can sometimes shorten your life, or make your life miserable. It needs to be very carefully considered, and other options must be ruled out, including clinical trials for experimental drugs and treatments. Get second opinions. Do what it takes to become committed to the process. That does not mean that preliminary preparation cannot continue at the same time, which is often a reasonable approach. But make the final decision carefully.
A BMT can only be accomplished with “starter cells” from a donor, and these cells must be blood stem cells, because only stem cells can continually renew the blood over long periods of time. There are no “artificial hearts” when it comes to the blood, so a donor must provide the starter blood stem cells. The goal is to use these starter cells to form a new blood making system which is free of disease. And once the new blood making system is in place, it must be self-perpetuating. Sounds easy, but it is not. Mainly because the body is very protective of what it allows inside, and that is especially true of the blood. Anything inside the blood that looks “foreign” will be attacked. So when “foreign” blood is introduced into the body, it must be done in a very careful manner, and the new blood cells must be a suitable match to prevent rejection and serious side effects.
Highly matched donor blood cells are certainly preferred for two reasons: 1) poorly matched donor cells are more likely to be rejected by the body (failure to engraft the new blood cells), so the new blood cells do not take hold, which would leave the patient without any blood cells at all; and 2) poorly matched donor cells can cause significant graft vs host disease (GVHD) whereby the body continually attacks the new blood cells which are seen as “foreign”, causing side effects that can range from discomfort to life threatening. So matching of donor blood cells to the recipient is likely the most important and time consuming part of the transplant process.
When discussing donor matching, it is not as simple as matching blood types such as O, A, B, or AB. The blood cells have markers on them called antigens which show they belong in the body. If the cell does not have the appropriate antigens, the body will seek to destroy it. This is how the body fights disease and infections, but it could also lead to rejection of the donor blood cells since they could be viewed as invaders. Matching is about selecting blood cells that the recipient’s body will find reasonably acceptable. The human body, and especially the blood, is a high security zone, meaning the body does not tolerate intruders. So the body is constantly doing cell identification to make sure only approved cells are in the body. It does this by looking at the surface of a cell, which in high magnification can look like a spaceship from Star Wars – all kinds of bumps and protrusions hanging out. Among these on the white blood cell surface are “human leukocyte antigens” (HLAs) which are important for identification purposes. The body will attack cells that do not have the proper HLA “bumps” in the right places and the right sizes, so the key to matching blood cells are to find cells that have very similar HLAs on the cell surface. This allows the recipient’s body to look at the new cells and deem them acceptable. If they are not deemed acceptable, they will be attacked as invaders, and the attacks can vary in intensity.
There are various degrees of acceptable matching, for which there is no magic formula, but there are established guidelines. And by the way, regardless of what anyone tells you about finding a “perfect match”, there are only two truly perfect matches to your blood cells – yourself, and an identical twin. All other blood matches are imperfect -- period. So a main issue involved is that donor blood cells must be from a “compatible” donor, not a perfect donor, since compatibility of blood cells is a relative term unless the donor is an identical twin (and even then not always perfectly matched).
So when doing this HLA matching, you may hear people talk about 6 out of 6 HLA match (6/6), or 8/8, or 10/10, or 12/12. You may also hear people say that some of these are a “perfect match”, but they are not, since there are hundreds of minor HLAs, not just 10 or 12. A so-called “perfect match” using the 10/10 or 12/12 or any higher matching scale is actually mismatched in many ways, but hopefully in less significant ways. So HLA matching is always some degree of non-matching, including siblings (except for an identical twin). The gold standard HLA match for a BMT is 10/10, and is often called a "perfect match", but it is not perfect at all since there are hundreds of antigens, not just 10. But we cannot change the whole world at once, so we will simply move on.
Matching a donor to a recipient is extremely important since an “acceptable match” is important to both survival and reducing graft vs host disease (GVHD). So a 10/10 match does not account for numerous minor HLAs, but fortunately these are usually not as important. But even a 10/10 match can sometimes result in GVHD, which shows that a somewhat significant mis-match has occurred among secondary antigens. The science is not very good at determining when secondary HLA mis-matches might become an issue, but they are normally not a significant issue.
A person receives half of their HLA type from each parent. So, for example, when a 10 out of 10 match is discussed, it means 2 sets of 5 antigen types, 5 received from each parent. So a person has one set of these 5 from their father and one set of the 5 from their mother, making up the 10 which should be matched when possible. So HLAs come in pairs, just as chromosomes do (23 chromosomes from each parent make up the 46 chromosomes in each cell of the child).
Transplant centers vary in how they describe HLA matching. The numbers are derived as follows. There are six “major” HLAs called HLA-A, HLA-B, HLA-C, HLA-DR, HLA-DQ, and HLA-DP, and a person has two of each of them – one of each passed down from each parent. So that is a total of twelve “major” HLAs, six from each parent. This is where the 12 out of 12 matching (12/12) comes from. But since HLA-DP is generally not considered as important as the others, it is often ignored, so the generally accepted "optimal match" if HLA-DP is ignored is 10/10. And although matching HLA-DP might be preferable, it is difficult to match 10/10 let alone 12/12. Most transplant centers attempt to achieve a 10/10 match. So if you have a 10/10 match, this should provide acceptable (not perfect) outcome, 9/10 should provide a very good outcome, and 8/10 can sometimes provide an acceptable outcome assuming it is as good as can be found. The caveat with playing the numbers game is that some HLAs are more important than others, so an 8/10 could be a bad match if the most important HLAs are unmatched -- this issue is often overlooked, so be careful here. Since some HLAs are more important than others, if the match is 9/10 and especially 8/10 but lacking one or more of the most important HLAs, the match is not as good as a 9/10 or 8/10 that includes the more important HLAs. In such cases, the match may not be acceptable at all. The most important HLAs are generally consided to be HLA-A, HLA-B, HLA-DRb1. Recall that cells have two of each of these HLAs, so when these three pairs all match the donor cells it is called a 6/6 match (also called a “clinical match”). The bone marrow Donor Registry only tests for “clinical matches”, which is why a true match cannot be found simply by looking at the Donor Registry information. So additional testing of the 6/6 matching potential donors is required before an acceptable match can be found.
Many transplant centers believe that HLA-C should also be in the list of the most important HLAs when matching. This is why they will require an 8/8 match using the 4 "most important" HLAs, and every person has 2 of each HLA, one set from Mom and one set from Dad. The 10/10 matching adds HLA-DQ. And as we have noted, the 12/12 adds HLA-DP to the list.

http://www.marrow.or...ping/index.html
http://www.bbmt.org/...0274-7/fulltext
So what is the process leading up to a BMT, and what are the timelines? They are different for each person, but in general they are as follows:
1) Determine that there is no other reasonable option except a BMT. A BMT will be neither fun nor risk-free. It needs to be very carefully considered, and other options must be ruled out, including clinical trials for experimental drugs and treatments. Get second opinions. Do what it takes to become committed to the process. But any patient can start the preliminaries for a BMT to shorten the timeline for later use, if desired. This is mainly looking for a suitable donor by testing siblings, which are more likely to match the recipient (25% chance per sibling). One caveat about most blood cancers – doctors are way too optimistic about what chemotherapy can do. Few are cured by the induction/consolidation strategy. Get the real story and decide.
2) Find a donor that is the best match possible, or determine that there is not a good match for you. If you have a matched sibling (probability is 25% for each sibling), then all is well. If not, this can be very time consuming, taking possibly months, so getting started before completing step 1 above is not a bad idea. See www.marrow.org
A side note here is that not everyone in the donor registry would actually commit to the procedure when the time comes to do so. Reality is tougher than the concept for some people. The percentage is small, but it does happen. A match is not a match until the cells are actually donated.
3) Look at the options for various BMT techniques based on donor matching results. Donor availability will drive the type of BMT used. If a good match is found, then a typical allogeneic (donor) BMT will likely be done. Otherwise, there are other options, even for those without a good match (see later).
https://network.bethematchclinical.org/transplant-centers/materials-catalog/haplogic-search-report-guide/

4) Close in sequence, or possibly simultaneous to 3 above, is selection of a transplant facility. Not all are equal. BMT is a risky procedure with many variables. There are degrees of quality among various centers. You need to select wisely. Above all use a certified transplant center in the National Marrow Donor Program (NMDP) Network:
http://www.marrow.or...ist_by_state.pl
The best facility for you may be far away from home. But then there is also something to be said for using a competent one that is closest to home (family & support groups, your own home, logistics of getting follow-up check-ups and care, etc). But local is not always the best choice. This could take some time – do your research well. Ask tough questions about the Center’s history and results.
5) Set the timing for the BMT and work toward it with purpose. There is a lot to do.
6) Get yourself in better physical condition. Walk, bike, work out, whatever. Eat better. You will need stamina. Get up and get moving.
7) Get your life in order -- well, to some degree at least. Off-load responsibilities, assign roles, assume you will be out of commission for quite a while. Maybe you won’t be, but plan for the longer and hope for the shorter. Get any dental cleaning and work done now, and other medical procedures which might be required within the next year or so.
8) Thoroughly clean your home environment. When you come back after BMT you will be susceptible to viruses, bacteria, etc. Clean with a purpose. And make everyone keep it clean. It cannot be too clean. And that goes for people, too. Especially the people. Think clean, be clean, require clean.
9) Depending on personality, if you want to know what is coming, read the blogs of those who have gone before you. If you prefer to live in the present, stay away from them.
Once the BMT process begins, it usually has three main steps (with many sub-steps). These main steps are: 1) Attempt to destroy the existing diseased blood making system, generally with chemotherapy and radiation, 2) Transfuse compatible non-diseased donor blood stem cells into the patient to form a new blood making system, and 3) Monitor and treat the patient while waiting for donor cell engraftment. This sounds simple, but it is not. There are a number of issues that come into play which will be discussed later. And the process will take several weeks at a minimum, but possibly months if complications occur.
Once the diseased blood making system (and the immunity along with it) is destroyed, the new blood stem cells must be infused immediately. This “in-between” period after the old blood has been destroyed, and the new blood cells have not yet taken hold (engraftment) leaves the patient defenseless against even routine ailments, bacterial infections, and so forth. These now become life-threatening events that require medications in place of the immune system. After the new cells are transplanted into the blood, the waiting begins as the new cells engraft to start up a new blood making system. This can take a couple weeks, or longer, depending on the type of transplant. Hopefully the new immune system will begin to become functional within a month or so, but there will still be a long way to go. Don’t let your guard down.
What are some of the variables involved in a BMT? First, the blood making system is hard to kill. The body protects the blood cells in a number of sophisticated ways that enable survival under extreme conditions. And the most difficult blood cells to kill are the stem cells. So killing all the diseased blood stem cells without killing the entire patient is a difficult and even tricky task. And this is very important since any diseased stem cells that escape could potentially reconstitute the entire disease over time (disease relapse). Chemotherapy and total body irradiation are used to attempt to eliminate the existing blood making system. Often this is successful, but sometimes it is not, since blood stem cells can hide deep in bone marrow niches where it is difficult for chemo to reach them, and radiation might miss them due to bone mass.
Another variable is the type of BMT that will be used. As discussed previously, this often depends on availability of a suitable donor. If a good match is found, the standard matched donor (either related to you or unrelated to you) will likely be used. If no suitable donor exists, there are several other options. These are nicely summarized in the following tutorial:
http://www.cancer.go.../allpages/print

So if no suitable donor exists, a BMT can use mis-matched blood cells under certain conditions. Remember as you read these that there are reasons why they are not the primary method for a BMT, since each has its own issues. So these are generally not used if a good HLA match can be found since they are considered generally higher risk procedures. Those risks can be risk of transplant failure, disease relapse, suseptibility to infection or virus, significant graft vs host disease, or other risks to the patient. Other types of BMT can be quickly summarized as follows:
Cord Blood Transplant:
Blood collected during childbirth from unrelated women (usually) can be used for a BMT. HLA matching is not as important since these very young blood stem cells have not fully developed their antigens, so they can often adapt to the recipient even though clinically mis-matched. But since the number of stem cells in a unit of cord blood is small, the transplant will usually involve two separate units from separate people, and one of the two cell types will hopefully engraft. Timeline for engrafting is often longer, and rejection rates are higher.
Mini-Transplant:
This is a misnomer, but “mini” means less chemotherapy and no radiation during the preparation phase. This is often used in much older patients who cannot withstand the harsh chemo and radiation. The patient’s blood cells are only “stunned”, not fully destroyed, then the mis-matched donor cells start a “war” in the blood and take over control, killing the old blood cells. So HLA matching is not required. There are a number of risks, as one might imagine.
Haplo-Identical Transplant:
This uses significantly mis-matched parents, children, or siblings as donors. As discussed earlier, a person receives half of their HLA type from each parent. So when a 10 out of 10 match is discussed, it means 2 sets of 5 antigen types, 5 received from each parent. These 5 generally more important antigen types are called A, B, C, DRB1, and DQB1. So a person has one set of these 5 from their father and one set of the 5 from their mother, making up the 10 which should be matched when possible. Since one of the two HLA-A, HLA-B, and HLA-DRb are often a match for these related persons, these partial (often 3/6) matches combined with other techniques can make this an option when there is not an acceptable HLA match otherwise. Delayed engraftment is an issue, keeping the patient at risk due to lack of immunity for an extended period. There are also issues related to whether the techniques used will work in each case, including T-cell depletion, and other techniques that seek to prevent graft failure and GVHD due to the high mis-match. This is still considered experimental in many ways, but has made progress over the years.
Autologous Transplant:
One’s own blood stem cells are harvested, sorted to attempt elimination of diseased cells, the existing blood system is either destroyed by chemo/radiation or not, and the supposedly non-diseased cells are put back in to re-start the blood production. Since these are the patient’s own cells, the HLA matching is not an issue. But since the “cell sorting” process is not entirely effective, relapse rates are high. This is normally only used when no better option exists, or to buy time for some reason, but can sometimes be a reasonable option for certain sub-types of blood diseases.
Earlier we discussed that diseased blood stem cells might evade attempts to destroy them using chemo and radiation. But a second line of defense is “graft vs leukemia effect” (GVLE) which is similar to graft vs host disease (GVHD). If any diseased blood cells survive the chemo/rad treatment, then they may be killed off when the new blood cells take over, see the old (diseased) blood cells as foreign, and attack and destroy them. This odd turnabout, where the old blood cells that belong to the body are now seen as foreign is poetic justice that can sometimes help permanently eliminate the disease. This does not mean that an identical twin should not be used as a donor, but it is one advantage in having a good but imperfect match. (Recall that the only perfect donor match is an identical twin). As a related issue, if the original BMT begins to fail at some point, a second infusion of donor stem cells (without the chemo/rad pre-treatment) can sometimes salvage the engraftment process. This procedure is called a “Donor Leukocyte Infusion”.
There are other issues involved with BMTs. Although HLA typing is the most important part of matching a donor to a patient, there are also other issues. Survival rates increase when the donor has the following characteristics:
Negative for cytomegalovirus (CMV), male, younger age, same blood type (i.e., A, B, O, AB), larger body weight, and matched race. However, these issues can only rarely be controlled.
BMT Outcomes -- Survival, Quality of Life, and Non-Survival:
BMT outcomes are “variable”. The statistics are not great, but are not unacceptable. It is also difficult to summarize all types of blood diseases and their associated statistics. But the theory is that a BMT is used only when the patient would not otherwise survive without it. Outcome is affected by the overall health of the patient going into the BMT, age, donor matching, and other factors. You should go into a BMT expecting that the probability of long term survival is about 50/50 in rough numbers, although positive factors can increase that number, and negative factors can decrease it. There is also an old 30/30/30 “rule” which says that 30% are cured and live a great life, 30% relapse or live a poor quality life (GVHD), and 30% don’t survive the BMT process (one year). And survival is not the only issue. Relapse is also a problem, since these blood cancers are hard to wipe out before starting over with the new blood system. And GVHD can certainly reduce the quality of life after the BMT, or it can also kill – which is why so much time was spent discussing HLA matching. These are hard things to discuss, but they must be considered. But if a person truly needs a BMT, then stats are irrelevant, and the person is a statistic of one. If you must have a BMT, do everything you can to increase your odds of survival. You have more control than you know. If you are asking “How?”, the re-read everything before this paragraph. Optimal HLA matching, getting into better shape, choosing the best timing, keeping your surroundings ultra-clean, keeping well meaning people away from you during low immunity, telling nurses and others to re-wash their hands – it all adds up. Be paranoid – it is about survival.
Here is some information about BMT survival, and shows the impact of timing, disease stage, and HLA matching on survival:
http://www.medscape.com/viewarticle/408451_8
http://bloodcell.transplant.hrsa.gov/RESEARCH/Transplant_Data/US_Tx_Data/Data_by_Disease/national.aspx

Here is a chart of one-year survival rates for the top rated transplant centers using www.marrow.org data:
http://www.cml-info.com/de/healthcare-professionals/about-cml/treatment-options/stem-cell-transplantation-sct.html
Some BMT trivia related to Matched Unrelated Donor BMTs:

1) The new blood will have a different DNA than your old blood (maybe you could fool the CSI detectives). But your other body tissue DNA is unchanged.

2) Your previous vaccinations are generally wiped out – new ones will be needed. The donor’s blood will have immunities built up, but they will not be the same ones you had with your old blood.

There is much, much more information that could be added. Likewise, each individual will have a strong opinion about this difficult issue, and will argue about certain points. This has been kept concise (sort of) and is only meant to help people get started who find themselves in this difficult situation. There are many blood diseases that can result in a BMT, and they have individual issues, treatment options, and variable outcomes. But hopefully this puts some of the basic issues into a more understandable format so you can begin to make sense of this difficult subject, and provide a basis for discussing personalized treatment options with your Hematologist/Oncologist.