8 replies to this topic

[Caregiver]

My b-i-l was diagnosed with accelerated-phase CML on 6/09 and was on Gleevac for 2 years 3 months.  He started out at 800 mg and then was decreased to 400 mg.  He is developmentally challenged and has limited understanding.  We became involved when it became apparent they needed help.  I've been taking crash courses trying to educate myself on these boards and elsewhere so we can help them as much as possible.  It is clear from studying his FISH results since diagnosis that he never achieved good results with Gleevac and another TKI should have been started long ago.  His FISH percentages steadily rose over the entire time.  He was hospitalized on 9/2/11...his blast count were 37% circulating and 34% marrow. 

9/2/11 - FISH ordered by local onc

nuc ish 9q34 (abl x 3), 22q11.2 (bcr x 2)

(abl con bcr x 1), 9q34 (ASS x 2) [169/229] : 74%

We took him to see a specialist at IU Med.  His diagnosis was chronic myeloid leukemia transformed to acute leukemia.  His recommendation was induction therapy and SCT.  Unfortunately, neither my b-i-l or his wife are phsycially, mentally, emotionally, or psychologically capable of undergoing a SCT.  The prognosis was very unfavorable.  It just was not a viable option for them for many reasons.  So the decision was made to begin taking Sprycel.  We were told the chances of achieving a remission status with Sprycel was very small.  We are basically just hoping for as much time as possible.

9/21/11 - FISH ordered by specialist

nuc ish(ASS x 2, ABL 1 x 3) 22q11.2 (BCR x 2) (BCR con ABL 1 x 1) [145/200] 72.50%

1/30/12 - FISH ordered by local onc after being on Sprycel 100 for 4 months

nuc ish 9q34 (abl x 3), 22q11.2 (bcr x 2)

(abl con bcr x 1), 9q34 (ASS x 2) [202/500] 40%

nuc ish 9q34 (abl x 3), 22q11.2 (bcr x 3)

(abl con bcr x 2), 9q34 (ASS x 2) [7/500] 1.4%

Please help me understand these numbers.  What is the new 1.4%?  What do you think of the 74% to 40% in 4 months?  Is Sprycel actually helping?  He has to go off the Sprycel periodically because of low counts.  He has been getting 3 units every 2 weeks for low HGB.  His latest CBC was:  WBC - 1.50; RBC - 2.77; HGB 7.8; HCT 23.4; MCV 84.5; MCH 28.2; MCHC33.3; PLT 46; Neutrophil ABC .60  We want to make sure we understand what reality is.  At this point I trust your answers more than I trust the local onc.  Thank you in advance for your help.

[Trey]

We salute your compassion.  We will help also, if possible,

The good news is that his overall FISH has dropped (must combine the 40% and 1.4% to equal 41.4%).  The lab codes are standard CML FISH codes.  He has the "normal" CML translocation and at least one other.  But it is worthy noting that he is responding better to Sprycel, at least for now. 

The bad news is not so easy. 

You suggested he has transformed to acute leukemia.  The FISH will not tell you that, so the Flow Cytometry and Bone Marrow Biopsy cytogenetics would be more instructive.  The high marrow and peripheral blood blast counts show continued transition of CML into probable blast phase, consistent with the Onc's assessment of transformation to acute leukemia.  If that is accurate, then it is not good at all.  When CML transitions into the advanced stages, it becomes more aggressive, and harder to control, and the CML drugs do not work very well, or if they do, usually not for very long.  This  advancement is often irreversible, but not always.  The "not always" would be the reason for hope, although somewhat slim. 

At this point there are no other real options if SCT is impossible -- and I can understand why it would be in this case.  So overall the prognosis is not good.  The Sprycel may work for a while (maybe a year) and then likely stop working.  But then again it may work longer, but unlikely.  These things are not an exact science. So the best you can do is see if Sprycel continues to work for a while, and then see if it works for a while longer.  But the odds are low (maybe 15% or less) that it will work for very long.  You wanted to know, so there it is.  Hope it helps with your expectations, even if not otherwise.

[scuba]

Trey is giving you the straight story here ... but I see the positive as well. He has had a signficant drop from 70+% to 41% in 4 months. So he is responding. Sprycel has shown to be effective for some in blast crisis. Your major concern now in addition to blasts is myelosuppression brought on by the Sprycel.

Rather than interrupting the dose - his doctors should consider lowering the Sprycel dose so that the Myelosuppression can be managed. Dr. Cortes at M.D. Anderson is an expert in this and should be consulted by your doctor. The key is to keep the drug in his body daily rather than stopping.

I would ask Trey, however, why he believes the prognosis can not improve if he continues to respond to Sprycel and his FISH counts continue downward? Why would Sprycel "stop" working in a year or so? Just curious as to your thinking on this, Trey. See abstract below from 2007. Results since then are even better.

Caregiver - please keep us posted. All the best to you. There is hope.

Dasatinib induces complete hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in blast crisis.

Cortes J, Rousselot P, Kim DW, Ritchie E, Hamerschlak N, Coutre S, Hochhaus A, Guilhot F, Saglio G, Apperley J, Ottmann O, Shah N, Erben P,Branford S, Agarwal P, Gollerkeri A, Baccarani M.

Source

M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA. jcortes@mdanderson.org

Abstract

The prognosis for patients with chronic myeloid leukemia (CML) in myeloid blast crisis (MBC) or lymphoid blast crisis (LBC) remains poor. Although imatinib can induce responses in a subset of these patients, resistance to the drug develops rapidly. Dasatinib is a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases. After promising phase 1 results, we report the results of phase 2 clinical trials of dasatinib in patients with imatinib-resistant or -intolerant blast crisis CML (MBC, n = 74; LBC, n = 42). At the 8-month follow-up, dasatinib induced major hematologic responses (MaHRs) in 34% and 31% of MBC- and LBC-CML patients and major cytogenetic responses (MCyRs) in 31% and 50% of these patients, respectively. Most (86%) of these MCyRs were complete cytogenetic responses (CCyRs). Responses were rapid and durable: 88% and 46%, respectively, of MBC- and LBC-CML patients achieving MaHR had not experienced disease progression at the 8-month follow-up. Response rates were similar in patients with and without BCR-ABL mutations known to confer resistance to imatinib. Dasatinib was well tolerated. Nonhematologic adverse events were mild to moderate. Cytopenias were common and could be managed by dose modification. Dasatinib is highly active and produces hematologic and cytogenetic responses in a significant number of patients with imatinib-resistant or -intolerant MBC- and LBC-CML. These trials were registered at www.clinicaltrials.gov as #CA180006 and #CA180015.

Message was edited by: Michael: added reference

[Trey]

Michael,

A couple comments.  The study only lasted 8 months, so it does not show what happened after the one year period where most of these responses are typically lost.  Also, you do not appear to be reading your referenced results properly.  The percentages are sequentially declining ones, for example look at the lymphoid blast crisis (LBC) numbers; 31% achieved a  hematological response, then 50% of that 31% achieved additional response (so down to 15.5%), and then 86% of that 15.5% achieved further response, so the end number is 13.3% who had a good response at 8 months.  Then we do not know what happened after that rather short period, and likely most eventually lost response and/or had a SCT.  The experience since has not shown any reason to be more hopeful about this issue.  A few can hold on to some level of response over a longer term, so as I previously stated, some amount of hope exists; but the stats are not very encouraging.  Note also that the original posting involves someone who has transitioned to acute leukemia.  That further limits the probability of holding onto any short term response. 

[scuba]

Trey,

What is the 'mechanism' for acute (M) Leukemia transition from chronic phase? Is it indicated only by blasts? In other words, if blasts are brought under control - is the Leukemia reverted to the chronic phase again?

[Trey]

I would prefer to keep this thread dedicated to helping Caregiver rather than get side-tracked.  But briefly, it is the very high circulating blast count that seems to confirm the acute transformation.  When blasts are mostly confined to the marrow, then it may not be as serious.  If Caregiver wants to discuss more details related to this patient, then I will.

[Caregiver]

Thank you Trey.  I appreciate your blunt and factual approach.  Cytogenetics were done for diagnosis.  While there is always hope...the truth is the truth.  Your conclusions are the same as what I came up with.  I wanted to make sure I was reading the data correctly and not over-reacting.  I find it much harder to help guide someone with limited abilities through this process than if it was myself.  I feel so responsible and don't want to make any mistakes in judgment or steer him in the wrong direction.  I wish we would have gotten involved sooner - but I suspect my b-i-l would have still been in that small percentage of people who do not respond well to treatment.   The Onc at IU Med gave him only a few months to live (September '11) and wanted to take him upstairs to begin the induction therapy immediately.  My b-i-l had NO understanding of what that would have involved with the chemo and SCT.  I almost felt he was going to be used for testing/educational purposes.  I'm all for testing....but not at the expense of someone that does not have the ability to make an informed decision.  He has already had 4 relatively good months with Sprycel.  I'm convinced that is more than he would have had going into induction/SCT.  We'll see how long he can continue to do well.  Every day that any of us have is a gift...we need to appreciate each day. 

[Pin]

I am so sorry that you are in this situation. This disease is difficult enough for those of us who respond reasonably to very well and who have the capacity to understand at least generally, what is happening. It is heartbreaking to hear of your brother in law's situation and I am so sorry for it. Please ask any questions you need or come on here for support whenever you want. Pin xxx.

[Trey]

The so-called "induction therapy" with chemo will not do anything to cure him or significantly delay the expected outcome.  For other leukemias that is done, but for CML and his specific situation it is not going to be very helpful.  Although it may prolong his life a short time (but maybe even shorten it), it will make him more miserable.  It is a delicate situation, but if it were me, I would not allow the chemo at this time, but wait until he completely fails the Sprycel (or is the very small percentage that succeeds on it in blast phase) and re-address the issue later to see if prolonging his life a couple months and adding the downsides of the chemo is worth it for him and the family.  If you choose the chemo, it will eliminate the possibility that Sprycel could work longer term.  Generally the chemo makes blast phase leukemia even more aggressive after it is removed.

You have not failed him.  The Onc should have done better, but there is no assurance it would have helped.  It is the disease that has caused this, not you.  Some are in that small percentage that just will not make it through this.