YMO Classroom whatsapp discussion - weekly case challenges
This week's discussion is about CML and the case is as below.
This week Patient scenario : P1
Young yr old lady, unmarried, job holder was found to have high WBC count ( 1.94L) during routine tests. Peripheral smear is s/o Chronic myeloproliferative disorder with variable percentage of myeloblast, myelocytes, metamyelocytes etc with blast 1%.She came to me 2 days back.
Q1. How to proceed now.
What are the next investigations.
Clinically asymptomatic. Examination, PS 0, No lymphadenopathy, Spleen 7cm below costal margin.
Available labs- Hb 13.5, Platelet - 4.4L/dl
More than 1 answers are welcome. Please don't hesitate to share what you know. If you are not clear on what you know, you will never be able to master the unknown.
ONLY
Once you answer, I will request excellent teachers in the group to guide us.
answers to include
Investigations - and why u order
Treatment options and why chosen
differentials (on history and labs) - CML, Splenic MZL, NHL, other MPNs (PV and ET), CMML
Investigations –
CBC with differential and Peripheral smear
Chemistry profile (LFT, RFT, LDH, Beta2 microglobulins, UA, calcium)
Bone marrowa aspirate and biopsy (morphology, fibrosis, cytogenetics)
Quantitative & Quantoitative RT-PCR (qPCR) IS for BCRABL1
Hepatitis B/C/HIV panel
CECT chest+abdomen+pelvis
Sir, asymptomatic young lady, with leucocytosis , splenomegaly, no lymphadenopathy, further evaluation
1) Cbc with differentials
2) RFT,LFT, LDH, UA
2) BM study ( morphology/cytogenetics)
4)q RT PCR for BCR ABL
5) viral markers
6) Pheriperal blood flow cytometry for clonality
All of you who want to learn please put your answers. Don't need to see what others think. At least affirm the answer if completely agree with a 👍🏽 for that answer 🙏🏼
Sir if peripheral smear is s/o CMPD, should we keep spleen in MZL and lymphoma as D/D ?
Was thinking of extra medullary hematopoisis as seen in Primary MF, presents as LNs only, although yes if PS is showing CMPD, I should have kept that as a last differential.
Yes, as mentioned by all of you, I have done a CBC, Peripheral smear, renal function tests, liver function tests, viral markers, blood group and Rh typing.
Bone marrow studies including morphology, biopsy, BM Cytogenetics ( FISH and Conventional)
Peripheral blood qualitative RT PCR for BCR ABL1
No role for CT imaging, got a CXR done as baseline.
Is LDH needed. What is the role . We expect it to be high in CML, CLL.
So what next. There is WBC - 2.9L. She is asymptomatic.
What will you advise till you wait for the reports
What is the essential points in your counseling as she is unmarried lady., 25 yrs
What is the score you plan to use if it is CML
Tab hydroxyurea 500 mg bd
Tab allopurinol 100 mg tds
Should be counselled about teratogenic effect of cml tki, she can't conceive while drugs on, 2nd generation drugs give deeper molecular response and can achieve treatment free remission earlier for planning of pregnancy, or other options of fertility preservation like oocyte preservation
EUTOS long term survival score is better in tki era than sokal score,,,in sokal importance of age is higher , which is not much determining factor in tki era
Tab hydroxyurea 500 mg bd
Tab allopurinol 100 mg tds
Should be counselled about teratogenic effect of cml tki, she can't conceive while drugs on, 2nd generation drugs give deeper molecular response and can achieve treatment free remission earlier for planning of pregnancy, or other options of fertility preservation like oocyte preservation
EUTOS long term survival score is better in tki era than sokal score,,,in sokal importance of age is higher , which is not much determining factor in tki era
Hydroxyurea 500mg PO BID (upto 100mg/kg per day)
Allopurinol 100mg PO TDS
Good oral water intake
Counseling -
Fertility preservation (oocyte/cryo/tissue)
Not to concieve while on Rx
Rx won't affect fertility in long term
Responses to 1st gen Vs 2nd gen TKI
Good chance for TFR with 2nd gen TKI (longer & deeper & quicker responses)
Scoring - EUTOS
Oocyte preservation is somewhat impractical for such a chronic disease. It is typically for an answer in exam only.
I would, rather, strive to get her into MMR.
Take her off the drug once she plans her pregnancy.
Complete the pregnancy, delivery and lactation and out her back in TKI.
We risk a relapse during this period. No sweat. We manage it with hydroxyurea.
Her baseline TLS parameters are normal. I have started her on Allopurinol 100mg TDS, Hydroxy Urea 500mg BD, Given Domstal BD . Have asked to drink lot of fluids, avoid juices for the time being.
What is the actual risk of TLS in CML?
Technically, blasts, especially lymphoblasts, are the most fragile...the leftward shift forms are not so fragile...but the risk is higher, with higher TLCs.
Yes Sir, she has very high counts. We need to take it as high risk though CML chronic phase is low risk disease as per the paper in BJH
What is the current best score to assess chances of response and survival in CML?
Nice article to read on CML. Happy Weekend. Will get insights tomorrow from all on management 🙏🏼
Carrying forward the case discussion, let's say the reports for patient is pending. Let us assume that she has BCR ABL1 positive in RTPCR and no additional high risk cytogenetics . Blasts - 2%, No Grade 2 or 3 marrow fibrosis.
25yr old unmarried female, IT professional, no financial constraints
Her ELTS score is low risk
Plan:
1) What is the first line TKI preferable and why?
2) Any other baseline workup necessary prior to start of treatment.
3) When is the next follow up disease evaluation planned: is any further marrow cytogenetics mandatory in follow up
4) She has baseline count WBC 2.9L. She has elder brother , healthy. Any need for HLA matching studies now
5)What will be the strategy for her if she gets married and wants to get pregnant
6) What will be the expected drug related toxicity and how to monitor her
7) What will be the evaluation and further treatment if she fails to attain MMR at any milestones.
1. Low risk disease. TKI can be choosen based on discussion with the patient . no difference in OS between first gen and second gen drugs. If however, TFR is important considering future pregnancy and marriage, would discuss about 2nd gen drug like nilotinib or dasatinib for faster and deeper molecular response.
2. ECG and electrolytes prior to initiation of 2nd gen drugs especially. Testing of amylase, lipase and lipid profile before nilotinib especially. May consider a baseline ECHO too.
3. Monitor CBC every 2 weeks till CHR achieved. Quantitative BCR-ABL on peripheral blood monitoring every 3 months till MMR achieved. Marrow cytogenetics if MMR not achieved within a year or any of the optimal endpoints not reached??
4. Can wait for HLA matching given availability of newer drugs in CML??
5. Counsel about avoiding pregnancy while on TKI in view of increased risk of miscarriage and teratogenicity. Ideal situation consider deferring pregnancy till 2 years of stable MMR (MR3-4)
6. Imatinib: Fatigue, cramps, cytopenia, edema. NIlotinib: Pancreatitis, Thrombotic events, QTc
Dasatinib: Pleural effusion, PAH, Bleeding, QTc. Bosutinib: Diarrhea . hence to monitor apart from CBC, biochem panels atleast monthly for the first few months. CXR if symptoms. ECG periodically every 3 months??
7. Bone marrow, cytogenetics and BCR ABL mutation domain. If still in chronic phasem then based on mutation and the TKI used in first line, another TKI can be used.
Nice points Dr Nitin. Dear residents, please ask any questions on this topic you have.
Where do we place Bosutinib ?
With regards to first line ?
Second line ?
Nice
Only thing to be more cautious is better to give 2nd gen TKI for atleast 4 years and DMR for 2 years...So that she will not lose response in Pregnancy and thus it will be easier for her and treating Physician
Sir, what if patient looses response within 1-2 months of pregnancy? Is it better to terminate the pregnancy or to monitor for next 7 months with hydroxyurea?
That is unlikely to happen as she will be in DMR at the time of pregnancy. It takes few months to lose response and failure is labelled after loss of MMR. most of the times pts will be in CHR hence serial monitoring is sufficient. After loss MMR gradually Counts starts to rise.
Sudden rise in bcr abl usually denotes emergence of mutations
Poor compliance leads to progressive rise in bcr abl
If patient is in DMR for 2 years...It's unlikely that she loses response in those 9 months to start TKI
My experience over past 8 years at NIMS...
Of all pregnancies, I had seen only one lady to loose MMR towards end of pregnancy for which we reassured to complete pregnancy and start TKI after that...She attained MMR again after restart of TKI