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CML VARAINT TRANSLOCATION t(4;9;22)(p16;q34;q11) BCR-ABL NEGATIVE . IMATINIB AND DASATANIB RESISTANT. PLS AVDICE WHAT TO DO

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DAIGNOSIS: CML
DAIGNOSIS ON 24/05/2018 DUE TO HIGH TLC.
DATE: 24/05/2018            TCL: 147500/CUB.MM
HYDROXYUREA START FROM 25/05/2018 DOSE: 500 MG THRIC IN A DAY
SAME DAY BLOOD SAME SENT FOR BCR ABL BY FISH: TEST RESULT
NUC ISH (BCR*3), (ABL1*2)                                  -120(60%)
NUC ISH (BCR*2);(ABL1*2)                                      80(40%)
IMPRESSION: NEGATIVE FOR BCR ABL 1 FUSION

DATE : 02/06/2018            TCL:51830/CUB.MM

HYDROXYUREA START FROM 02/06/2018 DOSE: 500 MG TWICE IN A DAY
ON 02.06.2018  BLOOD SENT FOR THE TESTS:
CALR MUTATION ANALYSIS   :             NEGATIVE
BCR-ABL QUALITATIVE            :            NEGATIVE
MPL MUTATION ANALYSIS     :            NEGATIVE
JAK2 EXON 12-15 MUTATION DETECTION: NEGATIVE

DATE:19/06/2018                      TCL 12440 /CUB.MM


ON 19.06.2018  HYDROXYUREA  DOSE:   500 MG TWICE IN A  DAY AND  500MG ONCE IN A DAY SECOND DAY.
ON 03.07.2018 CYTOGENETICS: CHROMOSOME ANALYSIS IN HEMATOGICAL DISORDERS; RESULT.
INTERPRETATIPON: SEVEENTEEN OF THE 20 METAPHASES ANALYSIS ARE ABNORMAL AND SHOW A THREE –WAY VARIANT  t(9;22) INVOLVING THE SHORT(P) ARM OF CHROMOSOME 4. THE PROGNOSTIC IMPACT OF STANDARD AND VARIANT t(9;22) APPEARS TO BE SIMILAR . THE t(9;22) IS CONSISTENT WITH CML AND ALL. IT MAY ALSO BE SEEN IN ~3% OF AML ~25%OF ADULT ALL.
  ON 03.07.2018 BONE MARROW BIOPSY ALSO HAD BEEN DONE.
ON 03.07.2018        TLC :38960/CUB.MM
ON 06.07.2018 START IMATIB 400 MG ONCE A DAY
ON 16.07.2018          TLC : 91000/CUB.MM
ON 26.07.2018          TLC : 120000/CUB.MM
ON 06.08.2018          TLC : 174960/CUB.MM
ON 06.08.2018 DOCTOR ADVICE THAT IMATIB RESISTANT AND STOP THE DOSE  ALSO ADVICE TO START DASATANIB (SYPCELL) 100 MG (2 TBS @50MG).AND ALSO ADVICE TO START HYDROXYUREA  FOR A WEAK  UNTILL  DASATANIB ARRIVED BY THE MEDICINE COMPANY.
ON 07.08.2018 START HYDROXYUREA   500 MG THRICE A DAY
ON 12.08.2018   TLC: 68,300/CUB.MM

ON 12.08.2018 STARTED DASATANIB 100 MG ( 2 TAB 50MG)
ON 19.08.2018  TCL: 80800/CUB.MM ( DASATANIB IS CONTINUE)
ON 23.08.2018  TCL: 69720/CUB.MM ( THIS TIME THE BLOOD SAMPLE IS GIVEN AFTER TAKEN THE DOSE OF DASATANIB AND ON EARILY I GAVE ALL THE BLOOD SAMPLE FOR TEST WITHOUT TAKEN THE DOSE ON IMATANIB OR DASATANIB )

ON 23.08.2018  THE BCR-ABL t(9;22) BY FISH DONE , THE RESULT:
Nuc ish(BCR*3)(ABL*20 [178/200]
  178/200 (89%) Interphase nuclei and 20 metaphases show 2O 3G signal for BCR ABL.

ON 30.08.2018  TLC : 116000/CUB.MM (dasatanib continue)
ON 03.09.2018  TLC: 166000/CUB.MM
ON 03.09.2018  HYDROXYUREA START 1500 MG ( 500 MG THRICE A DAY ) WITH 100 MG DASATANIB.
    
                PLEASE ADVICE AND GIVE SUGGUTION WHAT TO DO. PLS CONTRACT MY EMAIL: AAMIR1073@GMAIL.COM

Hi Aamir,

You've posted a lot of information, but not much questions. Is there something particular you're worried about or want to talk about?

It is very normal to take hydroxycarbamide for a while before a TKI. That said I am having trouble interpreting some of your report. The line "IMPRESSION: NEGATIVE FOR BCR ABL 1 FUSION" seems inconsistent with the rest of the report. BCR-Abl is the hallmark of CML. It sounds to me like there is more work to be done to adequately understand your disease as there is perhaps more chromosomal abnormality spoken about later in the report. Small things like spelling "Sprycell" incorrectly would worry me, however I understand English is likely not the doctors / writers first language given the rest of the report so perhaps this is unimportant. 

A few observations:

  • If the 2x 50mg Dasatinib intended to be taken only once a day (i.e. both together?). It should.
  • Your FISH test is below 100% (89%) which is good with CML.

David

"BCR/ABL negative or atypical chronic myeloid leukemia (CML) is a rare hematologic malignancy with an estimated incidence of 1–2% of BCR/ABL positive CML. Clinical features of BCR/ABL negative CML resembles those of BCR/ABL positive CML but does not have BCR/ABL fusion gene; rearrangement of platelet-derived growth factor receptor (PDGFR)-A, PDGFR-B or FGFR1 is also absent [Vardiman et al. 2008]."  

 

"The rarity of the disease has largely precluded conduction of any prospective study to optimize treatment strategy of BCR/ABL negative CML. Similarly, the mutations associated with the disease were hitherto undiscovered, which prevented identification of therapeutic targets and drug development. Consequently, BCR/ABL negative CML has been managed with palliative therapy such as hydroxyurea, low-dose cytarabine and interferon, which results in a median overall survival (OS) of approximately 2 years in small retrospective studies [Onida et al. 2002; Breccia et al. 2006]. A recent multicenter study demonstrated that BCR/ABL negative CML is distinct from unclassifiable myelodysplastic/myeloproliferative neoplasms and has a worse OS (12 versus 22 months) and acute myeloid leukemia-free survival (11 versus 19 months) [Wang et al. 2014]. A population-based study on the outcomes of BCR/ABL negative CML is lacking."  

 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4649605/