2 high resolution CEMRI and 2 LPs negative (according to the oncologist) for leptomeningeal spread. I think we should now start discussing the TAB results and rheumatologists opinion on if it's a GCA or CML vasculitis.
Do we have the TAB results?
Dr Shikha Bassi
Sankara Nethralaya
Chennai
India
Original Message:
Sent: 5/7/2025 2:20:00 PM
From: Andrew Carey
Subject: RE: CML / dasatinib and optic neuropathy?
Can you request the slides from the original LP to have it reviewed?
Best,
Drew
Original Message:
Sent: 5/7/2025 2:18:00 PM
From: Michel Van Lint
Subject: RE: CML / dasatinib and optic neuropathy?
I have only seen him bedside today. He is currently admitted because of hyperglycemia due to the steroids. He is also on plasmapheresis (second session today).
Hope to see him tomorrow, though.
I would feel safer with intrathecal chemotherapy and radiotherapy, but without any proof of the leukemia, there is obviously no way anyone will agree to this.
Michel
Original Message:
Sent: 5/7/2025 1:49:00 PM
From: Jade Schiffman
Subject: RE: CML / dasatinib and optic neuropathy?
Difficult case
What is his vision today?
If it is leptomeningeal disease, he needs different treatment ASAP if any vision is salvageable.
Waiting one month is too late.
Jade S. Schiffman MD, FAAO, FAAN
Co-Director of Neuro-Eye Clinical Trials, Inc.
Co-Director Neuro-ophthalmology of Texas, P.L.L.C.
Adjunct Professor, Department of Clinical Sciences, UH College of Medicine
Former Professor of Ophthalmology and Neurology, University of Texas MD Anderson Cancer Center
Original Message:
Sent: 5/7/2025 1:39:00 PM
From: Michel Van Lint
Subject: RE: CML / dasatinib and optic neuropathy?
I still feel like, I am missing something.
He is still on methylprednisolone 32 mg. Perhaps I should taper it quickly and then ask for a repeat LP one month after stopping the medication?
His first LP elsewhere showed numerous lymphoid cells, but the result was disregarded by the first hematologist .
The current LP could be false negative because of the steroids?
Michel
Original Message:
Sent: 5/7/2025 7:50:00 AM
From: Michel Van Lint
Subject: RE: CML / dasatinib and optic neuropathy?
Unfortunately, the flow cytometry did not help us further.
We are currently trying plasmapheresis in an attempt to see if there is anything we can still salvage, but I am not expecting anything major..
The patient prefers to have no optic nerve biopsy.
Flow cytometry negative for a lymphoproliferative process
Immunophenotyping review
A total of 1 129 viable nucleated CD45‑positive events were analysed.
-
T‑lymphocytes are present with a normal CD4/CD8 ratio.
-
Both the CD4‑positive and CD8‑positive T‑cell populations show a polytypic/polyclonal pattern on TRBC1 clonality analysis and display normal marker expression.
-
B‑lymphocytes are virtually absent; clonality cannot be evaluated.
Immunophenotyping conclusion
Flow‑cytometric analysis provides no evidence for a lymphoproliferative process.
Michel
Original Message:
Sent: 5/2/2025 7:27:00 AM
From: Andrew Carey
Subject: RE: CML / dasatinib and optic neuropathy?
The single case report of dasatinib optic neuropathy is highly suspicious as it does not appear they appropriately ruled out optic nerve infiltration and it is difficult to attribute asymmetric optic neuropathies to toxic etiologies.
I would be highly suspicious infiltrative optic neuropathy in your case. Hematologist are often in denial of leukemia relapse in the CNS although the CNS is a known reservoir and in particular the subarachnoid space of the anterior optic nerve.
1. Chronic Myelogenous Leukemia Relapse Presenting With Central Nervous System Blast Crisis and Bilateral Optic Nerve Infiltration. Mbekeani JN, Abdel Fattah M, Al Nounou RM, Chebbo W, Dogar MA. Journal of Neuro-Ophthalmology : The Official Journal of the North American Neuro-Ophthalmology Society. 2016;36(1):73-7. doi:10.1097/WNO.0000000000000326.
2. Bilateral Optic Nerve Infiltration in Central Nervous System Leukemia. Schocket LS, Massaro-Giordano M, Volpe NJ, Galetta SL. American Journal of Ophthalmology. 2003;135(1):94-6. doi:10.1016/s0002-9394(02)01847-0.
3. Leukemic and Lymphomatous Optic Neuropathy: A Case Series. Lee V, Farooq AV, Shah HA. Journal of Neuro-Ophthalmology : The Official Journal of the North American Neuro-Ophthalmology Society. 2021;41(4):e796-e802. doi:10.1097/WNO.0000000000001365.
Did they not do flow cytometry on the CSF? You could also do a cell free DNA PCR for the Philadelphia mutation from the CSF.
If there is no CSF left to test, I agree a repeat LP is needed.
I'm not sure the orbital MRI will distinguish between GCA and leukemia infiltration, but it could give you good reason to proceed with biopsy if LP is inconclusive.
Best of luck,
Drew
------------------------------
Andrew Carey
Associate Professor
Wilmer Eye Institute, Johns Hopkins Medicine
Baltimore MD
------------------------------
Original Message:
Sent: 05-02-2025 05:48
From: Shikha TALWAR
Subject: CML / dasatinib and optic neuropathy?
Advising a CEMRI of the brain and orbit , which may show sheath enhancement and a repeat atraumatic LP may appear extensive / aggressive but are a step in the right direction ,while TAB with normal esr and crp more than 2 weeks post treatment with steroids might be a futile invasive investigation.
At this point ruling out a new malignancy or a relapse of CML with HPE is important . There's a clinical doubt of CNS invasion in a pt in remission. No test is aggressive enough to show that he doesn't have any .
Thanks for sharing the case.
Dr Shikha Bassi
Director
Neuroophthalmology Services
Sankara Nethralaya
Chennai
India
Original Message:
Sent: 5/2/2025 5:18:00 AM
From: Sherif Ahmed Kamel Abdelbar
Subject: RE: CML / dasatinib and optic neuropathy?
Is there any Fundus picture to see here ?
Original Message:
Sent: 5/2/2025 4:52:00 AM
From: Michel Van Lint
Subject: CML / dasatinib and optic neuropathy?
Male, 73 years old.
Diagnosed with CML in September 2024 after an accidental finding of leukocytosis.
He was treated with dasatinib, which was stopped on 10th April.
Mid March he noticed a bilateral loss of vision.
On 11th April he got his first eye exam which revealed a bilateral optic disc edema
He was given oral methylprednisolone 64 mg/day.
Bloodwork and cerebral MRI were considered normal.
The hematologist considered the CML to be in remission and therefore unlikely to be the cause.
During follow-up in the next two weeks the optic disc edema resolved. Despite that, he continued to have further loss of vision and visual field in the right eye. The left eye mostly remained non-functional.
With a bit of fantasy, one might wonder if there is a quadrantanopsia in the right eye initially (and then a hemianopia??) against a background of diffuse loss of sensitivity.
Until now there has been no explanation for his going blind.
Lumbar puncture was refused by the hematologist as it was deemed unnecessary. The neurologist eventually did the LP after explaining its importance.
The results of the lumbar puncture read: "Cell-rich cytological sample with a predominance of lymphoid cells, which sometimes show varying diameters. No cytological evidence of an underlying epithelial lesion. Results must be strictly correlated with clinical biology to rule out an underlying lymphoma."
Despite that, the hematologist said that the lumbar puncture was traumatic and that this explains this result. They reassured us that the leukemia is inactive.
He is now coming to me for second opinion.
My current DD would be:
Giant cell arteritis (biopsy tomorrow, as the diagnosis had not been considered before, because of normal CRP and ESR)
Microscopic leukemic optic nerve infiltration
Paraneoplastic optic neuropathy
Dasatinib causing optic neuropathy has been described
My suggested approach would be:
Repeat lumbar puncture
MRI orbits
Plasmapheresis depending on results of the second lumbar puncture
Optic nerve biopsy if all else fails, his vision is not stable and the patient agrees
Would do you think?...
Since this is quite an aggressive approach, I do not feel too comfortable about this, but neither is the progression of his visual fields
Michel
PS.
- I was told, I am allowed to post images directly using this new medium - if not, please let me know
- Apologies if this is a double thread (I first tried starting one by sending an e-mail, but it probably/obviously does not work like that)