Adult ALL with isolated CNS relapse

[OTN]

Just got called to see an adult patient in her 50s with h/o ALL, s/p allo transplant 5+ years ago. Now presents with isolated CNS relapse with some evidence of leptomeningeal disease near the lesion. I've yet to see the images, but per report no evidence of spinal disease. Our program does do TBI, so I see a fair number of leukemia patients.

How would you dose/fractionate? I know kids with ALL are treated to 18-24 Gy (18 Gy more commonly now I believe) to the brain and 6 Gy to the spine, but I can't find much information about dose/fractionation/volume in adult patients with isolated late CNS relapse. Per the medonc, pt may receive IT CTx following RT. Tentatively I'm thinking 24 Gy to the whole brain, but 6 Gy to the spinal axis seems a bit on the weak side to me. Thoughts?

Thanks!

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[evilbooyaa]

Lot of questions to consider. Most of them will be answered with obtaining radiation records (at least treatment summary) of previous treatment.

Did patient have CNS disease before transplant? That affects TBI RT dose. Was it myeloablative conditioning or reduced intensity? Did the patient receive TBI?

Adults with ALL who have no CNS disease and receive appropriate IT MTX ppx routinely receive just TBI (13.2 at my instituion). History of CNS disease gets a boost up to ~18Gy (including the TBI). Active CNS disease gets up to 24, but these patients usually aren't going to transplant.

I'm not sure where you're getting 6Gy to the spinal axis - even if they got just TBI it'd be likely higher than that. The doses given at time of transplant are generally for prophylaxis, not for gross disease.

Patient needs ~24Gy whole brain if you're going to radiate IMO. Needs full spinal imaging and (if negative for leptomeningeal spread into spinal cord on imaging) CSF evaluation. Likely needs ~24 to entirety of CSI. If patient asymptomatic can kick the RT can down the road with IT MTX if desired.

 

[Neuronix]

Very little data. I've used this paper: The role of craniospinal irradiation in adults with a central nervous system recurrence of leukemia. - PubMed - NCBI to treat a few patients when I was a resident. My experience in this realm has only been for palliative intent therapy.

A few principles I use to guide this:
1. I want them to prove blasts in the CSF first before I consider radiating the entire neuroaxis. If there is a focal problem (chloroma, brain leptomeningeal disease, etc), I'd strongly consider just treating that focal issue (the chloroma, whole brain, etc)

2. Since CSI will likely do a lot of damage to their bone marrow, it's best that they've exhuasted all reasonable injectable options before going this route. I don't want to permanently lower their counts and prevent them from receiving other systemic therapies.

3. If you're planning for chemotherapy and radiation, do them sequentially, RT first. Systemic/intrathecal regimens used for CNS leukemia tend to hang out in the CSF for awhile. You should wait on the order of a month after such chemotherapy before radiating unless it's an emergency. On the flip side, you can do RT first then go on to systemic therapy quickly (next day even).

4. I dose these to 18 Gy with a boost to chloroma to 23.4 Gy. I have seen DRAMATIC responses with this dose, even by 12 Gy. Unfortunately, the responses are not durable. You could consider doing it again at that dose.

 

[Palex80]

Evilboyaa's response is very precise.

Bear in mind that the patient's bone marrow function will be limited since he has undergone intensive chemotherapy already and a bone marrow transplant. Expect lots of cytopenia during CSI.

I've treated one patient with a CNS recurrence a couple of years after 12 Gy TBI and BMT. I gave her 24 Gy CSI. She's alive and doing well.

 

[OTN]

This is very helpful, thanks everyone. She did receive TBI as part of her prior conditioning regimen, but I don't yet have the details. I would prefer just to irradiate the whole brain, as we don't have any evidence yet of spinal disease, blasts in the CSF. She did have imaging evidence of leptomeningeal disease in the brain, so I think whole brain is going to be necessary.

I should be able to get a better idea of her marrow function when I see her tomorrow and talk with her medonc. We're definitely thinking RT first, then IT CTx.

 

[evilbooyaa]

This is very helpful, thanks everyone. She did receive TBI as part of her prior conditioning regimen, but I don't yet have the details. I would prefer just to irradiate the whole brain, as we don't have any evidence yet of spinal disease, blasts in the CSF. She did have imaging evidence of leptomeningeal disease in the brain, so I think whole brain is going to be necessary.

I should be able to get a better idea of her marrow function when I see her tomorrow and talk with her medonc. We're definitely thinking RT first, then IT CTx.

Not infrequently, Heme at my institution fails to obtain MRI imaging of the entirety of C/T/L spine in these scenarios. It seems like it has been obtained in yours, just wanted to confirm that has been obtained. I've seen negative CSF but floridly positive MRI spine.

Agree that if no evidence for spinal disease, then whole brain alone (in this scenario) is appropriate.

 

[Neuronix]

I've seen negative CSF but floridly positive MRI spine.

The correlation of lumbar puncture to imaging in clinical leptomeningeal carcinomatosis is only about 2/3 - 3/4. Neither study really rules out leptomeningeal disease.

 

[Palex80]

If this is supposed to be curative i would strongly advise to do CSI and not whole brain only.

I would not do CSI and stick only to the brain if she's supposed to get another BMT with TBI conditioning, since then she would have get "anyway" 12ish Gy of TBI. However, since she already had TBI with a myeloablative dose (presumably) a repeat myeloablative TBI is out of the question.

My argument for high-dosed CSI comes from the fact that you are dealing here with cells who apparently survived intensive chemo & 12ish Gy of TBI. This is highly aggressive disease.

 

[seper]

I had a few very similar patients and the regimen agreed on was 18 Gy/1.5 fx CSI.