Lymphopenia after whole pelvic radiation

[BruceSF]

To anyone who received whole pelvic radiation:

16 months ago I had HDR brachytherapy followed by IMRT and whole pelvic radiation (WPR), after 7 months of lupron and zytiga (+pred) (I just finished 24 months of lupron+Z).

6 months ago I had a whole blood count (WBC) with differential, and in it I saw an absolute lymphocyte count (ALC) of 250 / uL. The normal range is 1500-3000, and anything under 1,000 is considered abnormal. I did some research, and I found that whole pelvic radiation can cause lymphopenia.

The evidence was in a 2019 paper by Schad et al that analyzed records of patients who had RT, and they found that among those who also had WPR, 60% had lymphopenia, but among those who just had RT only 20% had lymphopenia (ncbi.nlm.nih.gov/pmc/articl...

So, it looks like those of us who had WPR are at risk of lymphopenia, which probably puts us at risk if we get Covid-19. In the Schad study, most of the guys who got lymphopenia only had a mild case (800-1000). Anything under 500 is considered severe, and my reading of 250 was as low as any of the guys in the study.

Also, if you've had WPR, you should be sure to get a shingrix (non-live vaccine) shot for shingles.

I'm wondering if anyone else has lymphopenia after WPR, and how long it lasted. If so I'd like to talk about any steps you're taking to mitigiate your risk. I think I'm going to find a cabin in the woods for the next month or so...

(By the way, I had several perirectal lymph nodes treated, so I'm probably better off if the RadOnc chose to hit the bones instead of the bowels - maybe that's why my lymphopenia was so severe.

(Oh yeah, just to make things confusing, some labs divide the lymphocyte count by 1000, so they would report my absolute lymphocytes in the form .25x10^9/L which is mathematically the same, as 250/uL (250 cells per microliter)).

[timotur]

Bruce: I had the similar treatment (HDR-BT + IMRT, not WPR) and my ALC dropped dramatically also. In August, right after IMRT my ALC had dropped to 274 from 1325 before any radiation back in April. I haven't tested it since, but I'm seeing my Uro next week for a Lupron shot and ask to have it tested. I've eaten a good diet and exercised a lot since then, so will be interesting to see if it improved. I also had a mesorectal node treated during IMRT, and that was my only LN, so that area probably got full coverage. Vit C may help restore the lymphcyte count.

ncbi.nlm.nih.gov/pmc/articl...

What's a little scary is that Lymphocytopenia was present in 83.2% of the patients on admission on extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020

nejm.org/doi/10.1056/NEJMoa...

[BruceSF in reply to timotur]

Thanks for the reply. If you just had the treatment in August it could take a little while for the ALC to come back. I suspect that you had a 'mini' WPR if your RadOnc took out the whole chain that the mesorectal node was on.

I've been concerned by the clinical reports from China also.

There's also a recent article in Lancet

( thelancet.com/journals/lanc... ) that shows low lymphocyte count is correlated with lack of survival in Covid-19 in China.

(The lancet article found another blood marker, D-Dimer (it has to do with clotting), which was an even better predictor)

Let me know please how your next ALC comes out. If it's low, I can tell you about a simple Indonesian folk recipe that seems to have helped me, and it'd be interesting to see if it helps someone else (it's basically red rice cooked in coconut water with tofu on top - sounds pretty simple but an Indonesian researcher irradiated some mice and dosed them with placebo and increasing amounts of the mixture, and the mice that ate more of the stuff recovered lymphocytes faster than the ones that didn't).

Bruce

[timotur in reply to BruceSF]

Bruce: many thanks for the update. Next week, I will post my latest ALC and any comments from the Uro. Hopefully in six months time it has recovered some, but I'm not sure if radiation damage of the CD-4 cells is reversible. Thanks for the tip on the red rice recipe, I'll be sure to try it as we eat tofu about 1x/week. I'm also taking a red-rice supplement to help lower TC. Yes, the IMRT RO mentioned he treated the mesorectal node, but there was debate about whether it was a false-positive because the PSMA scan indicated a SUV of 3.5, right at the minimum threshold, and also because the mesorectal node is not on the typical path of progression, although it's frequency has been documented more recently with availability of PSMA and Aux scans. (I've thought if it were a true positive, it would have been caused by the original biopsy.)

[BruceSF in reply to timotur]

I had 8 perirectal nodes, clearly positive, and I've always wondered if the biopsy might have had something to do with that. It's apparently quite an anomaly!

Anyhow, with that many nodes there was no choice but to do wpr. My RadOnc, Mack Roach, said that not many people would go after perirectals, but he did, and so far I have not had any problems back there, so that's pretty good! If it weren't for Covid-19 I wouldn't have worried so much about the lymphopenia, though I was concerned it might interfere with getting Provenge later if I needed it (apparently for the extraction part of Provenge, you just need a good monocyte count [edit: in previous version I said neutrophil], which I have).

The paper on the red rice (he calls it EMSA eritin) says it helped the mice recover certain CD4 cells: "Furthermore, the number of CD4+ CD25+ CD62L+ T cells in irradiated mice with EMSA Eritin treatment was markedly increased from D1 (lower dose) to D3 (higher dose), respectively (15.03%, 23.94%, 69.68%; Figure 1), compared with irradiated mice. "

journals.sagepub.com/doi/ci...

It's a pretty obscure paper, only cited once since 2015, but it was enough for me to give it a try, since at the time my ALC had been 250.

3 months after the 250 reading, I started eating it for a couple of weeks, and I had a reading: my ALC was 390.

Then, just as a test, I didn't eat any for 6 weeks and then had another blood draw, and my ALC had declined by 60 to 330.

Then I started eating it again for 6 weeks, had another draw a couple of days ago, and my ALC was up 140 to 470, so that's at least consistent with the possibility there's a real benefit. I haven't told Dr Roach about the red rice/coconut/soy, but I'll see him again in June and I'll mention it then, especially if I get back up to 1000.

Bruce

[timotur in reply to BruceSF]

Bruce: I received my labs yesterday, and the ALC rose to 500 from 274 over the last six months, so I was happy to see some improvement, but I'm still a long way from 1173 level before tx, but not too far from the test min of 850. I'm taking a daily red rice supplement and will test again in three months.

Oddly my local Uro (who is only administering Lupron per direction of my MO) said he didn't think (edit: radiation) would lower ALC, and then I thought to myself he's fired when ADT is done by the end of the year if he's not aware of that!

europepmc.org/article/PMC/6...

Another thing is, it looks like long-term ADT has induced macrocytic anemia shown by elevated MCV and low RBC, probably caused by low B-12 from dropping red meat down to 1x/week. Although I eat kale/spinach, I guess I need to add a B-12 supplement to address that.

[BruceSF in reply to timotur]

That’s great about your ALC count, hopefully it’ll be >800 next time. Mine took a year and a half to get back to (almost) 500.

I’m not sure why you think ADT lowers ALC. I think the paper you referenced is about radiation lowering ALC.

Also, my RBC is barely above minimum (used to be below) but my platelet are still low. I take b-12 every day, but I did stop eating red meat. I had a steak about a year ago on my birthday, maybe I’ll switch to one every month...

[timotur in reply to BruceSF]

Oops, meant to say the Uro didnt think "radiation" (not ADT) lowers ALC. Thanks for the feedback on ALC, it just takes some time. Hope we make it through this pandemic without our immune system being challenged.

[Tall_Allen]

A contrary observation:

"In contrast to observations discussed previously,3, 4, 6, 7 our group has demonstrated no significant lymphopenia in 26 patients aged 62 to 86 years (median 73 years) undergoing radiotherapy for high-risk prostate adenocarcinoma.13 In this study, complete blood counts (CBCs) were retrospectively analyzed with differential data on prospectively collected blood samples. CBC data were collected before radiotherapy and at up to 4 time points thereafter (1-90 days, 91-180 days, 181-360 days, and > 360 days), and were compared with normal ranges from an outside laboratory reference (white blood cell [WBC] count, 3800-10,700 cells/μL; absolute lymphocyte count [ALC], 910-4280 cells/μL). Patients received conventional external beam radiotherapy (EBRT) from 64.8 to 81.0 Gy in 1.8-Gy fractions, with a small number receiving brachytherapy. Sixteen patients also received androgen deprivation therapy.

Baseline cell counts were within normal ranges (Table 1).13 Counts decreased in the 3 months after radiotherapy, although median values remained within the normal range. Thereafter, median WBC and then ALC increased gradually to 5800 and 1250 cells/μL, respectively, approximately 6 to 12 months after radiotherapy (Figure 2).13 Thus, median WBC and ALC remained within normal limits for the full follow-up period. These results challenge the view that standard radiotherapy in high-risk prostate adenocarcinoma is immunosuppressive. "

clinical-genitourinary-canc...

I don't know how many of the high risk patients in the Finkelstein study received whole pelvic radiation. According to both studies, there is some recovery after an initial minimum.

Did you ask your RO what was the radiation dose to the various pelvic bones? They should be able to contour around them to some extent.

[BruceSF in reply to Tall_Allen]

Hi TA,

Thanks for finding the Finkelstein study. It's very interesting.

I have to say, though, that I don't think the Finkelstein study contradicts the Schad study. Finkelstein's minimum ALC after radiation in table 1 was 700/uL, but for the whole pelvic radiation patients Schad had a minimum value of 250/uL (which was also my value). So, I don't think Finkelstein had very many WPR patients if at all.

[Edit: Schad had more patients (95 w/o WPR, 36 with) than Finkelstein (around 20), so the min is not really a fair comparison. Nevertheless, I think it's fair to say that Finkelstein was not really powered enough to show an effect, whereas Schad was.]

Since the whole point of Schad's study is that WPR increases the lymphopenia rate from 20% to 60%, it doesn't look like Finkelstein's study really negates this.

The interesting thing is that I don't think RadOncs want to admit that this connection exists. They have been researching prostate radiation for an awful long time, and the Finkelstein study and the Schad study are about the only research on this topic. I have some other papers that advocate for declaring the immune system an 'organ at risk' during radiotherapy, but I haven't seen this advocated for PCa RT.

By the way, I liked the Finkelstein paper a lot - I was kind of hoping that for me the radiation would induce some sort of abscopal effect on any micrometastases I might have outside of the radiation field. Unfortunately, the destruction of my T-cells by WPR made that impossible.

In retrospect, I wish I had asked them to delay the WPR for 6 months after the IMRT so I might have had a shot at an abscopal effect. Since I was node positive and taking lupron and abiraterone(+pred) for 2 years the delay probably wouldn't have mattered, though maybe I would've had to extend the lupron+abi for another 6 months.

Anyhow, thanks for your reply.

Bruce

[Tall_Allen in reply to BruceSF]

I'm not sure you can conclude that none of Finklestein's high risk patients received any pelvic LN radiation -why not ask him? I don't think that you are right that ROs are uninterested. And many would agree that there is much to be learned. However, the bottom line is not the T-cell response (although that is top-of-mind just now), it is whether the treatment is curative.

One interesting observation is that intense hypofractionation (SBRT or HDR brachy) may increase immune response in contrast to IMRT. I know Dr King's high risk protocol involves SBRT to the entire pelvic LN area. It would be interesting to compare the T-cell response of his patients to those who received IMRT to the pelvic LN area, but I don't think they collected that info.

[BruceSF in reply to Tall_Allen]

Maybe I'll ask Finkelstein if they had wpr patients. I suppose I could also ask Dr King if he tracked lyphocyte info. I think the fact that very few WPR studies track lymphocytes is an indication of lack of interest. I asked Mack Roach's research fellow if they were tracking lymphocytes in his gigantic WPR study, and she said he's not. I'm starting to conclude that severe lymphopenia only seems to happen in about 20% of the cases, and usually resolves up to a moderate level in a couple of years, so they just don't worry about it in their treatment plan. (Plus there's the fact that PCa is still 'cold' to immunotherapy (except Provenge), though hopefully that's changing).

Anyhow, thanks for the suggestion to contact Dr. Finkelstein, I hope he answers my email. I'll let you know what he says.

Bruce

[Tall_Allen in reply to BruceSF]

It's true that it isn't a deal-breaker for the therapy.

[treedown]

I had WPR (pretty sure though RO never used that term, mine was 28 pel ic, abdomen, 16 jus prostate) and have Lymphopenia. ALC dropped from 1400 to 221 about a month into RT, the RO said there's no evidence of RT causing this and that maybe it was a combination effect with Zytiga and had me stop Zytiga. I was off it for a approx 6 weeks and ALC went up to 599 but dropped slight right after Lupron shot #3 on 4/1. Started Zytiga again it dropped again yesterday to 472. WBC low normal 4.6 up from 3.6 2 weeks ago. My CD4 T-Cells were low but% was in normal range. I get CBC every 2 weeks now (maybe too often?) . I will try the red rice dish it sounds delicious, I hope making the tofu spicy doesn't negate any benefits.

[BruceSF]

I hope it works for you, let me know. I think you need to eat a certain amount for it to work. I was cooking 2 cups of raw rice in 4 cups of coconut water every week for a while (eating some of it every day), and my alc jumped from 330 to 470. Then I dropped off to just cooking 1 cup every week or two, and it only went up from 470 to 503. For my next 6 weeks I'm going back to cooking 2 full cups of raw rice at least once a week (I leave it in the fridge and nibble away at it over the course of a week), and hopefully I'll break 600 on the next test.

I'm afraid to eat too much because in mice it stimulates the stem cells in the marrow, and if this really works I'm a little afraid of maybe overstimulating them. Hmm, I guess it's time to tell my oncologist about this experiment and see what he thinks.

Bruce

PS I usually use either the silken smooth tofu or the spicy baked stuff, spicy does taste better! Also I've been mixing in chickpeas for some protein, but maybe the tofu has enough protein and the chickpeas are diluting the mixture, so I think I'll skip them this go 'round.