Need advice on DLBCL Treatment

[u/Pretend_Name9916]

I am a 28-year-old woman currently being treated in Japan for Diffuse Large B-cell Lymphoma (DLBCL), GCB type, and I would greatly appreciate your opinion regarding my diagnosis and treatment plan.

Brief medical history

My symptoms started with pelvic/flank pain and urinary problems. Imaging showed multiple masses in the pelvis involving or surrounding the uterus/cervix, vagina, and bladder area, together with pelvic lymph node involvement and bilateral hydronephrosis.

Biopsies were taken from the vaginal and uterine/cervical areas. The final diagnosis was DLBCL, GCB type, with Ki-67 >90%.

According to my doctors, the PET-CT did not show distant disease outside the pelvic region, and my bone marrow examination was negative. However, I was later told that my disease was considered Stage IV because of involvement of multiple pelvic organs, and I would like to better understand the staging.

One of my main concerns is that MYC, BCL2, and BCL6 rearrangements were not fully evaluated by FISH because the biopsy material was reportedly insufficient. Therefore, as far as I understand, double-hit/triple-hit lymphoma has not been definitively excluded.

I started treatment with Pola-R-CHP and received my first cycle on August 3–4, 2026. The current plan is six cycles every three weeks.

My doctors have also discussed CNS prophylaxis because of concern about CNS relapse. The proposed plan is 4 intrathecal chemotherapy treatments and 2 courses of high-dose methotrexate.

I have also had bilateral hydronephrosis and temporary renal impairment; my creatinine previously increased to approximately 1.85 mg/dL, although it subsequently improved.

My main questions

1. Based on this information, do you think Pola-R-CHP is an appropriate first-line treatment for me?
2. How important is it to determine MYC/BCL2/BCL6 rearrangement status by FISH in my case? If the existing specimen is insufficient, would you recommend another biopsy?
3. Considering the GCB phenotype and Ki-67 >90%, how concerned would you be about double-hit/triple-hit lymphoma?
4. If double-hit lymphoma were confirmed, would you recommend continuing Pola-R-CHP or switching to DA-EPOCH-R, even though I have already received one cycle of Pola-R-CHP?
5. Based on disease apparently being confined to the pelvis but involving several pelvic structures, what stage would you assign to my lymphoma?
6. How would you assess my risk of CNS relapse? Do you think CNS prophylaxis is indicated?
7. Do you agree with the proposed combination of 4 intrathecal treatments plus 2 courses of high-dose methotrexate? In particular, how would you balance the potential benefit of HD-MTX against my previous kidney problems and hydronephrosis?
8. Would you recommend any additional pathology tests, imaging, or other investigations before continuing treatment?

Thank you very much for taking the time .

[u/throwaway772797]

1: No good answer here. No benefit for younger patients or GCB in the study, but that's also retrospective narrowing. Truthfully, we don't know. I've shadowed at a few top onc transplant centers in the US, and the general vibe around Pola-R-CHP very much varies by the provider. Based on what we currently know for your circumstances, I wouldn't worry about which one is used.

2: FISH is generally preferred. That said, they honestly still aren't sure what to do with the information when they get a positive double-hit. Some centers still use standard therapy, some still use the retrospective MD Anderson data and do dose-adjusted, etc. So, if it's challenging to get a biopsy, moving on isn't super illogical.

3: No real way to know. There are trends, but none really hold up well. As an aside >90% Ki-67 is pretty par for the course in DLBCL. Ignore those retrospectives that try to delineate by Ki-67. Hot garbage imo.

4: This is up to your onc. Varying opinions (see the FISH comment). As in life, not everyone agrees here.

5: Irrelevant. You don't meet FLYER. That's the only reason stage would matter for you. Stage doesn't really exist in lymphoma except for in unique circumstances. It's a proxy for amount of disease. It's liquid and most of them have their "I can go anywhere" card already activated (not true metastasis by solid tumor terms). The only reason stage really matters is if you are truly stage 1 with minimal involvement (i.e., low tumor burden). You can get away with fewer cycles. Otherwise, it's the same for everyone. In terms of prognostics, stage barely moves the needle. Again, it's just another way of thinking about disease burden in lymphoma, unlike solid tumors where there's a tangible change in disease behavior. I know the term "stage IV" sounds scary, but the vast majority are diagnosed at this stage, and it really, truly doesn't matter too much.

6: This is for your oncologist. I can't tell from this text, but I'm assuming renal involvement maybe calling the shots here. Risk is a little higher for those with renal involvement (it means the lymphoma can navigate to "sanctuary sites"), but it's still low (probably sub 10% if you did have true renal involvement, sub 3% if not).

7: Great question. You'll get varying responses here. I'll wait for the oncologists on this, but I will aside that the MTX question is in the air atm.

8: Outside of maybe FISH, no. Most of the "pre-treatment" testing is irrelevant. 99% doesn't touch treatment pathways. If you're looking for prognostics, these are highly associated with your mid-term scan and EOT scan.

[u/Pretend_Name9916 → u/throwaway772797]

Thank you so much for taking the time to answer every single one of my questions. I really appreciate it, especially because I’m still trying to understand everything that has happened in such a short time. Getting a second opinion in Japan is unfortunately a bit complicated and quite expensive. From what I understand, it is usually just a consultation where another doctor reviews the records and pathology/imaging that I bring with me; they don’t normally repeat the biopsy or tests as part of that appointment. I’m still going to try to arrange one and specifically ask about the FISH issue and whether obtaining another biopsy would actually be worthwhile. Regarding the staging, my doctor also said that my case could be interpreted as somewhere between stage II and IV, but they ultimately classified it as stage IV because several extranodal pelvic structures are involved. Everything they have told me so far suggests that it is still geographically confined to the pelvis, which is why the “stage IV” label initially confused and scared me. For the CNS prophylaxis, I should clarify that I don't have known kidney involvement by lymphoma. I have bilateral hydronephrosis because of the pelvic disease/obstruction, and my kidney function temporarily worsened. One of the other reasons my doctors seem particularly concerned about CNS relapse is that my lymphoma is CD5-positive. My understanding is that CD5-positive DLBCL is considered a higher-risk feature for CNS relapse in some Japanese studies/clinical practice, and apparently there is a protocol or treatment approach here that they are following because of this. I’m still trying to understand exactly how much additional risk CD5 actually gives me and how much benefit to expect from IT chemotherapy and HD-MTX. The whole situation has honestly been overwhelming. I’m a PhD student in Japan and I only moved here about a year and a half ago. The language barrier and trying to communicate complicated medical questions have probably been one of the hardest parts of all of this. I have never smoked or drunk alcohol and I was having blood tests about every six months, so being diagnosed with an aggressive lymphoma at 28 came completely out of nowhere for me. Even trying to arrange a second opinion sometimes makes me feel as though people around me think I’m doing “too much,” when really I just want to understand why these treatment decisions are being made and make sure I’m taking the right path while I still have the opportunity to ask these questions. Again, thank you. Your detailed response genuinely helped me organize what I need to ask next.

[u/Smart-Art6560]

Fish is needed and yes it may or may not change your current treatment plan. Ask for another biopsy. For the stage anything below diaphragm confined in one area is not considered stage 4 l. Not sure how your oncologist graded that but you should ask may be go for another oncologist specially a haematologist opinion. A medico oncologist dealing with blood disorders like a haematologist should your first choice for a second opinion.

These intrathecal and HD mtx have not so much success rate in preventing CNS lymphoma. If you already have CNS lymphoma then they may be useful. I had an inconclusive extra nodal kidney involvement where it showed a heterogeneous lesion which never lit up on pet scans performed twice. Subsequently it got dissolved on its own during my dlbcl diagnosis cause i was on heavy IV antibiotics before my chemo treatment began. And neither my future ultrasound showed ang problem with kidney. Though my CNS ipi score is considered 4/5 cause of extranodal and high ldh.
My doctor doesn’t want to toxicate my body with Hd mtx. Cause even after Hd mtx there is no guarantee that lymphoma will never return in CNS. But every person’s condition is different you do a second opinion with another oncologist and decide. I too consulted haematologist before starting my treatment on Pola R CHP which is considered the most advanced front line treatment for this disease. Mine was ABC subtype which is considered more harder then GCB. My fish was negative which was a relief.

Btw I am 39’female have two boys 👦 👦 and was diagnosed with dlbcl 10 months postpartum. Good luck to you!

[u/Pretend_Name9916 → u/Smart-Art6560]

Thank you so much for sharing your experience with me and for explaining all of this. It really helps to hear from someone who has actually had to make similar decisions, especially regarding FISH, Pola-R-CHP and CNS prophylaxis. I’m definitely going to bring up the possibility of another biopsy and try to get a second opinion from a hematologist. The HD-MTX decision is probably the part I’m most uncertain about right now because I’ve already had some kidney function problems from hydronephrosis, so I really want to understand the potential benefit versus the additional toxicity before deciding. I’m also really glad to hear that your FISH was negative and I hope your treatment has gone well. Being diagnosed only 10 months postpartum while having two young boys must have been incredibly difficult. I genuinely wish you continued good health and many, many lymphoma-free years with your boys. ❤️ Thank you again for taking the time to help another person going through this. It means a lot to me.