Elevated LDH

[leahleah]

Hello, I haven’t posted before. My 44-year-old husband was diagnosed 2 years ago. He has been in watch and wait. We just met with his oncologist. His other blood counts are relatively stable, just increasing at a low rate. But his LDH has steadily increased the last 3 tests and is elevated. His oncologist recommended a CT scan and repeat staging testing if it goes up again in 3 months. How concerned should I be? I have read that consistent elevated LDH may indicate Richter’s or increased CLL activity. I would love some more information. Thanks.

[AussieNeil Partner Administrator]

Good on you for posting to find out more about what could be happening with your husband's health.

LDH (lactate hehydrogenase), is useful as an independent measure of CLL activity, because it's in a much higher concentration in your body cells than in your blood serum. So it can increase when there is a large amount of cell death (apoptosis) which correlates with a high tumour burden. Importantly, because Richter's Transformation (RT) is an aggressive lymphoma, if CLL has transformed to RT, the increase in LDH is typically, (but not always) several times the earlier baseline level. Also, because RT is aggressive, you typically feel very unwell. How does your husband feel?

I note that you live in the USA and your husband is seeing an oncologist. Typically oncologists don't see that many patients with CLL, as they primarily deal with common solid tumours. That your husband's oncologist has only asked for a review in 3 months indicates that they don't think your husband is likely to have RT, just slightly more active CLL. This would be a good time to seek out a CLL specialist, just in case your husband is approaching the need for treatment. CLL Society both offer one free video consult with a CLL specialist and maintain lists of CLL specialists. Here are the relevant links:

Expert Access to a CLL specialist

cllsociety.org/programs-and...

CLL doctor lists

cllsociety.org/newly-diagno...

Neil

[leahleah in reply to AussieNeil]

Thank you for the information. We have a local hematologist/oncologist as well as a CLL specialist, who we see on an annual basis. The specialist lives in a different area and is known in the CLL society (which we follow). They work a lot together, especially once it’s time for treatment.

My husband doesn’t feel unwell. He has more fatigue but he still exercises a lot. We live in Oregon and enjoy all the outdoor activities. He does not have any visible large nodes, they come and go and are on the smaller side, no drenching night sweats (though he does have night sweats). I will check the LDH numbers but I don’t think it has quite doubled in these 9 months though it may be close.

Essentially, with the LDH increasing at a noticeable amount each 3 months, it could mean the CLL is more active than we think? Even if the WBC and ALC are not increasing at the same rate? By repeat staging, would that be another flow cytometry or just a scan?

[AussieNeil Partner Administrator in reply to leahleah]

LDH is useful as a measure of the total tumour burden (lymphocytes in blood, in nodes (including the large, specialised spleen), bone marrow) and perhaps other organs. Other blood tests, such as B2M, can also be used to assess how active the CLL tumour is. CLL is very heterogeneous and where the CLL tumour most concentrates, its distribution and how its activity can change over time is different for all of us. ALC (absolute lymphocyte count) is a measure of one of the 5 different blood cell types that in total, adds up to your White Blood Cell count. Just concentrate on the ALC changes and neutrophil count changes (a measure of infection risk - lower correlates with higher risk of infection.

If your husband's oncologist is looking at doing a repeat staging, I'd recommend you bring forward your husband's CLL specialist appointment. Your husband's oncologist is more likely to schedule a CT scan, because oncologists usually don't have the experience with CLL patients to be able to assess how the CLL is going. A CLL specialist gets a good feel for what's happening with rarely the need for exposure to additional radiation.

Neil

[InFlorida in reply to AussieNeil]

I’m surprised by your Oncologist comment. I was diagnosed with CLL by a Denver Oncologist last December. I was in the midst of moving to FL so he referred me to another Oncologist for treatment. What makes you say that they typically only treat solid tumors?

[AussieNeil Partner Administrator in reply to InFlorida]

What I actually said was "Typically oncologists don't see that many patients with CLL, as they primarily deal with common solid tumours." In general, when you have CLL, you'll understandably get the best CLL management from someone who primarily sees CLL patients, then a haematologist specialising in blood cancers, then a haematologist-oncologist, then finally an oncologist. CLL is classified in the USA as an orphan disease, so oncologists are naturally unlikely to have many blood cancer patients in their clientele.

Neil

[InFlorida in reply to AussieNeil]

Thank you for the clarification. Have a good day, R

[HopeME in reply to InFlorida]

Read my posts about how treatment by a general oncologist, even a very experienced one at a world class hospital, can lead to suboptimal treatment selection. If it is possible for you to be seen by a CLL Specialist it is well worth the effort.

Best,

Mark

[leahleah in reply to HopeME]

Hi, thanks for responding. Yes, he has a CLL specialist. We see the specialist on an annual basis. He works with our local hematologist. He would be the one to determine his treatment regimen.

[Newdawn Administrator]

I’m wondering if your husband does a lot of exercise Leah because intense exercise can cause the LDH to rise. Use of aspirin too can apparently be implicated.

My LDH was always elevated during my W&W period of 7 years and I used to spook myself about this. Interestingly, raised LDH levels are more prevalent in Trisomy 12 patients and I’m a Tri12. Has your husband had a FISH test done? Does he know his biomarkers?

Our LDH levels do elevate as the CLL progresses but as Neil says, make sure you have a CLL specialist who understands and doesn’t over react to this phenomenon. A RT transformation would be very unusual at this stage and there would be other indications which he doesn’t appear to have but it’s good that his specialist is being mindful of all possibilities.

Wait to see how it trends and don’t be spooked by google searches which can induce unnecessary fear.

Best wishes,

Newdawn

[leahleah in reply to Newdawn]

Thank you. The Google search did me in and I had to stop. We have 2 children and I can get overwhelmed because my husband is so young. 9 months ago, he was still in the high normal for LDH and it has increased every 3 months. 6 months ago it went above normal. His hematologist did say he would get a Ct scan to be sure he wasn’t missing soemthing…but then I started reading and had more questions.

We did the FISH testing and I don’t think he was Tri12.

Thank you!

[Fowey2009]

Hello

I am sorry that you have this worry at the moment.

Last year my husband had a RT (Hodgkins) so I just looked up his LDH levels. Interestingly they decreased as he progressively became ill-er with RT. They dropped from 224 to 131 at his lowest point before treatment. Following treatment they increased to 234. (Levels may be reported differently in Uk).

Of particular concern was his CRP marker which went up from 10 to 253 (dropped quite quickly on treatment). He is now very well.

All the very best - I hope you get some answers soon.

Beryl

[leahleah in reply to Fowey2009]

Thank you

[thompsonellen2 in reply to Fowey2009]

Glad he's doing so well!

[Big_Dee]

Hello leahleah

I am not a doctor but have went though about the same thing. I had a CT scan a year ago and had massive bulky lymph nodes in abdomen with WBC of 42K and LDH of 275. The bulky nodes were a sign of possible Richter's Transformation. I went to my consultant CLL Specialist and he said LDH was too low for RT and to have PET scan before doing biopsies. I did not have any visible lymph nodes and no RT. My CLL is very aggressive and required treatment in 14 months after original diagnose. I am now finishing V&O treatment and have distended stomach again so will have PET scan again monday to check for RT. Blessing hope you can get CT scan sooner to put your mind at ease. Blessings.

[SeymourB]

leahleah -

I was diagnosed back in January, 2011, and this year started treatment. I keep all my test results in spreadsheet. As others mentioned, LDH goes up and down. Also note that different labs have different ranges, and the values might not be exactly comparable.

Date LDH U/L min max

4/20/2011 211 U/L 120 250

9/22/2011 184 U/L 120 250

1/26/2012 201 U/L 120 250

9/25/2012 183 U/L 120 250

3/21/2013 256 U/L 120 250

9/24/2013 216 U/L 120 250

4/01/2014 230 U/L 120 250

10/1/2014 181 U/L 120 250

3/31/2015 205 U/L 120 250

5/16/2016 234 U/L 121 224

11/16/2016 188 U/L 129 250

4/27/2017 196 U/L 120 250

10/23/2017 239 U/L 120 250

7/12/2018 194 U/L 120 250

10/25/2018 315 U/L 87 241

12/11/2018 313 U/L 87 241

7/22/2019 251 U/L 120 250

1/10/2020 321 U/L 113 226

7/31/2020 313 U/L 87 241

2/01/2021 388 U/L 87 241

7/21/2021 407 U/L 125 220

1/28/2022 420 U/L 120 250

5/12/2022 344 U/L 120 250

8/08/2022 586 U/L 135 225

11/15/2022 527 U/L 135 225

2/14/2023 496 U/L 135 225

Started treatment on 2/21/2023

2/21/2023 471 U/L 135 225

2/22/2023 421 U/L 135 225

2/22/2023 819 U/L 135 225

2/22/2023 1029 U/L 135 225

2/23/2023 1532 U/L 135 225

2/23/2023 1701 U/L 135 225

2/23/2023 1559 U/L 135 225

2/24/2023 1215 U/L 135 225

2/28/2023 356 U/L 135 225

3/07/2023 235 U/L 135 225

3/08/2023 214 U/L 135 225

3/17/2023 168 U/L 87 241

3/21/2023 180 U/L 135 225

3/28/2023 196 U/L 135 225

4/04/2023 185 U/L 135 225

4/11/2023 181 U/L 135 225

4/18/2023 181 U/L 135 225

5/02/2023 169 U/L 120 250

5/16/2023 160 U/L 135 225

5/30/2023 154 U/L 120 250

6/13/2023 184 U/L 135 225

6/28/2023 151 U/L 120 250

7/11/2023 177 U/L 135 225

7/25/2023 192 U/L 120 250

8/07/2023 201 U/L 135 225

8/22/2023 151 U/L 120 250

8/24/2023 138 U/L 120 250

9/05/2023 215 U/L 135 225

9/20/2023 150 U/L 120 250

10/3/2023 193 U/L 135 225

10/17/2023 162 U/L 120 250

I'm still on treatment. I inished Obin on 7/12/2023. Now still on Pirtobrutinib + Venetoclax. I get LDH and other tests every 2 weeks since about April.

You can see the LDH progressively increased, with some dips over the years. I haven't done the actual correlation with ALC or anything else, but ALC and other tests dipped less dramatically until November just before treatment, when ALC went up and down more than 25%.

I visited Dr. Philip A. Thompson at M.D. Anderson on 8/8/2022 for a workup due to increasing fatigue and a growing parotid lump on the side of my face - not the usual place for a lymph node. I'm Trisomy 12, IGHV unmutated, and have NOTCH1 and BLC2 mutations. Because of the lump, he was concerned about a possibly Richter's Transformation. I had a PET/CT done, peak SUV 4.6 in spleen, and a core biopsy of the lump, which showed only CLL. But we decided I was a good candidate for the trial. Sadly, Dr. Thompson moved back to Australia in January, 2023.

I think it's not unusual to get a CT just before treatment. If the oncologist is really worried about Richter's, they order a PET/CT and a biopsy of whatever node is expanding quickest.

The NCCN CLL Guidelines nccn.org/professionals/phys... (patient accessible with free patient account) recommends for Richter's :

"DIAGNOSIS

ESSENTIAL:

• Excisional biopsy, if lymph node is accessible. Biopsy the lesion with highest standardized uptake value (SUV) on PET scan.

• FNA biopsy alone is not suitable for the initial diagnosis of histologic transformation. In certain circumstances, when a lymph node is not easily accessible for excisional or incisional biopsy, a combination of core needle biopsy and FNA biopsy in conjunction with appropriate ancillary techniques for the differential diagnosis (ie, IHC, flow cytometry) may be sufficient for diagnosis.

• Hematopathology review of all slides with at least one paraffin block representative of the tumor. Bone marrow aspirate with biopsy can be pursued if lymph node biopsy material is nondiagnostic.

 Diffuse large B-cell lymphoma (DLBCL): Sheets of confluent large B cells that are not part of a proliferation center are sufficient to diagnose a Richter’s transformation to DLBCL. [a,b,c]

 Classic Hodgkin lymphoma (CHL): Rare transformation to CHL demonstrates large Reed-Sternberg (RS) cells that express CD30, CD15, and PAX-5 but lack strong, uniform CD20 and CD45 (also lack co-expression of both OCT-2 and BOB.1). The background lymphocytes in those CHL cases are CD3+ T cells with a varying degree of admixed eosinophils, histiocytes, and plasma cells. [d]

• Molecular analysis to establish clonal relatedness between CLL and DLBCL cells [e]

USEFUL UNDER CERTAIN CIRCUMSTANCES:

• FISH to detect +12; del(11q); del(13q); del(17p)

• CpG-stimulated metaphase karyotype for CK

• TP53 sequencing

[a] While occasionally an increase in proliferative rate can be shown with Ki-67, this is not considered diagnostic of a transformation.

Proliferation centers in CLL may express c-MYC and/or cyclin D1. This does not change the diagnosis.

[c] First, "CLL with expanded proliferation centers” or “accelerated CLL” may be diagnosed in cases where proliferation centers in CLL are expanded or fuse together (>20x field or 0.95 mm2) AND show Ki-67 proliferative rate >40% or >2.4 mitoses/proliferation center. Second, progression to "CLL with increased prolymphocytes” (CLL/PL) may occur when there are increased prolymphocytes in the blood (>10% to <55%). Neither of these findings should be considered a transformation event, but rather as progression of CLL. B-PLL should be reserved for the diagnosis of de novo leukemias that are not associated with CLL.

[d] If morphologic RS cells are identified but the background cells are still the B cells of CLL, an EBV stain such as EBER should be performed. EBV infection of CLL can produce RS-like proliferations, but the background cells are still CLL and not the reactive mix typically seen in Hodgkin lymphoma. These cases should NOT be considered a Richter’s transformation event.

[e] Immunoglobulin gene rearrangement studies of CLL and histologically transformed tissue may be performed to establish the clonal relationship."

=seymour=

[leahleah in reply to SeymourB]

Thank you. Yes, his other tests have had ups and down but the last 3 LDH tests have all increased.

[SeymourB in reply to leahleah]

leahleah -

The LDH increased from what to what?

I was above normal from 2018 to 2023, and generally increasing.

=seymour=

[leahleah]

I think it is around 260. And if it increases at the rate it has been then it will be over 300 at the next test in 3 months.

[thompsonellen2]

Glad you found this community. I was diagnosed when I was 47 and had a 16 year old so I understand your emotions. It's great your husband doesn't have the TP53 mutation (which I do). I looked up what my LDH was when I started treatment in 2016 and it went from 533 in March to 1083 in June 2016. I went from feeling fine to barely being able to climb the stairs. I never had a CT scan prior to diagnosis (but I have had plenty as part of my current trial). I did have a lymph node biopsy and a FISH test. There was no discussion of staging and I am lucky enough to see a top specialist. I have been in continuous treatment since 2016 (thank you TP53) and am in my second clinical trial and on my way to a third at some point. The way I deal with this is I try to live my best life between my 3 month visits and do my best not to think about it after I take my pills every day. At some point your husband will need treatment and I hope that is years away. If he's like most of us, he'll take a few pills, do great and have years until he needs to think about it. Of course this isn't an ideal situation to be in, but it sounds like he has a great family and a wonderful support system in you, so he'll be ok.

[Justasheet1 in reply to thompsonellen2]

Ellen,

You always do a great job of sharing your knowledge and experiences as you have with me a few times over the years.

God bless and good health to you.

Jeff

[leahleah in reply to thompsonellen2]

Thank you.

Did you have any concerns about your immune system while on treatment with a teenager in the house? We will likely be in that same boat with 2 teenagers bringing home all the germs..

I hope this trial is going well for you. Each year there seem to be better options for treatment.

[thompsonellen2 in reply to leahleah]

Slightly concerned but I really was pretty healthy until this year. (I got hammered with a sinus infection and recurring pinkeye. The later took months to properly diagnose.) But I still worked through it.