[Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here

Srikanth Nagalla Srikanth.Nagalla at UTSouthwestern.edu
Wed Aug 1 00:55:12 CDT 2018

Agree with repeat BM biopsy and using Anakinra at this time.


On Jul 31, 2018 11:43 PM, Christian Wysocki <Christian.Wysocki at UTSouthwestern.edu> wrote:

Hi all, sorry I was delayed in getting back to you.

I took a brief look through Mrs. Tran's case.  This certainly seems to have gotten considerably worse in the past week despite 50mg daily prednisone.  I am impressed that she is fevering through that, and am impressed by the extremely high soluble IL2R levels.  Those levels make me concerned for lymphoid malignancy (athough we don't have clear evidence of one). They also make me worried about her prognosis.  Not sure how the HBV is playing into this....I suppose it could be driving T cell activation?...

Given the substantial worsening in her cell counts in the past week or so, I do wonder whether a repeat BMbx is warranted. The first one wasn't entirely normal, with polytypic plasmacytosis and a small clonal B cell population.....perhaps something is declaring itself.  It looks like the axillary nodes on prior CT had shrunken on the recent CT chest, probably related to steroid (which is my concern....she's been on 50mg PDN for a week or so now and I wonder if that will make it tough at this point to get a solid diagnosis, if this is a lymphoma or lymphoproliferative disorder).

That being said, it doesn't look like we have much time to wait.

If a BMBx can get done tomorrow, I think it would be a good idea to repeat. I would also like an IL18 level to be sent to Cincinnati Children's, along with a cytokine panel (same place - have to order them separately).  May help us down the road decide between thinks like Anakinra or Tocilizumab).

My sense is that as soon as the biopsy is done, more aggressive therapies should be initiated.  An extensive infectious eval has been done.....agree with Bonnie that if EBV and CMV have not been repeated they should be before we get more aggressive with treatment.

I don't think she'll do well with etoposide right now with her severe neutropenia.

As we don't yet have clear evidence for malignancy, and there have been concerns about HBV associated autoimmunity/vasculitis driving this, my proposal would be to treat initially with a solumedrol pulse and anakinra, essentially treating presumptively for MAS.  Hopefully that would cool this off, and if the repeat bone marrow does show malignancy, get her to a state where she could tolerate definitive treatment.  I also think we need to continue antivirals while doing this!

What do others think of that plan?



From: Bonnie Prokesch
Sent: Monday, July 30, 2018 9:27 AM
To: Tri Le; adult-hlh-mas at lists.utsouthwestern.edu
Cc: Jananie Ramesh; Joseph Frankl; Roohi Cheema; Racha Halawi; Aena Patel; Dawn Klemow
Subject: Re: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here

Hi Tri,
Thanks for posting this case/alerting us all to the fact that Ms. Tran is back in the hospital. It is definitely a challenging one. I agree with current work up that is going on and feel like other than her known underlying hepatitis B, there is unlikely another infectious component playing a role (and definitely agree with holding off of antibiotic therapies for now especially in light of her prior likely DRESS). That being said, since she has been on high dose steroids for a while at this point, I think it is worth repeating EBV and CMV PCRs in the serum. I will defer discussion about length of immunosuppression and exact treatment to my immunology, heme, and derm colleagues. Chris and Sri, do you think she would be a candidate for etoposide? I wonder, too, if there would be any utility in repeating a bone marrow biopsy.


From: Tri Le <TRI.LE at phhs.org<mailto:TRI.LE at phhs.org>>
Date: Sunday, July 29, 2018 at 2:35 PM
To: "adult-hlh-mas at lists.utsouthwestern.edu<mailto:adult-hlh-mas at lists.utsouthwestern.edu>" <adult-hlh-mas at lists.utsouthwestern.edu<mailto:adult-hlh-mas at lists.utsouthwestern.edu>>
Cc: Jananie Ramesh <JANANIE.RAMESH at phhs.org<mailto:JANANIE.RAMESH at phhs.org>>, Joseph Frankl <JOSEPH.FRANKL at phhs.org<mailto:JOSEPH.FRANKL at phhs.org>>, Roohi Cheema <Roohi.Cheema at UTSouthwestern.edu<mailto:Roohi.Cheema at UTSouthwestern.edu>>, Racha Halawi <RACHA.HALAWI at phhs.org<mailto:RACHA.HALAWI at phhs.org>>, Aena Patel <AENA.PATEL at phhs.org<mailto:AENA.PATEL at phhs.org>>, Dawn Klemow <Dawn.Klemow at UTSouthwestern.edu<mailto:Dawn.Klemow at UTSouthwestern.edu>>
Subject: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here

Hello members of the HLH task force,

My name is Tri Le, one of the first-year hematology fellows covering CUH over the weekend. I am seeing Ms. Thi Tuyet Tran (MRN 71419053) at the request of the Foster Internal Medicine service. I am requesting the assistance of the HLH task force (whom I suspect is aware of this patient) for guidance regarding further workup of alternate diagnoses and consideration of more aggressive HLH-directed immunosuppression vs. macrophage directed therapy in this woman who previously had a possible history of HLH (did truly meet 5/8 criteria: elevated soluble IL2R at 65K, elevated ferritin in the upper 1000s, triglyceride 317, fever, and bicytopenia). However, this diagnosis was brought to question because the labs qualifying her for HLH criteria were not synchronous, she ultimately became relatively clinically well, and had improved with steroids for treatment of DRESS.

This is an unfortunate woman who was previously hospitalized throughout most of June for an FUO workup and progressive failure to thrive. During that hospitalization, she was seen by multiple services (ID, rheum, heme, GI/liver, immunology, dermatology) and underwent extensive infectious and rheumatologic workup that was notable for multiple UTIs (treated) and chronic hepatitis B (on treatment with entecavir). Treatment of these did not yield much in the way of defervescence or functional status. Bone marrow biopsy was pursued and revealed a hypercellular marrow with small monoclonal B lymphocytosis (1.1%) nondiagnostic of malignancy, but no hemophagocytosis. Her bone marrow aspirate cultures were negative. Moreover, she developed a morbiliform rash with eosinophilia suspicious for DRESS. For this suspected DRESS (tenofovir vs cephalosporins), she was treated with high-dose prednisone at 1 mg/kg. With this, her rash improved and fevers resolved. She was then discharged to SNF.

In the interim, she was in the MICU for severe sepsis related presumably to enteritis, from which she recovered with antibiotics and was discharged. She presents again to the hospital after a fall on 7/26/18 but is again found to be progressively pancytopenic with elevated inflammatory markers (ferritin now doubled to 15000), CRP in the 30s (albeit improved from prior when it was in the 70-100s), and intermittent fevers.

She still appears to have some inflammatory process that is brewing and breaking past her steroids. I am still uncertain of what her precise diagnosis is, whether it is HLH or another autoinflammatory condition. We have requested that the primary team resend her  soluble IL2R and ferritin. Moreover, I have asked the primary team to consult immunology and hepatology since I believe that this is a primary dysregulation of her inflammatory system with possible interaction with her chronic hepatitis B. That said, we are all somewhat uncertain and hope that this task force has familiarity with her case and further insight.


Tri Le

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