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

Jananie Ramesh JANANIE.RAMESH at phhs.org
Fri Aug 3 21:04:51 CDT 2018


Hello everyone,


Thank you all for your assistance in managing this very unfortunate and complex lady.  It has been a highly interesting case.  Dr. Wysocki, I am starting IVIG on her tonight per your recommendation.  Tomorrow morning, Joseph Frankl and I are signing over the Foster team to Dr. Joseph Obi (resident) and Dr. Justin Holmes (intern); Dr. Cheema will still be attending.  I am cc'ing them both on this thread so they can continue to follow along with the plan.  Please let me know how else I can help!


Best regards,

Jan Ramesh

________________________________
From: Christian Wysocki <Christian.Wysocki at UTSouthwestern.edu>
Sent: Friday, August 3, 2018 5:11:29 PM
To: Sita Bushan; Mingyi Chen; Weina Chen; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: RE: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here


OK thank you Sita, anxious to hear what you guys decide!!



From: Sita Bushan [mailto:SITA.BUSHAN at phhs.org]
Sent: Friday, August 03, 2018 4:55 PM
To: Christian Wysocki; Mingyi Chen; Weina Chen; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



I was told on the phone it had not been signed out yet. Regardless, I will discuss rituximab with the BMT attending in the morning. Thanks.



Sita



Get Outlook for iOS<https://aka.ms/o0ukef>



________________________________

From: Christian Wysocki <christian.wysocki at utsouthwestern.edu>
Sent: Friday, August 3, 2018 4:26 PM
To: Sita Bushan; Mingyi Chen; Weina Chen; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: RE: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



Are we still awaiting path or was Mingyi’s email the path result? I was under the impression it was the result. It sounded to me like they’re saying this is as good as we’re going to get without more tissue, and we’re saying there’s no more tissue to target for biopsy.



Mingyi could you confirm, or are there still things/stains you might do to finalize a diagnosis based on the bone marrow alone?.



If we’re stuck, we need to make a decision about treatment based on the data we have, soon.







From: Sita Bushan [mailto:SITA.BUSHAN at phhs.org]
Sent: Friday, August 03, 2018 4:12 PM
To: Christian Wysocki; Mingyi Chen; Weina Chen; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



I reviewed her imagining, and she has a 1 cm lymph node by her pancreas - I don't think that is suitable for biopsy.



I think neupogen would be reasonable.  I will be on BMT tomorrow, and I will discuss with the attending while we await path.  Thanks.



Sita



________________________________

From: Christian Wysocki <Christian.Wysocki at UTSouthwestern.edu>
Sent: Friday, August 3, 2018 4:01 PM
To: Mingyi Chen; Sita Bushan; Weina Chen; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: RE: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



Heme onc folks what do you think?   I don’t think we have anything to biopsy, and she’s extremely neutropenic.



Should we be thinking about neupogen btw?



From: Mingyi Chen
Sent: Friday, August 03, 2018 3:58 PM
To: Christian Wysocki; Sita Bushan; Weina Chen; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



The bone marrow biopsy IHC shows marked histiocytic infiltrate with mixed T-cells and clusters of large atypical B-cells.  In combination of the flow cytomety finding of Kappa restricted C5-/CD10- B-cells, we are worrying an underlying a B-cell lymphoma.  Biopsy of nodal or liver/splenic lesion may help for final diagnosis.





===========================



Mingyi Chen MD, PhD

Associate Professor of Pathology

Hematopathology

UT Southwestern Medical Center

BioCenter EB3.234A; 2330 Inwood Rd.

Dallas, Tx  75390

Tel: 214-648-4791

Email: mingyi.chen at utsouthwestern.edu<mailto:mingyi.chen at utsouthwestern.edu>

________________________________

From: Christian Wysocki
Sent: Friday, August 3, 2018 3:48 PM
To: Sita Bushan; Mingyi Chen; Weina Chen; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: RE: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



OK, in the meantime, let’s stop the Bactrim, and continue the steroid pulse and anakinra. If we decide to go ahead w Rituxan, based on her dropping IgG level, I would suggest replacement doses of IVIG every 3-4 weeks as well.



From: Sita Bushan [mailto:SITA.BUSHAN at phhs.org]
Sent: Friday, August 03, 2018 3:41 PM
To: Christian Wysocki; Mingyi Chen; Weina Chen; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



Hi Dr. Wysocki,



I actually just got off the phone with pathology, and they are leaning towards a diagnosis of T cell rich/histocyte rich b cell lymphoma.  I think rituxan would be a reasonable consideration for her, but we would need the final pathology, and I would need to discuss with the BMT attending.  Thanks so much.



Sita



________________________________

From: Christian Wysocki <Christian.Wysocki at UTSouthwestern.edu>
Sent: Friday, August 3, 2018 2:52 PM
To: Mingyi Chen; Weina Chen; Sita Bushan; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Dawn Klemow; Ellen Araj; Christopher Parrish
Subject: RE: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



Hi all,

I see the flow report now shows 17% clonal atypical B cells which are CD20 positive.



We don’t (unless heme/onc disagrees) have any nodal targets (even the borderline axillary nodes had shrunken on the CT 7/29, probably due to steroid).



Was the bone marrow hypocellular, I assume?



I am wondering 2 things:

1.       The downward trend in her neutrophils began the day after she started Bactrim ppx.  Seems pretty quick but I was going to suggest we stop bactrim, and use monthly inhaled pentamidine for PJP ppx.

2.       Does the bone marrow path look in any way compelling for B cell malignancy, and should we think about some Rituxan?



-Chris



From: Mingyi Chen
Sent: Thursday, August 02, 2018 8:00 PM
To: Weina Chen; Christian Wysocki; Sita Bushan; Franklin Fuda
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Drew Bird; Dawn Klemow; Ellen Araj
Subject: Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



1. Bone marrow aspirates shows increased histiocytes with occasional hemophagocytosis.  It supports HLH if clinical other creteria fits the diagnosis, but the morphology is nonspecific which can be seen a variety of reactive conditions as well as lymphoid malignancy.



2. Flow cytometry detects minute clonal B-cells.  IHC on bone marrow biopsy is pending.



3. Please check if any lymphadenopathy, or hepatosplenomegaly, if clinically indicated biopsy of nodal or extrondal lesions will help to rule out hematolymphoid malignancy.



===========================



Mingyi Chen MD, PhD

Associate Professor of Pathology

Hematopathology

UT Southwestern Medical Center

BioCenter EB3.234A; 2330 Inwood Rd.

Dallas, Tx  75390

Tel: 214-648-4791

Email: mingyi.chen at utsouthwestern.edu<mailto:mingyi.chen at utsouthwestern.edu>

________________________________

From: Weina Chen
Sent: Thursday, August 2, 2018 6:27 PM
To: Christian Wysocki; Sita Bushan; Franklin Fuda; Mingyi Chen
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Drew Bird; Dawn Klemow; Ellen Araj
Subject: Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



Hi Mingyi,



Would you please update the BM finding in this case?

Thi Tuyet Tran (MRN 71419053), BM18-645?



Thank you!

Weina



________________________________

From: Christian Wysocki
Sent: Thursday, August 2, 2018 6:04 PM
To: Weina Chen; Sita Bushan; Franklin Fuda; Mingyi Chen
Cc: Aena Patel; Arjmand Mufti; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Drew Bird; Dawn Klemow; Ellen Araj
Subject: RE: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



Hi all,

I see a note from the Heme/Onc folks that prelim read on BMBx showed hemophagocytosis…any more info?



From: Weina Chen
Sent: Wednesday, August 01, 2018 6:36 PM
To: Sita Bushan; Franklin Fuda; Mingyi Chen
Cc: Aena Patel; Arjmand Mufti; Christian Wysocki; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu; Jananie Ramesh; Joseph Frankl; Roohi Cheema; Whitney Blackwell; Racha Halawi; Wende Wells; Drew Bird; Dawn Klemow; Ellen Araj
Subject: Re: [Adult-hlh-mas] [External] Re: securemail - possible HLH...previously known to most services involved here



Buddy and Mingyi,

 please see below regarding this BM case, performed today.

Thanks

Weina



Sent from my iPhone

On Aug 1, 2018, at 3:40 PM, Sita Bushan <SITA.BUSHAN at phhs.org<mailto:SITA.BUSHAN at phhs.org>> wrote:

Hi everyone,



I performed the bone marrow biopsy for this patient today.  Thank you.



Sita



________________________________

From: Aena Patel
Sent: Wednesday, August 1, 2018 6:31 AM
To: Arjmand Mufti; Christian Wysocki; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu<mailto:adult-hlh-mas at lists.utsouthwestern.edu>
Cc: Jananie Ramesh; Joseph Frankl; Roohi Cheema; Racha Halawi; Dawn Klemow; Drew Bird; Whitney Blackwell; Ellen Araj; Wende Wells; Sita Bushan
Subject: Re: [External] Re: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here



I’m adding the current fellow (Sita Bushan) to this thread.





Thank you,



Aena Patel, PGY5

Hematology/Oncology Fellow

Pager: 972-229-0781



________________________________

From: Arjmand Mufti <arjmand.mufti at utsouthwestern.edu<mailto:arjmand.mufti at utsouthwestern.edu>>
Sent: Wednesday, August 1, 2018 5:30 AM
To: Christian Wysocki; Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu<mailto:adult-hlh-mas at lists.utsouthwestern.edu>
Cc: Jananie Ramesh; Joseph Frankl; Roohi Cheema; Racha Halawi; Aena Patel; Dawn Klemow; Drew Bird; Whitney Blackwell; Ellen Araj; Wende Wells
Subject: [External] Re: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here



*** This e-mail did not originate from a Parkland e-mail address. If you do not know or trust the sender, do not click on any links in this e-mail, open any attachments, or disclose any sensitive information such as your password. ***

________________________________

Hi Chris,



I saw her on Monday and I totally agree with this plan.  I also agree that she needs to absolutely continue antiviral therapy.



Thanks

Arji



Arjmand Mufti, MD, MRCP (UK)

Assistant Professor
Division of Digestive and Liver Diseases
UT Southwestern Medical Center





________________________________

From: Christian Wysocki
Sent: Tuesday, July 31, 2018 11:43 PM
To: Bonnie Prokesch; Tri Le; adult-hlh-mas at lists.utsouthwestern.edu<mailto:adult-hlh-mas at lists.utsouthwestern.edu>
Cc: Jananie Ramesh; Joseph Frankl; Roohi Cheema; Racha Halawi; Aena Patel; Dawn Klemow; Arjmand Mufti; Drew Bird; Whitney Blackwell; Ellen Araj; Wende Wells
Subject: Re: [Adult-hlh-mas] securemail - possible HLH...previously known to most services involved here



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?



-Chris

________________________________





From: Bonnie Prokesch
Sent: Monday, July 30, 2018 9:27 AM
To: Tri Le; adult-hlh-mas at lists.utsouthwestern.edu<mailto: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.



Bonnie



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.



Best,

Tri Le

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Medical Center



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CONFIDENTIALITY NOTICE This message (including any attachments) is intended only for the use of the addressee(s) and may contain information that is privileged and confidential. If you are the intended recipient, further disclosures are prohibited without proper authorization. If you are not the intended recipient or an authorized representative of the intended recipient, the use, dissemination or reproduction of this communication is prohibited and may be a violation of federal or state law and regulations. If you have received this communication in error, please destroy all copies of the message and its attachments and notify the sender immediately. The Dallas County Hospital District and its affiliated entities hereby claim all applicable privileges related to this information.

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