acute GVHD and pancytopenia post transplant

[Wife of Diver Down]

Hello all,

I finally have my own log in. My husband age 58 high risk MDS with complex cytogenetics was admitted on 2/14 for conditioning (happy valentines day) He had myeloablative conditioning with Fludarabine/Busulfan/ATG MUD 10/10 donor on 2/21 and is now D +33. There was a lot of debate about proceeding with transplant initially as he was not in remission and had a blast count of 14%.] Because of his poor cytogenetics and his good performance status they thought it best to proceed directly to transplant rather than proceeding with 7+3 induction and compromise his performance status.

On 2/21 he received the stem cells from a 10/10 donor. That evening he had a fever over 105.3 requiring ice baths. (Torture he calls it) No infection was found but of course he was on antibiotics pending negative cultures. It was thought to be related to ATG. He received steroids for 2 d and fever resolved. He ultimately recovered from that. His Nadir ANC was never less than 200 but was started on Neupogen on D2 which is standard for this center. On D +11 he engrafted and developed recurrent fever and rash ? engraftment syndrome vs acute GVHD. His total white count 3.4 Hgb 9.8 (good for him unsupported) platelets 150K He was discharged and then 1 d later had low grade fevers followed by rash >50 % of his body no blisters no diahrrea no LFT abnormalities. They decided to treat topically and hold on steroids but when fevers persisted after 5 d steroids were started at 2 mg/kg/d and Posaconozole and Pentamadine for prophylaxis was started Fevers resolved within hours and he has remained afebrile with improvement of rash. On Monday his Prednisone was tapered to 1.5 mg/kg but on Monday was found to have increased ALT/AST- 220/85 with normal Bili. They thought Posoconozole may be responsible so they held that 2 d ago, Also all his counts have declined and he required 2 U PRBC yesterday for Hgb of 7.5
Today LFT further increased with ALT/AST 341/130 Alk phos 150 and T Bili 1.4;
Further decline in Plat 44K ; WBC had declined but is stable for the last 2 d WBC 2.4

I am very worried about acute GVH;
Could this be the cause of the low counts as well?
Remarkably he feels better today than he has for the past week
Any input appreciated.

[Cheryl C]

I can't help with your question regarding GVH but just want to say I'm really sorry that your husband has been having such a hard time post transplant, and I pray that things will improve for him from here on.

[dfantle]

Hello, I'm so sorry to hear of your husbands challenges. Unfortunately I'm also not sure of the answer to your questions. If your husband is in an experienced transplant center I'm hopeful they can advise if this is GVHD and how to manage appropriately. In Seattle, one of the medications used post transplant to protect the Liver from GVHD is Ursodiol, though I had AA & I'm not sure if its used for MDS as well.

If he's still receiving neupogen, it is possible this may be taking some of the energy away from his red cell & platelet production which might explain these lower counts & why some centers don't use it close to transplant.

Antibiotics can also impact blood counts.

Wishing you all my best. This is the most challenging time until his counts improve.

[Wife of Diver Down]

Thank you for your support. This is such a complex process. Tonight we learned that he has a resurgence of EBV - the virus that causes mono. His CMV is negative but he is positive for EBV DNA by PCR which is 40,000; they are going to coordinate infectious disease consult next week ...I wish the consult was now but seems like nothing happens on a weekend. They are keeping the Tacrolimus level on the low end but not tapering the steroids further - a hard balance in treating the GVHD of his skin but limiting further immunosuppression which would worsen the EBV.
Does anyone know if there is treatment specific for the EBV and what the risks are??

[sstewart09]

My husband had reactivation of EBV early in the transplant process. He did not have any GVHD, so they immediately reduced his tacro and eventually took him off of it for a few weeks. He also had 4 rounds of rituxan, 1 dose a week, and that did the trick. Rituxan is a type of chemo and can have some nasty side effects (so they'll premed for it) because it's derived from mouse DNA. This did the trick for him, but there are other options if it doesn't work.

[DanL]

I did a little bit of research on this, not thorough - but it looks like Rituxan has been used in later EBV infections quite successfully in transplant patients. I thought that there was another anti-viral drug that they were using as well, but the name and the article are escaping me.

I am sending prayers your way.

[Heather8773]

Not sure if I'm answering correctly but .. My husband was positive CMV his donor was neg for CMV so they are watching him closely for flare ups. Shortly after transplant they were not happy w his (CMV levels?) so they switched his antiviral from valtrex to acyclovir. That knocked those levels back into place then they waited a couple more months before switching back to valtrex. All these antiviral/anti fungal /antibacterial meds affect the blood counts. He had some liver issues that looking back we think were low GVHD (they told us that back then but we/I refused to accept) he takes ursodiol for the liver now and that has helped tremendously. God bless. Words give life. I'll be praying!!

[Wife of Diver Down]

Dan L - Thank you for the both the info and the prayers; I hope you are doing well and counts continuing to improve.

Heather8773 Thank you for sharing your husbands experience.

Since my last post he had another EBV PCR done but results are pending- Urso was restarted and his liver tests are improving; Bili, Alk phis AST are normal and ALT is about 200; since no treatment specific for EBV was given they feel the EBV is likely not the culprit here;

Unfortunately the GVHD now involves about 80% of his body with rash or severe redness; no blisters fortunately and no open areas at all; Since the steroids did not control this they started on photopharesis - does anyone know much about it? They say they are trying this because they want to try to get him off steroids since his bone marrow biopsy D+30 shows persistent disease and they want to try and get as much GVL effect as possible.

The other problem now is he is in constant discomfort. He has other burning, itching, tightness , tingling or just pain all over the skin of his body. He can hardly tolerate anything touching is skin making sleeping nearly impossible -oxycodone, ativan atarax and topical steroids and aquaphor are of marginal help -

Does anyone know of anything that can help the pain/sensitivity associated with acute GVHD of the skin?

[DanL]

Here is the slightly technical version of what photopheresis is supposed to do:

"In medicine, photopheresis (aka extracorporeal photopheresis or ECP)[1] is a form of apheresis and photodynamic therapy in which blood is treated with a photosensitizing agent and subsequently irradiated with specified wavelengths of light to achieve an effect. Specifically, buffy coat (WBC + platelets) is separated from whole blood, chemically treated with 8-methoxypsoralen (instilled into collection bag or given per os in advance), exposed to ultraviolet light (UVA), and returned to the patient.[2] Activated 8-methoxypsoralen crosslinks DNA in exposed cells, ultimately resulting apoptosis of nucleated cells.[1] The photochemically damaged T-cells returned to the patient appear to induce cytotoxic effects on T-cell formation. The mechanism of such “antitumor” action has not been elucidated."

It is a good tool, and I have heard of good results from some patients locally.

I think that in addition to the oxycodone, maybe being on a continuous drip of Fentanyl (sp?) with on-demand features may be of use in dealing with the pains and discomfort your husband is experiencing. This combo seemed to help me quite a bit for a few days that it was needed.

Other possible options that i have seen out there is treatment with Campath, Rituxan, and other targeted chemo drugs to reduce the severity of attack while not completely destroying the donor marrow.

[sbk007]

Wife of Diver Down, I'm sorry your husband is having these issues and hope he overcomes them. Where did your husband have his BMT?. Protocols are different.. Some might use morphine, some what Danl said. photopheresis in layman's terms means blood is irradiated/exposed to light with specific wavelengths then returned to the patient.

Photopheresis is currently standard therapy approved by the U.S. Food and Drug Administration (FDA) for cutaneous T-cell lymphoma. Evidence suggests that this treatment might be effective in the treatment of graft-versus-host disease, though this evidence is largely observational and controlled trials are needed to support this use.

I wish you and your husband all the best

[Cheryl C]

I've heard that Emu Oil can be very soothing. You could do some web research on this.

[Wife of Diver Down]

Thank you all for your responses. The doctors here were trying to taper the steroids and keep the Tacrolimus level low in hopes of a possible GVL benefit. Unfortunately the skin GVH was getting more severe and exfoliation followed; 10 d ago it began to involve his oral mucosa and lips - unable to eat. He was therefore readmitted last week and started on IV steroids - Solumedrol 40 mg twice daily and the Tacrolimus increased to get his level up to 12. He responded well and is now eating 2300 calories a day and his skin though still severe is significantly improved. He is looking much better and felt well enough to get out of bed and walk in the hall of the unit today. Unfortunately this treatment has compromised the underlying persistent MDS and he is now requiring very frequent platelet and RBC support. I don't know where to turn or what to do- The team here is afraid to add Vidaza or other chemotherapy for fear of placing him at higher risk of infection and risk of aplasia. I don't know where to turn.

I love him so... we just "celebrated" our 29th anniversary last night...

[Relentless Against SAA]

I want you to know that I am deeply sorry your husband is having a difficult time. Please know that you and your husband are in my prayers. I am praying for you right now.

[DanL]

Sometimes even a little progress is great progress. We are all rooting for you and your husband to win this battle.

Congratulations on your 29th anniversary. That is good reason to celebrate.

[Cheryl C]

I wonder if this might be of assistance for the oral GVHD?

http://www.express.co.uk/life-style/...-survive-chemo

Thinking of and praying for you and all on the forum who are suffering aftereffects of chemo and transplantation.