Thursday, September 20, 2018

Autologous Graft Vs Host Disease

Epilogue: a piece of writing at the end of a work of literature, usually used to bring closure to the work. 

I have lovingly referred to my journey post HSCT as my epilogue. It marked the seeming end of a complicated medical journey and provided the miracle of closure to the most difficult time of my life. However, I have recently learned that life, similar to works of music or literature, often experience a reprise. A moment where you learn that there was in fact no period as you thought, but a semicolon. While one part of your story had ended, another was just beginning.  

In late July I found my legs and feet covered in painful, raised, red lumps. The lumps felt similar to the Leukocytoclastic Vasculitis I had experienced in the past, prior to my transplant. They burned instead of itched, and eventually faded into hard purple spots that left behind tiny dark scars. However, a skin biopsy showed they weren't Vasculitis but, were another sort of immune system reaction coined by an infiltration of eosinophils and lymphocytes. These lumps continued to pop up over the course of three weeks. By about the fourth week, after a weeks course of prednisone, the rash had faded, but new symptoms arose. I began losing large clumps of my hair while in the shower. Finding noticeably thinner spots where my scalp was clearly visibly. The hair loss was accompanied by a localized red, scaly rash. Particularly my eye lids, shoulders, hands, and neck. It was slightly raised, itchy, and looked similar to white scales in an angry red desert. These rashes ebed, growing and shrinking. Suddenly I was taken by exhaustion 4-5 weeks post my initial leg eruption. No matter how much, or how drugged I slept, the bags under my eyes were intensely noticeable. My eyes and mouth were terribly dry and my energy levels dipped to unbearable. I was stopping my car on the road side to take naps on the short drive home from work. I simply couldn't keep my eyes open. By early September my GI tract had reached an extent of disarray. However, not my typical disarray. This didn't particularly feel like a digestion issue, but rather an issue of irritation. It was as if the entire tract lining from my mouth to anus was on fire at all times. It was causing painful swallowing and regurgitation, plus diarrhea with constant nausea and pain. I found myself upping my dose of Domperidone and Nexium, while adding in Zantac a few times a day to keep any food down. Tums and Preparation-H become a daily staple.

In all honesty, I was in heavy denial regarding this barrage of symptoms. I simply wanted so much to believe in my perfect epilogue post HSCT. I waited to see my doctors in fears they would confirm a problem - and in fact they did. I met with my local Rheumatologist, Digestive Disease Specialist, Cardiologist, Dermatologist, and Scleroderma Specialist. Heaps of blood work was performed along side the biopsies and other tests - abnormalities began to reflect quickly. 

Wednesday, I met with my Scleroderma Specialist, who also happens to be one of the worlds leading researchers in Scleroderma HSCTs. He reviewed my labs, tests, biopsies, and clinical findings with a somber mannerism. I expected bad news, some sort of relapse post transplant perhaps? Alas, that was not the case. He knew exactly what was happening - and was as shocked as I was. Autologous Graft Verses Host Disease (AutoGVHD). In his 19+ years of performing and researching Scleroderma HSCTs he said I am only his second patient to ever present these unique and extremely rare symptoms following an Autologous HSCT. 

"Graft-versus-host disease (GVHD) is a common complication of allogeneic stem cell transplantation (allo-SCT). However, a similar syndrome has been reported in autologous stem cell transplantation (ASCT) as well. The target organs of GVHD in ASCT are the skin, liver and gastrointestinal (GI) tract, which are consistent with those in allo-SCT. Histologic findings from the skin and the mucosa of the GI tract also show similar features."

As you can image Acute or Chronic GVHD is a common occurrence post Allogenic HSCTs since the immune system used is another human beings, but autologous transplants which use your own cells? Almost never. GVHD is an allo-immune response where the donated blood cells view the recipient as foreign, so it attacks the body, causing wide spread damage, particularly in the GI tract, skin, mucous membranes, kidneys, liver, and lungs. Essentially, my new immune cells are attacking me because they see my entire body as a foreign agent. Highly illogical, but can you blame them? If you were forced to inhabit a dysfunctional body as a flawless new immune system, you might overcompensate too. GVHD can happen any time post HSCT. In recent medical literature, autoGVHD has presented as much less progressive than GVHD acquired from an Allogenic transplant. It moves slower, and is less severe overall. However, it is still a serious medical condition that can have fatal consequences if not treated diligently and quickly.

While a similar concept to organ transplant rejection, it is actually quite different. Organ rejection occurs when the recipients immune system sees the donated organ as a foreign agent and attacks its tissue. (Host vs Graft instead of Graft vs Host) This devastating condition typically stays localized to the specific transplanted organ - that is, until the failure of that organ creates the failure of other organs. With GVHD, the entire body is attacked, as blood cells (bone marrow) are a major building block to all human structure. Both are catastrophic conditions that result from the overreaction of an immune system rejecting what it believes to be a foreign agent - whether it be yours or your donors.

So how do we know this is simply not a relapse post HSCT? From what my specialist explained, none of my current symptoms directly correlate with my pre-transplant baseline. A relapse would reflect more typical MCTD symptoms, swollen fingers and joints, new skin tightening, shortness of breathe, etc. He also expressed that my current clinical findings, biopsies, and blood work represented classic GVHD features - and that my case presents identically to the one other patient he treated with autoGVHD. After expressing his sincere regret for my circumstances, he shared his confidence that this would be treatable. We caught it early. We parted ways with a solid game plan and a hug. I will be beginning immediate treatment with Rituxan to combat the autoGVHD. The hope is that the Rituxan will target the cells responsible for the autoGVHD and set me back to a recovery baseline. Yes, I am essentially fighting another autoimmune disease - but this time it's new me fighting old me. 

I am exhausted, uncomfortable, and frustrated - but hopeful. Unfortunately, this turn of events puts me at a much higher rate for transplant relapse. Only time will tell.

To learn more about autoGVHD (which goes by multiple different names in the medical community) please visit the extremely informative link below. You may also read any of the other above mentioned hyperlinks from specified case studies.

Autologous Graft Versus Host Disease: