Different Approaches Available for Identifying and Managing Chronic GVHD

CASE SUMMARY

A 48-year-old man underwent a myeloablative conditioning matched unrelated donor allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) with tacrolimus plus methotrexate as graft-vs-host-disease (GVHD) prophylaxis​. The donor was a cytomegalovirus seropositive 33-year-old woman with 3 children. Over 22 days after transplantation, acute GVHD of the skin emerged and was successfully treated with a slow steroid taper​. Three months after transplantation, a bone marrow biopsy confirmed his AML was in remission, and between 3 to 6 months after transplantation, the patient was then successfully tapered off tacrolimus.

Seven months after transplantation, the patient returned with complaints of new onset cutaneous changes marked by hyperpigmentation, xerostomis, and mild ocular discomfort. Approximately one-half of each arm exhibited lichen-planus. Superficial sclerotic features (able to pinch the skin) were evident on the lower trunk and lower extremities. His body surface area involvement was 18%. Pulmonary function tests showed no decrease in forced expiratory volume in 1 second/carbon monoxide lung diffusion capacity and his blood counts and laboratory profiles were within normal limits.

DISCUSSION QUESTIONS

• What is your approach/method toward chronic GVHD monitoring, assessment, and scoring? ​
• How do you distinguish patients at high risk for chronic GVHD? ​
• What are the challenges in identifying these patients?

RANGASWAMY CHINTAPATLA, MD: I am in a community practice in Washington state and, typically, we [treat these patients] in conjunction with the Fred Hutchinson cancer center.... We are seeing the patients frequently as we monitor them, and we're not necessarily scoring them at each visit, [but it's still a] comprehensive assessment. If we find anything abnormal, like physical signs of GVHD or abnormal lab work that suggests GVHD, we reach out to the transplant long-term care follow-up team, and then adjust based on their treatment plan.

LORI MUFFLY, MD, MS: Are you seeing the patients, or is the long-term follow-up team seeing them mostly?

Lori Muffly, MD, MS​

Hematologist, Blood and marrow transplant specialist

Hematologist-Oncologist

Associate Professor of Medicine

Blood and Marrow Transplantation and Cellular Therapy

Stanford University​

CHINTAPATLA: The long-term follow-up team initially sees the patients until they are more stable. In some instances, it could be 3 or 5 months [until we see them], but it depends upon when they are more stable and coming back to the community. We [are further away from these long-term care teams], so the patient can’t go back and forth [between the centers] easily. Once they're here, they are following up mostly with me once a day for 3 to 4 months, or whatever the timeline is for their long-term care.

MUFFLY: Has telehealth changed this approach at all?

CATHERINE LEE, MD: At this time, we've tried to bring people back into the clinic, face to face, as much as we can and only use telemedicine in dire situations where patients can't get back to us.... Now, before post-transplant cyclophosphamide became popular, some of the factors that would make me a little bit more alert about a patient developing severe chronic GVHD are those with a diagnosis of primary and secondary myelofibrosis, or those who had a history of acute GVHD. And of course, those who had a human leukocyte antigens mismatched donor [have a high potential to develop chronic GVHD]. I think as everyone has been aware that post-transplant cyclophosphamide has made a significant impact in the field, and we're now seeing less acute and chronic GVHD by using that as GVHD prophylaxis.¹

JI-LIAN CAI, MD: I think in some of the rare presentations of chronic GVHD, it's missed until the patient becomes very sick. For instance, they will have...diarrhea and after many episodes [we'll see GVHD], or they've been coming in with malnutrition.... These are the [patients who are] months late in the treatment of their chronic GVHD. This is especially [concerning] for patients from the local community who are not seen by the transfer physician frequently. So, I think the education of the community physicians, as well as the education of the patient, [is important, as well as] close collaboration between the transplant team and the local center.

MUFFLY: It's interesting because every center does this so differently. For example, I see all my patients come back and I do all my own follow-up management, so I see them frequently. If they have chronic GVHD, then sometimes myself and my nurse practitioner are seeing them every 2 weeks. We don't rely on a community program to manage [this]. Yes we need them to help, but they don't need to feel responsible, because that would be very challenging without the training and education.

PRASHANT SHARMA, MD: I work at Intermountain Healthcare, in Draper, Utah, and we are the other transplant center in Utah that follows up on our own patients, especially if they have GVHD, for the first 4 or 5 months. Then they might go to the community. We generally keep the patients who have severe chronic GVHD, and we also have a GVHD clinic where we'll do the standard assessment scoring and things like that. [We look out for] the standard risk factors and then use a post transplantation cyclophosphamide [PTCy], but I have had patients with things like a mutation of the GATA protein who then didn't get PTCy. In Utah, it's common to have multiparous women donors who donate to men [as well, and these are cases] particularly at risk for GVHD.

MUJAHID RIZCI, MD: I practice in southern Oregon and our transplant center...is about 4 and a half hours away from Portland and 5 hours from San Francisco, so we do a lot of the managing [of our own patients]. But we're always on the phone with the transplant folks and with the patient talking about their transplant, and if we worry about GVHD then a lot of times we'll biopsy the patient locally. So we do a fair amount of disease management, but it's always done in conjunction with the transplant center.

^Reference

^{Jain T, Tsai HL, DeZern AE, et al. Post-transplantation cyclophosphamide-based graft-versus-host disease prophylaxis with nonmyeloablative conditioning for blood or marrow transplantation for myelofibrosis. Transplant Cell Ther. 2022;28(5):259.e1-259.e11. doi:10.1016/j.jtct.2022.02.004}