Case study | Therapy-refractory chronic GvHD

During the GvHD Hub Steering Committee meeting, key opinion leaders met to discuss a case study on the diagnosis and management of a patient with therapy-refractory chronic GvHD (cGvHD). This recorded discussion was chaired by Hildegard Greinix, and featured Yi-Bin Chen, Mohamad Mohty, Attilio Olivieri, Arnon Nagler, and Florent Malard.

Case study

Hildegard Greinix presented a case study, including the treatment pathways and progression of symptoms, for discussion by the members of the steering committee. This case presentation is outlined in Figure 1.

Figure 1. Case study outline 

AML, acute myeloid leukemia; ANC, absolute neutrophil count; ATG, antithymocyte globulin; BM, bone marrow; b.w., body weight; CSA, cyclosporine A; CMV, cytomegalovirus; CR, complete response; ECOG, Eastern Cooperative Oncology Group; ELN European Leukemia Network; FB3, fludarabine busulfan 3 days; HCT-CI, hematopoietic cell transplant-comorbidity index; HLA, human leukocyte antigen; MIDAC, mitoxantrone and cytarabine; MMF, mycophenolate mofetil; PBSC, peripheral blood stem cells; plts, platelets; WHO, World Health Organization.

Following hematopoietic cell transplant (HCT), this patient was treated with steroids and cyclosporine, both of which were tapered when acute GvHD resolved. The patient later presented with lichenoid oral mucosa and the National Institute of Health (NIH)-cGvHD scores outlined in Figure 1, suggesting moderate cGvHD. The treatments indicated for this severity of GvHD are outlined in Figure 2.

Figure 2. Indications for treatment of moderate/severe cGvHD* 

cGvHD, chronic graft-versus-host disease; GvL, graft-versus-leukemia.
*Adapted from Wolff, et al.¹

Following cGvHD diagnosis, this patient was given a combination of steroids, cyclosporine, and extracorporeal photopheresis (ECP) due to their higher risk status. Four months post treatment initiation, the patient only had eye involvement and steroids were tapered. ECP was also discontinued, leaving only cyclosporine as the maintenance therapy.

Following steroid tapering, symptoms of lung involvement presented, including a cough and dyspnea. Pulmonary function tests revealed a reduced forced expiratory volume of 25%, indicating a severe obstruction using the NIH scoring system and a diagnosis of severe cGvHD.²

Discussion

In this historical case, ruxolitinib was not available. However, in a modern case, ruxolitinib could be indicated to inhibit the production of proinflammatory cytokines and reduce symptoms of GvHD. Ruxolitinib may be applied alongside or in place of ECP at first diagnosis of acute GvHD post HCT.

There is a question around when a lung biopsy is appropriate after a severe cGvHD diagnosis. A biopsy could provide more histological data that may inform management plans; however, this invasive procedure is not currently routinely performed on patients with cGvHD and lung involvement.

In this case, the addition of lung involvement and severe cGvHD diagnosis occurred after the tapering of steroids, which poses the question of determining if this manifestation is steroid refractory/dependent. However, to establish this it would be necessary to readminister and taper steroids. This could be detrimental to the patient and is therefore not an appropriate option to obtain a diagnosis. Considering multiple lines of therapy were delivered, and that it is impossible to make a steroid refractory diagnosis, this patient was considered to be therapy refractory by the GvHD Hub Steering Committee.