Homecare-based Motor Rehabilitation in Musculoskeletal Chronic Graft Versus Host Disease.

Chronic graft versus host disease (cGVHD) is a frequent complication of allogeneic stem cell transplantation. Extensive musculoskeletal and skin involvement may induce severe functional impairment, disability and quality of life deterioration. Physical rehabilitation is recommended as ancillary therapy in these forms, but experiences are sparse. A 39-year-old man affected by musculoskeletal and skin chronic graft versus host disease (cGVHD) was treated with a homecare-based motor rehabilitation program during palliation for disease progression. Significant functional improvement was obtained. Motor rehabilitation should be strongly considered for patients with musculoskeletal cGVHD, both in the palliative and in the curative phase of disease.

INTRODUCTION

Chronic graft versus host disease (cGVHD) belongs to the most serious and frequent (30–70%) complications in patients undergoing hemopoietic stem cells transplantation (HSCT) for hematological malignancies.[12] Musculoskeletal and skin cGVHD, by inducing fibrotic changes in tissues, may result in reduction of joints range of motion (ROM), loss of muscular strength and, finally, in functional impairment, compromising the activities of daily living (ADL). Standard cGVHD treatment is represented by immunosuppression. Supportive cares, such as physical rehabilitation and occupational therapy, although recommended as ancillary therapy, have been rarely experienced in such a condition. The case report of Choi et al.,[3] recently presented, dealt with a single case of motor rehabilitation in a patient with cGVHD-related contractures. At the best of our knowledge, it represents the first reported case of extensive cGVHD with skin and musculoskeletal involvement treated with physical rehabilitation in an adult patient. Thereby, we described an additional case of a patient with similar cGVHD involvement recently treated with physical rehabilitation within our homecare program.

CASE REPORT

A 39-year-old man affected by chronic myeloid leukemia (CML) in third relapse after allogeneic HSCT and not eligible for further active therapy was referred to our homecare service as advanced/terminal patient in June 2008. At diagnosis, in 1992, he had been submitted to HLA identical sibling allogeneic HSCT, obtaining complete remission (CR); in 1998, a disease relapse, as accelerate phase of CML, occurred. Therefore, a second HLA identical sibling allogeneic HSCT, from a different donor, was performed and both hematological and cytogenetic remission were achieved. In 2004, the patient developed a second hematological relapse (myeloid blast crisis) and he was given donor lymphocyte infusions (DLI) and imatinib; after three DLIs at escalating doses, a molecular CR was obtained. However, 8 months later, he developed extensive cGVHD (skin, mouth, eye) and, therefore, immunosuppressive therapy (steroids and extracorporeal photoferesis) was started, without improvement, such that cGVHD progressed with the addition of lung involvement. Therefore, the patient received multiple lines of immunosuppressive drugs (rituximab, cyclosporine, plaquenil and mycophenolate) with only a poor response. Meanwhile, in June 2007, he developed a third relapse (extramedullary lung and bone involvement) and was treated with imatinib and dasatinib without response and therefore he was considered not eligible for further causal therapy. At admission in the homecare service, the patient presented with an extensive skin and musculoskeletal cGVHD; Barthel Index (BI), as ADL measure, was 40 (moderate–severe reduction; normal = 100), as a result of diffuse contractures with severe reduction of joints ROM [Table 1]; secondary, legs muscles hypotrophy was increased due to spinal cord disease-related compression. The Karnowsky Performance Score was 50%. Laboratory findings revealed severe thrombocytopenia and anemia. The patient was assisted with a fully homecare program, with medical and nursing periodic examination, transfusions support and motor rehabilitation. Both physical and occupational therapy were promptly started, with particular attention to stretching exercises for joints; planned intensity was 3 sessions per week. After 4 weeks of treatment, planned intensity was respected and no rehabilitation-related complications were noted. Although BI did not improve, the ROM of treated joints increased and the mean ROM improvement (expressed as percentage of baseline value) was 52.5% [Table 1]; both motor skills, psychological aspects and patient quality of life had significant amelioration. After 5 weeks, rehabilitation was discontinued because of infectious pneumonia and, 1 month later, an attempt to restart failed due to rapid deterioration. In November 2008, the patient died for CML progression.

Table 1

Range of motion in major joints: normal value, baseline value (T0), after 1 month of treatment (T1) and improvement expressed as percentage of baseline value (Δ)

DISCUSSION

Musculoskeletal involvement, in the course of cGVHD, is a rare phenomenon; larger reported series describe cGVHD-related fasciitis or myositis in less than 1% of the patients undergoing allogeneic SCT.[45] Musculoskeletal cGVHD, expression of an immunological response toward recipient antigens, is considered an organ involvement in the course of a widespread disease, and systemic immunosuppressive therapy is the standard approach of treatment. However, local treatment should be used in order to improve response and to reduce toxicity, allowing a prompt and rapid escalation of systemic treatment. Although data derived from experiences in different immunologically mediated musculoskeletal contractures suggest an important role of physical rehabilitation,[6] such a therapy remains a poorly explored issue in patients with cGVHD, with few data reported in adult patients.[78] However, physical rehabilitation is recommended as ancillary therapy in cGVHD.[9] Our data, although limited, confirm the possibility of almost temporary results, also in long-lasting cGVHD-related contractures. Monitoring for musculoskeletal involvement in patients at risk for or with initial features of cGVHD is required, both to prospectively evaluate cGVHD-related muscoloskeletal involvement and to enroll patients at an initial disease stage. Clinical trials have to be developed to adequately assess feasibility, safety and efficacy of motor rehabilitation in response to the need to prevent disease progression toward ROM limitation and consequent disability.