Rehabilitation Interventions in the Multidisciplinary Management of Patients With Sclerotic Graft-Versus-Host Disease of the Skin and Fascia.

Graft-versus-host disease (GVHD) is a multisystemic disorder that affects 30%-80% of patients who undergo allogeneic hematopoietic stem cell transplantation 10%-15% of GVHD patients develop sclerotic features affecting the skin or deeper tissues, leading to functional limitations and poor quality of life. There is limited literature regarding the indications and efficacy of specific rehabilitative interventions in sclerotic GVHD (sclGVHD). In this article, we summarize the current evidence supporting rehabilitation intervention in sclGVHD and offer our approach to the multidisciplinary management of this disease. In addition, we review techniques that have been employed in other sclerotic skin diseases (eg, iontophoresis, extracorporeal shock waves, botulinum toxin A, adipose derived stromal vascular fraction), but that require further validation in the sclGVHD setting. Ultimately, optimal care for this complex disease requires a multidisciplinary approach that includes a rehabilitation and adaptive program tailored to each patient's needs.

Are graft-versus-host-disease patients missing out on the vital occupational therapy services? a systematic review.

The aim of this review is to show the importance of occupational therapy/hand therapy for chronic graft-versus-host-disease (GVHD) patients and to outline the current state of the literature. GVHD of the hand can cause functional loss, reduced activities of daily life, poor social interaction, and loss of income because of limitations in work. Hand therapy, which is a specialty practised by both occupational therapists and physical therapists, has been proven to be an effective approach for hand-related musculoskeletal disorders; however, the literature search suggests that it is an underutilized specialty around the world. An electronic search was performed from 1997 to 2017 using OneFile (GALE), Medline/PubMed (NLM), Scopus (Elsevier), Science Citation Index Expanded (Web of Science), ProQuest Central (New), ProQuest Hospital Collection, Health Reference Center Academic (Gale), Health Research Premium Collection, Science Direct Journals (Elsevier), ProQuest Health & Medical Complete, Medical Database, Wiley Online Library, and SciTech Premium Collection for the period from 1994 to April 2017. Only randomized-controlled trials involving occupational therapy or hand therapy in patients with chronic hand GVHD were included in the final analysis. The search was limited to articles in English. Two reviewers independently assessed the methodological quality and extracted the data. The JADAD scoring method was used to score the articles. After the duplicates were excluded, 5466 articles were identified by the electronic database search for screening, out of which 5465 articles were excluded after reviewing. One article was further excluded on obtaining the full text as it was a case study. Hand therapy specialty, although a vital part of the recovery process for the patients with hand GVHD, is an underutilized specialty and well-designed trials are urgently needed for musculoskeletal hand GVHD, especially for focused hand therapy interventions.

Functional Outcomes of Acute Inpatient Rehabilitation in Patients With Chronic Graft-Versus-Host Disease.

BACKGROUND: Growing numbers of allogeneic stem cell transplants and improved posttransplant care have led to an increase of individuals with chronic graft-versus-host disease (cGVHD). Although cGVHD leads to functional impairment for many, there is limited literature regarding the benefits of acute inpatient rehabilitation for patients with cGVHD. OBJECTIVE: To assess Functional Independence Measure (FIM) outcomes of patients with cGVHD during acute inpatient rehabilitation and to compare inpatient rehabilitation outcomes with patients with burn injuries, a rehabilitation patient population with similar comorbidities. DESIGN: Retrospective chart review. SETTING: Acute rehabilitation center at a large academic medical center. PATIENTS (OR PARTICIPANTS): A total of 37 adult patients with cGVHD and 30 with burn injuries admitted to inpatient rehabilitation from 2010 to 2015. METHODS OR INTERVENTIONS: Linear regression analysis to evaluate group (cGVHD versus burn) differences in functional gains. Effect size and minimal detectable change at the 90% confidence level (MDC90) were used to evaluate change in FIM outcomes. MAIN OUTCOME MEASUREMENTS: Total FIM gain, motor FIM gain, and FIM efficiency. RESULTS: Patients with cGVHD had statistically significant lower functional gains than patients with burn injuries, with an average of 11.66 fewer total FIM points (P ≤ .001), 10.54 fewer motor FIM points (P = .01), and 2.45 units less of FIM efficiency (P = .01). At the time of discharge, 7 (18%) patients with cGVHD exceeded the MDC90 values for total FIM gain versus 9 (30%) patients with burn injuries (P = .26). Eight (21%) patients with cGVHD exceeded the MDC90 for motor FIM gain versus 13 (43%) patients with burn injuries (P = .048). Effect sizes for patients with cGVHD and with burn injury were moderate to large, respectively, with patients with burn injuries having nearly twice the magnitude of gains as patients with cGVHD. CONCLUSIONS: Despite achieving more modest functional gains than patients with burn injuries, patients with cGVHD improved in function after acute inpatient rehabilitation. If replicated in larger studies, patients with functional impairment from cGVHD can be considered for inpatient rehabilitation. Future work should also determine minimal clinically important differences in function gain from inpatient rehabilitation for patients with cGVHD. LEVEL OF EVIDENCE: II.

Rehabilitation in Chronic Graft-Versus-Host Disease.

Chronic graft-versus-host disease is a potentially debilitating complication of allogeneic hematopoietic stem cell transplantation. Due to the direct inflammatory effects of the disease on tissue, and the impact on muscle and bone of the high-dose glucocorticoid immunosuppression used to treat the disease, patients are at risk of developing multifactorial functional impairment. This review outlines the clinical assessment and rehabilitation interventions to manage aspects of the disease that cause the most impairment: involvement of the skin/fascial and cardiopulmonary organ systems, as well as steroid-induced myopathy and bone and joint destruction.

Musculoskeletal, Neurologic, and Cardiopulmonary Aspects of Physical Rehabilitation in Patients with Chronic Graft-versus-Host Disease.

Chronic graft-versus-host disease (cGVHD) has the potential to cause significant morbidity and mortality in people who undergo allogeneic hematopoietic stem cell transplantation. Management of complications due to cGVHD can be challenging because of multiorgan involvement and variable presentation of the disease. This paper outlines the diagnosis and management of musculoskeletal, neurologic, and cardiopulmonary manifestations of cGVHD that have the potential to cause profound functional impairment and that may significantly impact quality of life and lifespan. Expert evaluation by a physical medicine and rehabilitation physician and multidisciplinary team may be beneficial in the treatment of the disease sequelae, and examples of specific rehabilitation interventions are described.

Long-term recovery after hematopoietic cell transplantation: predictors of quality-of-life concerns.

This prospective longitudinal study examined the quality of life (QOL) after hematopoietic cell transplantation (HCT) and identified risk factors of poor QOL in 312 adult autologous and allogeneic HCT patients. Physical, psychological, social, and spiritual well-being was assessed before HCT, 6 months, and 1, 2, and 3 years after HCT. For all HCT patients, physical QOL was stable from before to after HCT (P > .05); psychologic (P < .001), social (P < .001), and spiritual (P = .03) QOL improved at 6 months. Study noncompleters (because of illness or death) had worse QOL. Allogeneic patients reported worse physical and psychologic well-being (P < .05). Older patients reported worse physical but better social well-being regardless of HCT type (P < .05). Two or more domains were affected by race/ethnicity, household income, and education in autologous patients, and by body mass index (BMI), decline in BMI, primary diagnosis, and chronic graft-versus-host disease (GVHD) in allogeneic patients (P < .05). At 3 years, 74% of HCT patients were employed full or part time. Older autologous patients with lower pre-HCT income were less likely to work (P < .05); allogeneic patients with chronic GVHD were less likely to work (P = .002). Multidisciplinary efforts to identify and support vulnerable subgroups after HCT need to be developed.

Rapid immune recovery and graft-versus-host disease-like engraftment syndrome following adoptive transfer of Costimulated autologous T cells.

PURPOSE: Previously, we showed that adoptive transfer of in vivo vaccine-primed and ex vivo (anti-CD3/anti-CD28) costimulated autologous T cells (ex-T) at day +12 after transplant increased CD4 and CD8 T-cell counts at day +42 and augmented vaccine-specific immune responses in patients with myeloma. Here, we investigated the safety and kinetics of T-cell recovery after infusing ex-T at day +2 after transplant. EXPERIMENTAL DESIGN: In this phase I/II two-arm clinical trial, 50 patients with myeloma received autografts after high-dose melphalan followed by infusions of ex-T at day +2 after transplant. Patients also received pretransplant and posttransplant immunizations using a pneumococcal conjugate vaccine only (arm B; n = 24) or the pneumococcal conjugate vaccine plus an HLA-A2-restricted microltipeptide vaccine for HLA-A2(+) patients (arm A; n = 26). RESULTS: The mean number of T cells infused was 4.26 x 10(10) (range, 1.59-5.0). At day 14 after transplant, the median CD3, CD4, and CD8 counts were 4,198, 1,545, and 2,858 cells/microL, respectively. Interleukin (IL)-6 and IL-15 levels increased early after transplant and IL-15 levels correlated significantly to day 14 T-cell counts. Robust vaccine-specific B- and T-cell responses were generated. T-cell infusions were well tolerated with no effect on hematopoietic recovery. Eight patients (16%) developed a T-cell "engraftment syndrome" characterized by diarrhea and fever that was clinically and histopathologically indistinguishable from grade 1 to 3 acute graft-versus-host disease (GVHD) of the gastrointestinal tract (seven patients) and/or grade 1 to 2 cutaneous GVHD (four patients). CONCLUSIONS: Adoptive T-cell transfers achieve robust T-cell recovery early after transplant and induce moderate-to-severe autologous GVHD in a subset of patients.

Therapeutic experience on multiple contractures in sclerodermoid chronic graft versus host disease.

INTRODUCTION: A 25-year-old male underwent allogenic peripheral blood stem cell transplantation and developed sclerodermoid chronic graft versus host disease. He complained of limitation of motion of major joints and some difficulties with activities of daily living (ADL) performances. DISCUSSION: He had been treated with physical and occupational therapies. After the rehabilitative managements, range of motion and ADL performances improved slightly. CONCLUSION: Active and continuous multimodal rehabilitative treatment would be helpful in managing contracture and functional impairment and preventing the progression of the disease.

Quality of life and recovery after graft-versus-host disease.

Acute and chronic graft versus host disease (GVHD) has a significant impact on short- and long-term morbidity as well as mortality in patients undergoing hematopoietic-cell transplantation (HCT). As a result of the physical as well as emotional aspects of the transplant process and development of GVHD, quality of life (QOL) in transplant survivors can be adversely affected. The strongest association between reduced QOL and impaired functional status following HCT is the presence of chronic GVHD. Chronic GHVD can have a negative impact on an individual's general health and mental health, and can lead to the development of functional impairments and activity limitations. In HCT survivors without chronic GVHD, self-reported QOL tends to be very similar to that in comparison groups by 1-2 years after HCT. In addition, in individuals who have been successfully treated for chronic GVHD, QOL and overall health status are not different from those with no history of chronic GVHD. These findings suggest that effective new therapies for chronic GVHD are essential, as are standardized tools for the assessment of QOL and functional outcomes in HCT survivors with chronic GVHD in order to gain a better understanding of the overall impact of the condition, as well as the effectiveness of new treatments.

Enfermedad de injerto contra huésped. Presentación atípica / Graft versus host disease, a typical presentation

La enfermedad de injerto contra huésped(EICH) es la complicación más grave del trasplante de precursores hematopoyéticos alogénico y se puede presentar de forma aguda o crónica. La EICH aguda ocurre en el 40-70% de los pacientes y es causa de muerte en más del 20 %. La forma crónica aparece en un 20-50 % de los supervivientes a largo plazo.Presentamos el caso de un paciente con antecedente personal de leucemia mieloblástica aguda que había requerido trasplante de precursores hematopoyéticos alogénico de un hermano HLA compatible y presentó una EICH de presentación atípica como sinovitis de flexores de carpo y síndrome doloroso regional complejo asociado

Graft versus host disease (GVHD), which can occur in acute or chronic form, is the most serious complication of allogeneic hematopoietic stem cell transplantation(HSCT). The acute GVHD occurs in 40 % to 70 % of the patients and is the first cause of death in about 20 %. The chronic type occurs in 20 % to 50 % of long-term survivors.We present the case of a patient with acute myeloblasticleukemia who received allogeneic HSCT from his HLA-identical brother, and presented atypical GVHD with carpal flexor synovitis associated with complex regional pain syndrome

Rehabilitation of chronic graft versus host disease in children. A clinical series.

The study was aimed at evaluating clinical and functional assessment and results obtained following rehabilitative treatment in children affected by chronic graft versus host disease (cGVHD) after allogeneic transplantation of hemopoietic stem cells (HSCT). From 1999 to 2003 we evaluated 6 children with cGVHD after HSCT presenting severe complications and disabilities. Clinical and functional assessment was performed prior to rehabilitative treatment (T1), at follow-up at 6 (T6) and 12 (T12) months after treatment. Each child received a personalized rehabilitative treatment program based on the use of neuromotor re-education techniques, massotherapy, chest rehabilitation and occupational therapy. Six children presented sclerodermoid skin lesions, joint contractures, anchylosis, respiratory insufficiency, postural and walking alterations which led to reduction in motor performance and autonomy in daily living activity. After 1 year of rehabilitation treatment, 3 patients showed improvement in motor performance, 2 remained stable and 1 patient worsened. Rehabilitative treatment associated with pharmacological therapy has proven to be useful in patients affected by cGVHD. We believe that cGVHD is a pathology which must be seen by a physiatrist as early as possible at onset of first cutaneous signs of cGVHD to limit its invalidating evolution.

Topical treatment of sclerodermoid chronic graft vs. host disease.

Sclerodermoid chronic graft vs. host disease is a severe adverse immunologic reaction following allogeneic bone marrow transplantation, with deposition of collagen in the skin and possibly other soft tissues, resulting in loss of range of motion and functional capabilities. We present a case of a 14-yr-old girl who received a matched, unrelated donor bone marrow transplant for myelodysplastic syndrome complicated by sclerodermoid chronic graft vs. host disease, causing severe contractures of the shoulders, elbows, wrists, fingers, hips and knees. This case report and review of the literature regarding chronic graft vs. host disease suggest that a controlled trial of a multimodality therapeutic approach, including topical treatment, is warranted to determine whether this approach improves function in these patients.

Rehabilitation following bone marrow transplantation.

Bone marrow transplantation and stem cell transplantation are increasingly used to treat hematologic malignancies and some solid tumors. The treatment entails bone marrow-ablative therapies and intensive medical support to sustain the patient through pancytopenia and other complications of the disease, transplantation process, or drug side effects. Patients who develop graft-versus-host disease are the most difficult subset of transplant recipients to manage. Most transplant recipients perform at normal or near-normal functional levels at the inception of the transplantation process but are at high risk for developing functional deficits as a result of cumulative impairments. These impairments arise from their disease, their prior cancer treatment, transplant induction, graft-versus-host disease, immobility, infection, steroid-related side effects, and other sequelae of transplantation. Preventive and preemptive rehabilitation interventions can minimize functional loss and facilitate recovery, but the transplantation team must be sensitive to and regularly assess for early functional declines in these patients. The physiatrist and the other members of the rehabilitation team must be thoroughly acquainted with the unique needs and challenges of the bone marrow transplantation population in order to design and modify treatment programs effectively and safely. Outcome research has shown that some patients have continued limitations in function despite successful transplantation. Few evidence-based data are available that addresses factors correlating with poor functional outcomes other than graft-versus-host disease. However, this disease has not been investigated utilizing objective functional instruments. Future research should more clearly elucidate the functional impact of allogeneic and autologous transplants by using standardized physical performance measures as well as thorough function-based symptomatology questionnaires.