19 chronic%20 gvhd[1]

2,893 views

Published on

Published in: Health & Medicine, Technology
0 Comments
2 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
2,893
On SlideShare
0
From Embeds
0
Number of Embeds
4
Actions
Shares
0
Downloads
98
Comments
0
Likes
2
Embeds 0
No embeds

No notes for slide
  • In allogeneic transplantation, chronic graft-versus-host disease (cGVHD) remains the most prevalent late effect of hematopoietic progenitor cell transplantation (HPCT). Although major improvements in acute GVHD (aGVHD) have been implemented, the occurrence of cGVHD has not been reduced. As the paradigm of blood and marrow transplantation shifts to an increased use of alternative donors, reduced-intensity conditioning regimens, and heavily pretreated patients, the incidence of cGVHD is predicted to increase.
  • cGVHD occurs when the T-cell lymphocytes present in the graft (donor cells) recognize the antigens and cells of the recipient (the host) as foreign. In cGVHD, the T lymphocytes not only recognize the minor human leukocyte antigen (HLA) antigens (not usually matched) but also the major antigens. This phenomenon may be related to the damaged thymus. The thymus is damaged by the conditioning regimen (radiation and chemotherapy) and aGVHD. Damage of the thymus results in autoantibody formation, as seen in other chronic autoimmune disorders. cGVHD is poorly understood and difficult to manage. Families have heard of cGVHD in the context of graft vs. leukemia. Families are aware that a little GVHD is a good thing. However, most families are not prepared for the magnitude of compromise that is associated with extensive cGVHD.
  • These are the types of cGVHD. Progressive cGVHD occurs in about 45% of patients, de novo cGVHD occurs in 12% of patients, and quiescent cGVHD occurs in 43% of patients.
  • This slide lists the organs targeted by cGVHD.
  • This slide illustrates the spectrum and magnitude of manifestations in cGVHD.
  • cGVHD can affect almost any organ system. This diagram depicts the numerous possible complications of cGVHD. Recent publications would suggest that there is evidence of cardiac manifestations of cGVHD. cGVHD has been reported in patients who develop bradycardia, cardiomyolysis, and coronary artery disease. The symptoms were reported to be responsive to immunosuppression. Pericardial effusion is a manifestation of polyserositis associated in patients with cGVHD. In addition, there have been reports of parotitis and submandibular lymphadenopathy in patients with cGVHD. The physical findings were swelling of the neck and cheeks, facial edema, eosinophilia, and fever. Computed tomography (CT) of the neck may reveal diffuse soft-tissue edema of the face and submandibular and parotid glands with no focal abnormalities. Up to 60% of patients with cGVHD die from infectious complications. Sullivan K. (1994) Graft Vs Host Disease. In S.J. Forman, K.G. Blume, E.D. Thomas (Eds) Bone Marrow Transplantation. (pp. 339-362) Blackwell Scientific Publications, Boston.
  • cGVHD risk factors are divided into two categories: transplant related or recipient related. Based on the research and current trends up to 2009: Factors affecting the incidence of cGVHD include: Mismatched related or unrelated donor (marrow) Prior aGVHD ATG or Campath in the conditioning regimen Age (older) Use of PBSCs Mismatched cord blood The BMT-related risk factors include HLA disparity (mismatch), older donor age, peripheral blood as a hematopoietic progenitor cell source as opposed to bone marrow, short-course cyclosporine, donor lymphocyte infusion, previous GVHD, female-to-male transplant, and alternative donor transplants. The recipient-related risk factors are older recipient age, viral infections, number of post-BMT transfusions, splenectomy, and prolonged steroid use.
  • There are no laboratory markers to predict the severity and morbidity of cGVHD.
  • Who is at higher risk: patient 1 Patient 1 Risk factors: Female donor to male recipient Matched unrelated donor Older age donor/recipient aGVHD Viral infection Patient 2 Risk factors: Female donor to male recipient Use of PBSCs Matched unrelated donor
  • Significant shifts in stem cell source, conditioning protocols, degree of HLA mismatch, supportive care, and immunosuppressive regimens influence the incidence of cGVHD. Forty percent of patients receiving an allogeneic HLA-identical sibling HPCT will suffer from some degree of cGVHD. It is reported that up to 70% of unrelated BMT recipients will experience cGVHD. Recent data have demonstrated an increased incidence of Grades III and IV cGVHD in patients receiving PBSCs. The above photo depicts alopecia associated with cGVHD.
  • The skin is the most frequently involved organ system in cGVHD. There are two types of involvement: sclerodermatous (comparable to scleroderma) and lichenoid (similar to lichen planus). Initially, the skin may be erythematous, with plaques and areas of desquamation, which can progress to skin that is hyper- or hypopigmented with tightening (hide-like skin) and atrophy. Joint contractures may result secondary to the fibrotic thickening and sclerodermatous changes. The distribution of skin cGVHD is not the typical allocation seen with acute involvement. Other clinical presentations include atrophy of the skin with pigmentation, changes of the fingernails with vertical ridging, and alopecia. Skin previously involved with aGVHD or herpes zoster is usually more susceptible to cGVHD.
  • This slide lists the most commonly seen clinical manifestations of skin cGVHD.
  • This slide illustrates involvement of three different HPCT recipients with cGVHD demonstrating sclerodermatous skin involvement. Take note of the atrophy of the skin with nodular appearance of the thighs and calves in these photos. Also present in the pictures are hypo- and hyperpigmentation with hide-like skin.
  • To evaluate the skin, you must feel and move it. When you look at the chest, it may appear to have old GVHD signs of hypo/hyperpigmentation. When you feel the skin, you will see that there are areas of thickening and it is difficult to pinch or move the skin.
  • This slide depicts cGVHD. The upper left photo depicts hypopigmentation of the buttock area with cGVHD. The right upper photo portrays a child with sclerodermatous and lichenoid skin involvement (arrow) as a result of cGVHD. The lower head photo demonstrates lichenoid changes with both hypo- and hyperpigmentation of the head, neck, and shoulders.
  • Top left: deep red macular rash with dry scaling skin Top right: hyperpigmentation Middle: shiny smooth skin with small and scaly plaques: papulosquamous Bottom left: multicolor epidermal atrophy, red, brown, hypopigmented skin: poikiloderma Bottom right: dry scaling shiny skin, may have some cigarette paper wrinkling of skin: lichen sclerosus
  • This slide depicts a normal skin biopsy and a skin biopsy of a patient with cGVHD. In the cGVHD slide, note the following: The top of the tissue in the image shows a relatively thin purple-blue layer (red arrow), the epidermis. Normally it is thicker than in the picture. The dermis, the pink area below the epidermis, is practically empty in this case. There are few small capillaries and some cells, but normally the dermis has hair follicles and sweat glands, which are gone (blue arrow) in this case. The pink material is collagen, demonstrating dermal fibrosis. The typical changes in cGVHD of the skin are epidermal and dermal atrophy, as is seen here. There are many different findings, depending on the type of skin change.
  • The patient with cGVHD of the skin requires comprehensive assessment of the skin. The skin should be monitored daily for the development of new areas of cGVHD, alterations in the integrity of the skin and nails, and infection. Zoster is on the left and fungal infection on right.
  • The goal of nursing management for the patient with cGVHD of the skin is to keep the recipient’s skin clean (with a mild, nonirritating soap) and well hydrated and lubricated (with gentle, moisturizing lotions) to help decrease the pruritus that is commonly experienced. Select patients may require topical antipruritic or steroid therapy. Ointments are preferable to creams for skin cGVHD. Ointments will better penetrate the skin. Dermatology consultation may be indicated. Administer immunosuppressant therapy and obtain necessary drug levels. Remember to monitor drug levels in those patients receiving topical Protopic because it is readily absorbed via the skin. Instruct the recipient and family about immunosuppressant therapy, as well as special precautions, toxicities, and instructions. Special attention must be paid to the patient’s nails. Clear nail polish is helpful in sealing the vertical ridging seen in these patients. Educate the recipient and family regarding sun precautions (sunblock, protective clothing, avoidance) with skin GVHD involvement. Physical and occupational therapy are necessary consultations because these patients lose joint mobility rapidly as their GVHD progresses. The psychological effect of cGVHD on the patient and the family is quite significant. The recipient may feel guilt, denial, anger, and despair and avoid social interactions. Psychosocial support is imperative and should be addressed as soon as a diagnosis is made. Extensive cGVHD can be devastating to a patient because it has a negative effect on the recipient’s quality of life and self-image.
  • The oral mucosa is commonly involved in cGVHD. The recipient develops dryness, sensitivity to acidic or spicy foods, and oral pain. The patient may have xerostomia (dryness) that is uncomfortable and interferes with nutrition. The patient is at increased risk for dental caries. At physical examination, the oral mucosa will show white lacy appearing striae to plaque-type lesions on the buccal mucosa and/or lateral tongue. This is sometimes misdiagnosed as oral candidiasis.
  • These photos depict oral cGVHD. Oral cavity 1: erythema, flat villi, sclerodermatous fibrosis that causes her to be unable to open her mouth Oral cavity 2: lingual ulceration Oral cavity 3: erythema with lichenoid lesions Oral cavity 4: smooth tongue with papular growth
  • Careful assessment of cGVHD oral involvement is essential; pay particular attention to the recipient’s ability to eat and drink. Also during the examination of the patient’s oral cavity, the patient’s ability to open his or her mouth must be assessed. Inability to open the mouth will affect nutritional status and speech.
  • The treatment of the patient with oral cGVHD is focused on instructing the patient about aggressive mouth care, which may include the use of steroid rinses. Consultations are necessary with the dietary and dental services when diagnosing cGVHD as necessary to obtain a baseline of the recipient’s condition. Ongoing education must address dietary recommendations, dental care, and proper use of the prescribed supplements.
  • The patient may present with an array of symptoms. Initially, the HPCT recipient may have excessive tearing, then progress to complaints of burning and/or a gritty sensation and/or photophobia (sensitivity to light). Over time, there will be a decrease in the ability to tear and keep the eyes moist. The patient may also have sicca syndrome (dry, burning, and itchy eyes). In extreme cases of ocular cGVHD, the HPCT recipient may develop a pseudomembrane (false membrane) that may lead to blindness. As a result of cGVHD, keratitis (inflammation of the cornea) and scarring may occur.
  • These photos depict the significant ocular changes seen in cGVHD.
  • The patient’s ability to tear is assessed by a Schirmer’s test performed by an ophthalmologist or a trained member of the HPCT team. The Schirmer’s test involves using litmus-type paper to determine how much tearing is formed in the eye; less than 5 mm is abnormal and considered to indicate cGVHD. Serial examinations may be needed to determine the extent of cGVHD involvement and to assess the efficacy of treatment.
  • All patients diagnosed with cGVHD should be seen by ophthalmology to assess for sicca syndrome.
  • Assist with all ophthalmic medications. Administer immunosuppressants and draw drug levels as indicated. The patient and family will need an explanation of all procedures. Patients should be instructed to wear protective eye gear, particularly on windy and sunny days. Punctal plugs, sutures, and protective lenses are all mechanisms of therapy in relieving dry eyes caused by cGVHD.
  • The patient with hepatic involvement with cGVHD may have relatively few symptoms until the process becomes severe. The disease manifests itself as a cholestatic obstructive picture. Before the patient starts immunosuppressive therapy, numerous other diseases should be ruled out, such as hepatitis, Epstein-Barr virus (EBV), infection (viral and fungal), iron overload, and pharmacologically induced hepatitis. It is of the utmost importance that the etiology of hepatic inflammation be clarified. Treating GVHD with immune suppression in the presence of an undiagnosed infection may cause, with high likelihood, a potential fatal flare of infection. Treating an infection without diagnosing GVHD will allow for an acute exacerbation of GVHD.
  • The target in cGVHD are the bile ducts. A healthy bile duct is not infiltrated by lymphocytes. Instead, in cGVHD, there are features of degeneration. The cells vary in size and shape. Some cells have dark nuclei (black arrow), whereas others have clear nuclei (green arrow). The epithelial lining of the bile duct is very disorganized, with some nuclei forming clumps and other areas in which nuclei are not seen (red arrow). This bile duct is also shrunken. It should be bigger. This is not appreciated in the image. If this persists, the bile duct can continue degenerating and even disappear. In cGVHD, the bile duct has collapsed syncytia of different sizes and irregularly arranged or missing nuclei.
  • The recipient's range of symptoms of hepatic cGVHD include nausea and vomiting, increasing hepatic size, hepatic tenderness, right upper quadrant pain, pruritus secondary to the associated hyperbilirubinemia, and jaundice. The nurse will assess the patient for jaundice and the sclera for icteric appearance. The abdomen can be palpated for hepatic size. The patient should be assessed for pain with age-appropriate pain scales. The nurse will assess skin irritation.
  • The goal of the treatment of the patient with hepatic GVHD is to prevent further damage to the liver with hepatotoxic medications and support the patient until the immunosuppressant agents can be optimized. Hepatotoxic medications should be avoided or dose adjusted based on the patient’s hepatic function. Coagulation studies and infectious disease studies (EBV and hepatitis) should be performed. The HPCT team will also need to prepare and educate the recipient and family for a diagnostic hepatic biopsy and radiographic studies.
  • There is a 5%–10% incidence of sinopulmonary manifestations in individuals with cGVHD. Late onset noninfectious pulmonary complications include Bronchiolitis Obliterans (BO), Bronchiolitis Obliterans organizing pneumonia (BOOP), and restrictive pulmonary disease.
  • Sinusitis is a common complication of cGVHD as a result of sicca syndrome. BO syndrome is a fibrotic process. The patient has dyspnea, a cough, and/or exercise intolerance. The chest CT reveals patchy hyperaeration, bronchial dilation, and increased density. BOOP is a nonfibrotic disease process. The patient is short of breath, is usually febrile, and has a cough. A chest CT reveals peripheral patchy airspace consolidation and nodular opacities.
  • National Institutes of Health (NIH) cGVHD Consensus recommendations: No cGVHD: PFT every 3 months x 4, then every 6 months x 2, then every year cGVHD (active): PFT every 1 to 3 months or sooner, as clinically indicated Systemic GVHD treatment discontinued: PFT every 1 to 3 months x 6 months, then every 3 to 6 months x 1 year, then every 6 to 12 months x 1 year, then yearly (Vogelsang, G, and Paveletic, S, 2009)
  • The assessment of the patient with pulmonary GVHD involvement is outlined here. These points should be assessed in all cGVHD patients.
  • The nurse will encourage the patient to perform incentive spirometry and other forms of pulmonary rehabilitation. Chest pulmonary toilet may be indicated. The patient may require follow-up scans and PFTs. As in all other cGVHD complications, administering medications and drawing drug levels is critical. The treatment of the patient with pulmonary components of GVHD are specific to the disease process the patient is experiencing. In general, the recipient and family should receive education about all immunosuppressants (purpose, side effects, and special precautions), disease process, compliance with steroids, and keeping surveillance study and consultation appointments.
  • What type of cGVHD does she have? De novo cGVHD What test do you want to do? PFT and CXR or CT scan Then next two slides will go over the diagnostic information.
  • The pretransplant PFT FEV 1 was 93%. The PFT taken with increased respiratory distress has an FEV 1 of 34%. Note changes in FEV 1 decreased more than 10% from baseline FEV 1 . This change of greater than 10% and the FEV 1 of less than 80% are indicative of airflow obstruction on the basis of the NIH cGVHD Consensus criteria. Note to instructor: It is important for participants to know that age, effort, and cooperation play a role in PFT results. Institutions will set guidelines for age on the type of examination they can do.
  • Examination: A high-resolution chest CT was obtained and was normal. Examination: Chest PA and Lateral Findings: There are opacities seen in both lung bases, and bilateral pleural effusions are greater on the left than the right. It is difficult to compare size on the plain film, which was done in the erect position, versus the CT scan, which was done in the supine position. No pneumothorax. Case Study The radiology findings do not indicate BO; the pleural effusions may be related to the GVHD. The child improved within 2 days with a steroid pulse. The patient has cGVHD of the skin, and the fluid build up has also been seen as a symptom of cGVHD. She does not have the classic pulmonary changes of BO typically seen with cGVHD.
  • GI symptoms are listed but may be complicated by associated infection. Cytomegalovirus (CMV), bacterial overgrowth, other viral etiologies, and c lostridium difficile may complicate the overall clinical picture. Other symptoms associated with GI cGVHD include painful swallowing, nausea and vomiting, anorexia, diarrhea, abdominal pain and/or cramping, and wasting syndrome (malabsorption, weight loss, poor performance status, dysphagia, and early satiety). Weight loss occurs in about 20% to 30% of patients after HPCT. The cGVHD scoring system explained later associates severe weight loss with poor outcome. The etiology of weight loss is poorly understood. Possible causes include GVHD, poor intake, malabsorption, increased caloric needs, hypercatabolism, increased energy expenditure, and pancreatic insufficiency. Pancreatic exocrine insufficiency with steatorrhea can be seen on CT as volume loss of pancreas and notable nausea, vomiting, loss of appetite, and weight loss with or without abdominal pain. This occurs in about 16% of patients with GI complications of cGVHD. Supplementation with pancreatic enzymes has been reported to be beneficial.
  • The best endoscopic diagnosis strategy for GI symptoms of cGVHD is unknown. For patients with diarrhea, the biopsy with the highest yield for diagnosis was the distal colon. Patients with complaints of nausea and vomiting had variable biopsy results, and some had esophageal strictures that needed to be opened. A combination of upper endoscopy with sigmoidoscopy and colonoscopy with ileal biopsies may be beneficial. These pictures depict a normal and a cGVHD gut biopsy. The image on the right is from the colon; it shows severe cGVHD. The black arrows depict the glands in a normal biopsy. The most noticeable feature in the cGVHD gut biopsy is that there are no glands (green arrow). Apoptosis in the neck region of the gastric gland is commonly seen in cGVHD.
  • The patient with gut GVHD requires an all-inclusive assessment of his or her symptoms. The recipient's gut GVHD range of symptoms include nausea and vomiting and diarrhea to early satiety and malabsorption. A detailed patient history should be obtained regarding the patient’s symptoms. The goal of the treatment of the patient with gut GVHD is to control the symptoms and support the patient until the immunosuppressant agents have a chance to work.
  • The interventions listed here include some of the many activities of the nurse caring for a patient with cGVHD. The HPCT team will also need to prepare and educate the recipient and family for diagnostic tests, depending on the clinical manifestations, such as endoscopy, stool cultures, stool fecal fat studies, amylase, absorption tests, and indicated radiographic studies. The HPCT nurse will administer immunosuppressant therapy and obtain necessary drug levels. Instruct the recipient and family regarding immunosuppressant therapy, as well as special precautions, toxicities, and instructions. Educate the recipient and family about food restrictions (milk products and caffeine) and to consume a low-fat, low-fiber diet. In extensive cases of gut GVHD, the patient’s ability to absorb oral medications may be impaired.
  • Extensive cGVHD can affect the vaginal epithelium, causing inflammation, stricture formation, and narrowing. The patient may complain of painful sexual intercourse and the need for a lubricant and a change in menstrual flow secondary to stricture formation.
  • Gynecological involvement should be assessed within the context of normal growth and development. The diagnostic evaluation, diagnosis, and management should be performed by an adolescent gynecologist.
  • Musculoskeletal involvement is the direct result of the sclerodermatous changes seen in skin cGVHD. The constellation of symptoms is listed here. Patients with cGVHD have a lower physical performance test result compared to the control group. The testing can be done of children as young as 6 years. Some of the decreased physical performance may be attributed to stiffness and SOB. There was a strong association between muscle weakness and cGVHD.
  • These pictures depict the contractures seen in significant skin cGVHD involvement. Long-term and conservative management with physical therapy and orthotics is generally successful in restoring most of the individual’s premorbid functional status. Surgical interventions do not seem to improve functional status in those affected by cGVHD.
  • Physical therapy is encouraged; monitoring the child’s ability to do the walk test can give some insight into his or her function. The NIH cGVHD Consensus Group recommends that a grip strength be measured in all children big enough to grasp the device.
  • Many studies have adopted this simple exercise to help clinicians when a physical therapist is not available. The gross exam used in clinical trials to evaluate the chronic GVHD. This is a evaluation form adapted from the quality of life study for the Fred Hutchinson HPCT program.
  • Diagnosis of fasciitis may be made with clinical signs and a magnetic resonance image showing the presence of inflammation or thickening of the fascia. Those with fasciitis frequently had BO and sicca syndrome and less often had complications of oral and skin involvement. Make sure to rule out other causes of fasciitis and/or myositis. Treatment: immunosuppressive therapies should be intensified and/or restarted.
  • The patient experiencing musculoskeletal involvement exhibits an array of signs and symptoms of physiologic dysfunction: weakness, fatigue, pain, muscle weakness, muscle wasting, limited ROM, neuropathy, and an inability to complete ADL. The diagnostic workup is determined by the recipient’s symptoms. The battery of tests may include EMG, physical therapy and occupational assessment, and bone density studies. The management is based on the patient’s symptoms and diagnostic test results. Several options in management include calcium, antiosteoporosis medications, and aggressive physical and occupational therapy.
  • A child may be seen in clinic and sent back with simple instructions for at-home therapy and goal setting.
  • cGVHD as a disease process is immunosuppressive, and the treatment is further immunosuppressive. The combination acts as a double-edged sword in that both the disease and the treatment further compromise the patient’s ability to fight infection. The combination results in functional asplenia (poor splenic function), variable IgG levels, opportunistic infections, cytopenia (thrombocytopenia and lymphocytopenia), and eosinophilia and place the patient at high risk for infection. Immune recovery is slower for those people affected by cGVHD. The cytopenias seen in cGVHD can be isolated (platelets: single cell line) or in multiple lines (neutrophils and platelets). A complete blood cell count with differential will usually demonstrate eosinophilia. A bone marrow examination may be needed to show if the problem is due to graft failure, relapse, or an immune process.
  • Careful assessment of the patient’s relative risk of infection as a result of cGVHD must be assessed. Questions to ask include: Was the donor or recipient CMV positive, herpes simplex virus positive? Has the recipient been exposed to sick contacts? What environmental factors place the patient at risk? Diagnostic tools are dependent on relative infectious risk, as evidenced by infectious titers (CMV, herpes simplex virus, adenovirus, EBV, and hepatitis). IgG levels are drawn to determine the need for immunoglobulin therapy. The nursing responsibilities consist of administering medications; preparing the recipient for diagnostic tests; obtaining blood samples; educating the patient and family regarding the disease process, the relative risk of infections, and immunosuppressant treatment’ and (if applicable) administering appropriate vaccines. Patients should receive endocarditis prophylaxis for invasive procedures. Post-BMT prophylaxis should be maintained according to the American Society for Blood and Marrow Transplantation (ASBMT) guidelines for infection released in 2009. Refer to GVHD pharmacology module for detailed information on prophylaxis in high-risk HPCT recipients.
  • From Filipovich, A. H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J. R., Lee, S. J., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation , 11( 12), 946.
  • From Filipovich, A. H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J. R., Lee, S. J., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation, 11 (12), 952-953.
  • This is an example of what the NIH cGVHD forms look like. They can be downloaded from www.asbmt.org. From Filipovich, A. H., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation, 11 (12), 945-956. Reprinted with permission of Elsevier.
  • Here are a few examples of diagnostic signs versus distinctive symptoms taken from Filipovich, A. H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J. R., Lee, S. J., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation , 11 (12), 948. Reprinted with permission of Elsevier.
  • To obtain the guidelines and forms from the NIH cGVHD Consensus Group, visit to www.asbmt.org. Click on Guidelines, Policies & Reviews. The guidelines and forms are listed. Adapted from From Filipovich, A. H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J. R., Lee, S. J., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation , 11( 12), 952.
  • The Global Severity of cGVHD replaces the “limited-extensive” nomenclature. The global scoring includes both the number of organs or sites affected and the severity within each organ. Mild, moderate, and severe should reflect the degree of organ effect and functional impairment (Filipovich et al, 2005). This is used after the diagnosis of cGVHD is confirmed. One limitation is that the scoring does not distinguish between fixed deficits and disease activity. Filipovich, A. H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J. R., Lee, S. J., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation , 11 (12), 954
  • Advances in the understanding of cGVHD have helped in the treatment of the process. cGVHD treatment is based on maintaining a fine balance between the amount of immunosuppression and the cGVHD. The selection of cGVHD treatment is often protocol and institutional specific. The following drugs are employed: tacrolimus, steroids, cyclosporine, and mycophenolate mofetil. From Filipovich, A. H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J. R., Lee, S. J., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation , 11 (12), 954.
  • In the event that the HPCT recipient does not respond to conventional cGVHD therapy, there are other treatment options. Newer options of therapy based on an understanding of the cellular pathophysiology of GVHD include the use of monoclonal (etanercept [Enbrel ® ], infliximab [Remicade ® ], and alemtuzumab [Campath-1H ® ]) or polyclonal (antithymocyte globulin) antibodies. Additional newer options for the treatment of cGVHD include the use of thalidomide, hydroxychloroquine, and pentostatin as pharmaceutical agents. Ultraviolet (UV) radiation, in addition to systemic immunosuppression, has been used in the treatment of refractory cGVHD. The two approaches used are ECP and psoralen and UVA irradiation (PUVA). The advantage of ECP and PUVA are that the treatments may allow a reduction in systemic immunosuppression. Evaluate the treatment option that will best help keep the patient compliant with therapy. There are different salvage therapies to choose from that may be effective for the organs involved. The HPCT team will need to give each treatment choice at least a month or two before deciding it is a treatment failure.
  • Most people are familiar with the side effects of corticosteroids and calcineurin inhibitors (cyclosporine, tacrolimus).
  • ECP is not fully understood in the treatment of cGVHD. ECP leads to the apoptosis, programmed cell death, of mononuclear cells. UV, in addition to systemic immunosuppression, has been used in the treatment of refractory cGVHD. The two approaches used are ECP and PUVA. The advantage of ECP and PUVA are that the treatments may allow a reduction in systemic immunosuppression. PUVA has been used for numerous other dermatological diseases; however, its success in cGVHD is not clearly understood. HPCT recipients are given methoxypsoralen 2 hours before the UV exposure, occurring on a structured treatment regimen.
  • A schematic overview of the ECP procedure. Using the UVAR ® Photopheresis System, whole blood is removed from the patient. The red blood cells are separated from the white blood cells (buffy coat) by centrifugation. The red blood cells are returned to the patient. UVADEX ® (methoxsalen) Sterile Solution is injected directly into the harvested white blood cells. The buffy coat and drug mixture is then exposed to UVA light (320-400 nm) to photoactivate the UVADEX ® (methoxsalen). The photoactivated cells are then reinfused into the patient, where they exhibit immunomodulatory properties.
  • The ECP process entails the use of methoxypsoralen and UV light on cells collected by apheresis and infused into the patient. During the usual apheresis institutional procedure, 150 to 300 ml of buffy coat (white cells) is collected and methoxypsoralen (photosensitizing agent) is injected into the collection bag, exposed to UV light, and then infused into the patient. Research is ongoing on determining the length, regularity, and timing of ECP in the treatment of cGVHD. ECP is well tolerated, with some hypo- or hypertension during the procedure. Preexisting conditions should be evaluated. Medications may be adjusted for procedure days (hold Lasix until after procedure). The incidence of infections is not greater with ECP.
  • Before and after the use of ECP for a few years. ECP causes an enhancement of T regulatory cell reactivity (Bladon, 2008). The regulatory T cells inhibit immune response, allowing for immune tolerance. Complete responses of cutaneous cGVHD have been noted, with improvement in sclerodermal skin, less consistently in the liver and gut. Responses are more frequent when started earlier. There have been several reports of the steroid sparing effect of ECP.
  • Cord blood transplants had a decreased incidence of cGVHD. The age and prior aGVHD were reproducible findings in other centers.
  • The management of cGVHD requires a multidisciplinary team approach. The HPCT recipient and family may become frustrated with the intensity of cGVHD and the length of the treatment. Many HPCT centers often employ a team approach for the management of cGVHD.
  • This slide depicts the numerous psychosocial issues that surround the HPCT recipient. These issues are discussed in the following slides .
  • In summary, GVHD is an effect of the function of the immune system. GVHD occurs when the T-cell lymphocytes present in the graft (donor cells) recognize the antigens and cells of the recipient (the host) as foreign. This attack results in varying degrees of damage to the recipient’s tissues. The targeted tissues in aGVHD are the skin, gut, and liver, causing significant symptoms and complications. Despite numerous advances in ongoing research in BMT, cGVHD continues to be a major cause of increased morbidity and mortality. The role of the nurse in providing care for the patient with cGVHD is vital to the well-being of the recipient. cGVHD is a major complication of allogeneic BMT; nursing input is imperative. The key nursing responsibilities are numerous and affect the outcome for the BMT patient. The nurse administers the necessary prophylactic and treatment immunosuppressants and monitors for toxicities as well as the effectiveness of the treatment. Ongoing education of the patient and family regarding GVHD, recognition of symptoms, treatment, and management is another role for the nurse, as well as assessing the patient for ongoing symptoms, such as infection, electrolyte abnormalities, malnutrition, and alterations in skin integrity, which remains vital to outcome. Nurses also provide comprehensive multidisciplinary continuity of care for these very complex patients, obtaining the necessary consultations and referrals. This all can be a challenge.
  • Used in the MNDP webcast.
  • C. Skin is the most frequently involved organ.
  • C. GLEEVEC ® is being used for severe sclerodermal changes.
  • B. Moderate: the lung score of 1 pushes the person to the next level even if everything else is resolving. Moderate: 1 organ site with significant disability (score 2) 3 organ sites affected (minimal impairment: score 1) Lung score 1
  • A. Mild
  • C. Quiescent
  • 19 chronic%20 gvhd[1]

    1. 1. Hematopoietic Progenitor Cell Transplantation: Chronic Graft-Versus-Host DiseaseKimberly Thormann Powers, MA RN CPNP APHON/PBMTC’s Foundations of Pediatric Hematopoietic Progenitor Cell Transplantation: A Core Curriculum, 2nd Edition© 2012 APHON © 2012 APHON 1
    2. 2. Objectives • Define chronic graft versus host disease (cGVHD). • Identify risk factors for cGVHD. • Discuss cGVHD diagnosis and evaluation. • List the factors associated with poor prognosis in cGVHD. • Describe cGVHD management and treatment.© 2012 APHON 2
    3. 3. cGVHD: Process • Donor T lymphocytes (graft) attack the immunologically incompetent recipient (host)  Damage of host tissues • Often resembles an autoimmune collagen vascular disease • Poorly understood© 2012 APHON 3
    4. 4. cGVHD: Types • Progressive cGVHD  Extension of acute GVHD (aGVHD) • De novo cGVHD  Without preceding GVHD • Quiescent cGVHD  After resolution of aGVHD© 2012 APHON 4
    5. 5. cGVHD: Target Organs • Skin • Oral • Ocular • Hepatic • Pulmonary • Gastrointestinal (GI) • Gynecological • Musculoskeletal • Immunologic© 2012 APHON 5
    6. 6. Spectrum of manifestations in cGVHD© 2012 APHON 6
    7. 7. cGVHD Complications© 2012 APHON 7
    8. 8. cGVHD: Risk Factors • Hematopoietic progenitor cell • Recipient related transplantation (HPCT) related  Older age  aGVHD  Viral infection  Number of post-HPCT  Human leukocyte antigen (HLA) transfusions disparity  Splenectomy  Older donor age  Prolonged steroid  Peripheral blood stem cells treatment (PBSCs) as hematopoietic progenitor cell source  Short-course cyclosporine  Donor lymphocyte infusion  Female-to-male bone marrow transplantation (BMT)  Unrelated HPCT© 2012 APHON 8
    9. 9. cGVHD: Poor Prognostic Signs • Persistent severe thrombocytopenia • Lichenoid changes on skin histology • Serum bilirubin >1.2 mg/dl • Progressive onset from acute to chronic • Karnofsky performance <70%© 2012 APHON 9
    10. 10. Who Is at Higher Risk of DevelopingcGVHD? • Case study  1. A 12-year-old boy with AML s/p matched unrelated donor (45-year-old woman) bone marrow with nonmyeloablative HPCT who has a viral infection after being treated for aGVHD.  2. A 4-year-old boy with MDS s/p matched unrelated donor (30-year-old woman) peripheral blood HPCT with myeloablative conditioning who has never had aGVHD.© 2012 APHON 10
    11. 11. cGVHD: Incidence • 40% in patients receiving HLA-identical sibling HPCT • >50% in HLA-mismatched related sibling HPCT • 40% to 60% unrelated HPCT, 70% in patients >50 years • Greater incidence of cGVHD with PBSCs© 2012 APHON 11
    12. 12. Skin cGVHD • Most commonly involved organ • Inflammatory changes cause  Sclerodermatous presentation o Fibrotic thickening o Leads to contractures and nerve compression  Lichenoid changes o Erythematous raised papular skin rash o May present with only dryness, hypo- or hyperpigmentation© 2012 APHON 12
    13. 13. Skin cGVHD: Clinical Manifestations • Itching • Pain • Burning • Flakiness • Ulcerations • Shiny appearance • Erythema • Vertical ridging and • Hyperpigmentation splitting of the nail beds • • Alopecia Hypopigmentation • • Graying hair Atrophy • Loss of sweating© 2012 APHON 13
    14. 14. cGVHD: Sclerodermatous SkinInvolvement© 2012 APHON 14
    15. 15. © 2012 APHON 15
    16. 16. cGVHD: Lichenoid Skin Changes© 2012 APHON 16
    17. 17. © 2012 APHON 17
    18. 18. Skin cGVHD: Diagnostic Biopsy Healthy Skin cGVHD Skin Biopsy Biopsy© 2012 APHON 18
    19. 19. Skin cGVHD: Nursing Assessment • Assess for  Altered integrity  Altered body image  Nail integrity  Monitor for infection© 2012 APHON 19
    20. 20. Skin cGVHD: Nursing Management • Promote skin care • Administer hydrating lotions, pain medications, antibiotics, and topical medications • Give immunosuppressant therapy and obtain drug levels as indicated • Use clear nail polish to strengthen nails and prevent breakage • Encourage frequent nail care • Consult dermatology • Educate on sun damage and use of sunscreen • Promote range of motion (ROM) exercises • Support the altered body image and give multidisciplinary team support© 2012 APHON 20
    21. 21. Oral Mucosa cGVHD • Changes range from erythema to lichenoid eruption to ulceration • Xerostomia • Associated infection is frequent • Commonly misdiagnosed as oral candidiasis© 2012 APHON 21
    22. 22. Oral Mucosa cGVHD Oral cavity 1 Oral cavity 2 Oral cavity 3 Oral cavity 4© 2012 APHON 22
    23. 23. Oral Mucosa: NursingAssessment • Assess for  Intake  Altered taste  Anorexia  Increased sensitivity to acidic or spicy foods  Oral pain  Oral infections  Ability to open the mouth© 2012 APHON 23
    24. 24. Oral Mucosa cGVHD: NursingManagement • Provide steroid rinses as indicated • Instruct patient and family on dental hygiene • Assist with mouth care • Educate regarding dietary recommendations • Consult dental and nutrition© 2012 APHON 24
    25. 25. Ocular cGVHD: Clinical Manifestations • Incidence of ocular cGVHD in those with cGVHD: 65% to 80% • Presentation  Initially, may have excessive tearing  Burning or gritty sensation  Sicca syndrome  Photophobia  Corneal abrasions  Pseudomembrane formation may lead to blindness© 2012 APHON  Keratitis and scarring may occur 25
    26. 26. Ocular cGVHD Lymphoplasmacytic infiltrates around ductal structures of lacrimal glands© 2012 APHON 26
    27. 27. Schirmer’s Test© 2012 APHON 27
    28. 28. Ocular cGVHD: Nursing Assessment • Assess  Ability for eyes to tear  Need for preservative-free artificial tears  Vision changes  Pain or gritty sensation© 2012 APHON 28
    29. 29. Ocular cGVHD: Nursing Management • Assist and instruct family with ophthalmic medication • Give immunosuppressants  Obtain indicated levels • Prepare patient and family for Schirmer’s test • Educate the patient and family • Discuss therapeutic treatment  : drops/ lubrications  Punctal plugs  Sutures  Protective lenses© 2012 APHON 29
    30. 30. Hepatic cGVHD • May have few relatively mild symptoms until cGVHD hepatic disease becomes severe  Jaundice  Mild hepatomegaly  Abnormal coagulation  Elevated alkaline phosphatase© 2012 APHON 30
    31. 31. Liver: Diagnostic Biopsy Healthy Hepatic cGVHD Hepatic Biopsy Biopsy© 2012 APHON 31
    32. 32. Hepatic cGVHD: NursingAssessment • Assess  Jaundice  Hepatic size  Right upper quadrant pain  Skin irritation associated with hyperbilirubinemia© 2012 APHON 32
    33. 33. Hepatic cGVHD: Nursing Management • Administer immunosuppressants. • Avoid hepatotoxic agents. • Send necessary laboratory tests. • Prepare for diagnostic testing. • Provide skin care.© 2012 APHON 33
    34. 34. Pulmonary cGVHD: ClinicalManifestations • 5% to 10% incidence • Range of clinical manifestations and presentations of pulmonary cGVHD  Sinusitis  Bronchiolitis Obliterans (BO) syndrome  Bronchiolitis Obliterans organizing pneumonia (BOOP)  Restrictive pulmonary disease© 2012 APHON 34
    35. 35. cGVHD: SinopulmonaryComplications • Sinusitis  Sicca syndrome • Bronchiolitis Obliterans (BO)  Fibrotic process  Dyspnea, cough, and/or exercise intolerance  Computed tomograpy (CT) scan: patchy hyperaeration, bronchial dilation, increased density • Bronchiolitis Obliterans organizing pneumonia (BOOP)  Shortness of breath (SOB), cough, and fever  CT scan: peripheral patchy airspace consolidation, nodular opacities© 2012 APHON 35
    36. 36. Pulmonary Function Test(PFT) • Ideally obtained at Day 100 and at 3-month intervals with any new significant air-flow obstruction • Significant airflow obstruction  Defined as a decrease in forced expiratory volume in 1 second (FEV1) by > 10% compared to pretransplant values and the FEV1 is < 80%, with an FEV1/forced vital capacity ratio < 0.7 without response to bronchodilators • Obtain full PFT when the FEV1 is < 80% of the predicted normal value • Significant air trapping: a residual volume > 120% or air trapping noted on high-resolution CT scan • Pulmonary consultation for significant obstructive pulmonary changes© 2012 APHON 36
    37. 37. Pulmonary cGVHD: NursingAssessment • Assess  Breath sounds  Color  Dyspnea  Cough  Oxygen saturation  Activity intolerance and fatigue  Inability to complete activities of daily living (ADL)  Infection© 2012 APHON 37
    38. 38. Pulmonary cGVHD: NursingManagement • Encourage breathing exercises • Perform pulmonary toilet as necessary • Prepare for follow-up scans and PFTs • Administer immunosuppressants and draw appropriate levels© 2012 APHON 38
    39. 39. Case Study • 13-year-old girl who underwent matched related sibling donor peripheral blood HPCT for AML. She has falling chimerism, and the immune suppression was manipulated. She developed cGVHD of the skin. During the next few months she noticed some SOB with activity and was treated with steroids. Symptoms resolved, and 3 months after all immune suppression stopped, she again had an increase in her SOB and new lichenoid skin findings.© 2012 APHON 39
    40. 40. Pre-HPCT PFT FEV1 % predicted 93% PFT evaluation for SOB FEV1 % predicted ↓ to 34%© 2012 APHON 40
    41. 41. Case Study: Radiographic Findings CXR: Opacities seen in both lung bases and bilateral pleural effusions greater on the left than the right High-resolution chest CT© 2012 APHON 41
    42. 42. Gut cGVHD: Clinical Manifestations • Diarrhea • Anorexia • Nausea and vomiting • Abdominal pain and cramping • Wasting syndrome  Malabsorption  Weight loss  Poor performance status  Progressive GI symptoms (early satiety, dysphagia) • Infection© 2012 APHON 42
    43. 43. Gut: Diagnostic Biopsy Normal Gut cGVHD Gut Biopsy Biopsy© 2012 APHON 43
    44. 44. Gut cGVHD: Nursing Assessment • Assess  Nausea and vomiting  Diarrhea  Pain  Dysphagia  Weight loss  Bleeding  Fluid status  Caloric intake© 2012 APHON 44
    45. 45. Gut cGVHD: NursingManagement • Test stools for blood • Measure stool output • Administer fluids • Provide nutritional support  Enteral  Parenteral • Administer medications  Immunosuppressants  Supportive care agents • Prepare for diagnostic procedures • Consult nutrition • Educate regarding diet, immunosuppression, and associated infection© 2012 APHON 45
    46. 46. Gynecological cGVHD:Clinical Manifestations • Vaginal epithelial damage occurs due to cGVHD  Inflammation  Stricture formation  Narrowing • Vaginal sicca • Vaginal atrophy  Leads to painful sexual intercourse • Symptoms may include  Inflammation  Dry vagina  Obstruction of menstrual flow because of strictures© 2012 APHON 46
    47. 47. Gynecology: Nursing Assessmentand Management • Assess (within the • Management context of normal  Consult gynecologist growth and  Encourage use of development) lubricants  Sexual dysfunction  Encourage discussion of  Pain sexual issues  Altered body image  Encourage  Infection interdisciplinary team management/specialty referral  Administer medications© 2012 APHON 47
    48. 48. Musculoskeletal cGVHD:Clinical Manifestations • The severe damage done by sclerodermatous skin cGVHD can cause significant musculoskeletal involvement  Stiffness  Contractures  Joint pain  Limited ROM  Muscle cramps  Carpal spasm  Swelling  Arthralgias© 2012 APHON 48
    49. 49. cGVHD: Contractures© 2012 APHON 49
    50. 50. Physical Therapy Evaluation Therapist objective findings: 2-minute walk test: 7 laps (patient not out of breath after test, limited by shoes, wearing sandals with heel) (1 lap = 50 feet) Grip Strength Trial Left Right 1 18 kg/40 lb 19 kg/42 lb 2 21 kg/45 lb 20 kg/45 lb 3 20 kg/43 lb 22 kg/52 lb Dominant hand: right Dynamometer position: 2© 2012 APHON 50
    51. 51. Physical Therapy Clinician EvaluationROM is measured for all the joints by physical therapy, but the MD/APN can do a basic evaluation: 1- poor mobility to 7= full mobilityShoulder 2 3 6Elbow 2 4 7Wrist and Fingers Foot Dorsiflexion 1 4 6 2 3© 2012 APHON 51
    52. 52. cGVHD: Fasciitis and Myositis • Fasciitis  Diagnostic sign of cGVHD  Skin swelling: skin taut, bound down, and irregularly thickened, with small depressed areas (orange peel)  Contractures, joint stiffness  Pathology: lymphocytic infiltrates, increase of collagen fibers • Myositis  Distinctive sign of cGVHD  Moderate to severe proximal muscle weakness, myalgia, fever, contracture, and skin induration  Elevated creatinine phosphokinase and aldolase enzyme  Pathology: degeneration, necrosis, and regeneration of muscle fibers© 2012 APHON 52
    53. 53. Musculoskeletal: NursingAssessment and Management • Assess • Management  Performance score  Prepare for diagnostic  Ability to perform ADL tests  Pain  Consult rehabilitation  ROM services  Monitor for signs and  Consult orthopedics symptoms of  Administer physiologic dysfunction medications  Monitor for bone  Collaborate with damage interdisciplinary team  Nutritional status© 2012 APHON 53
    54. 54. Physical Therapy: Evaluation Report Summary: patient reports functionally ↑ endurance. Low 2-minute walk test d/t patient’s choice of footwear and self-selected pace. Educated patient on gastroc stretch and reviewed importance of hydration to prevent cramping. GOAL TIME FRAME MET COMMENTS Will report no Goal to be met 1 No New goal cramps with session from activity 7/9/2010 Will increase Goal to be met 1 No New goal 2-minute walk session from to 8 7/9/2010 Follow-up: continue to see patient at each clinic visit, every 2 weeks© 2012 APHON 54
    55. 55. Immune System: ClinicalManifestations • cGVHD is immunosuppressive, and cGVHD treatment is further immunosuppressive, resulting in  Functional asplenia  Variable immunoglobulin G (IgG) levels  Opportunistic infections  Cytopenia (thrombocytopenia)© 2012 APHON 55
    56. 56. cGVHD: Infection Risk • Assess • Management  Signs and symptoms  Administer medications of infection  Prepare for diagnostic  Relative risk of tests infection  Obtain laboratory work  Home environment  Educate patient and  School reentry family o Immunosuppressive treatment  Administer appropriate vaccines© 2012 APHON 56
    57. 57. cGVHD: NIH ConsensusScoring Criteria • cGVHD is defined by the presence of at least one distinctive manifestation with support by histologic, radiologic, or laboratory evidence or diagnostic clinical sign of cGVHD without the features of aGVHD overlap syndrome where there are features of aGVHD and cGVHD present • There is no time limit after stem cell transplant for the diagnosis of any clinical features • The differential diagnosis must be ruled out for each system affected • Clinical score of 0 to 3 for involved sites/organs© 2012 APHON 57
    58. 58. NIH Consensus: ScoringCriteria • Clinically based • Organs/sites assessed/scored  Skin  Mouth  Eyes  GI tract  Liver  Lungs  Joints and fascia  Genitourinary tract© 2012 APHON 58
    59. 59. NIH cGVHD organ-specific staging From Filipovich, A. H., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation, 11(12), 945-956. Reprinted with permission of Elsevier.© 2012 APHON 59
    60. 60. Classification of GVHD Site or Organ Diagnostic Distinctive Other Skin Poikiloderma Depigmentation Keratosis pilaris Lichen planus Hyperpigmentation Sclerotic Hypopigmentation Morphea like Sweat impairment Lichen sclerosus Ichthyosis GI Esophageal web Exocrine pancreatic Esophageal stricture insufficiency Esophageal stenosis Lung BO on biopsy BO by PFT and radiology Muscles, joints, fascia Fasciitis Myositis Edema Stiff joints Polymyositis Muscle cramps Contractures Arthralgias/arthritis Mouth Lichen type Xerostomia Hyperkeratosis plaques Mucocele Mouth opens less Ulcers Pseudomembranes From Filipovich, A. H. et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I.© 2012 APHON Diagnosis and staging working group report. Biology of Blood and Marrow Transplantation , 11(12), 948. Reprinted with permission of Elsevier. 60
    61. 61. NIH Consensus: Scoring Criteria • Scoring  0: no manifestations or symptoms  1: no significant impairment of function  2: significant impairment of ADL and www.asbmt.org no major disability  3: significant impairment of ADL and major disability© 2012 APHON 61
    62. 62. cGVHD: NIH GlobalScoring • Mild  No significant impairment of function  Only 1 or 2 organs (except lung)  Maximum organ score of 1 • Moderate  Significant impairment but no major disability  3 or more organs with maximum score of 1  One organ with maximum score of 2  Lung score of 1 • Severe  Major disability  Score of 3 in any organ or site  Lung score >2 62© 2012 APHON
    63. 63. cGVHD: PrimaryTreatment • Systemic treatment  Multiple organs sites affected >3  Pulmonary involvement  Onset of cGVHD while on steroid therapy  Progressive onset  Thrombocytopenia • Initial treatment often employs corticosteroids  Single agent  Combination with calcineurin inhibitor© 2012 APHON 63
    64. 64. cGVHD: Salvage Therapy • Refractory cGVHD treatment  Monoclonal antibodies o Infliximab o Etanercept o Alemtuzumab  Polyclonal antibodies o Antithymocyte globulin  Other agents and modalities o Thalidomide o Hydroxychloroquine o Pentostatin o Imatinib mesylate (GLEEVEC®) o Ultraviolet (UV) radiation  Extracorporeal photopheresis (ECP)© 2012 APHON 64
    65. 65. Treatment Side Effects Agent Class Side effect Pentostatin Nucleoside analogue Nausea, vomiting, infections, anemia Etanercept TNF receptor Infections Imatinib Tyrosine kinase inhibitor, Myelosuppression, PDGF inhibitor weight gain, hepatitis Montelukast Leukotriene inhibitor Nausea, headache Infliximab Anti-TNF-a Hypersensitivity, infections ECP UV irradiation, 8-MOP Skin hypersensitivity, nausea, bleeding Sirolimus Macrocyclic lactone Myelosuppression, hyperlipidemia, HUS, TTP, renal impairment, fluid accumulation© 2012 APHON 65
    66. 66. Extracorporealphotopheresis (ECP)© 2012 APHON 66
    67. 67. What Is Extracorporealphotopheresis? The photoactivated white blood cells are returned to the patient Photoactivatio n with UVA light Methoxsalen White blood cells are treated with methoxsalen and exposed to UVA Blood is light The UVAR XTS Instrument separated by draws blood from the patient centrifugation and red blood cells are returned© 2012 APHON 67
    68. 68. Extracorporeal photopheresis:Procedure • Procedure  150-300 ml of buffy coat (white cells) is collected by apheresis  Methoxypsoralen (photosensitizing agent) is added to collection bag  Cells are exposed to UV light  Infused into the patient  Well tolerated o Hypo- or hypertension may occur o Fluid shifts • Research  Ongoing to determine length, regularity, and timing of ECP© 2012 APHON 68
    69. 69. Before ECP After ECP Before ECP After ECP© 2012 APHON 69
    70. 70. cGVHD: Pediatric PoorPrognostic Signs • Recipient age • aGVHD Grade II-IV • Female donor to male recipient • Diagnosis of malignancy • TBI in conditioning© 2012 APHON 70
    71. 71. cGVHD: The Team Family/Caregivers BMT Team Physical Therapy Nursing Staff Pharmacy Medical Consultants Home Care Company Child Life Psychology Insurance Nutrition Referring Team Social Work© 2012 APHON 71
    72. 72. Quality of Life Issues Facing HPCTRecipients • Fatigue • Depression • Sleep disturbance • Stress • Nutrition: weight loss or gain • Activity and exercise • Friendships • Growth and development • School or work© 2012 APHON 72
    73. 73. Fatigue • Symptoms  Tired, unable to do what peers are doing  General weakness  Unable to concentrate  Irritability  Lasting months to years • Management  Create schedule with quiet time  Encourage routine exercise  Get 10 to 12 hours of sleep a night  Consider stimulant medication© 2012 APHON 73
    74. 74. Nutrition • Symptoms  cGVHD increases your calorie needs  Encourage well-balanced meals  Give healthy snacks throughout the day  Increase the protein in the child’s diet  Increase fluids to keep well hydrated • Management  Follow up with HPCT team  Check dietary restrictions d/t medications  May need supplements if diet is not well balanced  May need help creating a diet plan with the nutritionist  Follow up with diabetic educator if diabetes from long-term steroid use© 2012 APHON 74
    75. 75. Depression • Symptoms  Sleeping more  Lack of energy  Body image altered  Noncompliance  Easily agitated  Withdrawn  Lack of interest in activities • Management  Planned activities  Schedule breaks  Talk to specialist  Medications© 2012 APHON 75
    76. 76. Transitions • Transition to school  Sharing information with school  Preparing student for the transition  Planning curriculum, educational support  Establishing connections • After school  Vocational planning in high school  Guidance counselor assistance for planning postsecondary education  Seek colleges and technical schools with learning support programs© 2012 APHON 76
    77. 77. Health Maintenance Guidelines • Physical examination with labs • Eye examination • Dental examination • Pulmonary evaluation • Gynecological examination (if of age) • Physical therapy evaluation with ROM testing • Endocrine evaluation© 2012 APHON 77
    78. 78. cGVHD: Conclusion • Major cause of morbidity and mortality • Nurse’s role is vital  Assessment  Medications  Treatments  Education  Provide comprehensive multidisciplinary continuity of care o Challenge© 2012 APHON 78
    79. 79. Resources • American Society for Blood and Marrow Transplantation  www.asbmt.org • BMT InfoNet  www.bmtinfonet.org • Candlelighters Childhood Cancer Foundation  www.candlelighters.org • Children and Adults with Attention-Deficit/ Hyperactivity Disorder (CHADD)  www.chadd.org • Children’s Oncology Group  www.childrensoncologygroup.org • CureSearch  www.curesearch.org • Chronic GVHD Learning  www.asbmt.org/policystat/policy.htm • Lance Armstrong Foundation  www.laf.org© 2012 APHON 79
    80. 80. cGVHD: Resources • Learning Disabilities Association of America  www.ldanatl.org • Leukemia & Lymphoma Society  www.lls.org • Leukemia Research Foundation  www.leukemia-research.org • National Cancer Institute  www.cancer.gov/cancertopics/eatinghint • National Marrow Donor Program  www.nmdp.org • National Sleep Foundation  www.centers.sleepfoundation.org/insomnia/children • Pediatric Oncology Resource Center  www.acor.org/ped-onc/© 2012 APHON 80
    81. 81. cGVHD: Resources • Pediatric Blood and Marrow Transplant Consortium  www.pbmtc.org • Schwab Learning  www.schwablearning.org • Supplementary information and updates  www.marrow.org • Books  Educating the Child with Cancer, A Guide for Parents and Teachers, edited by Nancy Keene. 2003, Candlelighters Foundation  Childhood Cancer Survivors, A Practical Guide to Your Future, Keene, Hobbie, Ruccione. 2000, O’Reilly and Associates© 2012 APHON 81
    82. 82. Questions 1. What is the most frequently involved organ for cGVHD? A. Gut B. Lungs C. Skin D. Eyes E. Liver© 2012 APHON 82
    83. 83. Questions 2. What treatments would you think of using for cGVHD of the skin? A. ECP B. Pentostatin C. GLEEVEC® D. Hydroxychloroquine E. Thalidomide© 2012 APHON 83
    84. 84. Questions 3. A child with some cGVHD of the skin that is resolving and a lung score of 1 would be rated per the cGVHD global scoring as? A. Mild B. Moderate C. Severe© 2012 APHON 84
    85. 85. Questions 4. A child with a diagnostic clinical sign of cGVHD with no signs of aGVHD would be rated per the cGVHD global scoring as? A. Mild B. Moderate C. Severe© 2012 APHON 85
    86. 86. Questions 5. What type of cGVHD comes after a resolution of aGVHD? A. De novo B. Progressive C. Quiescent© 2012 APHON 86
    87. 87. References • Akhtari, M., Langston, A. A., Waller, E. K., & Gal, A. A. (2009). Eosinophilic pulmonary syndrome as a manifestation of GVHD following hematopoietic stem cell transplantation in three patients. Bone Marrow Transplant, 43(2), 155-158. • Andree, H., Hilgendorf, I., Leithaeuser, M., Junghanss, C., Holzhueter, S., Loddenkemper, C., et al. (2008). Enteral budesonide in treatment for mild and moderate gastrointestinal chronic GVHD. Bone Marrow Transplant, 42(8), 541- 546. • Arora, M., Nagaraj, S., Witte, J., DeFor, T. E., MacMillan, M., Burns, L. J., et al. (2009). New classification of chronic GVHD: added clarity from the consensus diagnoses. Bone Marrow Transplant, 43(2), 149-153. • Barkholt, L. (2009). Importance of CsA drug monitoring in SCT recipients to minimize GVHD and maximize graft vs. leukemia. Pediatr Transplant, 13(4), 400- 403. • Benson, D. M., Jr., Smith, M. K., Krugh, D., & Devine, S. M. (2008). Successful therapy of chronic graft-versus-host disease manifesting as pure red cell aplasia with single-agent rituximab. Bone Marrow Transplant, 41(6), 595-596. • Berger, M., Pessolano, R., Albiani, R., Asaftei, S., Barat, V., Carraro, F., et al. (2007). Extracorporeal photopheresis for steroid resistant graft versus host disease in pediatric patients: a pilot single institution report. J Pediatr Hematol Oncol, 29(10), 678-687.© 2012 APHON 87
    88. 88. References • Chiang, C. C., Lin, J. M., Chen, W. L., & Tsai, Y. Y. (2007). Allogeneic serum eye drops for the treatment of severe dry eye in patients with chronic graft-versus-host disease. Cornea, 26(7), 861-863. • Couriel, D., Carpenter, P. A., Cutler, C., Bolanos-Meade, J., Treister, N. S., Gea- Banacloche, J., et al. (2006). Ancillary therapy and supportive care of chronic graft-versus-host disease: National Institutes of Health consensus development project on criteria for clinical trials in chronic Graft-versus-host disease: V. Ancillary Therapy and Supportive Care Working Group Report. Biol Blood Marrow Transplant, 12(4), 375-396. • Daguindau, E., Lioure, B., Buzyn, A., Robin, M., Faucher, C., Kuentz, M., et al. (2009). Evidence for anti-tumour effect of allogeneic haematopoietic SCT in cases without sustained donor engraftment. Bone Marrow Transplant. • Drew, D. Z., Donohue, T., Ramos, C., Cook, L., Goodwin, R., Patronas, N., et al. (2009). Chronic GVHD manifesting as parotitis after allogeneic hematopoietic SCT. Bone Marrow Transplant. • Filipovich, A. H., Weisdorf, D., Pavletic, S., Socie, G., Wingard, J. R., Lee, S. J., et al. (2005). National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant, 11(12), 945-956. • Fry, T. J. (2009). Is a little GVHD a good thing? Blood, 113(25), 6274-6275.© 2012 APHON 88
    89. 89. References • Furlong, T., Martin, P., Flowers, M. E., Carnevale-Schianca, F., Yatscoff, R., Chauncey, T., et al. (2009). Therapy with mycophenolate mofetil for refractory acute and chronic GVHD. Bone Marrow Transplant, 44(11), 739-748. • Garland, P., Dazzi, F., & Marin, D. (2009). Dasatinib may not suppress the GVL effect of donor lymphocyte infusions for CML. Bone Marrow Transplant. • Gassas, A., Sung, L., Saunders, E. F., & Doyle, J. (2007). Graft-versus-leukemia effect in hematopoietic stem cell transplantation for pediatric acute lymphoblastic leukemia: significantly lower relapse rate in unrelated transplantations. Bone Marrow Transplant, 40(10), 951-955. • Hausermann, P., Walter, R. B., Halter, J., Biedermann, B. C., Tichelli, A., Itin, P., et al. (2008). Cutaneous graft-versus-host disease: a guide for the dermatologist. Dermatology, 216(4), 287-304. • Hidaka, M., Iwasaki, S., Matsui, T., Kawakita, T., Inoue, Y., Sakai, T., et al. (2009). Efficacy of bezafibrate for chronic GVHD of the liver after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant.© 2012 APHON 89
    90. 90. References • Hovi, L., Kurimo, M., Taskinen, M., Vettenranta, J., Vettenranta, K., & Saarinen- Pihkala, U. M. (2009). Suboptimal long-term physical performance in children and young adults after pediatric allo-SCT. Bone Marrow Transplant. • Ishaqi, M. K., Afzal, S., Dupuis, A., Doyle, J., & Gassas, A. (2008). Early lymphocyte recovery post-allogeneic hematopoietic stem cell transplantation is associated with significant graft-versus-leukemia effect without increase in graft- versus-host disease in pediatric acute lymphoblastic leukemia. Bone Marrow Transplant, 41(3), 245-252. • Jacobsohn, D. A. (2008). Shedding some LIGHT on chronic GVHD. Blood, 112(7), 2593-2594. • Jacobsohn, D. A., Rademaker, A., Kaup, M., & Vogelsang, G. B. (2009). Skin response using NIH consensus criteria vs Hopkins scale in a phase II study for steroid-refractory chronic GVHD. Bone Marrow Transplant. • Kamble, R. T., Selby, G. B., Mims, M., Kharfan-Dabaja, M. A., Ozer, H., & George, J. N. (2006). Iron overload manifesting as apparent exacerbation of hepatic graft- versus-host disease after allogeneic hematopoietic stem cell transplantation. Biol Blood Marrow Transplant, 12(5), 506-510.© 2012 APHON 90
    91. 91. References • Kew, A. K., Macaulay, R., Burrell, S., Rubin, S., Dow, G., & Couban, S. (2007). Central nervous system graft-versus-host disease presenting with granulomatous encephalitis. Bone Marrow Transplant, 40(2), 183-184. • Kim, D. H., Sohn, S. K., Baek, J. H., Lee, K. H., Lee, J. H., Choi, S. J., et al. (2007). Time to first flare-up episode of GVHD can stratify patients according to their prognosis during clinical course of progressive- or quiescent-type chronic GVHD. Bone Marrow Transplant, 40(8), 779-784. • Kissin, E. Y., Schiller, A. M., Gelbard, R. B., Anderson, J. J., Falanga, V., Simms, R. W., et al. (2006). Durometry for the assessment of skin disease in systemic sclerosis. Arthritis Rheum, 55(4), 603-609. • Li, A. M., Yin, J., Au, J. T., So, H. K., Tsang, T., Wong, E., et al. (2007). Standard reference for the six-minute-walk test in healthy children aged 7 to 16 years. Am J Respir Crit Care Med, 176(2), 174-180. • Lorenzoni, P. J., Scola, R. H., Carsten, A. L., Trentin, A. P., Teive, H. A., Pasquini, R., et al. (2007). Chronic inflammatory demyelinating polyradiculoneuropathy in chronic graft-versus-host disease following allogeneic hematopoietic stem cell transplantation: case report. Arq Neuropsiquiatr, 65(3A), 700-704.© 2012 APHON 91
    92. 92. References • Magro, L., Catteau, B., Coiteux, V., Bruno, B., Jouet, J. P., & Yakoub-Agha, I. (2008). Efficacy of imatinib mesylate in the treatment of refractory sclerodermatous chronic GVHD. Bone Marrow Transplant, 42(11), 757-760. • Martin, P. J., Weisdorf, D., Przepiorka, D., Hirschfeld, S., Farrell, A., Rizzo, J. D., et al. (2006). National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: VI. Design of Clinical Trials Working Group report. Biol Blood Marrow Transplant, 12(5), 491- 505. • Mitchell, S. A., Leidy, N. K., Mooney, K. H., Dudley, W. N., Beck, S. L., Lastayo, P. C., et al. (2009). Determinants of functional performance in long-term survivors of allogeneic hematopoietic stem cell transplantation with chronic graft-versus-host disease (cGVHD). Bone Marrow Transplant. • Mohty, M., Marchetti, N., El-Cheikh, J., Faucher, C., Furst, S., & Blaise, D. (2008). Rituximab as salvage therapy for refractory chronic GVHD. Bone Marrow Transplant, 41(10), 909-911. • Nakasone, H., Ito, A., Endo, H., Kida, M., Koji, I., & Usuki, K. (2009). Pancreatic atrophy is associated with gastrointestinal chronic GVHD following allogeneic PBSC transplantation. Bone Marrow Transplant. • Nishio, N., Yagasaki, H., Takahashi, Y., Muramatsu, H., Hama, A., Tanaka, M., et al. (2009). Late-onset non-infectious pulmonary complications following allogeneic hematopoietic stem cell transplantation in children. Bone Marrow Transplant, 44(5), 303-308.© 2012 APHON 92
    93. 93. References • Nozzoli, C., Guidi, S., Paglierani, M., Wnekowicz, E., Saccardi, R., Bosi, A., et al. (2008). Immunohistochemical and FISH analyses identify synovitis associated with chronic GVHD after allogeneic hematopoietic SCT. Bone Marrow Transplant, 42(4), 289-291. • Oda, K., Nakaseko, C., Ozawa, S., Nishimura, M., Saito, Y., Yoshiba, F., et al. (2009). Fasciitis and myositis: an analysis of muscle-related complications caused by chronic GVHD after allo-SCT. Bone Marrow Transplant, 43(2), 159- 167. • Ogawa, Y., Dogru, M., Uchino, M., Tatematsu, Y., Kamoi, M., Yamamoto, Y., et al. (2009). Topical tranilast for treatment of the early stage of mild dry eye associated with chronic GVHD. Bone Marrow Transplant. • Oh, S. J., Cho, S. B., Park, S. H., Piao, C. Z., Kwon, S. M., Kim, I., et al. (2008). Cell cycle and immune-related processes are significantly altered in chronic GVHD. Bone Marrow Transplant, 41(12), 1047-1057. • Palmer, J. M., Chen, B. J., Deoliveira, D., Le, N. D., & Chao, N. J. (2009). Novel mechanism of Rapamycin in GVHD: increase in interstitial regulatory T cells. Bone Marrow Transplant. • Prot-Labarthe, S., Therrien, R., Champagne, M. A., Duval, M., & Joubert, C. (2007). Toxic serum levels of tacrolimus after topical administration in an infant with severe cutaneous graft-versus-host disease. Bone Marrow Transplant, 40(3), 295-296.© 2012 APHON 93
    94. 94. References • Pulanic, D., Lozier, J. N., & Pavletic, S. Z. (2009). Thrombocytopenia and hemostatic disorders in chronic graft versus host disease. Bone Marrow Transplant, 44(7), 393-403. • Rackley, C., Schultz, K. R., Goldman, F. D., Chan, K. W., Serrano, A., Hulse, J. E., et al. (2005). Cardiac manifestations of graft-versus-host disease. Biol Blood Marrow Transplant, 11(10), 773-780. • Robbins, R. A., Floreani, A. A., Buchalter, S. E., Spurzem, J. R., Sisson, J. H., & Rennard, S. I. (1992). Pulmonary complications of transplantation. Annu Rev Med, 43, 425-435. • Ruck, S., Hilgendorf, I., Muller-Hilke, B., Kiefel, V., Junghanss, C., Freund, M., et al. (2008). Autoantibody-mediated agranulocytosis in association with chronic GVHD. Bone Marrow Transplant, 42(5), 359-360. • Sato, K., Eizumi, K., Fukaya, T., Fujita, S., Sato, Y., Takagi, H., et al. (2009). Naturally occurring regulatory dendritic cells regulate murine cutaneous chronic graft-versus-host disease. Blood, 113(19), 4780-4789. • Schneiderman, J. (2008). Non-pharmacologic strategies in hematopoietic stem cell transplantation. Curr Pharm Des, 14(20), 1987-1996. • Schrauder, A., Saleh, S., Sykora, K. W., Hoy, H., Welte, K., Boos, J., et al. (2009). Pharmacokinetic monitoring of intravenous cyclosporine A in pediatric stem-cell transplant recipients. The trough level is not enough. Pediatr Transplant, 13(4), 444-450.© 2012 APHON 94
    95. 95. References • Shapira, M. Y., Abdul-Hai, A., Resnick, I. B., Bitan, M., Tsirigotis, P., Aker, M., et al. (2009). Alefacept treatment for refractory chronic extensive GVHD. Bone Marrow Transplant, 43(4), 339-343. • Shelton, M. L., Lee, J. Q., Morris, G. S., Massey, P. R., Kendall, D. G., Munsell, M. F., et al. (2009). A randomized control trial of a supervised versus a self- directed exercise program for allogeneic stem cell transplant patients. Psychooncology, 18(4), 353-359. • Skert, C., Damiani, D., Michelutti, A., Patriarca, F., Arpinati, M., Fili, C., et al. (2009). Kinetics of Th1/Th2 cytokines and lymphocyte subsets to predict chronic GVHD after allo-SCT: results of a prospective study. Bone Marrow Transplant, 44(11), 729-737. • Sleight, B. S., Chan, K. W., Braun, T. M., Serrano, A., & Gilman, A. L. (2007). Infliximab for GVHD therapy in children. Bone Marrow Transplant, 40(5), 473-480. • Soiffer, R. (2008). Immune modulation and chronic graft-versus-host disease. Bone Marrow Transplant, 42 Suppl 1, S66-S69. • Tam, P. M., Young, A. L., Cheng, L. L., & Lam, P. T. (2009). Topical 0.03% tacrolimus ointment in the management of ocular surface inflammation in chronic GVHD. Bone Marrow Transplant.© 2012 APHON 95
    96. 96. References • Thompson, B., Salzman, D., Steinhauer, J., Lazenby, A. J., & Wilcox, C. M. (2006). Prospective endoscopic evaluation for gastrointestinal graft-versus-host disease: determination of the best diagnostic approach. Bone Marrow Transplant, 38(5), 371-376. • Tomblyn, M., Chiller, T., E.insele, H., Gress, R., Sepkowitz, K., Storek, J., Wingard, J., Young, J. and Boeckh, M. (2009). Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective. Biol Blood Marrow Transplant 15: 1143-1238. • Veeraputhiran, M., & Mangan, K. (2009). Sudden loss of the GVL effect following use of the TNF inhibitor infliximab in a chronic myelogenous leukemia patient with chronic GVHD. Bone Marrow Transplant. • Zaja, F., Bacigalupo, A., Patriarca, F., Stanzani, M., Van Lint, M. T., Fili, C., et al. (2007). Treatment of refractory chronic GVHD with rituximab: a GITMO study. Bone Marrow Transplant, 40(3), 273-277. • Zhang, P. L., Wilkerson, M. L., & Schworer, C. M. (2008). C4d staining is a valuable marker in identifying chronic GVHD in colonic biopsies following BMT. Bone Marrow Transplant, 42(3), 209-211.© 2012 APHON 96

    ×