Graft Versus Host Disease Follow-up

  • Author: Romeo A Mandanas, MD, FACP; Chief Editor: Mary C Mancini, MD, PhD   more...
 
Updated: Oct 28, 2010
 

Further Inpatient Care

  • Manage severe diarrhea with octreotide, IV hydration to prevent dehydration, and total parenteral nutrition in patients with severe malabsorption.
  • Treat infections and prescribe prophylactic antibiotics, antiviral agents, and antifungals.
  • Patients may need meticulous care of grade IV skin lesions (ie, bullae, vesicles), which may be similar to the care for second-degree burns.
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Deterrence/Prevention

  • Donor and host factors should be addressed.
    • Refinement of methods to select the donor based on molecular characterization of HLA class I and II antigens may minimize HLA disparity between the donor and recipient and therefore decrease the incidence of GVHD.
    • Use of a CMV-seronegative donor for a CMV-seronegative patient appears to reduce the risk of both CMV infection and GVHD in the recipient.
  • Laminar airflow protective isolation with gut decontamination can decrease the incidence of GVHD and improve survival in patients with aplastic anemia undergoing BMT.
  • Posttransplantational immunosuppressive prophylaxis has been used.
    • Single agents or combinations of agents have been used to prevent acute GVHD. The most common effective regimen consists of CSP administered for 180 days combined with a short course of MTX administered on days 1, 3, 6, and 11. The combination is better than either agent administered alone. In 1 study, the addition of prednisone on days 7-180 further reduced the incidence of acute GVHD from 23% to 9%.
    • Tacrolimus, a more potent immunosuppressant than CSP, is also being used in combination with MTX and appears to be more effective than CSP at preventing acute GVHD, especially in patients receiving a transplant from an unrelated donor. The cumulative incidence of chronic GVHD also seems to be less with tacrolimus-MTX combination (48%) than with the CSP-MTX combination (64%).[28] Prolonged immunosuppression (extending beyond the usual day 180) may be indicated for patients at high risk for chronic GVHD (ie, patients who have had acute GVHD).
  • Antibody prophylaxis with IV Ig (IVIG), when administered weekly through day 90 after transplantation, reduces the incidence and mortality rate of acute GVHD. Continuing IVIG treatment from day 90 to day 360 after transplantation does not seem to change the cumulative incidence of chronic GVHD in treated patients compared with a control group that was not receiving IVIG.
  • Marrow T-cell depletion by in vitro methods (eg, soybean-lectin agglutination, counterflow centrifugation, use of antibodies against T lymphocytes or their subsets) can substantially reduce the incidence and severity of acute and chronic GVHD (50% in T cell–depleted HLA-identical marrows). However, the overall survival rate is not improved because of increased incidence of graft failure and recurrent leukemia. In long-term survivors who received T cell–depleted unrelated donor marrows, chronic GVHD still occurred in 85%.
  • In vivo T-cell depletion by the addition of anti – T-cell globulin to standard CSP/MTX prophylaxis decreased the incidence of both acute and chronic GVHD without affecting relapse or nonrelapse mortality or compromising overall survival in recipients of matched unrelated donor transplants in a randomized, open-label, multicenter, phase 3 trial.[19]
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Complications

  • Late infections are possible. Multiple immune defects, such as impaired mucosal defense, chemotactic defects, functional asplenia, T-cell alloreactivity, and qualitative and quantitative B-cell abnormalities, are observed in patients with chronic GVHD.
  • Bacteremia and sinopulmonary infections due to Streptococcus pneumoniae and Haemophilus influenzae can occur in patients with chronic GVHD.
    • The incidence of pulmonary infections after day 100 is 50% in patients with chronic GVHD versus 21% in those without GVHD.
    • In patients who undergo unrelated donor transplantation, the risk of bacteremia and septicemia due to chronic GVHD and HLA-nonidentity is increased, and hypogammaglobulinemia occurs frequently.
  • Treatment of patients with chronic GVHD with azathioprine is associated with an increased risk of secondary neoplasms, such as squamous cell carcinomas of the skin and buccal mucosa.
  • Sclerodermatous lesions could lead to contractures of several joints, impairing mobility and the patient's ability to perform certain routine body movements.
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Prognosis

  • The overall grade of acute GVHD correlates well with outcome, as well as response to treatment.
    • Patients achieving a complete response have approximately a 22% mortality rate compared with a 75% mortality rate in patients who have progressive GVHD or no change with treatment.
    • Factors associated with impaired survival are HLA-nonidentical marrow donors, liver abnormalities in addition to GVHD, and early time to onset and treatment of GVHD.
  • For chronic GVHD, the 6-year survival rate is about 42% and is worst (10%) in patients with progressive onset.
  • Factors linked to high mortality rates are extensive disease, progressive onset, thrombocytopenia, HLA-nonidentical marrow donors, elevated bilirubin value at 2 mg/dL or greater, lichenoid histology on skin biopsy, and failure to taper prednisone treatment for acute GVHD before the onset of progressive chronic GVHD.
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Patient Education

  • Avoidance of excessive exposure to the sun by using sunblock lotion, sun-blocking headgear, and appropriate garments can decrease the incidence of sunburn, which can exacerbate GVHD reactions.
  • Patients should pay attention to good skin care, using moisturizing lotions or creams to prevent skin breakdown.
  • While receiving corticosteroid therapy, patients should be encouraged to preserve muscle tone and mass by avoiding sedentary activity and by regularly exercising.
  • Patients should avoid unnecessary exposure to potentially hazardous infections while they are receiving highly immunosuppressive treatment for GVHD. Examples of unnecessary exposure are the inhalation of fungal spores from the soil while gardening, working on farms, and working with animal excreta.
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Contributor Information and Disclosures
Author

Romeo A Mandanas, MD, FACP  Research Site Leader, Integris Cancer Institute of Oklahoma

Romeo A Mandanas, MD, FACP, is a member of the following medical societies: American College of Physicians, American Medical Association, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Oklahoma State Medical Association

Disclosure: Nothing to disclose.

Specialty Editor Board

Antoni Ribas, MD  Assistant Professor of Medicine, Division of Hematology-Oncology, University of California at Los Angeles Medical Center

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Marcel E Conrad, MD  Distinguished Professor of Medicine (Retired), University of South Alabama College of Medicine

Marcel E Conrad, MD is a member of the following medical societies: Alpha Omega Alpha, American Association for the Advancement of Science, American Association of Blood Banks, American Chemical Society, American College of Physicians, American Physiological Society, American Society for Clinical Investigation, American Society of Hematology, Association of American Physicians, Association of Military Surgeons of the US, International Society of Hematology, Society for Experimental Biology and Medicine, and Southwest Oncology Group

Disclosure: No financial interests None None

Chief Editor

Mary C Mancini, MD, PhD  Professor and Chief, Cardiothoracic Surgery, Department of Surgery, Louisiana State University Health Sciences Center-Shreveport

Mary C Mancini, MD, PhD is a member of the following medical societies: American Association for Thoracic Surgery, American College of Surgeons, American Surgical Association, Phi Beta Kappa, Society of Thoracic Surgeons, and Southern Surgical Association

Disclosure: Nothing to disclose.

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Autologous graft versus host disease (GVHD) involving the skin of a patient's arm appeared shortly after signs of engraftment appeared. The patient had undergone autologous peripheral blood stem-cell transplantation to treat ovarian cancer. Courtesy of Romeo A. Mandanas, MD, FACP.
Acute graft versus host disease (GVHD) involving desquamating skin lesions in a patient after allogeneic bone marrow transplantation for myelodysplasia. Courtesy of Romeo A. Mandanas, MD, FACP.
Oral mucosal changes in a patient with chronic graft versus host disease (GVHD). Note the skin discoloration (vitiligo), which can be a result of GVHD. Courtesy of Romeo A. Mandanas, MD, FACP.
Interactive factors involved in the pathogenesis of graft versus host disease (GVHD.) Courtesy of Romeo A. Mandanas, MD, FACP.
This boy developed stage III skin involvement with acute graft versus host disease (GVHD) despite of receiving prophylaxis with cyclosporin A. The donor was his HLA-matched sister; the sex disparity increased the risk for acute GVHD. Courtesy of Mustafa S. Suterwala, MD.
Same boy as in previous image progressed to grade IV graft versus host disease (GVHD). High-dose cyclosporin A and methylprednisolone had been administered intravenously. He later died from chronic pulmonary disease due to chronic GVHD. Courtesy of Mustafa S. Suterwala, MD.
Acute graft versus host disease (GVHD). Hematoxylin and eosin–stained tissue shows dyskeratosis of individual keratinocytes and patchy vacuolization of the basement membrane. Moderate superficial dermal and perivascular lymphocytic infiltrate are also observed. Courtesy of Melanie K. Kuechler, MD.
Table 1. Procedures Associated with a High Risk of GVHD*
ProcedureGroups at High Risk
Allogeneic HCTPatients receiving no GVHD prophylaxis



Older patients



Recipients of HLA-nonidentical stem cells



Recipients of graft from allosensitized donors



Recipients of grafts from unrelated donors



Solid-organ transplantation (organs containing lymphoid tissue)Recipients of small-bowel transplants
Transfusion of unirradiated blood productsNeonates and fetuses



Patients with congenital immunodeficiency syndromes



Patients receiving immunosuppressive chemoradiotherapy



Patients receiving directed blood donations from partially HLA-identical, HLA-homologous donors



Table 2. Clinical Staging of Acute GVHD
StageSkin FindingsLiver Findings (Bilirubin level, mg/dL)Gut Findings
+Maculopapular rash on < 25% of body surface2-3Diarrhea 500-1000 mL/d or persistent nausea
++Maculopapular rash on 25-50% of body surface3-6Diarrhea 1000-1500 mL/d
+++Generalized erythroderma6-15Diarrhea >1500 mL/d
++++Desquamation and bullae>15Pain with or without ileus
Table 3. Clinical Grading of Acute GVHD
Overall GradeStage
SkinLiverGutFunctional Impairment
0 (None)0000
I (Mild)+ to ++000
II (Moderate)+ to ++++++
III (Severe)++ to +++++ to +++++ to +++++
IV (Life-threatening)++ to ++++++ to ++++++ to +++++++
Table 4. Clinicopathologic Classification of Chronic GVHD
ClassificationClinicopathology
LimitedLocalized skin involvement and/or hepatic dysfunction due to chronic GVHD
ExtensiveGeneralized skin involvement or localized skin involvement and/or hepatic dysfunction due to chronic GVHD, plus 1 of the following:



- Liver histology showing chronic aggressive hepatitis, bridging necrosis, or cirrhosis



- Involvement of the eye (Schirmer test with < 5-mm wetting)



- Involvement of minor salivary glands or oral mucosa demonstrated on labial biopsy



- Involvement of any other target organ



Table 5. Screening Studies for GVHD by Organ or System
Organ or SystemClinical FindingsScreening Studies
SkinDyspigmentation, xerosis, erythema, scleroderma, onychodystrophy, alopeciaSkin biopsy with a 3-mm punch-biopsy sample from the back and forearm areas
MouthLichen planus, xerostomiaOral biopsy with sample from lower lip
EyesSicca, keratitisSchirmer test
LiverJaundiceAlkaline phosphatase, AST, bilirubin determinations
LungsObstructive and/or restrictive lung diseasePulmonary function studies, arterial blood gas analysis
VaginaSicca, atrophyGynecologic evaluation
GI (nutrition)Protein and calorie deficiencyWeight, measurement of muscle and/or fat stores
Multiple (clinical performance)Contractures, debilityDetermination of Karnofsky score and Lansky play index
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