Graft Versus Host Disease Follow-up

Updated: Aug 02, 2017
  • Author: Romeo A Mandanas, MD, FACP; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Follow-up

Further Inpatient Care

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

To minimize graft versus host disease (GVHD), donor and host factors should be addressed, as follows:

  • 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; for example, Japanese researchers recommend that reported that mismatched HLA-C*14:02 should be considered a non-permissive HLA-C mismatch in donor selection for unrelated donor hematopoietic stem cell transplantation, as it is a potent risk factor for severe acute GVHD and mortality [54]
  • Use of a cytomegalovirus (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 bone marrow transplantation

Posttransplantational immunosuppressive prophylaxis

Single agents or combinations of agents have been used to prevent acute GVHD. The most common effective regimen consists of cyclosporine administered for 180 days combined with a short course of methotrexate administered on days 1, 3, 6, and 11. The combination is better than either agent administered alone. In one 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 cyclosporine, is also being used in combination with methotrexate and appears to be more effective than cyclosporine at preventing acute graft versus host disease (GVHD), especially in patients receiving a transplant from an unrelated donor. The cumulative incidence of chronic GVHD also seems to be less with the tacrolimus-methotrexate combination (48%) than with the cyclosporine-methotrexate combination (64%). [40] 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 intravenous immunoglobulin (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 did not seem to change the cumulative incidence of chronic GVHD in treated patients compared with a control group that was not receiving IVIG. [55]

In a prospective, multicenter, open-label, randomized phase 3 study, the inclusion of antihuman T-lymphocyte immune globulin (ATG) in a myeloablative conditioning regimen for patients with acute leukemia resulted in a significantly lower rate of chronic GVHD after allogeneic transplantation than the rate without ATG. [56]

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 cyclosporine-methotrexate 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. [29]

Prevention is the most important aspect in managing transfusion-associated GVHD. Encourage the hospital's blood bank to automatically irradiate all blood products that may be transfused into high-risk patients.

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Complications

Late infections are possible. Multiple immune defects are observed in patients with chronic GVHD, such as impaired mucosal defense, chemotactic defects, functional asplenia, T-cell alloreactivity, and qualitative and quantitative B-cell abnormalities. Bacteremia and sinopulmonary infections due to Streptococcus pneumoniae and Haemophilus influenzae can occur. [57] 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.

Other complications include the following:

  • 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 can lead to joint contractures, 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, as follows:

  • 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. Other factors linked to high mortality rates are as follows:

  • Extensive disease
  • Thrombocytopenia
  • HLA-nonidentical marrow donors
  • Elevated bilirubin value at 2 mg/dL or greater
  • Lichenoid histology on skin biopsy
  • Failure to taper prednisone treatment for acute GVHD before the onset of progressive chronic GVHD
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Patient Education

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  • To decrease the incidence of sunburn, which can exacerbate GVHD reactions, patients should avoid excessive exposure to the sun by using sunblock lotion, sun-blocking headgear, and appropriate garments.
  • 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 exercising regularly.
  • 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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