Acute Graft-Versus-Host Disease (GVHD)
Treatment Options & Monitoring
Updated: November 2010
The response to primary therapy is of central importance as responses correlate with survival.
Glucocorticoids are the mainstay of acute GVHD therapy. Complete responses are seen in 25% to 40% of patients, and clinically relevant improvement, defined as regression of skin rash or decrease in the volume of diarrhoea and the extent of liver function abnormalities in 40%-50% of patients with grades II or IV acute GVHD.
Treatment
At the onset of acute GVHD
A biopsy is not mandatory prior to commencing treatment.
Monitoring of Response
If no progression (increase in the stage in any system) after the 6th dose, then continue same therapy. If complete remission, or less than Grade II after the 10th dose of MP start a steroid taper:
Suggested Steroid Taper:
Days 6-10: 1.5mg/kg/day
Days 11-15: 1 mg/kg/day
Days 16-20: 0.5 mg/kg/day
Days 21-28: 0.25mg/kg/day
Days 29+: taper as tolerated; suggest 10% per week
Management of Steroid Refractory Acute GVHD
Definition: If manifestations of GVHD in any organ worsen over 3 days of treatment of if the skin does not improve by 5 days, it is unlikely that a response will be achieved in a timely fashion, and secondary therapy should be considered.
| Organs with Predominant GVHD Manifestation | Potential Secondary/Tertiary Therapies |
| Skin | Anti-CD25 monoclonal antibody (basiliximab); ATG**; |
| Liver | ATG**; Anti-CD25 |
| GI Tract | "Non-absorbable" steroids (beclomethasone, budesonide)*; ATG**; TNF-α blockade (entanercept); |
* In patients with prominent intestinal manifestation, the addition of beclomethasone or budesonide may allow a reduction in the dose of sytemically administered steroids.
** Substitute Anti-CD52 in patients whose conditioning regimen included ATG
Other Considerations
Infections are the major non-relapse cause of death in patients receiving therapy for GVHD and all patients should receive infection prophylaxis. This should include PCP prophylaxis with Septra and prevention of herpes virus with acyclovir. While on GVHD therapy, patients need to be monitored for viral reactivation, in particular CMV (and EBV in patients receiving ATG). If there is evidence of reactivation treatment with ganciclovir (and rituximab for EBV), should be given. All patients should receive azole prophylaxis against fungal infections. Invasive molds, especially aspergillus are common in patients with prolonged steroid use.
Chronic immunosuppressive therapy has multiple toxicities. Prolonged therapy with steroids results in muscle weakness and wasting. It is important to make every effort to keep patients mobile and to involve a physiotherapist to develop an individual exercise program. Diabetes, hypertension, osteoporosis, avascular necrosis and other Cushingoid features are common with chronic steroid use and should be monitored for.Calcineurin inhibitors frequently cause renal impairment and levels need to be monitored.
| The information contained in these guidelines is a statement of consensus of Leukemia/BMT Program of BC professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult these documents is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. Use of these guidelines and documents is at your own risk and is subject to the Leukemia/BMT Program of BC’s terms of use available at Terms of Use. |