Primary prevention

Prolonged use of immunosuppressive drugs has not been shown to prevent chronic to prevent acute graft versus host disease (GVHD).[61]​ There is currently no effective prophylaxis for chronic GVHD. Nonetheless, early intervention guided by a multidisciplinary approach to treatment, including appropriate immunosuppressive drugs medications and aggressive supportive care, is critical in the management of chronic GVHD.

Prophylaxis is the primary strategy to prevent acute GVHD.[62][63]​​

The most commonly used drug combination for acute GVHD prophylaxis includes a calcineurin inhibitor (cyclosporine or tacrolimus, which act to block T-cell activation) and low-dose methotrexate or mycophenolate.[64][65]

Evidence continues to influence the management of GVHD prophylaxis, and alternative prophylactic treatment strategies may be considered for specific patient populations.

Abatacept

A selective T-cell costimulation modulator, abatacept is approved by the Food and Drug Administration (FDA), in combination with a calcineurin inhibitor and methotrexate, for the prevention of acute GVHD in patients undergoing allogeneic hematopoietic cell transplantation (HCT) from a matched or 1 allele-mismatched unrelated donor.

In one phase 2 randomized trial, the addition of abatacept to standard prophylaxis with a calcineurin inhibitor and methotrexate numerically reduced rates of severe (grade III or IV) acute GVHD (6.8% vs. 14.8%), and significantly improved severe acute GVHD-free survival (93.2% vs. 82%), in patients with hematologic malignancies who had undergone HCT from an HLA-matched (8/8) unrelated donor.[66] 

Posttransplant cyclophosphamide (combined with standard prophylaxis of tacrolimus plus mycophenolate)

Increasingly favored for primary GVHD prevention based on results from large-scale, multi-site clinical trials.[63][67]​​​​​[68]​ In one phase 3 trial of patients undergoing allogeneic HLA-matched HCT with reduced-intensity conditioning, GVHD-free, relapse-free survival at 1 year was significantly more common in patients randomized to cyclophosphamide-based prophylaxis (cyclophosphamide, tacrolimus, and mycophenolate) than those assigned to standard prophylaxis (52.7% vs. 34.9%).[67]​ Posttransplant cyclophosphamide-based prophylaxis is commonly used in patients who have undergone allogeneic HCT from an HLA-haploidentical (i.e., half-matched) donor or unrelated donor.[69][70]

Rabbit anti-thymocyte globulin

A polyclonal immunoglobulin G, rabbit anti-thymocyte globulin reduces the cumulative incidence of both acute and chronic GVHD in patients undergoing HCT from unrelated donors. In one randomized phase 3 trial, the addition of rabbit anti-thymocyte globulin to standard prophylaxis (cyclosporine or tacrolimus plus methotrexate or mycophenolate) reduced acute GVHD incidence at 30 and 100 days compared with standard prophylaxis (30 days: 22% vs. 37%; 100 days: 50% vs. 65%).[71] At 24 months, this regimen reduced incidence of chronic GVHD (26.3% vs. 41.3%), and lead to improved survival (70.6% vs. 53.3%) and reduced use of immunosuppressive therapy.[72] Rabbit anti-thymocyte globulin effectively reduces GVHD incidence after HLA-matched sibling donor HCT.[73]

Sirolimus combined with standard prophylaxis (cyclosporine plus mycophenolate)

Lowers the incidence of grade II to IV acute GVHD (at day 100) compared with cyclosporine plus mycophenolate alone in patients who have undergone allogeneic HCT from an HLA-matched unrelated donor with non-myeloablative conditioning.[74]

Tacrolimus plus sirolimus

Suggested as an alternative regimen to standard GVHD prophylaxis.[75][76][77][78]​ Incidence of acute GVHD (by day +114) is similar between tacrolimus plus sirolimus and tacrolimus plus methotrexate in patients who have undergone allogeneic HCT from a matched related donor.[78]

Secondary prevention

A critical component in the management of GVHD is its early recognition and prompt, effective intervention that may ultimately prevent the progression to severe disease.[79]

Routine monitoring and open communication between the patient and physician guide the duration and intensity of immunosuppressive drugs. Preventive actions include infection prophylaxis (antibacterial, viral, and fungal), vaccinations, general hygiene, and involvement of necessary consultants (dental, ophthalmology, gynecology, physical therapy, psychosocial therapy).

Recommendations regarding screening and preventive practices for long-term survivors after hematopoietic cell transplantation are available.[80][169][179] Children's Oncology Services Opens in new window​​​ National Marrow Donor Program Opens in new window European Society for Blood and Marrow Transplantation Opens in new window Center for International Blood and Marrow Transplant Research Opens in new window American Society for Transplantation and Cellular Therapy Opens in new window​​​​​​

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