Early Complications of HCT

Oral mucositis is inflammation of oral mucosa that typically manifests as erythema or ulcerations. It can result from the cytotoxic effects of chemotherapy- and radiation-based pre-transplant conditioning regimens. [2,3]

Mouth sores associated with acute graft-versus-host disease (GVHD) may also develop 2-4 weeks post-transplant. The severity and the patient's hematologic status govern appropriate oral management. Meticulous oral hygiene and palliation of symptoms are essential.

Acute GVHD is a common complication of allogeneic transplantation in which activated donor T cells attack the tissues of the transplant recipient after recognizing host tissues as antigenically foreign. The resulting inflammatory cytokines can cause tissue damage, and the commonly involved organs include the liver, skin, mucosa, and the gastrointestinal tract.

By classical definition, GVHD appearing before day 100 post-transplant is acute GVHD, and GVHD appearing after day 100 is chronic GVHD. However, acute GVHD may still occur later than 100 days post transplant (e.g., during tapering of immunosupressive drugs, or following a donor lymphocyte infusion). Some patients may also develop an overlap syndrome, where features of both acute and chronic GVHD are present. [4,5]

Graft failure is a rare, but life-threatening complication following allogeneic HCT. The most common cause of graft failure is an immunological rejection of the graft mediated by recipient T cells, natural killer cells, and/or antibodies. Other causes are infection, recurrent disease, or an insufficient number of stem cells in the donated graft. Graft failure occurs in approximately 5% of allogeneic transplants. [6]

The rate of failure can vary by graft source, and is increased in HLA-mismatched grafts, unrelated-donor grafts, T cell-depleted grafts, and umbilical cord blood grafts. Patients allo-sensitized through prior blood transfusions or pregnancy, and those receiving reduced-intensity conditioning are also at a higher risk of experiencing graft failure.

If graft failure occurs, treatment is a second HCT, using cells from the same donor or from a different donor. Patients experiencing graft failure after a cord blood transplant cannot get backup cells from the same cord blood unit. However, it may be possible to use a different cord blood unit or a backup adult donor instead.

All transplant recipients are susceptible to infections and require careful monitoring, which allows for timely administration of antibacterial, antiviral, and/or antifungal agents. [7]

Average times of full immune recovery are:

• Neutrophils and phagocytes: 1 month
• T cells: 6-12 months
• B cells: 12-24 months

Common infections in early and later post-transplant time periods are shown below.

> 0-3 Months:

• Most bacteria
• Candida, Aspergillus, other fungi
• Herpes simplex
• Pneumocystis carinii
• Cytomegalovirus (CMV)

> 3 Months:

• P. carinii
• Varicella-Zoster viruses
• Cytomegalovirus (CMV)
• Encapsulated bacteria

Organ injury and toxicity following transplant can include hepatic veno-occlusive disease (VOD) also known as sinusoidal obstruction syndrome, renal failure, pulmonary toxicity, thrombotic microangiopathy (TMA), and cardiovascular complications.

Pulmonary Complications

In the early post-transplant neutropenic period, there is an increased risk of various bacterial, fungal, and viral infections of the lung, and pneumonia develops in 40% to 60% of transplant recipients. [8] The pneumonias that can occur include herpes simplex pneumonitis, cytomegalovirus pneumonitis, and Pneumocystis carinii pneumonia.

Bronchiolitis obliterans syndrome and bronchiolitis obliterans organizing pneumonia can appear later (post day 100) in the transplant recovery period. Bronchiolitis obliterans is closely associated with chronic GVHD and may result from alloimmunologic injury to host bronchiolar epithelial cells. [8,9]

Renal Complications

Chronic kidney disease (CKD) is associated with the use of TBI in the transplant conditioning regimen, although many cases are idiopathic. TBI-associated CKD has a typical latency of 3-6 months from irradiation to injury. CKD after transplantation may not be recognized early due to competing clinical priorities such as the treatment of GVHD, and monitoring for infections and disease recurrence. [10]

Liver Complications

Sinusoidal obstructive syndrome (SOS) also known as veno-occlusive disease (VOD) of the liver (SOS/VOD) is the result of damage to the hepatic sinusoids, resulting in biliary obstruction. Risk factors include the use of busulfan, TBI, infection, acute GVHD, and pre-existing liver dysfunction due to iron overload or hepatitis. [11]

Thrombotic Microangiopathy

Transplant-associated TMA is a rare complication after allogeneic transplantation, and can occur after autologous transplantation. Risk factors for TMA include pre-transplant conditioning with busulfan, fludarabine, platinum-based chemotherapy, and total body irradiation (TBI). TMA is also associated with the use of the calcineurin inhibitors, tacrolimus and cyclosporine. Transplant-associated TMA syndromes present as hemolytic uremic syndrome (HUS) or thrombotic thrombocytopenic purpura (TTP). [12]

Cardiovascular Complications

Cardiovascular complications may manifest as subclinical abnormalities or present as overt congestive heart failure or angina. The cardiac complications include any cardiac dysfunction due to cardiomyopathy, valvular anomaly, or conduction anomaly. [13]