Side effects of transplantation regimens and immunosuppressive regimens (GVHD-prophylaxis)

Here we will discuss only the direct side effects owed to the toxicity of the total body irradiation and the drugs used for the conditioning and the GVHD-prophylaxis.

Side effects of myeloablative conditioning regimens

Myeloablative conditioning regimens are not only toxic for the hematopoietic cells but also for other type of cells (organs). It is not always straight-forward whether complications in organs are directly caused by toxicity of the regimen of by combinations of the regimen and for instance GVHD. Almost all organs can be involved and the listing of the complications below is far from being complete.

Liver: Liver complications are the most frequent regimen related complications. Mild hepatic dysfunction (biluribin < 5mg/dl) to severe complications with formation of ascites may occur. Veno-occlusive disease may occur in 10-30% of the patients.
Heart: Complications may vary from mild to severe ECG abnormalities sometimes leading to heart failure. The mechanism is not clear but it has been established that high doses of cyclophosphamide cause hemorrhagic carditis in laboratory animals
Lungs: All non-infectious pneumonia may be considered as a result of the regimen related toxicity. Complications may vary from mild to severe dyspnea needing ventilatory support
Gastrointestinal complications: Nausea and vomiting, abdominal pain and diarrhea are common but these complications are seldom life-threatening
Hemorrhagic cystitis, the ulceration of the bladder mucosa is common while Mucositis is by far the most common complaint in HSC-transplanted patients.

Side effects of agents used for GVHD-prophylaxis (immunosuppressive drugs)

Methotrexate, glucocorticoids and the calcineurin inhibitors such as cyclosporine or tacrolimus are the agents used. All come with characteristic side effects. Methotrexate is toxic for the bone marrow and the graft takes may be slow as a consequence. Other sensitive tissues are the oral mucosa and the gastrointestinal tract. Glucocorticoids cause fluid retention, hypertension and many other adverse effects. The calcineurin inhibitors are nephrotoxic with resulting lower glomerular filtration rates and the risk of hypertension.