Chapter 108. Hematopoietic Cell Transplantation (Part 4)

Complications Following Hematopoietic Cell TransplantEarly Direct ChemoradiotoxicitiesThe transplant preparative regimens commonly used cause a spectrum of acute toxicities that vary according to the specific regimen but frequently result in nausea, vomiting, and mild skin erythema (Fig. 108-1). Regimens that include high-dose cyclophosphamide can result in hemorrhagic cystitis, which can usually be prevented by bladder irrigation or with the sulfhydryl compound mercaptoethanesulfonate (MESNA); rarely, acute hemorrhagic carditis is seen. Most preparative regimens will result in oral mucositis, which typically develops 5–7 days posttransplant and often requires narcotic analgesia. Use of a patient-controlled analgesic pump provides the greatest patient satisfaction and...
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Chapter 108. Hematopoietic Cell Transplantation (Part 4) Chapter 108. Hematopoietic Cell Transplantation (Part 4) Complications Following Hematopoietic Cell Transplant Early Direct Chemoradiotoxicities The transplant preparative regimens commonly used cause a spectrum ofacute toxicities that vary according to the specific regimen but frequently result innausea, vomiting, and mild skin erythema (Fig. 108-1). Regimens that includehigh-dose cyclophosphamide can result in hemorrhagic cystitis, which can usuallybe prevented by bladder irrigation or with the sulfhydryl compoundmercaptoethanesulfonate (MESNA); rarely, acute hemorrhagic carditis is seen.Most preparative regimens will result in oral mucositis, which typically develops5–7 days posttransplant and often requires narcotic analgesia. Use of a patient-controlled analgesic pump provides the greatest patient satisfaction and results in alower cumulative dose of narcotic. Patients begin losing their hair 5–6 daysposttransplant and by 1 week are usually profoundly pancytopenic. Figure 108-1 Major syndromes complicating marrow transplantation. VOD, venoocclusive disease; GVHD, graft-versus-host disease; HSV,herpes simplex virus; CMV, cytomegalovirus; VZV, varicella-zoster virus. Thesize of the shaded area roughly reflects the risk of the complication. Approximately 10% of patients will develop venoocclusive disease of theliver, a syndrome resulting from direct cytotoxic injury to hepatic-venular andsinusoidal endothelium, with subsequent deposition of fibrin and the developmentof a local hypercoagulable state. This chain of events results in the clinicalsymptoms of tender hepatomegaly, ascites, jaundice, and fluid retention. Thesesymptoms can develop any time during the first month posttransplant, with thepeak incidence at day 16. Predisposing factors include prior exposure to intensivechemotherapy, pretransplant hepatitis of any cause, and use of more intenseconditioning regimens. The mortality of venoocclusive disease is ~30%, withprogressive hepatic failure culminating in a terminal hepatorenal syndrome. Boththrombolytic and antithrombotic agents, such as tissue plasminogen activator,heparin, and prostaglandin E, have been studied as therapy, but none has proven ofconsistent major benefit in controlled trials, and all have significant toxicity. Earlystudies with defibrotide, a polydeoxyribonucleotide, seem encouraging. Although most pneumonias developing posttransplant are caused byinfectious agents, in ~5% of patients a diffuse interstitial pneumonia will developthat is thought to be the result of direct toxicity of the preparative regimen.Bronchoalveolar lavage typically shows alveolar hemorrhage, and biopsies aretypically characterized by diffuse alveolar damage, although some cases may havea more clearly interstitial pattern. High-dose glucocorticoids are often used astreatment, although randomized trials testing their utility have not been reported. Late Direct Chemoradiotoxicities Late complications of the preparative regimen include decreased growthvelocity in children and delayed development of secondary sex characteristics.These complications can be partly ameliorated with the use of appropriate growthand sex hormone replacement. Most men become azoospermic, and mostpostpubertal women will develop ovarian failure, which should be treated. Thyroiddysfunction, usually well compensated, is sometimes seen. Cataracts develop in10–20% of patients and are most common in patients treated with total-bodyirradiation and those who receive glucocorticoid therapy posttransplant fortreatment of GVHD. Aseptic necrosis of the femoral head is seen in 10% ofpatients and is particularly frequent in those receiving chronic glucocorticoidtherapy.