Infections

Patients undergoing stem cell transplantation have increased risks of infection related to their disease and its status. Patients with more than two relapses who undergo stem cell transplantation develop more infectious complications than those who receive transplants during the first remission. The adequacy of treatment of any infection in the patient prior to marrow ablation influences the risk of subsequent complications. Prolonged duration of neutropenia, use of central venous catheters, and slow speed of marrow engraftment are important risk factors.

Table 25-13 lists prophylaxis and supportive care for stem cell transplantation. Table 25-14 lists the infections most frequently seen at different times post-transplantation.

Table 25-13. Prophylaxis and Supportive Care for Stem Cell Transplantation

1. Mouth care: Peridex or Biotin solution and Mycostatin every 3-4 hours daily

2. Recombinant hematopoietic growth factors: G-CSF or GM-CSF (Chapter 26)a

3. Prophylaxis against Pneumocystis carinii: trimethoprim/sulfamethoxazole 5 mg/kg in two divided doses (3 times per week) starting after engraftment; continue if chronic GVHD is present6

4. Prophylaxis against Candida: fluconazole 4-6 mg/kg once a day

5. Prophylaxis for herpes simplex and CMV: IV acyclovir 250 mg/m2 every 8 hours for first 3-6 months or longer if patient continues to be on immunosuppressive drugs.

6. Additional prophylaxis for CMV:

a. CMV-negative blood products should be used if patient and donor are CMV-negative patients; if CMV-negative blood is not available, leukocyte filters to remove leukocytes should be employed b. Ganciclovir 5 mg/kg/dose twice a day for 1 week followed by 5 mg/kg once a day until day 100 post-transplant. Ganciclovir should be started when absolute neutrophil count is above 1000/mm3.c

7. IVIG (only in recipient of allogeneic stem cell transplant): 500 mg/kg every 2-3 weeks for first 3 months after transplanta; then check IgG levels periodically if less than within normal limits; then infuse accordingly

8. Nutrition: total parenteral nutrition given if enteral nutrition is not possible or inadequate

"Does not increase relapse and GVHD rates. Stimulates hematopoietic recovery.

If patients are allergic to trimethoprim/sulfamethoxazole or if severe cytopenia is present, aerosolized pen-tamidine (300 mg) or intravenously 4 mg/kg once a month can be used. cDrug-related neutropenia is a major side effect.

dFor its immunomodulatory (decreased incidence of GVHD) effect and antimicrobial activity, especially CMV. It also decreases gram-negative sepsis.

Table 25-14. Infections Most Frequently Seen at Different Times Post-Transplantation

I. Infections in first 30 days post-transplantation

A. Bacteremia

Gram-positive organisms: Staphylococcus epidermidis Gram-negative aerobes and anaerobes

B. Invasive fungal infections: Aspergillus, Candida

C. Reactivation of herpes simplex I

II. Infections 30-120 days post-transplantation

A. Protozoal infections Pneumocystis carinii Toxoplasma

B. Viral infections Cytomegalovirus (CMV) Adenovirus

Epstein-Barr virus (EBV) Human herpesvirus 6 (HHV-6)

C. Fungal infections

Candida (C. albicans and C. tropicalis)

Aspergillus

Trichosporon

Fusarium

Candida krusei

III. Infections after 120 days post-transplantation

A. Sinopulmonary infections with encapsulated organisms

B. Viral infections Cutaneous herpes zoster

During the first 30 days, the most frequently documented infection is coagulase-negative staphylococcal epidermidis infection associated with the use of indwelling central venous catheters. During the second and third months, infections with CMV and interstitial pneumonia occur. CMV infection occurs within approximately 20-100 days after transplantation, with the highest infection rate in patients who are CMV seropositive before transplantation or seronegative recipients receiving a seropositive graft. CMV infection arises from exogenous introduction of virus in blood products or from reactivation of endogenous virus.

The clinical manifestations of CMV infection are variable, ranging from asymptomatic viral excretion to fever, arthralgia, arthritis, hepatitis, secondary bone marrow hypoplasia with thrombocytopenia and leukopenia, retinitis, esophagitis, gastroenteritis, and pneumonia with up to 80% mortality.

Early treatment with the antiviral drug ganciclovir plus high-titer CMV intravenous gammaglobulin has reduced morbidity to less than 20%. Prophylactic or preemptive therapy in seropositive patients or patients receiving a seropositive graft is an effective way to prevent the development of CMV.

The following guidelines for the prophylaxis and treatment of CMV infections should be carried out (as recommended by the U.S. Centers for Disease Control and Prevention along with the American Society of Blood and Marrow Transplantation):

1. Allogeneic transplantation patients who are seronegative at the time of transplant and have a seronegative donor do not require additional CMV prophylaxis other than the strict use of CMV-negative blood products.

2. Allogeneic transplantation patients who are CMV positive at transplant or those who received a transplant from a CMV-positive donor should receive prophylactic or preemptive ganciclovir.

3. Allogeneic transplantation patients should have surveillance for CMV antigen-emia assay or a polymerase chain reaction (PCR) assay and blood, urine, and throat cultures obtained weekly for the first 120 days post-transplant. Those patients with evidence of CMV cultured from blood, bronchial washings, the throat, or the gastrointestinal tract should be treated with ganciclovir and gam-maglobulin at least until day 100 after transplant or for 2-3 weeks past the latest date of positive cultures.

4. Autologous transplantation patients who are seronegative at the time of transplant should preferably receive CMV-negative blood products but may, as an alternative, receive leukocyte-filtered blood products.

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