Gardner, A., Mattiuzzi, G., Faderl, S., Borthakur, G., Garcia-Manero, G., Pierce, S., & Estey E. (2008). Randomized comparison of cooked and noncooked diets in patients undergoing remission induction therapy for acute myeloid leukemia. Journal of Clinical Oncology, 26, 5684–5688.

This study was an evaluation of whether a diet including fresh fruits and vegetables increased the risk of infection in adult patients with cancer who were receiving induction chemotherapy for either acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) in a protective environment.

Patients were randomized to either a “raw group” (n = 75) that was allowed a general diet including fresh fruits and vegetables or to a “cooked group” (n = 78) that was restricted to a low-microbial diet of all cooked food but no fresh fruit or vegetables. Patients remained in a protective environment from the initiation of induction chemotherapy until recovery of the absolute neutrophil count (ANC) over 500 mcl.  

Patients received routine antimicrobial prophylaxis with levofloxacin, valacyclovir, and an antifungal agent (itraconazole, voriconazole, or lipid amphotericin B).

Granulocyte–colony-stimulating factor was not used routinely.

Endpoints for the study were pneumonia, bacteremia, major infection, fever of unknown origin, and death.

• A total of 153 patients were in the study.
• Patients were all newly diagnosed with either AML or MDS and received induction chemotherapy in a protective environment (with a high-efficiency particulate air-filtered room).
• Median age of the patients in the raw group was 63 years.
• Median age of the patients in the cooked group was 64 years.
• The most frequent chemotherapy used was cytarabine.
• One-third of the new patients (n = 53) refused to participate in the study and were placed in a nonrandomized group. They stayed on the low-microbial diet and were given a separate consent for chart review.

A single institution

The statistical design was the Bayesian multiple outcome design of Thall and Sung. The X2 or Kruskal-Wallis test was used to compare various pretreatment characteristics.

There was no statistically significant difference in the rate of infection, pneumonia, fever of unknown origin, or overall survival between the raw and cooked groups. A significantly higher rate of bacteremia was found in the raw group; however, the authors noted that most of the organisms responsible for the baceteremia were not of enteric origin.

The median number of days with an ANC less than 500 mcl was 20 days in the cooked group and 21 days in the raw group.
The median number of days with an ANC less than 100 mcl was 15 in the cooked group and 16 in the raw group.

• Major infection rates: raw group: 35%; cooked group: 29% (p = 0.6)
• Pneumonia rates: raw group: 5%; cooked group: 15% (p = 0.06)
• Bacteremia or fungemia rates: raw group: 23%; cooked group: 9% (p = 0.03)
• Fever of unknown origin rates: raw group: 36%; cooked group: 51% (p = 0.07)
• Rate of infection or fever of unknown origin: raw group: 76%; cooked group: 87% (p = 0.09)
• No significant difference existed in the rate of enteric organisms cultured from blood in either group (p = 0.12).
• Survival rates: raw group: 61%; cooked group: 56%; non-randomized: 64%
• Survival in all three groups was as expected in older patients with newly diagnosed AML or MDS.

A diet that includes raw fruits and vegetables did not increase the risk of infection or death in patients with MDS or AML treated with remission induction chemotherapy in a protective environment when compared to a diet that restricted raw fruits and vegetables.

One strength of the study is that the sample was a population of high-risk patients who had an ANC less than 500 mcl for a median of 20 days. In comparison, patients with solid tumors treated with chemotherapy are at low risk for infection, and the patients that experience neutropenia generally have an ANC less than 500 mcl less than seven days. Because this study demonstrated an absence of efficacy of the low-microbial diet in high-risk patients; it is unlikely to be of benefit in low-risk patients with a much shorter duration of neutropenia. However, further research is warranted to confirm the findings in other populations of neutropenic patients.

• The study was done at a single institution.
• The study was conducted with patients in a protective environment, and patients were treated routinely with prophylactic antimicrobial agents. Therefore, findings are not generalizable to outpatients, patients cared for in non-protective environments, or patients not treated with prophylactic antimicrobial agents.
• The rates of infection and death were the same between study groups; however, the rate of bacteremia was significantly higher in the raw group. Although the incidence of bacteremia was higher in the raw group, the authors reported that a substantial part of the difference reflected isolation of organisms not resident in the gut; the presence of such organisms would not be expected to be influenced by cooking of fruits and vegetables. In addition, the incidence of fever of unknown origin was higher in the cooked group, suggesting that some cases of bacteremia in the cooked group were not identified.