Critical illness-related corticosteroid insufficiency in cancer patients.

PURPOSE: Critically ill cancer patients with sepsis represent a high-risk sub-group for the development of critical illness-related corticosteroid insufficiency (CIRCI); however, the incidence of CIRCI in this population is unknown. The purpose of this study was to determine the incidence of CIRCI in cancer patients with severe sepsis or septic shock. METHODS: A single-center, retrospective, observational study was conducted in a 52-bed medical-surgical intensive care unit of a National Cancer Institute-recognized academic oncology institution. Eighty-six consecutive patients with a diagnosis of severe sepsis or septic shock who received a high-dose 250-µg cosyntropin stimulation test were included. CIRCI was identified by a maximum delta serum cortisol of 9 µg/dL or less post cosyntropin. RESULTS: Overall, 59% (95% CI, 48-70%) of cancer patients with severe sepsis or septic shock were determined to have CIRCI. When compared to patients without CIRCI, patients with CIRCI had higher baseline serum cortisol (median, 26.3 versus 14.7 µg/dL; p = 0.002) and lower delta cortisol levels (median, 3.1 versus 12.5 µg/dL; p < 0.001). Mortality did not differ between the two groups. An inverse relationship was identified between baseline serum cortisol and maximum delta cortisol (maximum delta cortisol = -0.27 × baseline cortisol + 14.30; R (2) = 0.208, p < 0.001). CONCLUSIONS: The incidence of CIRCI in cancer patients with severe sepsis or septic shock appears high. Further large-scale prospective trials are needed to confirm these findings.

Endoscopic biopsy diagnosis of acute gastrointestinal graft-versus-host disease: rectosigmoid biopsies are more sensitive than upper gastrointestinal biopsies.

OBJECTIVES: The diagnosis of gastrointestinal (GI) graft-versus-host disease (GVHD) is based upon histologic findings in endoscopic mucosal biopsy specimens. The portion of the GI tract with the highest diagnostic yield is a topic of debate. Our aim was to evaluate the sensitivity of simultaneous biopsy of the stomach, duodenum, and rectosigmoid in establishing the diagnosis of GI GVHD. METHODS: We identified 112 patients who had simultaneous endoscopic biopsies of the stomach, duodenum, and rectosigmoid within the first 100 days following allogeneic hematopoietic stem cell transplantation (HSCT). GVHD was defined histologically as the presence of gland apoptosis, not explained by other inflammatory or infectious etiologies. The patient was diagnosed with GI GVHD if at least one biopsy site was positive. RESULTS: Overall, 81% of the patients had GI GVHD. Of these, 66% had involvement at all three biopsy sites. Rectosigmoid biopsies had the highest sensitivity, specificity, positive predictive value, and negative predictive value for diagnosing GI GVHD, at 95.6%, 100%, 100%, and 84%, respectively. The sensitivities of gastric and duodenal biopsies were 72.5% (P < 0.0001 vs rectosigmoid) and 79.2% (P = 0.0018), respectively. The negative predictive values of gastric and duodenal biopsies were 45.6% (P = 0.0039 vs rectosigmoid) and 52.5% (P = 0.0205), respectively. Rectosigmoid biopsies had a higher sensitivity and negative predictive value than biopsies at other sites whether the patient presented with diarrhea or nausea/vomiting. No association between the degree of mucosal injury and the presence of GVHD was found at any site. CONCLUSIONS: Biopsy of the rectosigmoid is the single best test for diagnosing GI GVHD.

Allogeneic hematopoietic stem cell transplantation for the treatment of high-risk acute myelogenous leukemia and myelodysplastic syndrome using reduced-intensity conditioning with fludarabine and melphalan.

Reduced-intensity conditioning has extended the use of allogeneic hematopoietic stem cell transplantation (HSCT) to patients otherwise not eligible for this treatment due to older age or frailty. One hundred twelve acute myelogenous leukemia/myelodysplastic syndromes patients received fludarabine and melphalan (FM) conditioning with allogeneic HSCT. Most patients (73%) were not in remission. Graft-versus-host disease (GVHD) prophylaxis consisted of tacrolimus and mini-methotrexate. Median age was 55 years (range, 22-74). Donors were related (53%) and unrelated (47%). Median follow-up of surviving patients (n = 43) was 29.4 months (range, 13.1-87.7). The complete remission (CR) rate was 82%. Estimates of 2-year survival were 66%, 40%, and 23% for patients in CR, with active disease without and with circulating blasts at HSCT, respectively. In multivariate analysis, survival was negatively influenced by active disease at HSCT and development of grade II-IV acute GVHD. Presence of circulating blasts at HSCT negatively influenced freedom from disease progression. Incidence of nonrelapse mortality (NRM) was significantly higher for patients with active disease, but was not influenced by patient age. Patients in CR had a day-100 and 2-year NRM of 0% and 20%, respectively. Use of unrelated donors increased the risk of NRM only among patients with active disease. FM and HSCT elicited long-term disease control in a significant fraction of this high-risk cohort.

Hyperacute GVHD: risk factors, outcomes, and clinical implications.

Acute graft-versus-host disease (GVHD) is a major limiting factor in allogeneic hematopoietic stem cell transplantation (HSCT), and the timing of acute GVHD may affect patient outcomes. We evaluated the incidence, risk factors, clinical manifestations, and outcomes of hyperacute GVHD, defined as that occurring within 14 days after transplantation, among 809 consecutive HSCTs at the University of Texas M.D. Anderson Cancer Center. Of 265 patients with grade II-IV acute GVHD, 27% had biopsy-proven hyperacute GVHD. Skin involvement was significantly more common (88% versus 44%) and more severe (stage III-IV, 88% versus 66%) in the hyperacute group compared with acute GVHD diagnosed after day 14. On multivariate analysis, significant risk factors for hyperacute GVHD included a mismatched related or matched unrelated donor, a myeloablative conditioning regimen, more than 5 prior chemotherapy regimens, and donor-recipient sex mismatch. Hyperacute GVHD was associated with a significantly lower response rate to first-line therapy and a higher rate of nonrelapse mortality in patients with a mismatched related or matched unrelated donor graft. In conclusion, hyperacute GVHD accounts for a substantial proportion of grade II-IV acute GVHD after HSCT. Patients at high risk or with a diagnosis of hyperacute GVHD should be included in clinical studies.

Respiratory viral infections in adults with hematologic malignancies and human stem cell transplantation recipients: a retrospective study at a major cancer center.

Community respiratory viruses (CRVs) have been recognized as a potential cause of pneumonia and death among hematopoietic stem cell transplantation (HSCT) recipients and patients with hematologic malignancies. We reviewed the Microbiology Laboratory records dated from July 1, 2000, to June 30, 2002, to identify patients who had respiratory specimens positive for influenza, parainfluenza, respiratory syncytial virus, or picornavirus. We identified 343 infections among patients with underlying hematologic malignancies and HSCT. We collected data on type of disease, age, sex, type of infection, neutrophil and lymphocyte counts, therapy, and outcome. Influenza, parainfluenza, and respiratory syncytial virus accounted for most cases and were approximately equal in frequency. Most infections occurred predominantly among recipients of allogeneic transplants. Infection progressed to pneumonia in 119 patients (35%) and occurred with similar frequency for the 3 viruses. Patients at greatest risk for developing pneumonia included those with leukemia, those aged more than 65 years, and those with severe neutropenia or lymphopenia. Lack of respiratory syncytial virus-directed antiviral therapy (p=0.025) and age (p=0.042) were associated with development of respiratory syncytial virus pneumonia, and an absolute lymphocyte count

Extracorporeal photochemotherapy for the treatment of steroid-resistant chronic GVHD.

Chronic graft-versus-host disease (GVHD) is a major limitation of successful allogeneic hematopoietic stem cell transplantation (HSCT). Extracorporeal photochemotherapy (ECP) has been tested extensively in small cohorts of patients with chronic GVHD. In this study, we retrospectively evaluated 71 patients with severe chronic GVHD treated with ECP. Response rate was 61% (n = 43), and 14 patients had complete responses (CRs). The best responses were observed in skin, liver, oral mucosa, and eye. Factors affecting outcomes were assessed in the less heavily pretreated subgroup (n = 63). Thrombocytopenia was associated with a lower response rate (P = .04), and there was a trend toward a higher response rate in de novo chronic GVHD. At 6 months, a total of 27 (69%) of 39 patients who were alive continued to have a sustained response (CR 4 [10%] of 39, and partial response [PR] 23 [59%] of 39). The cumulative incidence of steroid discontinuation at 1 year was 22%. The overall survival since initiation of therapy was 53% at 1 year. Response to ECP and platelet count at initiation of therapy were the strongest predictors of nonrelapse mortality (NRM) on univariate analysis. Objective responses were observed in a substantial number of patients with both skin and visceral chronic GVHD failing corticosteroids and other immunosuppression.