John R. Wingard

Personal changes, dispositional optimism, and psychological adjustment to bone marrow transplantation.

We investigated the number and direction of personal changes experienced by long-term survivors of bone marrow transplantation (BMT) and the relationships of those changes and dispositional optimism to psychological adjustment (current and future life satisfaction and mood). Surveys were returned by 86.0% (N=135) of all eligible long-term survivors; respondents primarily were young males who were 6 to 149 months post-BMT. Subjects reported more positive changes in the relationship and existential/psychological domains and more negative changes in the physical health domain; there was no difference on the plans/activities domain. Negative changes were more strongly related to adjustment than were positive changes. The number of negative changes reported was significantly related to current and future life satisfaction and negative mood after controlling for demographic and illness variables and dispositional optimism. The interaction term for negative and positive changes was significantly related to future life satisfaction after controlling for all other variables.

Diagnosis and therapeutic monitoring of invasive candidiasis by rapid enzymatic detection of serum d-arabinitol

BACKGROUNDnUsing a rapid automated enzymatic assay, we prospectively investigated serum D-arabinitol (DA), a biochemical marker of invasive candidiasis, in a large population of high-risk patients to determine its potential diagnostic, therapeutic, and prognostic significance in invasive candidiasis.nnnPATIENTS AND METHODSnA total of 3,223 serum samples were collected from 274 patients with cancer. Serum DA concentrations were determined in coded serum samples analyzed by rapid enzymatic assay. Creatinine also was analyzed in the same system to determine a serum DA and creatinine ratio (DA/Cr). The sensitivity, specificity, correlation with therapeutic response, and prognostic significance were analyzed for all patient study groups.nnnRESULTSnA DA/Cr of > or = 4.0 mumol/L per mg/dL was detected in 31 (74%) of all 42 cases of fungemia and 25 (83%) of the 30 cases of the subset of persistent fungemia. Elevated DA/Cr was detected in 4 (40%) of 10 patients with tissue-proven, deeply invasive candidiasis and negative blood cultures (eg, hepatosplenic candidiasis or localized abscess) and 7 (44%) of 16 cases of deep mucosal candidiasis (eg, esophageal candidiasis). Elevated serial DA/Cr levels also were detected in persistently febrile and granulocytopenic patients requiring empirical amphotericin B. Among 26 assessable cases of fungemia, abnormally elevated DA/Cr values were detected in 14 (54%) before, 10 (38%) after, and 2 (8%) simultaneously with the first microbiologic report of fungemia. The trends of serial DA/Cr values correlated with therapeutic response in 29 (85%) of 34 patients with assessable cases of fungemia, decreasing in 8 (89%) of 9 patients with clearance of fungemia and increasing in 21 (84%) of 25 patients with persistence of fungemia. Among the 34 assessable patients with fungemia, mortality was directly related to the trend of serial DA/Cr determinations over time: 71% among fungemic patients who had persistently elevated or increasing DA/Cr, and 18% among the fungemic patients who had resolving DA/Cr or never had elevated DA/Cr (P < 0.01).nnnCONCLUSIONSnRapid enzymatic detection of DA in serially collected serum samples from high-risk cancer patients permitted detection of invasive candidiasis, early recognition of fungemia, and therapeutic monitoring in DA-positive cases. Serially collected serum DA determinations complement blood cultures for improving detection and monitoring therapeutic response in patients at risk for invasive candidiasis.

Loss and Recovery Themes of Long-Term Survivors of Bone Marrow Transplants

This article presents findings on how survivors of an intensive treatment for cancer-bone marrow transplantation (BMT)- conceptualize and describe their current lives. The presence of 11 themes of loss (e.g., loss of reproductive capability) and 11 themes of recovery (e.g., finding new meaning in life) were rated from statements made by 135 survivors of BMT in response to items from an in-depth, structured questionnaire. No significant differences were found in the frequency of themes of loss versus recovery. A classification of respondents revealed that 26.7 percent focused more on loss, 21.5 percent focused more on recovery, and 51.8 percent had a balanced view of their lives. The frequencies of specific loss and recovery themes were related to gender, age at BMT, marital status, and time since BMT. The authors discuss the possibility that subgroups of survivors, on the basis of life stage, find different routes to recovery.

Viral Infections in Leukemia and Bone Marrow Transplant Patients

Infections by herpesviruses are common phenomena in patients being treated for acute leukemia and those undergoing bone marrow transplantation. Reactivation of endogenous latent virus caused by the immunosuppressive and cytotoxic effects of cytoreductive therapies is a common mechanism of infection. With cytomegalovirus (CMV), acquisition of exogenous virus by transfusion of blood products containing virus and from the bone marrow graft in the case of bone marrow transplantation can occur. Serious morbidity can result and occasional mortality. CMV infections in allogeneic BMT recipients have high case fatality rates. Treatment and preventive strategies for herpes simplex virus (HSV), CMV, and varicella zoster virus (VZV) have been developed to reduce morbidity. Acyclovir, either given prophylactically or as treatment of active infection, has been highly successful in reducing illness from HSV and VZV infection. For CMV, provision of CMV-seronegative blood products is the mainstay of prevention of morbidity in seronegative patients and is especially important in the care of patients undergoing allogeneic BMT. Ganciclovir given either prophylactically or as early therapy for patients detected to be shedding CMV appears to be a promising strategy. Bolstering host immunity through augmentation of anti-CMV cytotoxic T-cell responses appears to be an exciting candidate therapy under development.

Development of the Satisfaction with Life Domains Scale for Cancer

This article describes the development of the Satisfaction with Life Domains Scale for Cancer (SLDS-C), a self report instrument for assessing the subjective quality of life of patients receiving aggressive cancer treatment. The SLDS-C asks respondents to rate their satisfaction with 17 areas of life using seven faces (three smiling, one neutral, and three frowning). The instrument has the following advantages: it is acceptable to patients, is easily understood, and allows different degrees of either positive or negative responses. The authors present evidence of the reliability and validity of the scale on the basis of the responses of 109 long-term cancer survivors who had received bone marrow transplants.

Viral infections in severely immunocompromised cancer patients

Immunocompromised cancer patients are susceptible to infection by many viral pathogens. The most serious morbidity results from active infection by members of the herpes virus family. Reactivation of latent virus occurs as a sequela of cytotoxic therapy and deficiency of cell-mediated immunity, especially cytotoxic responses, the major host protective defense. Herpes simplex virus and varicella zoster virus infections are problematic in patients with all types of cancer; cytomegalovirus infections cause life-threatening morbidity in bone marrow transplant patients. Several antiviral agents are highly active against these pathogens and different strategies of using them have resulted in reduced morbidity and mortality. Ultimately, the resolution of these infections is dependent on the control of the malignancy and the ability of the patient to mount an adequate immune response.

Successful engraftment after primary graft failure in aplastic anemia using G-CSF mobilized peripheral stem cell transfusions

A 19-year-old male underwent allogeneic BMT for severe aplastic anaemia (SAA) from his HLA- and blood group-identical sister. He was conditioned with cyclophosphamide (CY) and single fraction total lymphoid irradiation (TLI). GVHD prophylaxis consisted of FK506 and a short course of methotrexate. The patient failed to achieve durable trilineage hematopoietic engraftment. There was no significant myeloid response to GM-CSF or G-CSF. Evaluation of FACS-sorted peripheral T cells from the patient by fluorescence in situ hybridization (FISH) revealed mixed chimerism (44% host origin). Fifty-three days after the first BMT, he was treated with G-CSF primed, unmanipulated PBSC transfusions (5.28u2009×u2009108/kg mononuclear, 4.28u2009×u2009106/kg CD34+, 292.51u2009×u2009106/kg CD3+ cells) from his original donor without reconditioning. FK506 was continued at the same dose. Neutrophil recovery to 0.5u2009×u2009109/l and platelet engraftment to 20u2009×u2009109/l was achieved 11 and 27 days following the first dose of allogeneic PBSC transfusion, respectively. On day 23 a repeat FISH on the patient’s sorted peripheral T lymphocytes revealed 91% donor origin T cells. The patient is currently well with a stable engraftment 6 months following allogeneic PBSC transfusion, with no signs of acute of chronic GVHD.

The Use of Fluconazole Prophylaxis in Patients with Chemotherapy-Induced Neutropenia

Systemic Candida infections are a major cause of infectious morbidity and mortality during chemotherapy-induced neutropenia. Because of the unreliability of conventional diagnostic tests to detect systemic infection early in its course, treatment of established disseminated Candida infection has been generally disappointing with mortality rates of 60-80% in leukemia and bone marrow transplant patients and 30-40% in solid tumor patients. The use of empiric amphotericin B in patients with fever not responding to empiric antibacterial agents has been shown to be successful in reducing morbidity and mortality from fungal infections. However, its toxicity has mitigated the success of this approach. Fluconazole given prophylactically at the institution of chemotherapy has been shown to be a safe and effective alternative. It, however, is not active against all fungal species, especially Aspergillus and some of the less virulent Candida species. Some centers have reported break-through infections by these less susceptible organisms. Whether or not these limitations in its spectrum of activity will limit its usefulness in the future remains unanswered at this time and could pose a cloud to an otherwise bright promise.