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Biomedical subjects

Ann Jakubowski

Publications and source records attributed to Ann Jakubowski.

7 recordsLinked to original sources

Immunogenicity of recombinant hepatitis B vaccine (rHBV) in recipients of unrelated or related allogeneic hematopoietic cell (HC) transplants.

Current European and US guidelines for recombinant hepatitis B vaccine (rHBV) after hematopoietic-cell transplantation (HCT) vary. The European Group for Blood and Marrow Transplantation (EBMT) recommends rHBV starting 6 to 12 months after HCT. Immunization is optional in the Centers for Disease Control and Prevention (CDC) guidelines. Nevertheless, rHBV is required for re-entry to school and certain workplaces. To determine the immunogenicity of rHBV following HCT, the prevaccine and postvaccine titers of 292 allogeneic transplant recipients who were immunized with rHBV were analyzed. Immunization was initiated in patients off immunosuppression who achieved specific minimal milestones of immune competence. Overall, 64% of patients seroconverted. In multivariate analyses, response was adversely affected by age older than 18 years (P < .01) and history of prior chronic graft-versus-host disease (GVHD; P < .001) but not by donor type or by use of T-cell depletion, adoptive immunotherapy, or rituximab. By comparison, 89% of rHBV nonresponders mounted a 3-fold or greater rise in polio titers following 3 doses of inactivated poliovirus. These data demonstrate that the rate of seroconversion following rHBV is lower in allogeneic HC transplant recipients compared with age-matched healthy controls. The data emphasize the need to document prevaccine and postvaccine titers to ensure response and suggest that immunization guidelines based on time interval from HCT, irrespective of immune competence, may not ensure adequate protection against certain vaccine-preventable diseases.

Adolescent↗

Developing a cancer-specific geriatric assessment: a feasibility study.

BACKGROUND: As the U.S. population ages, there is an emerging need to characterize the "functional age" of older patients with cancer to tailor treatment decisions and stratify outcomes based on factors other than chronologic age. The goals of the current study were to develop a brief, but comprehensive, primarily self-administered cancer-specific geriatric assessment measure and to determine its feasibility as measured by 1) the percentage of patients able to complete the measure on their own, 2) the length of time to complete, and 3) patient satisfaction with the measure. METHODS: The geriatric and oncology literature was reviewed to choose validated measures of geriatric assessment across the following domains: functional status, comorbidity, cognition, psychological status, social functioning and support, and nutritional status. Criteria applied to geriatric assessment measurements included reliability, validity, brevity, and ability to self-administer. The measure was administered to patients with breast carcinoma, lung carcinoma, colorectal carcinoma, or lymphoma who were fluent in English and receiving chemotherapy at Memorial Sloan-Kettering Cancer Center (New York, NY) or the University of Chicago (Chicago, IL). RESULTS: The instrument was completed by 43 patients (mean age, 74 yrs; range, 65-87 yrs). The majority had AJCC Stage IV disease (68%). The mean time to completion of the assessment was 27 minutes (range, 8-45 mins). Most patients were able to complete the self-administered portion of the assessment without assistance (78%) and were satisfied with the questionnaire length (90%). There was no association noted between age (P = 0.56) or educational level (P = 0.99) and the ability to complete the assessment without assistance. CONCLUSIONS: In this cohort, this brief but comprehensive geriatric assessment could be completed by the majority of patients without assistance. Prospective trials of its generalizability, reliability, and validity are justified.

Activities of Daily Living↗

Patterns of toxicity in older patients with breast cancer receiving adjuvant chemotherapy.

OBJECTIVE: To retrospectively determine the relationship of age to toxicity from adjuvant chemotherapy for breast cancer. DESIGN AND METHODS: We identified 1,405 consecutive patients age 65 or older with primary invasive breast cancer who were seen at Memorial Sloan-Kettering Cancer Center from January 1998 to December 2000. Patients selected from this cohort for analysis were aged 65 or older at diagnosis; received their follow-up care at Memorial Sloan-Kettering Cancer Center; had stage I, II, or III breast cancer; and received adjuvant chemotherapy consisting of CMF (cyclophosphamide, methotrexate, and 5-fluorouracil), an anthracycline-based regimen (AC [doxorubicin and cyclophosphamide], or AC-T [AC and paclitaxel or docetaxel]). Exclusion criteria included prior chemotherapy or previous breast cancer. RESULTS: One hundred thirty-two patients were included in this study, with a mean age of 70 (range 65--79). Comorbidity measured by the Charlson comorbidity index was low: score 0 (83%), 1 (12%), 2 (5%); with stages: I(18%), IIA (41%), IIB (27%), IIIA (8%), IIIB (6%), T1Nx (1%). Patients receiving an anthracycline-based regimen were more likely to experience grade 3 or 4 toxicity (p=0. 01), require hospitalization (p<0.001), and/or develop febrile neutropenia (p<0.001). Treatment delays due to myelosuppression occurred more frequently in patients receiving CMF (p<0.001). The type of chemotherapy regimen (anthracycline compared to CMF) was a better predictor for toxicity than increased age or comorbidity score. CONCLUSIONS: In this cohort of older patients with breast cancer, the risk for toxicity from adjuvant chemotherapy depended more on the type of regimen (anthracycline vs. CMF) than the patient's chronological age.

Age Factors↗

Change in cycle 1 to cycle 2 haematological counts predicts toxicity in older patients with breast cancer receiving adjuvant chemotherapy.

PURPOSE: To determine the association between changes in complete blood counts and grade 3 or 4 toxicities from cycle 1 to cycle 2 during adjuvant chemotherapy in women > or =65 years of age with breast cancer. DESIGN AND METHODS: A retrospective review was performed on 1405 patients > or =65 years of age who were treated for primary invasive breast cancer at Memorial Sloan-Kettering Cancer Center between January 1998 and December 2000. From this cohort, we identified patients with stage I-III breast cancer who received adjuvant chemotherapy: cyclophosphamide, methotrexate and fluorouracil (CMF) or the anthracycline-based regimens doxorubicin and cyclophosphamide (AC) or AC followed by paclitaxel (AC-T). Patients were excluded from the analysis if they had a prior history of breast cancer or chemotherapy, or if they had no baseline blood counts available for review. Toxicities, dose modification and causality were recorded. RESULTS: The 104 patients who met our criteria had received either CMF (n = 58; mean age 70.6 years, range 65-78) or an anthracycline-based regimen (n = 46; mean age 68.9 years, range 65-77). Of these patients, 50% experienced treatment delay or treatment-related grade 3 or 4 toxicity. A decrease in white blood cell count and absolute neutrophil count from cycle 1 to cycle 2 was associated with grade 3 or 4 haematological toxicity, febrile neutropenia, hospitalisation and initiation of filgrastim for secondary prophylaxis. A decrease in haemoglobin was associated with febrile neutropenia and hospitalisation. Advanced age was not associated with a significant change in complete blood counts, other than a decline in absolute neutrophil count in patients receiving CMF. CONCLUSIONS: In this cohort of older patients who received chemotherapy for breast cancer, changes in blood counts from cycle 1 to cycle 2 were associated with increased risk of treatment-related grade 3 or 4 toxicity.

Aged↗

Effect of creatinine clearance on patterns of toxicity in older patients receiving adjuvant chemotherapy for breast cancer.

OBJECTIVE: A number of age-related physiological changes contribute to an increased risk of toxicity of cancer chemotherapy in the elderly. One of the most important of these changes is the progressive decline in renal function with aging. We sought to determine the association between calculated creatinine clearance (CL(CR)) and grade 3 or 4 toxicities during adjuvant chemotherapy in women > or =65 years of age with breast cancer. DESIGN AND METHODS: We identified 1405 patients > or =65 years of age who had been treated for primary invasive breast cancer at Memorial Sloan-Kettering Cancer Center between January 1998 and December 2000. Patients were included in this analysis if they had stage I-III breast cancer and had received adjuvant chemotherapy. Patients were excluded if they had a prior history of breast cancer or chemotherapy, or had no baseline creatinine value available for review. RESULTS: The 126 patients who met our criteria had received either cyclophosphamide, methotrexate and fluorouracil (CMF) [n = 65, mean age 71, range 65-78] or an anthracycline-based regimen (n = 61, mean age 69, range 65-79). The majority of patients (97%) had a normal creatinine. CL(CR), as calculated by the Cockcroft-Gault and Jeliffe formulas, decreased with increasing age (increased age associated with decreased Cockcroft-Gault [p = 0.02]; increased age associated with decreased Jeliffe [p < 0.01]). In multivariate analysis, after controlling for age and co-morbidity, a CL(CR) <50 mL/min by the Cockcroft-Gault formula was associated with an increased risk of fever and neutropenia (odds ratio [OR] 3.60; 95% CI 1.00, 12.94; p = 0.05) and a CL(CR) <50 mL/min by the Jeliffe formula was associated with a trend towards an increased risk of fever and neutropenia (OR 3.30; 95% CI 0.91, 12.33; p = 0.07), grade 3 or 4 haematological toxicity (OR 2.43; 95% CI 0.90, 6.55; p = 0.08), and need for erythropoietin (OR 4.15; 95% CI 0.81, 2.99; p = 0.09). An increase in creatinine (as a continuous variable) was associated with a trend towards an increased risk of grade 3 or 4 haematological toxicity (OR 5.81; 95% CI 0.96, 35.33; p = 0.06). CONCLUSIONS: In this cohort of older breast cancer patients, a decreased CL(CR) and increased creatinine was associated with an increased risk of fever and neutropenia or haematological toxicity. CL(CR) should be considered when determining chemotherapy dosage in the elderly.

Age Factors↗

Prevention of peritransplantation viridans streptococcal bacteremia with early vancomycin administration: a single-center observational cohort study.

BACKGROUND: Viridans streptococcal bacteremia (VSB) after allogeneic hematopoietic stem cell transplantation (HSCT) is associated with substantial mortality. Prevention of this serious complication is therefore a high priority. The objective of this study was to evaluate the effect of early vancomycin administration on rates and outcomes of VSB. METHODS: We analyzed the effect of early vancomycin on the incidence of VSB in a cohort of 430 consecutive HSCTs performed during the period of 1 January 1998 to 30 September 2002. The primary end point was time to diagnosis of VSB. Early vancomycin was defined as >or=2 doses of vancomycin between days -7 through +7 after HSCT or diagnosis of VSB, whichever occurred first. Risk factors for VSB were identified in univariate and multivariate Cox proportional hazard models. RESULTS: The incidence of VSB in the cohort was 7.4%. The incidence of VSB in patients who did not receive early vancomycin was 24.8%, compared with 0.3% in patients who did (P<.001). Additional risk factors were female sex, conditioning with total body irradiation, and diagnosis of chronic myelogenous leukemia. CONCLUSIONS: The attributable mortality rate for VSB in our cohort was 21%. Early vancomycin was associated with decreased VSB (hazard ratio, 0.02; 95% confidence interval, 0.003-0.19) after controlling for age, sex, underlying disease, and transplantation variables. The benefits of vancomycin prophylaxis for the prevention of VSB and associated mortality need to be evaluated in a prospective clinical trial.

Adolescent↗

Breakthrough trichosporonosis in a bone marrow transplant recipient receiving caspofungin acetate.

We report a case of invasive trichosporonosis due to Trichosporon beigelii originating in the left wrist of a bone marrow transplant recipient who was receiving caspofungin acetate as prophylaxis against invasive Aspergillus infection. While the patient's neutrophil count was recovering, treatment with fluconazole and amphotericin B lipid complex resulted in a complete clinical response.

Adult↗