Analysis of dermatologic events in patients with cancer treated with lapatinib.

PURPOSE: Dermatologic events (DEs) in patients with cancer treated with lapatinib, a small-molecule dual tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR [ErbB1]) and HER2 (ErbB2), were characterized. PATIENTS AND METHODS: Nine clinical trials of metastatic cancer were included in this analysis. Lapatinib was administered at doses ranging from 1000 to 1500 mg/day as monotherapy (n=928) or in combination with paclitaxel or capecitabine (n=491). Patients not treated with lapatinib comprised the control group. Dermatologic events included hand-foot syndrome, rash, hair disorder, dry skin, pruritus/urticaria, skin disorder, skin infection, and nail disorder; DEs were characterized based on type, time to onset, severity, duration, and required interventions. RESULTS: Fifty-eight percent of patients treated with lapatinib monotherapy, 74% treated with lapatinib plus paclitaxel or capecitabine, and 53% in the control group developed DEs. Among patients receiving lapatinib monotherapy, 55% experienced grade 1/2 DEs, 3% had grade 3 DEs, and no grade 4 DEs were observed. The most common DE was rash (43%); all other events occurred in

A long-term follow-up report on allogeneic stem cell transplantation for patients with primary refractory acute myelogenous leukemia: impact of cytogenetic characteristics on transplantation outcome.

The prognosis of patients with primary refractory acute myelogenous leukemia (AML) is poor. Our initial report suggested that some patients could achieve durable remission after allogeneic stem cell transplantation (SCT). Herein, we update our initial experience and report further analysis of this group of patients to determine whether there are pre-SCT prognostic factors predictive of posttransplantation relapse and survival. We reviewed the records of 68 patients who consecutively underwent transplantation at the City of Hope Cancer Center with allogeneic SCT for primary refractory AML between July 1978 and August 2000. Potential factors associated with overall survival and disease-free survival were examined. With a median follow-up of 3 years, the 3-year cumulative probabilities of disease-free survival (DFS), overall survival (OS), and relapse rate for all 68 patients were 31% (95% confidence interval [CI], 20%-42%), 30% (95% CI, 18%-41%), and 51% (95% CI, 38%-65%), respectively. In multivariate analysis, the only variables associated with shortened OS and DFS included the use of an unrelated donor as the stem cell source (relative risk, 2.23 [OS] and 2.05 [DFS]; P =.0005 and.0014, respectively) and unfavorable cytogenetics before SCT (relative risk: 1.68 [OS] and 1.58 [DFS]; P =.0107 and.0038, respectively). Allogeneic SCT can cure approximately one third of patients with primary refractory AML. Cytogenetic characteristics before SCT correlate with transplantation outcome and posttransplantation relapse.

Successful transplantation of HLA-matched and HLA-mismatched umbilical cord blood from unrelated donors: analysis of engraftment and acute graft-versus-host disease.

To reduce the morbidity and mortality associated with unrelated donor bone marrow (BM) transplantation and potentially extend the pool of suitable donors, cryopreserved unrelated donor umbilical cord blood was considered as an alternate source of hematopoietic stem cells for transplantation. Patients with leukemia, BM failure syndrome, or inborn error of metabolism were eligible for a phase I clinical trial designed to estimate the risk of graft failure and severe acute graft-versus-host disease after transplantation of umbilical cord blood from unrelated donors. As of December 21, 1995, unrelated donor umbilical cord blood was used to reconstitute hematopoiesis in eighteen patients aged 0.1 to 21.3 years weighing 3.3 to 78.8 kg with acquired or congenital lympho-hematopoietic disorders or metabolic disease. Patients received either HLA-matched (n = 7) or HLA-1 to 3 antigen disparate (n = 11) grafts collected and evaluated by the New York Blood Center (New York, NY). The probability of engraftment after unrelated donor umbilical cord blood transplantation was 100% with no patient having late graft failure to date. The probability of grade III-IV acute graft-versus-host disease at 100 days was 11%. With a median follow-up of 6 months (range, 1.6 to 17 months); the probability of survival at 6 months is 65% in this high risk patient population. We conclude that cryopreserved umbilical cord blood from HLA-matched and mismatched unrelated donors is a sufficient source of transplantable hematopoietic stem cells with high probability of donor derived engraftment and low risk of refractory severe acute graft-versus-host disease. Limitations with regard to recipient size and degree of donor HLA disparity remain to be determined.

Blood component and immunotherapy in neonatal sepsis.

The future role of IVIG remains unclear. Many, but not all, studies indicate efficacy in the prevention of late-onset disease in premature infants. The role of type-specific IVIG is evolving and may hold promise for both prevention and treatment of neonatal sepsis. Granulocyte transfusions, as adjuvant therapy in neonatal sepsis, seem to be beneficial. However, the difficulty and expense of collection, as well as the advent of colony-stimulating factors, have shifted the focus away from their routine use. Colony-stimulating factors present varied and exciting potential uses, including modulating neonatal hematopoiesis. Current studies are primarily aimed at understanding their effects on neonatal hematopoiesis. Future studies will need to expand on this knowledge and examine what effects they have on treating or preventing neonatal sepsis.

Telephone usage in the hearing-impaired population.

The purpose of this project was to determine if the hearing-impaired population reports satisfaction with their ability to converse over the telephone in both aided and unaided situations. For this study, we surveyed 104 hearing-impaired persons using a 43 item questionnaire that investigates problems that hearing-impaired people encounter when using the telephone. The questionnaire also probes the solutions that hearing-impaired people use for overcoming these problems. Of the 91 respondents who wear hearing aids, 55% use their aids while operating the telephone. However, 70% of these respondents reported that coupling the hearing aid to the telephone is problematic. Use of a telephone amplifier was reported by 73% of the sampled population. The majority of the subjects, 75%, indicated an interest in improvements in telephone communications for hearing-impaired people.

Processing the telephone speech signal for the hearing impaired.

Speech intelligibility scores from 16 subjects with sensorineural hearing loss were evaluated using a digitized version of the California Consonant Test that was presented via headphones through a 300 to 3000 Hz bandpass filter to simulate the telephone band. Each subject was tested with an unprocessed signal that was frequency-equalized to compensate for the individual's hearing loss, and a signal that was equalized and compressed by the use of a compressor compression technique. Subjects were tested at three sound pressure levels above a pure-tone average threshold for frequencies 1 and 2 kHz. Two digital signal processing techniques designed to compensate for high-frequency hearing loss were examined: frequency domain processing and time domain processing. Frequency domain involved modification of the short-term spectrum obtained through a fast Fourier transform, whereas time domain processing involved passing the signal through a bank of finite impulse response filters. Both techniques showed significant intelligibility improvements (15-30%). In a second experiment, 16 additional subjects with high-frequency hearing loss compared an amplified telephone signal to three processed signals: (1) 6 dB per octave emphasis; (2) a signal frequency equalized for their hearing loss; and (3) a signal that was equalized for their hearing loss and was compressed according to their uncomfortable loudness levels. Most subjects preferred the signal with the 6 dB per octave emphasis.