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Biomedical subjects

Ka Wah Chan

Publications and source records attributed to Ka Wah Chan.

12 recordsLinked to original sources

Medical and non-medical barriers to outpatient treatment of fever and neutropenia in children with cancer.

BACKGROUND: A number of clinical trials have employed clinical criteria that can identify pediatric patients at low-risk for complicated episodes of fever and neutropenia (F&N) and have successfully treated low-risk patients in the outpatient setting. Despite this, inpatient management remains the standard of care. This trial tested the hypothesis that a strategy of initial hospitalization followed by continuation of therapy in the outpatient setting could be practically implemented in the majority of episodes. PROCEDURE: Patients presenting with F&N were initially evaluated to determine if they had high-risk clinical criteria that would exclude them from this approach. Eligible patients were then hospitalized and treated with iv antibiotics. On subsequent days the attending physician determined whether the patient had exhibited improvement and could continue therapy in the outpatient setting with oral antibiotics. Outpatients were seen three times weekly and continued antibiotics until recovery from F&N. RESULTS: Outpatient oral antibiotic therapy was practically implemented in less than one-quarter of episodes of pediatric F&N. Forty-nine percent of episodes were excluded from study by medical and social protocol exclusion criteria. One hundred five episodes were enrolled and among these 59 episodes included outpatient management. Common barriers to outpatient care included serious medical comorbidities, non-medical barriers including language and distance of residence from the medical center, and lack of interest. The average duration of outpatient care was 3.6 days following an average of 3.5 days of hospitalization. Ninety percent did not require rehospitalization. They experienced no complications. CONCLUSIONS: In only a minority of episodes can outpatient antibiotic management be implemented. Medical comorbidities and social barriers can make the transition to outpatient care difficult. However, initial hospitalization followed by oral antibiotic outpatient management appears safe and effective for low-risk patients who exhibit good responses to initial antibiotic therapy in hospital.

Administration, Oral↗

Intensive extracorporeal photochemotherapy in pediatric patients with chronic graft-versus-host disease (cGVHD).

Extracorporeal photochemotherapy (ECP) is an alternative treatment approach in the management of chronic graft-versus-host disease (cGVHD). However, few reports have investigated the optimal treatment schedule of ECP. We treated seven pediatric patients with steroid-resistant or -dependent cGVHD with ECP. Using the Therakos UVAR XTS system, ECP was begun three (three patients) or five (four patients) times a week initially. Complete and partial responses were obtained in three patients. Three of seven patients died of GVHD-related complications. In this group initial intensive ECP did not improve the rate of response. However, this schedule appeared well tolerated.

Adolescent↗

Extracorporeal photopheresis in children with graft-versus-host disease.

Acute and chronic graft-versus-host disease (GVHD) are major complications after allogeneic hematopoietic stem cell transplantation. Systemic corticosteroid is the first line of therapy but only half of the patients will respond. The management of steroid-refractory or steroid-dependent GVHD is challenging. Intensification of immunosuppression has been the main strategy but the response rate is not satisfactory. Furthermore, the incidence of treatment-related toxicity and opportunistic infection is unacceptably high. Extracorporel photopheresis (ECP) has been used in the management of refractory GVHD. Retrospective analysis of the experience in adult patients showed activity in both acute and chronic GVHD. The procedure was well tolerated with minimal changes in the hematologic and biochemical parameters. However the machine currently approved is designed for patients over 40 kg of body weight. Significant fluid shift and venous access are major concerns when ECP is performed in children. Various modifications of the ECP procedure have been tried to manage patients with low body weight. Experience with ECP in children is limited but preliminary data also showed favorable response in children with resistant GVHD. Further investigations are needed to refine the optimal schedule, duration, and treatment technique for pediatric patients.

Child↗

Flow cytometry and fluorescence in situ hybridization to detect residual neuroblastoma cells in bone marrow.

BACKGROUND: In patients with neuroblastoma morphological assessment of BM for residual NB cells is not precise, particularly when the number of tumor cells is small. PROCEDURE: To develop a sensitive and rapid method of detecting NB cells in BM, we assessed the efficiency of flow cytometry (FCM) using markers CD9, CD56, and CD45. The percent of CD9+/CD56+/CD45- (NB phenotype) cells was determined by FCM in 41 samples (16 patients) at various time points. For confirmation fluorescence in situ hybridization (FISH) for 17q gain was performed. RESULTS: Nineteen of the 22 (86%) samples that were negative by morphology were positive by FCM (>0.006% CD9+/CD56+/CD45- cells). The longest time to complete the FCM study was 3 hr. In six FISH experiments the sorted CD9+/CD56+/CD45- population had a higher percentage of cells with 17q gain (11.5-95%) compared to a CD56-/CD45+ internal control population (2-8%). CONCLUSIONS: Our preliminary results suggest that FCM determination of the percent of CD9+/CD56+/CD45- cells is an effective method of rapidly detecting NB cells in BM.

Adolescent↗

Umbilical cord blood transplantation.

Over the past decade umbilical cord blood has been established as a viable source of hematopoietic stem cell for allogeneic transplantation. Early experience with umbilical cord blood transplantation (CBT) demonstrated a lower incidence of graft-versus-host disease even though the procedure was performed with HLA-disparate grafts. The overall outcome of CBT appears similar to that of allogeneic bone marrow transplant. The expansion of the donor selection is particularly beneficial to ethnic minorities, whose representation in the marrow registries is relatively small. The major drawbacks of CBT are slow hematopoietic recovery and a high incidence of graft failure, as a result of a lower number of progenitors infused. This paper reviews the current results of CBT and ongoing investigations to increase its availability to a larger number of recipients.

Child↗

Cardiac manifestations of graft-versus-host disease.

Graft-versus-host disease (GVHD) is a major cause of morbidity and mortality after bone marrow transplantation. Well-documented manifestations of GVHD include dermatologic, gastrointestinal, hepatic, pulmonary, musculoskeletal, and hematologic manifestations and sicca syndrome. To date, the heart has only rarely been reported to be a target of GVHD. We report a series of patients who developed bradycardia, coronary artery disease, or cardiomyolysis in association with acute or chronic GVHD. The severity of these manifestations ranged from asymptomatic to fatal. The bradycardias were responsive to increased immunosuppression. Although they are uncommon, it is important to recognize these cardiac manifestations, because they may reflect GVHD activity and may be reversible by increasing immunosuppression.

Adolescent↗

Pharmacokinetics and individualized dose adjustment of intravenous busulfan in children with advanced hematologic malignancies undergoing allogeneic stem cell transplantation.

We investigated the pharmacokinetics (PK) of a recently approved intravenous busulfan (IVBU) formulation as a part of the preparative regimen in 20 children with advanced hematologic malignancies undergoing allogeneic hematopoietic stem cell transplantation. Seventeen patients received a thiotepa, IVBU, and cyclophosphamide-based regimen, and 3 patients received an IVBU and cyclophosphamide-based regimen. All patients received IVBU 0.8 mg/kg for the first 2 doses; thereafter, the IVBU dose was modified, if required, to achieve a final area under the concentration-time curve (AUC) at steady state of 1150 micromol/L/min per dose (range, 1000-1300 micromol/L/min per dose; SD +/-13%) based on the first-dose PK determination. PK studies were repeated on subsequent doses to verify the final AUC. Initial mean IVBU clearance and half-life were 3.96 mL/min/kg and 1.98 hours, respectively. Sixteen (80%) of the 20 patients received dose adjustments: 14 patients required dose escalations, and 2 required dose reductions. Overall, thirteen (72%) of 18 available sample sets at final follow-up PK analysis showed the IVBU exposure to be within the targeted range. IVBU PK was linear, and interpatient variability was much lower than that observed with oral busulfan. IVBU was well tolerated, and no case of hepatic veno-occlusive disease was encountered. Mild and transient hyperbilirubinemia was observed in 7 patients. Thirteen of the 20 patients were alive at a median follow-up of 651 days (range, 386-1555 days). We conclude that a standardized IVBU dose of 0.8 mg/kg in children does not always result in an AUC within the reference range defined in this study. Therapeutic drug monitoring with dose adjustment based on first-dose PK can optimize the systemic busulfan exposure for children undergoing allogeneic hematopoietic stem cell transplantation.

Adolescent↗

Clofarabine, a novel nucleoside analog, is active in pediatric patients with advanced leukemia.

Despite progress in leukemia therapy, most children who experience relapse have a dismal prognosis. New, effective approaches are needed. We conducted a phase 1 study of a novel nucleoside analog, clofarabine, in pediatric patients with refractory and relapsed leukemia. Clofarabine was infused intravenously over 1 hour each day for 5 days. Six dose levels, between 11.25 and 70 mg/m(2) per day for 5 days, were studied in 25 patients. A modified 3 + 3 phase 1 design was followed with 30% dose escalation until the dose-limiting toxicity (DLT) was defined. The maximum tolerated dose (MTD) was 52 mg/m(2) per day for 5 days. At the end of infusion at MTD, clofarabine triphosphate levels in leukemia blasts varied between 6 microM and 19 microM, which resulted in complete and sustained inhibition of DNA synthesis. The DLT was reversible hepatotoxicity and skin rash at 70 mg/m(2) per day for 5 days. Twenty-five patients were treated. Five patients achieved complete remission (CR), and 3 achieved partial remission (PR), for an overall response rate of 32%. Clofarabine is well tolerated and shows significant antileukemic activity in heavily pretreated children. Multicenter phase 2 trials in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) are ongoing.

Adenine Nucleotides↗

Fludarabine and once-daily intravenous busulfan for allogeneic bone marrow transplantation for Chediak-Higashi syndrome.

An HLA-identical sibling bone marrow transplant was done for a patient with Chediak-Higashi syndrome. The preparative regimen included intravenous fludarabine (40 mg/m2/dx4) and busulfan (130 mg/m2/dx4). Busulfan was given once daily. Pharmacokinetic studies showed the area under the concentration-time curve of the once-daily intravenous busulfan was similar to that seen with the total daily dose administered with an every-6-hourly regimen. Toxicity was minimal. Myeloid engraftment occurred on day +17 and donor chimerism was complete. Fludarabine and once-daily intravenous busulfan is well tolerated and is adequate for engraftment of sibling transplant in Chediak-Higashi syndrome.

Bone Marrow Transplantation↗

Acute lymphoblastic leukemia.

Acute leukemia is the most common childhood malignancy, representing 30% of all cancer in American children under the age of 15 years and 12% of cancer cases in those ages 15 to 19 years old. In the United States, approximately 2500 new cases are diagnosed annually; 80% of these are acute lymphoblastic leukemia, 15% are acute myelogenous leukemia, and 5% belong to the chronic leukemia category.(1) The survival rates of children with acute leukemia have increased dramatically in the last 40 years.(2-5) The most success in outcome has occurred in acute lymphoblastic leukemia, although improvement is also being reported in acute myelogenous leukemia in the past few years. Progress comes from treatment strategy modifications on the basis of observations made in sequential large-scale therapeutic trials, an approach that serves as a paradigm for research in other malignant diseases.

Adolescent↗

Bone marrow donation in childhood: one donor's perspective.

Allogeneic bone marrow transplantation is an established treatment modality for leukemia, hematologic disorders and inborn errors of metabolism. while the focus of attention is the transplant recipient, the bone marrow donor (often a sibling) is both physically and emotionally involved in the process. Few reports have been written from the donor's perspective, however. One of the authors of this report (G.P.) was a marrow donor as a child, and he reflects on this experience at the completion of his first year of training in medical school.

Bone Marrow Transplantation↗