Prospective evaluation of propofol anesthesia in the pediatric intensive care unit for elective oncology procedures in ambulatory and hospitalized children.

OBJECTIVES: To evaluate our experience with propofol anesthesia delivered by pediatric intensivists in the pediatric intensive care unit (PICU) to facilitate elective oncology procedures in children performed by pediatric oncologists. METHODS: Elective oncology procedures performed with propofol anesthesia in our multidisciplinary, university-affiliated PICU were prospectively evaluated over a 7-month period. Ambulatory and hospitalized children were prescheduled for their procedure, underwent a medical evaluation, and met fasting requirements before the start of anesthesia. Continuous cardiorespiratory and neurologic monitoring was performed by a pediatric intensivist and a PICU nurse, while the procedure was performed by a pediatric oncologist. Propofol was delivered in intermittent boluses to achieve the desired level of anesthesia. Information studied included patient demographics, procedures performed, induction and total doses of propofol used, the duration of the different phases of the patient's PICU stay, the occurrence of side effects, the need for therapeutic interventions, and the incidence of recall of the procedure. RESULTS: Fifty procedures in 28 children (mean age: 7.5 +/- 4.3 years) were evaluated. Sixty-one percent of patients had established diagnoses. Fifty-four percent of procedures were lumbar puncture with intrathecal chemotherapy administration and 26% of procedures were bone marrow aspirations with biopsy. Induction propofol doses were 2. 0 +/-.8 mg/kg for ambulatory and hospitalized patients, while total propofol doses were 6.6 +/- 2.3 mg/kg and 7.9 +/- 2.4 mg/kg for ambulatory and hospitalized patients, respectively. Induction time was 1.5 +/-.7 minutes, recovery time was 23.4 +/- 11.5 minutes, and total PICU time was 88.8 +/- 27.7 minutes. Transient decreases in systolic blood pressure less than the fifth percentile for age occurred in 64% of procedures, with a mean decrease of 25% +/- 10%. Intravenous fluids were administered in 31% of these cases. Hypotension was more common in ambulatory patients but was not predicted by propofol dose, anesthesia time, or age. Partial airway obstruction was noted in 12% of procedures while apnea requiring bag-valve-mask ventilation occurred in 2% of procedures. Neither was associated with age, propofol dose, or the duration of anesthesia. All procedures were successfully completed and there were no incidences of recall of the procedure. CONCLUSIONS: Propofol anesthesia is effective in achieving patient comfort and amnesia, while optimizing conditions for elective oncology procedures in children. Although transient hypotension and respiratory depression may occur, propofol anesthesia seems to be safe to use for these procedures in the PICU setting. Recovery from anesthesia was rapid and total stay was brief. Under the proper conditions, propofol anesthesia delivered by pediatric intensivists in the PICU is a reasonable option available to facilitate invasive oncology procedures in children.

Successful prevention of post-transfusion Rh alloimmunization by intravenous Rho (D) immune globulin (WinRho SD).

Alloimmunization to the D blood group antigen following the transfusion of D-positive red blood cells to a D-negative recipient may be prevented in most persons by a prompt and adequate dose of Rho (D) immune globulin (RhIG). Until recently, the only RhIG approved by the US Food and Drug Administration (FDA) for this indication required intramuscular injection, an inconvenient and painful route for the relatively large volume that may be required. We describe the successful prevention of Rh alloimmunization following the unintentional transfusion of D-positive red blood cells to a D-negative infant by the intravenous infusion of WinRho SD, a new RhIG that is FDA-approved for prevention of post-transfusion Rh alloimmunization by intravenous administration. We believe that this more convenient and less painful approach should be the treatment of choice for preventing Rh alloimmunization following the transfusion of D-positive red cells to a D-negative recipient.

Precursor B-Lymphoblastic lymphoma presenting as a solitary bone tumor and mimicking Ewing's sarcoma: a report of four cases and review of the literature.

Precursor B-lymphoblastic lymphoma (B-LBL) may present as a solitary bone tumor. Fewer than 10 cases with a proven precursor B-cell phenotype have been reported in the English literature. In this report, we describe four cases of B-lymphoblastic lymphoma presenting as a localized intraosseous mass, which clinically and histologically mimicked Ewing's sarcoma. Three tumors occurred in the tibia and one in the humerus. In all four cases, the initial diagnosis was either "Ewing's sarcoma" or "consistent with Ewing's sarcoma." All four patients were female. Three were children and one was an adult; mean age was 12.5 years (range, 4 to 31 years). All had extremity pain without significant constitutional symptoms. In three cases, the tumors were osteolytic on radiographic evaluation, and in one case, osteosclerotic. Immunohistochemical stains on paraffin-embedded tissue showed that the neoplastic cells expressed terminal deoxynucleotidyl transferase, CD43, vimentin, and CD99 (MIC2 gene product) in all cases. Three cases were negative for CD45. CD79a was positive in all four cases studied; however, CD20 (L26) was positive in only two of four cases. CD3 was negative in all cases. Two cases showed focal granular cytoplasmic staining for keratin. Two cases analyzed by polymerase chain reaction (PCR) revealed clonal rearrangement of the immunoglobulin heavy chain (IgH) gene. Follow-up revealed that the three pediatric patients, who received a high-dose multiagent chemotherapy regime for LBL, are disease free at follow-up intervals of more than 1, 11, and 12 years, respectively. The adult patient died two years after diagnosis with disseminated disease. Although rare, B-lymphoblastic lymphoma should be considered in the differential diagnosis of small round cell tumors of bone. A diagnosis of Ewing's sarcoma should be made only after complete immunophenotyping and, if necessary, molecular diagnostic tests to exclude lymphoblastic lymphoma. A limited panel of antibodies can lead to an erroneous diagnosis; B-lymphoblastic lymphoma may be negative for CD45 and CD20 but positive for CD99 and even for keratin, mimicking Ewing's sarcoma. Correct diagnosis is extremely important because LBL usually is curable in the pediatric age group with appropriate therapy.

Late effects in long-term survivors of high-grade non-Hodgkin's lymphomas.

PURPOSE: To evaluate long-term survivors of high-grade non-Hodgkin's lymphomas (NHLs) for late effects and to attempt to assess the relative contributions of the primary treatment modalities to these late effects. PATIENTS AND METHODS: Of 103 young survivors followed up for 1 to 20 years, 74 patients were interviewed and underwent various investigations, and an additional 12 patients were interviewed only. Of the 86 patients, 65 had previously suffered from small non-cleaved-cell lymphoma, 16 from lymphoblastic lymphoma, and five from large-cell lymphoma. RESULTS: Left ventricular dysfunction was identified in eight of 57 (14.0%) patients who had received doxorubicin (DOX) in doses greater than 200 mg/m2, of whom four were symptomatic and four were asymptomatic. A ninth patient required a pacemaker. Of the 86 patients, 23 (26.7%) reported pregnancies, 18 of whom had 30 children. Two of the 86 (2.3%) patients developed second cancers. Other major late effects included posttransfusion viral hepatitis, eight patients; CNS toxicity, two patients; endocrine impairment, 14 patients; vitamin B12 deficiency, two patients; esophageal stricture, one patient; urinary tract problems, two patients; and musculoskeletal defects, three patients. Major late effects occurred in 11 of 21 (52.4%) patients who had received radiation as well as chemotherapy, eight of 22 (36.4%) patients who had surgical resections as well as chemotherapy, and 17 of 74 (23.0%) patients who had received chemotherapy alone. CONCLUSION: The predominant major late effects observed were late cardiac toxicity related to DOX therapy and hepatitis C virus infection that presumably resulted from blood product transfusions administered before the introduction of screening for the hepatitis C virus. Fertility was not greatly impaired, and second malignancies were uncommon. No patient had clinically significant impairment of growth. Radiation appeared to increase the likelihood of late effects.

Severe atypical neuropathy associated with administration of hematopoietic colony-stimulating factors and vincristine.

PURPOSE: We have observed a severe atypical neuropathy (SAN) in patients with small non-cleaved-cell (SNCL) and large-cell lymphoma (LCL) treated with intensive chemotherapy and hematopoietic colony-stimulating factors (CSFs). The present analysis was undertaken in an attempt to identify factors associated with the development of this syndrome. PATIENTS AND METHODS: Fifty-four adult and pediatric patients consecutively treated according to the same chemotherapy protocol were included in the analysis. Low-risk patients received three cycles of cyclophosphamide, vincristine, doxorubicin, and high-dose methotrexate (CODOX-M) while in high-risk patients this drug combination was alternated with high-dose cytarabine (ara-C), etoposide, and ifosfamide (IVAC) for a total of four cycles. Twenty-eight patients received a CSF (granulocyte [G]- or granulocyte-macrophage [GM]-CSF), and 26 patients received no CSF. A statistical analysis, which included a logistic regression model, was undertaken to examine the importance of potential contributing factors to the development of SAN. RESULTS: SAN, which consisted of excruciating foot pain, usually associated with marked motor weakness, was observed in 12 patients. There was a highly significant association between the occurrence of this syndrome and the administration of CSFs, and an independent association with the cumulative dose of vincristine given in the first cycle of chemotherapy. Furthermore, the analysis suggested a synergistic effect between administration of the CSFs and vincristine in the genesis of this neuropathy. CONCLUSION: Our results indicate that CSFs can precipitate SAN when given in conjunction with vincristine. The development of SAN was associated most strongly with the cumulative dose of vincristine -- the size of individual doses and the number of doses given in cycle 1 were important to the extent that they influenced the cumulative dose.

Role of tissue diagnosis in pulmonary involvement in pediatric human immunodeficiency virus infection.

BACKGROUND: Pulmonary complications occur commonly during HIV infection. The aim of this study was to evaluate the clinical value of lung tissue examination in the diagnosis and treatment of pulmonary disorders in children with HIV infection. METHODS: The medical records of 347 children enrolled between January, 1990, and April, 1994, into various antiretroviral therapy protocols were reviewed to identify patients who underwent a lung biopsy. RESULTS: Fourteen patients underwent diagnostic lung biopsies on 16 separate occasions. The most common radiologic findings were nodular infiltrates which were localized in 7 patients and diffuse in 6. Eight patients presented with fever and progressive respiratory distress unresponsive to empiric therapy, whereas the rest had progressive nodular infiltrates. The pathologic diagnoses included opportunistic infection in 7 patients, lymphocytic interstitial pneumonitis in 5, non-Hodgkin's lymphoma in 3 and interstitial fibrosis in 1. The biopsy led to a major change in the treatment of 7 patients which resulted in a significant improvement of the pulmonary process in all of them. In an additional patient the excisional biopsy proved curative. CONCLUSIONS: When patients are selected appropriately, lung biopsy might have a significant impact on therapy and outcome in HIV-infected children with pulmonary infiltrates.

Age, thymopoiesis, and CD4+ T-lymphocyte regeneration after intensive chemotherapy.

BACKGROUND: Inadequate reconstitution of CD4+ T lymphocytes is an important clinical problem complicating chemotherapy, human immunodeficiency virus infection, and bone marrow transplantation, but relatively little is known about how CD4+ T lymphocytes regenerate. There are two main possibilities: bone marrow-derived progenitors could reconstitute the lymphocyte population using a thymus-dependent pathway, or thymus-independent pathways could predominate. Previous studies have suggested that the CD45RA glycoprotein on CD4+ T lymphocytes is a marker for progeny generated by a thymus-dependent pathway. METHODS: We studied 15 patients 1 to 24 years of age who had undergone intensive chemotherapy for cancer. The absolute numbers of CD4+ T lymphocytes in peripheral blood and the expression of CD45 isoforms (CD45RA and CD45RO) on these lymphocytes were studied serially during lymphocyte regeneration after the completion of therapy. Radiographic imaging of the thymus was performed concomitantly. RESULTS: There was an inverse relation between the patients' ages and the CD4+ T-lymphocyte counts six months after therapy was completed (r = -0.92). The CD4+ recovery correlated quantitatively with the appearance of CD45RA+CD4+ T lymphocytes in the blood (r = 0.64). There was a higher proportion of CD45RA+CD4+ T lymphocytes in patients with thymic enlargement after chemotherapy than in patients without such enlargement (two-sided P = 0.015). CONCLUSIONS: Thymus-dependent regeneration of CD4+ T lymphocytes occurs primarily in children, whereas even young adults have deficiencies in this pathway. Our results suggest that rapid T-cell regeneration requires residual thymic function in patients receiving high-dose chemotherapy.

Lymphocyte depletion during treatment with intensive chemotherapy for cancer.

Recently we have observed an increased incidence of opportunistic infections in patients treated with intensive chemotherapy for cancer. Because T-cell depletion is associated with similar clinical events in human immunodeficiency virus infection and after bone marrow transplantation, we have analyzed peripheral blood lymphocyte populations in a series of patients during treatment with intensive chemotherapy for cancer. Although neutrophil, monocyte, and platelet numbers consistently recovered to greater than 50% of pretreatment values after each sequential cycle of therapy, lymphocyte numbers did not recover within the same time period. B cells decreased rapidly from a mean value of 149 +/- 46/mm3 before chemotherapy to 4 +/- 1/mm3 during chemotherapy (P = .01). CD4+ T cells decreased from a mean of 588 +/- 76/mm3 before chemotherapy to 105 +/- 28/mm3 during chemotherapy (P = .0002) and CD8+ T cells decreased from a mean of 382 +/- 41/mm3 before chemotherapy to 150 +/- 46/mm3 during chemotherapy (P = .0009). Natural killer cell numbers did not show significant declines (171 +/- 30/mm3 before, 114 +/- 24/mm3 during, P = .19). Based on the history of opportunistic complications in patients with other disorders who display similar degrees of CD4+ T-cell lymphopenia and preliminary observations in this population, immune incompetence could surface as a dose-limiting toxicity for highly dose-intensive chemotherapy regimens.