High-dose carboplatin with etoposide in patients with recurrent thymoma: the Indiana University experience.

Thymoma is a chemotherapy-sensitive tumor with a 30-50% 5-year survival in previously untreated patients. Unfortunately, durable CRs with salvage chemotherapy are rarely observed. We initiated a phase II trial of high-dose carboplatin and etoposide in patients with relapsed thymoma or thymic carcinoma. All patients had progressive disease (PD) after initial or salvage chemotherapy, but were not cisplatin-refractory. PBSCs were mobilized using 10 microg/kg/day G-CSF. Patients received carboplatin 700 mg/m(2) and etoposide 750 mg/m(2) i.v. on days -5, -4, -3. Five patients were enrolled and evaluated after tandem transplants 4 weeks apart. All patients had pleural-based and lung parenchymal metastasis, one or two prior surgeries and two or more courses of prior cisplatin-based chemotherapy regimens. Chemotherapy was well tolerated, although grade IV hematological toxicity occurred in all patients. Progression-free survival following HDC ranged from 3.5 to 16.5 months. One patient maintained a CR for 12.8 months, then died from an unrelated cause. With a minimum of 2 years follow-up for all patients, three of five patients remain alive at 26+, 36+, and 49+ months. High-dose carboplatin and etoposide in relapsed thymoma is feasible with acceptable toxicity; however, these limited data do not appear superior to standard-dose salvage therapy.

Efficacy of erythromycin for postpyloric placement of feeding tubes in critically ill children: a randomized, double-blind, placebo controlled study.

BACKGROUND: Erythromycin enhances gastric emptying and has been suggested to facilitate nasoenteric feeding tube placement in adults. Our primary objective was to evaluate the effect of erythromycin on the transpyloric passage of feeding tubes in critically ill children, and second, to evaluate the effect of erythromycin on the distal migration of duodenal feeding tubes. METHODS: Seventy-four children were randomly assigned to receive erythromycin lactobionate (10 mg/kg) IV or equal volume of saline placebo 60 minutes before passage of a flexible weighted tip feeding tube. Abdominal radiographs were obtained 4 hours later to assess tube placement. If the tube was proximal to the third part of the duodenum, two additional doses of erythromycin/placebo were administered 6 hours apart. Those receiving additional doses had repeat radiographs 14 to 18 hours after tube placement. RESULTS: The number of postpyloric feeding tubes was similar in the erythromycin and placebo treated groups 4 hours after tube insertion (23/37 vs 27/37, p = .5). Of those with prepyloric tubes at 4 hours, none in the erythromycin group and 3 in the placebo group had the tube migrate to the postpyloric position by 14 to 18 hours (p < .05). Of those with postpyloric tubes proximal to the third part of the duodenum at 4 hours, additional doses of erythromycin did not cause more tubes to advance further into the intestine than did placebo (p = .6). CONCLUSIONS: Erythromycin does not facilitate transpyloric passage of feeding tubes in critically ill children. The distal migration of duodenal tubes further into the small bowel is also not enhanced by erythromycin.

Indicators of postpyloric feeding tube placement in children.

OBJECTIVE: To determine the validity of five indicators (color, pH, and concentrations of bilirubin, pepsin, and trypsin in aspirated gastrointestinal secretions) in predicting postpyloric placement of feeding tubes in critically ill children. DESIGN: Prospective, observational study. SETTING: University teaching hospital. PATIENTS: A total of 96 gastrointestinal aspirates were obtained from 53 children requiring placement of a nasoenteric feeding tube. INTERVENTIONS: Feeding tubes were aspirated by applying suction with a 20-mL syringe. Repeat aspirates from the same patient were obtained on different days. All aspirations were performed within 30 mins of obtaining a radiograph to assess tube position. MEASUREMENTS AND MAIN RESULTS: Aspirates were inspected visually for color. pH and bilirubin concentrations were determined at the bedside by using reagent strips. Pepsin and trypsin concentrations were measured spectrophotometrically in a research laboratory. The sensitivity, specificity, predictive values, and efficiency for each indicator and their 95% confidence intervals were determined based on the position of the feeding tube on the radiograph. Aspirate pH > or =6 had the lowest positive predictive value (76%, range 67% to 85%) but high negative predictive value (94%, range 89% to 99%) for determining postpyloric positioning of the feeding tube. Bilirubin concentration > or =5 mg/dL (> or =86 micromol/L) had the highest positive predictive value (96%, range 91% to 100%) and lowest negative predictive value (88%, range 81% to 95%). Overall efficiency was best for the appearance of a clear yellow aspirate color (93%, range 88% to 98%), pepsin concentration < or =20 microg/mL (94%, range 89% to 99%), and trypsin concentration > or =50 microg/mL (94%, range 89% to 99%). CONCLUSIONS: Simple bedside assessment of gastrointestinal aspirate color, pH, and bilirubin concentration is useful for predicting feeding tube position. Use of these tests may reduce the number of radiographic studies needed to confirm postpyloric positioning. Laboratory-determined pepsin and trypsin concentrations predict tube position with a high degree of accuracy. Development of simple and inexpensive bedside tests for the detection of gastrointestinal enzymes may be useful.

Autologous transplantation of mobilized peripheral blood CD34+ cells selected by immunomagnetic procedures in patients with multiple myeloma.

In the use of autologous PBPC transplantation in patients with multiple myeloma, contamination of PBPC with myeloma cells is commonly observed. Enrichment for CD34+ cells has been employed as a method of reducing this contamination. In this study the reduction of myeloma cells in PBPC was accomplished by the positive selection of CD34+ cells using immunomagnetic bead separation (Isolex 300 system). PBPC were mobilized from 18 patients using cyclophosphamide (4.5 g/m2) and G-CSF (10 microg/kg/day). A median of two leukaphereses and one selection was performed per patient. The median number of mononuclear cells processed was 3.50 x 10(10) with a recovery of 1.11 x 10(8) cells after selection. The median recovery of CD34+ cells was 48% (range 17-78) and purity was 90% (29-99). The median log depletion of CD19+ cells was 3.0. IgH rearrangement, assessed by PCR, was undetectable in 13 of 24 evaluable CD34+ enriched products. Patients received 200 mg/m2 of melphalan followed by the infusion of a median of 2.91 x 10(6)/kg CD34+ cells (1.00-16.30). The median time to absolute neutrophil count >0.5 x 10(9)/l was 11 days, and sustained platelet recovery of >20 x 10(9)/l was 14 days. We conclude that immunomagnetic-based enrichment of CD34+ cells results in a marked reduction in myeloma cells without affecting engraftment kinetics.

Rapid engraftment after allogeneic transplantation using CD34-enriched marrow cells.

Bone marrow cells expressing the surface antigen CD34 comprise approximately 1% of harvested marrow and are highly enriched for marrow progenitor cells, including the cells believed to be responsible for long-term engraftment following bone marrow transplantation (BMT). Selection of CD34-expressing cells was applied in allogeneic BMT (alloBMT) to decrease the number of T lymphocytes in the infused marrow in an attempt to prevent severe graft-versus-host disease (GVHD). We report 14 patients who underwent HLA-identical sibling-matched alloBMT with marrow-enriched for CD34 cells using the Isolex 300 SA device. Patients received total body irradiation, thiotepa, cyclophosphamide, antithymocyte globulin and methylprednisolone prior to marrow infusion. No post-transplantation immunosuppressive therapy was given except for a 5-week course of steroids. The purity of the infused marrow was 64.9+/-6.0% (mean +/- s.e.m.) CD34-positive cells and patients received a mean of 1.24+/-0.21 x 10(6) CD34 cells/kg. A mean of 9.4+/-1.7 x 10(4) CD3 T cells/kg were present in the CD34-enriched product, representing a 2.7+/-0.1 log depletion. There were no graft rejections and patients achieved a sustained absolute granulocyte count of >500 in a median of 10.5 days and a sustained platelet engraftment of >20000 untransfused in a median of 27 days. Patients were discharged a median of 21.5 days after marrow infusion. There were no instances of grade III or IV graft-versus-host disease (GVHD) and no unexpected adverse events during the transplant hospitalization. With a median follow-up of 12 months, the estimated 100 day survival is 86+/-9%. CD34 selection in alloBMT permits rapid engraftment without unanticipated toxicities.

Acute iron poisoning.

Accidental iron ingestion is not uncommon in children and has become a leading cause of unintentional pharmaceutical ingestion fatality. Difficulty in obtaining urgent serum iron levels in majority of hospitals in India, lack of objective indices for starting and stopping the chelation therapy and the cost of chelation therapy, all pose a significant challenge for a clinician in managing an acutely intoxicated patient. This review emphasizes the need for early recognition and correct intervention of a child with acute iron overdose to avoid undue morbidity and mortality.

Posttransplantation lymphoproliferative disorders in bone marrow transplant recipients are aggressive diseases with a high incidence of adverse histologic and immunobiologic features.

Posttransplantation lymphoproliferative disorders (PT-LPDs) occurring in T-cell depleted (TCD) allogeneic bone marrow transplant recipients seem to be different from those that arise in solid organ recipients in their early development, the high incidence of extensive dissemination at presentation, and their aggressive course and high fatality rate. We report a series of 10 patients with PT-LPDs after TCD allogeneic bone marrow transplant. We studied the correlation between the morphology of the lesions; their clonality based on immunoglobulin (Ig) heavy chain gene rearrangement analysis and immunohistochemistry; their proliferative activity as measured by immunoperoxidase staining for the proliferating cell nuclear antigen (PCNA) and the presence of p53 gene product overexpression. Histologically, our cases corresponded to the two morphologic categories of polymorphic B-cell lymphoma (PBCL, seven cases) and malignant lymphoma immunoblastic (ML-IB, three cases). Ig light-chain staining showed monoclonality in a minority of the cases, whereas Ig gene rearrangement analysis by polymerase chain reaction revealed B-cell clonality in three of seven cases of PBCL and in all three cases of ML-IB. The Epstein-Barr virus (EBV) genome, the expression of EBV latent membrane protein or both were found in all 10 specimens. High proliferative activity (PCNA > or = 66%) was found in all cases, with a mean PCNA value of 56% in PBCL and 84% in ML-IB. Five specimens were p53+ (two of seven PBCL and three of three ML-IB). Two of four PBCL cases resolved with the administration of donor leukocytes. All of the remaining patients died of the PT-LPD within a short time from admission. Our results show that the PT-LPDs after TCD bone marrow transplantation are characterized by a high frequency of high-grade histologic subtypes, frequent monoclonality, high proliferative activity, frequent overexpression of p53 gene product, and poor prognosis. These characteristics observed in only a minority of cases of PT-LPDs occurring after solid organ transplantation may account for the less aggressive clinical behavior observed in those diseases.

Lymphocytosis of donor origin in cerebrospinal fluid, and marrow aplasia after donor leukocyte infusion for EBV-lymphoproliferative disease.

A 29-year-old woman underwent a T cell-depleted unrelated donor transplant for CML in chronic phase. Sixty-three days after marrow infusion, the patient developed fevers and generalized lymphadenopathy. Lymph node biopsy was consistent with monoclonal EBV-associated immunoblastic lymphoma for which the patient received 10(5) CD3-positive donor leukocytes per kilogram. Six days after leukocyte infusion the patient developed mental status changes without focal neurological deficit. MRI revealed no mass lesions. Cerebral spinal fluid revealed a white blood cell count of 1650 cells/mm3 which were shown to be T lymphocytes of donor origin. The CSF was tested and found to be PCR positive for EBV virus interval repeat 1 sequence (IR1). The lymphocytosis and mental status changes resolved without specific intervention. Subsequently she developed marrow aplasia, which was believed to be secondary to the infusion of donor leukocytes. Possible mechanisms for these two previously unreported side-effects of donor leukocyte infusion are discussed.

Thrombotic thrombocytopenic purpura associated with FK506 following bone marrow transplantation.

Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) have been observed after bone marrow transplantation (BMT), typically occurring 1-6 months following BMT. We describe two patients who developed TTP very early after BMT while receiving intravenous FK506. They were treated with platelet support and plasma exchange (PE) using either fresh frozen plasma (FFP) or cryosupernatant fraction of plasma (CFP), resulting in remission of TTP activity.

Color Doppler evaluation of uteroplacentofetal circulation in management of high risk pregnancies.

The study group consisted of 75 high risk singleton pregnancies in whom color duplex Doppler evaluation of the uteroplacental circulation was determined and correlated with perinatal outcome. Uterine, umbilical and middle cerebral artery flow velocity waveforms (FVW) were analysed and the resistance index (RI), pulsatility index (PI) and the systolic/diastolic (S/D) ratios measured. On the basis of the FVW the uteroplacentofetal blood flow was classified as normal, increased resistance to flow, absent end diastolic flow (AEDF), and reversed end diastolic flow (REDF). Ultrasound biometry was simultaneously performed for all fetuses, while non stress testing was performed as and when indicated. Of the 75 fetuses studied 33 (44%) had abnormal FVWs and only 30.3% of these had an uncomplicated outcome as compared to 81% of those with normal flows. The mortality in cases with abnormal flows was 43% as compared to 7% in those with normal flows. There were 40 growth retarded fetuses in the study group of which 30 (75%) had abnormal umbilical artery FVWs. Of the 18 fetuses with AEDF or REDF, all (n = 7) in whom timely obstetric intervention was not done died in utero, irrespective of fetal weight and gestational age, however 75% of these with weight > 1000 g survived when delivered by cesarean section.

Use of 'split' plateletpheresis products for alloimmunized patients.

Single donor platelets obtained using the COBE Spectra were split into two halves and administered to alloimmunized patients with leukemia at two different points in time. The mean platelet yield was 6.83 x 10(11) (n = 63) with 56% of collections having yields of > 6.0 x 10(11) (i.e. twice the current AABB recommendation for an apheresis platelet transfusion). In 58 instances, the two halves were administered to the same patient 24-96 h apart. The differences in the correct increments of the split transfusions administered 24-48 h apart were not statistically significant, although there were decreased increments after 72 and 96 h of storage. In 5 instances when the CCI for first transfusion was unacceptably low, the second half was successfully transfused to another patient. This study proves it is feasible to split apheresis platelets into two transfusions, and discusses approaches to optimally use this strategy for the transfusion support of alloimmunized patients.

Maternal heart disease and perinatal outcome.

Between January 1991 and August 1992, 62 singleton pregnancies with heart disease were managed at the Wadia Maternity Hospital, Bombay. In 51 (82.3%), the heart disease was of rheumatic origin, while in 11 (17.7%), the disease was nonrheumatic. Thirteen cases of rheumatic disease (25.4%) were graded as Class III or IV, as per New York Heart Association (NYHA) classification. Six cases with rheumatic disease had closed mitral commisurotomy done, while none had a prosthetic heart valve. There was no maternal mortality. The average birth weight of neonates born to mothers with Class III or IV rheumatic heart disease was significantly lower (p < 0.05) than the average noted in singleton, normal, uncomplicated, non high risk pregnancies, during this period. There was also a significant difference (p < 0.05) in birth weight between infants born to mothers with NYHA Class I or II and Class III or IV symptoms. No infant had a congenital heart disease. Our findings suggest that though the presence of maternal heart disease did not affect the perinatal outcome, all infants born to mothers with NYHA Class III or IV had intrauterine growth retardation.