Budget impact analysis of a breast rapid diagnostic unit.

BACKGROUND: The Odette Cancer Centre's recent implementation of a rapid diagnostic unit (rdu) for breast lesions has significantly decreased wait times to diagnosis. However, the economic impact of the unit remains unknown. This project defined the development and implementation costs and the operational costs of a breast rdu in a tertiary care facility. METHODS: From an institutional perspective, a budget impact analysis identified the direct costs associated with the breast rdu. A base-case model was also used to calculate the cost per patient to achieve a diagnosis. Sensitivity analyses computed costs based on variations in key components. Costs are adjusted to 2015 valuations using health care-specific consumer price indices and are reported in Canadian dollars. RESULTS: Initiation cost for the rdu was $366,243. The annual operational cost for support staff was $111,803. The average per-patient clinical cost for achieving a diagnosis was $770. Sensitivity analyses revealed that, if running at maximal institutional capacity, the total annual clinical cost for achieving a diagnosis could range between $136,080 and $702,675. CONCLUSIONS: Establishment and maintenance of a breast rdu requires significant investment to achieve reductions in time to diagnosis. Expenditures ought to be interpreted in the context of institutional patient volumes and trade-offs in patient-centred outcomes, including lessened patient anxiety and possibly shorter times to definitive treatment. Our study can be used as a resource-planning tool for future rdus in health care systems wishing to improve diagnostic efficiency.

Unrelated donor bone marrow transplantation for children with severe aplastic anemia: minimal GVHD and durable engraftment with partial T cell depletion.

Both increased graft rejection and increased graft vs host disease (GVHD) remain obstacles to success for unrelated donor (URD) BMT for patients with SAA. Partial T cell depletion (PTCD) may decrease the risk of severe GVHD, while still maintaining sufficient donor T lymphocytes to ensure engraftment. We report on 12 patients with SAA who underwent PTCD URD BMT. All patients had failed medical therapy or relapsed following initial responses, and were transfusion dependent. The median age was 6 years, and there were five males. Donors were matched for four patients, and mismatched for eight. All patients received total body irradiation with either Ara-C or thiotepa and cyclophosphamide. PTCD was accomplished using monoclonal antibody T10B9 or OKT3 and complement. All patients engrafted, with a median time of 18 days to ANC >500. Only one patient had greater than grade II acute GVHD; two patients had limited and one patient extensive chronic GVHD. Nine patients are alive and transfusion independent at a median months post BMT. Three patients died from infection or renal failure. This series suggests that an aggressive immunosuppressive conditioning regimen with PTCD results in successful engraftment and minimal GVHD in pediatric patients with SAA, even with HLA mismatched donors.

Outcomes of transplantation with partial T-cell depletion of matched or mismatched unrelated or partially matched related donor bone marrow in children and adolescents with leukemias.

Graft-versus-host disease (GVHD) remains a major barrier to successful hematopoietic stem cell transplant for patients who lack a matched related donor. Partial T-cell depletion (TCD) of the graft may decrease the risk of severe GVHD with unrelated donors (URD) and partially matched related donors (PMRD) while retaining an antileukemic effect. We analyzed our experience using URD and PMRD for pediatric patients with leukemias from 1990 to 2001. A subgroup of 'matched' URD donor pairs was retrospectively analyzed for high-resolution class I. Partial TCD was accomplished with monoclonal antibody T10B9 or OKT3 and complement. There were 76 URD (45% matched) and 28 PMRD recipients. Event-free survival (EFS) was 38.3%, and overall survival (OS) 45.1% at 3 years. On multivariate analysis, there was no difference in survival based upon marrow source, but nonrelapse mortality was higher with the use of PMRD. Relapse occurred in 6% of ALL patients, and 22.8% of AML/MDS patients. Grades III-IV GVHD was observed in only 6.7% of patients. Partial TCD allows use of matched or mismatched URD, or PMRD with little mortality from GVHD, durable engraftment, and no increase in relapse risk.

Metachronous Epstein-Barr virus-related smooth muscle tumors in a child after heart transplantation: case report and review of the literature.

Soft tissue tumors are uncommon manifestations of Epstein-Barr virus (EBV) infection in patients who have had transplants. The authors report 2 metachronous EBV-containing smooth muscle tumors in a child who had a heart transplant, and review the literature on posttransplant soft tissue tumors.

Post-transplant lymphoproliferative disease in children.

Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disease (PTLD) is an important cause of morbidity and mortality following transplantation, and it occurs more frequently in children than in adults. Of 22 (5%) children at our institution who developed tissue-proven PTLD 1-60 months (mean 16.5 months) following organ transplant, 11 died: nine of these 22 patients developed PTLD between 1989 and 1993, and seven (78%) died; the remaining 13 developed PTLD between 1994 and 1998, and four (31%) died (p = 0.08). All nine patients who developed PTLD < 6 months after transplant died, but 11 of 13 patients who manifested disease > or = 6 months after transplant survived (p = 0.0002). Ten of 11 (91%) survivors, but only two of eight (25%) children who died, had serologic evidence of EBV infection at the time of PTLD diagnosis (p = 0.04). EBV seroconversion identified patients at risk for developing PTLD, but also characterized patients with sufficient immune function to survive EBV-related lymphoid proliferation. In situ hybridization for EBER1 mRNA was diagnostically helpful because it detected EBV in tissue sections of all 20 patients with B-cell PTLD, including those with negative serology.

Autopsy pathology of pediatric posttransplant lymphoproliferative disorder.

OBJECTIVES: Posttransplant lymphoproliferative disorder (PTLD) causes significant morbidity and mortality, is related to Epstein-Barr virus (EBV) infection, and is more common in children than in adults. We reviewed autopsies of children who died with PTLD to compare postmortem with antemortem PTLD histology, to assess the extent of PTLD, to document associated pathology, and to identify cause of death. METHODS: Postmortem examinations were performed on 7 patients after bone marrow (n = 3) or liver (n = 4) transplant. PTLD was classified histologically as hyperplasia or lymphoma. In situ hybridization for EBER1 messenger RNA was performed on tissue samples from all cases. EBV serologies were used to categorize infections as negative, primary, or reactive. RESULTS: PTLD was diagnosed in 5 children 12 to 35 (mean: 22) days before death, and 1.5 to 4 (mean: 3) months after transplant; PTLD was diagnosed in 2 cases at autopsy 2.5 and 4 months after transplant. Postmortem PTLD histology resembled antemortem histology; 5 PTLDs were lymphoma, 1 was hyperplasia, and 1 contained both lymphoma and hyperplasia. EBER1 messenger RNA was detected in 6 B-cell PTLDs, including lesions from patients who did not have EBV serology that indicated active infection. Complete autopsy of 4 patients who died with biopsy-proven PTLD revealed widely disseminated disease, and lymph node, brain, gastrointestinal tract, and kidney were involved in all 4 patients. Cases diagnosed at autopsy were 1 widely disseminated PTLD that had been suspected but not proven antemortem, and 1 PTLD confined to abdominal lymph nodes that was not suspected antemortem. Severe organ dysfunction (renal failure, gastrointestinal hemorrhage) was caused by massive PTLD infiltration in 2 patients. The conditions other than PTLD that contributed to morbidity and death were organ infection (5 cases), infarcts (4 cases), and diffuse alveolar damage (3 cases). CONCLUSIONS: PTLD may occur within weeks after transplant in children. The distribution of PTLD comprises a spectrum from localized and subclinical to widely disseminated and symptomatic. PTLD may cause demise quickly after the onset of signs and symptoms, through massive organ infiltration or associated conditions, such as diffuse alveolar damage. EBV serology may not accurately reflect the presence or extent of PTLD. Autopsy studies of transplant patients are necessary to identify the true incidence, natural history, and response to treatment of PTLD.

Novel multiagent chemotherapy for bone marrow relapse of pediatric acute lymphoblastic leukemia.

BACKGROUND: Despite improvements in the treatment of pediatric acute lymphoblastic leukemia, approximately one in five patients will develop recurrent disease. The majority of these patients do not survive. This limited institution study sought to improve event-free survival (EFS) by intensification of chemotherapy. PROCEDURE: Twenty-one patients with either an isolated marrow (n = 16) or a combined marrow and central nervous system relapse (n = 5) received treatment according to Children's Hospital of Philadelphia protocol CHP-540. Six patients had an initial remission of <36 months, and five patients had relapsed within 1 year of completion of phase III therapy. Induction and reinduction therapy consisted of idarubicin, vincristine, dexamethasone, asparaginase, and triple intrathecal chemotherapy. Consolidation and reconsolidation therapy employed high-dose cytarabine, etoposide, and asparaginase given in a sequential manner. Maintenance therapy included courses of high- or low-dose cytarabine followed by sequential etoposide and asparaginase pulse, moderate-dose methotrexate with delayed leukovorin rescue, and vincristine/dexamethasone pulses. Therapy continued for 2 years from the start of interim maintenance in the 16 patients who did not receive a bone marrow transplant (BMT). Two patients underwent an HLA-identical sibling BMT specified by protocol. Four received a nonprotocol-prescribed alternative donor BMT. RESULTS: The complete remission induction rate was 95%. With a median follow-up from date of relapse of 49 months in survivors, the actuarial EFS based on intent to treat is 75%. There were three toxic deaths in patients in CR and two deaths from relapse. CONCLUSIONS: This regimen is toxic but effective and deserves study in a larger setting.

Longitudinal evaluation of cardiopulmonary performance during exercise after bone marrow transplantation in children.

OBJECTIVE: Abnormalities in cardiopulmonary performance during exercise have been reported in children after bone marrow transplantation (BMT). We sought to study changes in exercise performance over time in pediatric BMT survivors. STUDY DESIGN: We retrospectively reviewed the results of serial cardiopulmonary exercise tests performed by patients who had undergone BMT at our institution. Four measurements of cardiopulmonary function are reported: maximum cardiac index (MCI), maximal oxygen consumption (Max VO(2)), oxygen consumption at ventilatory threshold (VO(2) at VT), and maximum work (Max Work) performed. A linear mixed-effects model was fitted to assess changes in these parameters over time. RESULTS: Thirty-three patients performed 96 cardiopulmonary exercise tests. MCI and VO(2) at VT were depressed at initial testing and did not change over time. Max VO(2) increased by 4% per year to 69% predicted, and Max Work increased to 77% predicted at 6 years after BMT. CONCLUSIONS: In spite of an impaired cardiovascular response to exercise as indicated by the persistently low MCI, aerobic and physical working capacity increase. Improved Max VO(2) suggests that oxygen extraction at the musculoskeletal level becomes more efficient with recovery from BMT. This may represent a compensatory response to an impaired ability to increase cardiac output.

Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions.

The efficacy and toxicity of donor leukocyte infusions (DLI) after unrelated donor bone marrow transplantation (BMT) is largely unknown. We identified 58 recipients of unrelated DLI (UDLI) for the treatment of relapsed disease from the National Marrow Donor Program database. A retrospective analysis was performed to determine response, toxicity, and survival after UDLI and to identify factors associated with successful therapy. UDLI was administered for relapsed chronic myelogenous leukemia (CML) (n = 25), acute myelogenous leukemia (AML) (n = 23), acute lymphoblastic leukemia (ALL) (n = 7), and other diseases (n = 3). Eight patients were in complete remission (CR) before UDLI, and 50 were evaluable for response. Forty-two percent (95% confidence interval [CI], 28%-56%) achieved CR, including 11 of 24 (46%; 95% CI, 26%-66%) with CML, 8 of 19 (42%; 95% CI, 20%-64%) with AML, and 2 of 4 (50%; 95% CI, 1%-99%) with ALL. The estimated probability of disease-free survival (DFS) at 1 year after CR was 65% (95% CI, 50%-79%) for CML, 23% (95% CI, 9%-38%) for AML, and 30% (95% CI, 6%-54%) for ALL. Acute graft-versus-host disease (GVHD) complicated UDLI in 37% of patients (grade II-IV, 25%). A total of 13 of 32 evaluable patients (41%) developed chronic GVHD. There was no association between cell dose administered and either response or toxicity. In a multivariable analysis, only a longer interval from BMT to relapse and BMT to UDLI was associated with improved survival and DFS, respectively. UDLI is an acceptable alternative to other treatment options for relapse after unrelated donor BMT. (Blood. 2000;95:1214-1221)

Alternative donor bone marrow transplantation for children with juvenile myelomonocytic leukemia.

The purpose of this study was to evaluate the outcome of children with juvenile myelomonocytic leukemia (JMML) treated with alternative donor bone marrow transplantation (BMT). Twelve consecutive patients with JMML confirmed by in vitro clonogenic assays underwent alternative donor BMT. Ten patients received pretransplant chemotherapy for one to seven cycles (cytosine arabinoside regimens). Eight underwent splenectomy before the transplant. Donors were unrelated for nine patients and partially matched related for three. Conditioning included total body irradiation for all but one patient. Graft-versus-host disease (GVHD) prophylaxis included in vitro partial T-lymphocyte depletion for five patients with cyclosporine arabinoside, and cyclosporine arabinoside and methotrexate for seven. Acute GVHD developed in all patients, and chronic GVHD developed in 7 of 11 evaluable patients. Relapses occurred in two patients, and two died of transplant-related causes. Eight patients remain in remission with a median follow-up of 31 months after the BMT. The event-free survival rate for this series is 64% (95% confidence interval, 27%-85%). The roles of pretransplant chemotherapy and splenectomy for leukemic reduction to prevent relapse, and the use of conditioning regimens with total body irradiation require study in a larger series of patients. GVHD may be beneficial in preventing relapses, which has been the major cause of treatment failure for these patients.

Late effects of chemotherapy compared to bone marrow transplantation in the treatment of pediatric acute myeloid leukemia and myelodysplasia.

BACKGROUND: As more pediatric patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) survive, comparison of the late effects of various therapies becomes increasingly important. This study of survivors of AML is the largest to date comparing the late effects of patients treated with chemotherapy (CT) with or without irradiation (RT) or CT followed by bone marrow transplantation (BMT). PROCEDURE: In a retrospective review of 228 patients with AML or MDS from 1970 to 1995, 62 survived and had follow-up data available more than 1 year following completion of therapy. Ten patients with Down syndrome were excluded. Twenty-six received CT and 26 underwent BMT. Weight and height Z scores, endocrine, ophthalmologic, renal, and cardiac function following CT +/- RT or BMT +/- total body irradiation (TBI) were compared at a mean follow-up of 7.4 and 5.6 years, respectively. RESULTS: Both groups experienced a decrement in height and increase in weight. The mean height Z score in the CT group fell from -0.29 to -0.72 (P = 0.02) and mean weight Z score rose from -0.06 at diagnosis (T0) to 0.51 at last follow-up (T2) (P = 0.02), a finding no longer significant when patients who received RT were excluded. The mean height Z score in the BMT group fell from -0.17 at TO to -0.65 at T2 (P = 0.02), while the mean weight rose from 0.29 at T0 to 0.84 at T2, (P = 0.07). Six of 9 BMT adolescent girls experienced ovarian failure versus 0 of 11 girls treated with CT (P = 0.002). Seven adolescent CT males and seven BMT males showed normal pubertal progression. Two BMT patients require thyroid hormone supplementation, and one receives growth hormone. Six BMT patients and one CT patient developed cataracts, all of whom received irradiation (P = 0.10). Serum creatinine level, hypertension, or left ventricular shortening fraction were not different in the two groups. One BMT patient has chronic graft versus host disease. CONCLUSIONS: Growth, renal, and cardiac functions were similar in the two groups. The need for estrogen supplementation was more frequent following BMT. Recommendations concerning therapy for AML should depend on the probability of cure.

Bone marrow transplantation in pediatric patients with therapy-related myelodysplasia and leukemia.

Eleven children underwent BMT for therapy-related MDS or leukemia, four from HLA-identical siblings and seven from unrelated donors. Ten of the 11 were conditioned with busulfan and cyclophosphamide as the majority had received prior irradiation to the chest and/or abdomen. All patients engrafted. Regimen-related toxicity was more common when compared to historical controls. Eight patients developed acute GVHD and four of eight who survived 100 days post transplant developed extensive chronic GVHD. Non-relapse related mortality occurred in three patients. Five patients developed recurrent malignancy: one died from recurrence of osteosarcoma, three died of recurrent leukemia or MDS and another developed two subsequent malignancies (duodenal carcinoma and anaplastic astrocytoma). Three survive disease-free at 14+, 22+ and 43+ months for a 2 year actuarial cancer-free survival of 24% (95% confidence interval = 5-53%). Although allogeneic BMT can be curative, regimen-related toxicity is frequent and recurrent malignancy remains the major obstacle.

Successful use of extracorporeal membrane oxygenation (ECMO) during BMT for SCID.

An 8-month-old girl with SCID presented with severe bronchiolitis. She received an HLA-identical sibling BMT without conditioning or GVHD prophylaxis. She deteriorated despite mechanical ventilation but had normal cardiac, hepatic and renal function. ECMO was instituted on day +3 and subsequent improvement was seen concurrently with emergence of CD4+ cells on day +11. She was taken off ECMO on day +18 and suffered a left-sided stroke evidenced by a dense left hemiplegia. She was extubated on day +25 and weaned from supplemental oxygen on day +36 and at day +100 has recovered strength in her extremities. This is the first successful use of ECMO as a bridge to engraftment in a BMT patient.

Molluscum contagiosum eyelid lesions as the initial manifestation of acquired immunodeficiency syndrome.

PURPOSE: To report molluscum contagiosum as the initial manifestation in acquired immunodeficiency syndrome (AIDS). METHOD: Case report. A 34-year-old man was examined with atypical, extensive molluscum contagiosum of the eyelids. RESULTS: Biopsy of the lesions confirmed molluscum contagiosum, and a previously normal fundus now disclosed bilateral cotton wool spots and classic signs of cytomegalovirus retinitis in the left eye. Human immunodeficiency virus (HIV) antibody testing was positive. CONCLUSIONS: Manifestation of atypical and extensive eyelid molluscum contagiosum may warrant additional history taking, comprehensive ophthalmic examination, including dilated ophthalmoscopic examination, and HIV testing.

A phase I/II study of idarubicin (Ida) with continuous infusion fludarabine (F-ara-A) and cytarabine (ara-C) for refractory or recurrent pediatric acute myeloid leukemia (AML).

PURPOSE: The goal was to conduct a phase I/II trial of escalating doses of Idarubicin (Ida) in conjunction with the previously established maximum tolerated dose (MTD) of F-ara-A/ara-C in children with refractory or recurrent acute myeloid leukemia (AML). PATIENTS AND METHODS: We conducted a phase I/II trial in parallel with Children's Cancer Group (CCG) study 0922, which involved dose escalation of Ida at levels of mg/m2, 9 mg/m2, and 12 mg/m2 over 15 minutes on days 0, 1, and 2. As phase I safety was documented by CCG, we increased the dose of Ida given on day 0, 1, and 2 of the F-ara-A/ara-C infusion (F-ara-A: 10.5 mg/m2 over 15 minutes and 1.27 mg/m2/hour for 48 hours followed by ara-C: 390 mg/m2 over 15 minutes and 101 mg/m2/hour for 72 hours). RESULTS: Ten of 15 patients achieved remission. There was one toxic death due to adult respiratory distress syndrome. The median time to an absolute neutrophil count (ANC) > 200/microliter was 29 days; ANC > 1,000/microliter was 41 days; and platelets > 100,000/microliter was 45 days. CONCLUSIONS: A dose of 12 mg/m2/day x 3 of Ida did not exceed dose-limiting toxicity with this combination of F-ara-A/ara-C. Substantial activity of this regimen was seen in pediatric patients with AML.

Spectrum of mutations in the OCRL1 gene in the Lowe oculocerebrorenal syndrome.

The oculocerebrorenal syndrome of Lowe (OCRL) is a multisystem disorder characterized by congenital cataracts, mental retardation, and renal Fanconi syndrome. The OCRL1 gene, which, when mutated, is responsible for OCRL, encodes a 105-kD Golgi protein with phosphatidylinositol (4,5)bisphosphate (PtdIn[4,5]P2) 5-phosphatase activity. We have examined the OCRL1 gene in 12 independent patients with OCRL and have found 11 different mutations. Six were nonsense mutations, and one a deletion of one or two nucleotides that leads to frameshift and premature termination. In one, a 1.2-kb genomic deletion of exon 14 was identified. In four others, missense mutations or the deletion of a single codon were found to involve amino acid residues known to be highly conserved among proteins with PtdIns(4,5)P2 5-phosphatase activity. All patients had markedly reduced PtdIns(4,5)P2 5-phosphatase activity in their fibroblasts, whereas the ocrl1 protein was detectable by immunoblotting in some patients with either missense mutations or a codon deletion but was not detectable in those with premature termination mutations. These results confirm and extend our previous observation that the OCRL phenotype results from loss of function of the ocrl1 protein and that mutations are generally heterogeneous. Missense mutations that abolish enzyme activity but not expression of the protein will be useful for studying structure-function relationships in PtdIns(4,5)P2 5-phosphatases.

Recombinant human erythropoietin reduces the need for erythrocyte and platelet transfusions in pediatric patients with sarcoma: a randomized, double-blind, placebo-controlled trial.

OBJECTIVE: To evaluate the effect of recombinant human erythropoietin (EPO) and iron supplementation on transfusion requirements in pediatric patients with sarcoma who were receiving chemotherapy, we performed a double-blind, placebo-controlled, randomized trial. METHODS: Twenty-four pediatric patients with malignant solid tumors were randomly assigned to receive either placebo (saline solution) or EPO for a 16-week study period. The starting dose was 150 IU/kg per dose three times a week and was escalated by 50 IU/kg per dose increments monthly until packed red blood cell (PRBC) transfusion independence was achieved or a dosage of 300 IU/kg per dose was reached. Iron supplementation was prescribed at a dose of 6 mg of elemental iron per kilogram daily. The primary study end point was the comparison of PRBC transfusion requirements in the two groups. RESULTS: Of 24 patients, 20 were evaluable for response. The median PRBC transfusion requirement during the 16-week period was 23 ml/kg in EPO-treated patients versus 80 ml/kg in placebo patients (p = 0.02). The median number of single-donor platelet units transfused was zero in the EPO-treated patients compared with four in the placebo group (p = 0.005). No statistical difference in the intensity of bone marrow suppression was seen, as measured by the median number of complete blood cell counts with an absolute neutrophil count of < 1000 cells/microliter. CONCLUSIONS: Treatment with EPO and iron significantly reduces PRBC transfusions in pediatric patients receiving concomitant chemotherapy for malignant sarcomas. A decrease in the number of platelet transfusions was also seen and deserves further study.

Haemophilus influenzae central corneal ulcer associated with cosmetic lens wear.

PURPOSE: We report a case of keratitis caused by Haemophilus influenzae involving daily wear contact lens use. METHODS: After positive cultures from corneal scrapings and contact lenses, the patient was diagnosed with Haemophilus influenzae keratitis. RESULTS: After 16 days of treatment with topical ciprofloxacin and trimethoprim sulfate-polymyxin B sulfate, the keratitis resolved. CONCLUSIONS: Cultures will help identify rare corneal pathogens such as Haemophilus influenzae and help in directing appropriate treatment.

A study of thiotepa, etoposide and fractionated total body irradiation as a preparative regimen prior to bone marrow transplantation for poor prognosis patients with neuroblastoma.

We report the toxicity and efficacy of a new conditioning regimen for bone marrow transplantation (BMT) in children with poor prognosis neuroblastoma (NBL). Twenty-seven patients with poor prognosis NBL were treated with teniposide (360 mg/m2) or etoposide (500 mg/m2), thiotepa (600-900 mg/m2), and 1200 cGy fractionated total body irradiation (fTBI) followed by autologous marrow rescue (n = 19) or allogeneic BMT from HLA-identical siblings (n = 8). The two patients who received teniposide, 600 mg/m2 thiotepa and fTBI had minimal toxicity but relapsed 4 and 12 months post-auto BMT. The next two patients received 750 mg/m2 thiotepa, 500 mg/m2 etoposide and TBI. They tolerated the conditioning regimen well and are alive and in remission 77 and 75 months post-BMT. At the next thiotepa dose level (900 mg/m2), the first two allograft recipients both experienced fatal regimen-related toxicity. All subsequent allograft recipients received 750 mg/m2 thiotepa and autograft recipients received 900 mg/m2 thiotepa. As of 1 April 1995, eight of the 19 patients who received autologous marrow are surviving disease-free 21 to 77 months post-BMT. Nine autograft recipients relapsed at 2 to 37 months following transplantation. One patient died of hepatic veno-occlusive disease 2 months after auto BMT, and one of pneumonia 6 months post-transplantation. Three allograft recipients have relapsed at 6, 10 and 39 months post-transplant and three are alive and in remission 75, 53 and 27 months post-BMT. Overall, 11/27 patients (41%) are alive and in remission 21-77 months (median 47 months) following BMT. A conditioning regimen consisting of 500 mg/m2 etoposide, thiotepa (750 mg/m2 for allograft recipients and 900 mg/m2 for autograft recipients) and 1200 cGy fTBI has acceptable toxicity and is at least as effective as melphalan-containing regimens in the treatment of high-risk NBL.

Recombinant human tissue plasminogen activator for the treatment of severe hepatic veno-occlusive disease in pediatric bone marrow transplant patients.

Nine pediatric patients were treated with recombinant human tissue plasminogen activator (tPA) for severe hepatic veno-occlusive disease (VOD) which developed after bone marrow transplantation. Recombinant human tPA (5-10 mg/day x 2-4 days) and heparin were begun a median of 15 days (range, 11-32 days) post-transplant. A second course was given if the patient did not respond. The median total serum bilirubin and percent weight gain above baseline were 5.5 mg/dl (range, 1.3-26.1 mg/dl) and 22% (range, 7-44%) respectively at the start of tPA administration. Three patients had their heparin infusion interrupted or discontinued for bleeding symptoms, none of which were life-threatening. Five of the nine patients had complete resolution of their VOD. Another patient was salvaged with a partial maternal liver transplant. We conclude that the incidence and severity of bleeding complications with these doses of tPA and heparin do not preclude their use in pediatric patients. Further study in a larger group setting will be necessary to determine the optimal dosing regimen as well as treatment efficacy.