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B Bostrom

Publications and source records attributed to B Bostrom.

At least 19 recordsLinked to original sources
PubMed1997

Cellular expression of antiapoptotic BCL-2 oncoprotein in newly diagnosed childhood acute lymphoblastic leukemia: a Children's Cancer Group Study.

We found a marked variation in BCL-2 oncoprotein expression levels of primary leukemic cells from 338 children with newly diagnosed acute lymphoblastic leukemia (ALL). None of the high-risk features predictive of poor treatment outcome in childhood ALL, such as older age, high white blood cell (WBC) count, organomegaly, T-lineage immunophenotype, ability of leukemic cells to cause overt leukemia in severe combined immunodeficient (SCID) mice, presence of MLL-AF4, and BCR-ABL fusion transcripts were associated with high levels of BCL-2 expression. Overall, high BCL-2 levels were not associated with slow early response, failure to achieve complete remission, or poor event-free survival. High BCL-2 levels in primary leukemic cells predicted slow early response only in T-lineage ALL patients, which comprised approximately 15% of the total patient population. Even for this small subset of patients, the level of BCL-2 expression did not have a significant impact on the short-term event-free survival.

Adolescent↗
PubMed1997

Relationship of plasma pharmacokinetics of high-dose oral busulfan to the outcome of allogeneic bone marrow transplantation in children with thalassemia.

We analyzed plasma pharmacokinetics of busulfan in 64 children and young adults (age 2.8-26; median 11 years) with homozygous beta-thalassemia transplanted with bone marrow from HLA-identical sibling donors. A uniform conditioning regimen was employed, using busulfan 14 or 16 mg/kg in 12 divided doses, and cyclophosphamide 120 or 200 mg/kg. Three sets of parameters were examined in this homogenous patient population: (1) factors that affect the plasma kinetics of busulfan, such as age and pre-transplant liver status defined by liver function tests, ferritin levels and liver biopsy; (2) busulfan-related toxicity: occurrence of veno-occlusive disease, seizures and idiopathic interstitial pneumonitis; and (3) the relationship between busulfan exposure and transplant outcome: engraftment delay or rejection, aplasia, occurrence of mixed chimeras and mortality. Kinetic analysis of first and 10th dose (using area under the curve (AUC), maximum and minimum concentration) as comparable, showing no sign of accumulation or decline in busulfan plasma levels over time. Age and liver status did not influence busulfan metabolism. No relationship was found between busulfan exposure and toxicities or transplant outcome. We conclude that busulfan monitoring is not predictive in children and young adults with homozygous beta-thalassemia receiving busulfan and high-dose cyclophosphamide along with histocompatable sibling donor marrow.

Administration, Oral↗
PubMed1996

Pleuropulmonary blastoma: a marker for familial disease.

OBJECTIVE: To catalog and evaluate patterns of disease in families of children with pleuropulmonary blastoma (PPB). METHODS: Data have been collected since 1988 on 45 children with PPB and their families. All pathologic materials were centrally reviewed. Preliminary molecular genetic analyses were performed when possible. RESULTS: In 12 of 45 patients, an association was found between PPB and other dysplasias, neoplasias, or malignancies in the patients with or in their young relatives. The diseases found to be associated with PPB include other cases of PPB, pulmonary cysts, cystic nephromas, sarcomas, medulloblastomas, thyroid dysplasias and neoplasias, malignant germ cell tumors, Hodgkin disease, leukemia, and Langerhans cell histiocytosis. Abnormalities of the p53 tumor suppressor gene, Wilms tumor suppressor gene (WT1), and the putative second genetic locus for Wilms tumor (WT2) were not found in preliminary investigations. CONCLUSIONS: The occurrence of PPB appears to herald a constitutional and heritable predisposition to dysplastic or neoplastic disease in approximately 25% of cases. All patients with PPB and their families should be investigated carefully. Further research of this new family cancer syndrome may provide insight into the genetic basis of these diseases.

Adult↗
PubMed1996

Pilot study of high-dose thiotepa and etoposide with autologous bone marrow rescue in children and young adults with recurrent CNS tumors. The Children's Cancer Group.

PURPOSE: This study was designed to determine the toxicity, radiographic response rate, and outcome following high-dose thiotepa, etoposide, and autologous bone marrow rescue (ABMR) for young patients with recurrent malignant brain tumors. METHODS: Eligibility criteria required adequate renal, hepatic, and pulmonary function, and no bone marrow infiltration. Thiotepa 300 mg/m2 and etoposide 500 mg/ m2 were infused on 3 consecutive days, and autologous bone marrow was infused 72 hours following chemotherapy. RESULTS: Forty-five patients with recurrent high-grade brain tumors, aged 8 months to 36 years (median, 8 years), were treated. Seven patients (16%) died of treatment-related toxicities within 56 days of marrow reinfusion. Delayed platelet engraftment occurred in 44% of patients who survived beyond day 56. Of 35 patients with radiographically measurable disease who survived at least 28 days following ABMR, there were two complete responses (CRs) and six partial responses (PRs), for an overall response (CRs plus PRs) rate of 23% (SE = 7%). Objective responses were observed in four of 14 assessable patients with high-grade glioma and in two of six with primitive neuroectodermal tumors (PNETs)/ medulloblastoma. Survival was significantly improved in patients treated with minimal residual disease (P < .0005). Five of 18 patients (28%) with high-grade gliomas remain free of disease at 39+, 44+, 49+, 52+, and 59+ months post-ABMR. CONCLUSION: The combination of high-dose thiotepa and etoposide has activity against a variety of recurrent childhood brain tumors. These results merit further evaluation in children and young adults with both recurrent and newly diagnosed high-grade brain tumors.

Adolescent↗
PubMed1994

Clonogenicity of circulating neuroblastoma cells: implications regarding peripheral blood stem cell transplantation.

Peripheral blood stem cells (PBSCs) are being used as an alternative to autologous marrow rescue for hematopoietic reconstitution after high-dose chemotherapy in patients with neuroblastoma and other solid malignancies. Use of PBSCs is preferred by some because of the belief that there is less risk of tumor contamination. Because tumor stem cell contamination is thought to be one contributing cause of relapse after myeloablative therapy and autologous reconstitution, we examined the potential risk of reinfusing circulating neuroblastoma cells by in vitro evaluation of their clonogenicity. Immunocytologic and tumor cell clonogenic analyses were performed on 74 blood samples obtained from 56 children with advanced-stage neuroblastoma. Concurrently drawn bone marrow specimens were evaluated in 30 instances. Circulating neoplastic cells were detected in 19 of 74 (26%) for all specimens and by immunologic techniques (26%). Using a clonogenic assay, 13 grew identifiable tumor colonies. Comparing results with the two techniques showed tumor colony growth in 10 of the 19 positive specimens by immunocytology. However, 3 of 53 samples (6%) that were negative by immunocytology were positive by the clonogenic assay. Of the 11 positive blood samples, 9 concurrent marrows contained neuroblastoma cells; of the 19 negative blood specimens, 3 concurrent marrows had metastatic disease. We conclude that circulating neuroblastoma cells are present in peripheral blood and have clonogenic properties in vitro. This supports the view that tumor cell contamination may well be one cause of relapse after autologous reconstitution. Consequently, PBSC collections should also undergo meticulous monitoring for tumor contamination before autologous reinfusion.

Child↗
PubMed1994

Autologous peripheral blood cell transplantation in the treatment of advanced neuroblastoma.

PURPOSE: We review the experience with autologous peripheral blood cell transplantation (APBCT) in children with neuroblastoma at the University of Minnesota. PATIENTS AND METHODS: Aspects of peripheral blood cell collection and use in nine patients who had advanced neuroblastoma (eight Evans stage IV, 1 stage III), who were median age 4 years (range 10 months-22 years) and who were treated with high-dose chemotherapy without total body irradiation and APBCT between September 1987 and December 1989 are reviewed. RESULTS: A median of 4.8 x 10(8) (range 3.3-8.9) mononuclear cells per kilogram of body weight were obtained by a median of six (range four-eight) collections. In vitro assay of granulocyte-monocyte colony-forming cells (CFU-GM) demonstrated a median of 3.6 x 10(4) (range 0.7-7.8) CFU-GM/kg of body weight. After APBCT, granulocyte recovery (absolute neutrophil count > 500 x 10(6)/L) occurred at a median of 28 days (range 14-72) and platelet recovery (> 150 x 10(9)/L) occurred at a median of 34 days (range 19-202). All patients but one, who had progressive disease, were transplanted with residual disease. Immunocytological analysis of peripheral blood stem cell harvest showed the presence of circulating neuroblastoma cells in three of nine patients, all of whom had minimal marrow residual disease by biopsy. One patient is still alive with no evidence of disease after 5 years. The others died of recurrent neuroblastoma a median of 14 months (range 3-29) after transplant. CONCLUSION: APBCT is safe and effective for hematopoietic reconstitution after high-dose chemotherapy, and may be useful when a bone marrow harvest cannot be performed because of prior pelvic radiation or minimal residual bone marrow metastasis. Immunocytological methods to ensure that the product is free of tumor contamination should be performed.

Adolescent↗
PubMed1994

Antithymocyte globulin, cyclosporine, and prednisone for the treatment of severe aplastic anemia in children. A pilot study.

PURPOSE: The aim of the therapeutic trial was to try to optimize the treatment of severe and moderate aplastic anemia in children who lack a suitable bone marrow donor using the most successful available drugs, with the least amount of side effects. PATIENTS AND METHODS: A pilot study for the treatment of severe aplastic anemia in children was conducted by four institutions. The treatment protocol included antithymocyte globulin (ATG), prednisone, and cyclosporine A. Twelve patients were enrolled, and 11 were evaluable. All patients had severe aplastic anemia (SAA); three had hepatitis-induced severe aplastic anemia (HI-SAA). RESULTS: Of 11 evaluable patients, eight have responded with normalization of their blood counts. Two of the three patients with HI-SAA responded to the therapy. CONCLUSION: The results of our pilot study compare favorably with previous therapeutic trials. All the patients who responded achieved complete response, i.e., restoration of blood counts to within the normal range.

Adolescent↗
PubMed1993

Cellular pharmacology of 6-mercaptopurine in acute lymphoblastic leukemia.

PURPOSE: The cellular pharmacology of 6-Mercaptopurine (6MP) in acute lymphoblastic leukemia (ALL) is reviewed. DESIGN: Relevant studies on the clinical pharmacology of 6MP were reviewed. RESULTS: 6MP is one of the major drugs used in maintenance therapy of acute lymphoblastic leukemia (ALL). It is also used to treat steroid unresponsive inflammatory bowel disease. 6MP is an inactive prodrug that requires absorption, cellular uptake, and intracellular anabolism to nucleotides for cytotoxic activity. These nucleotides are ultimately incorporated into DNA and RNA, resulting in cell death. Two analogs of 6MP, azathioprine and 6-thioguanine, are also anabolized to the same intracellular metabolites, suggesting they should be therapeutically equivalent to 6MP. 6MP may be anabolized to nonmethylated nucleotides or may undergo methylation by the enzyme thiopurine methyltransferase to S-methylated nucleotides, which are also cytotoxic. CONCLUSION: Recent studies of 6MP pharmacokinetics in children with ALL have suggested that a higher systemic exposure, as measured by a greater area under the plasma concentration time curve or a higher concentration of 6MP metabolites in red blood cells, is associated with a decreased risk of relapse.

Biological Availability↗
PubMed1992

Depot characteristics and biodistribution of interleukin-2 liposomes: importance of route of administration.

Due to rapid clearance of interleukin-2 (IL-2), it has had limited effective use as an in vivo immunostimulant. Current experimental and clinical protocols generally must utilize large doses, multiple injections, or continuous infusions of IL-2 in order to achieve significant immunostimulation, often at the expense of systemic toxicity. Therefore, the pharmacodynamics of IL-2 liposomes were investigated. IL-2 liposome incorporation efficiency was 80.4% (SD 5.5); vesicle diameter was 1.65 microns (SD 0.09) as determined by fluorescence-activated cell sorting (FACS). Both formulation (free cytokine vs. IL-2 liposomes) and route of administration were important variables in determination of the biodistribution and pharmacokinetic characteristics of IL-2. When free [125I]IL-2 was given i.v. to mice, only 6.5% was in the blood and 3% in liver and spleen 2 h after injection; on the other hand, at 2 h greater than 70% of i.v. [125I]IL-2 liposomes were detected in the blood, liver, spleen, and lungs. Mean i.v. elimination t1/2 from the blood of rats given 20 x 10(6) U/kg free cytokine or IL-2 liposomes was 41 versus 102 min, respectively, as measured by bioassay and 59 and 119 min as measured by enzyme immunoassay (EIA). After i.v. administration, the estimated Vd of IL-2 liposomes was 13-fold smaller than the free cytokine. Intrathoracic (i.tx.), i.p., and s.c. administration of [125I]IL-2 to mice also demonstrated significant depot effects when IL-2 was incorporated into liposomes. These data suggest IL-2 liposomes may provide in vivo immunostimulation superior to the free cytokine due to biodistribution and depot characteristics.

Animals↗
PubMed1991

Therapy-related myelodysplastic syndrome and acute myeloid leukemia in children: correlation between chromosomal abnormalities and prior therapy.

We have studied 20 children with therapy-related myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) who were 3 months to 16 years old at diagnosis of their primary neoplasm and 1 to 24 years old at diagnosis of their secondary neoplasm. The median interval from initial treatment for the first malignancy to diagnosis of therapy-related MDS or AML was 46 months (range, 12 to 116 months). Twelve patients had chromosomal abnormalities resulting in loss of material from the long arm of chromosomes 5 and/or 7, three patients had abnormalities of chromosome 11 band q23, one patient had both classes of abnormalities, three patients had other abnormalities, and one patient had a normal karyotype. Ten of 12 patients with chromosome 5 and/or 7 abnormalities had been exposed to an alkylating agent, and two of three patients with 11q23 abnormalities had been exposed to an epipodophyllotoxin. The patient with both classes of abnormalities had been exposed to both types of therapy. We conclude that abnormalities of chromosomes 5 and/or 7 are common in children with therapy-related MDS or AML. The proposed relationships between exposure to alkylating agents and abnormalities of chromosomes 5 and/or 7 and between exposure to epipodophyllotoxins and abnormalities of 11q23 are supported in this pediatric series.

Adolescent↗
PubMed1991

Collection and use of peripheral blood stem cells in very small children.

Collections of peripheral blood stem cells (PBSC) from children weighing less than 25 kg have been limited by concern about citrate toxicity. We developed a modified collection technique on the Fenwal CS3000 blood cell separator and used it in three children weighing 8.3, 20 and 24 kg with neuroblastoma involving the marrow. The saline prime was discarded as a mixture of 250 ml red cells, 100 ml fresh frozen plasma, and 100 ml 5% albumin was run into the separator. Heparin (1500 units/h) was used to supplement ACD, which was infused at a low rate (1:25-1:32 vs blood, vs the usual 1:13). No serious difficulties were encountered during or after the collections. A total of 5.7, 4.8 and 6.4 x 10(8) mononuclear cells/kg were collected in six procedures per patient. After cell cryopreservation and patient preparation using high-dose chemotherapy, the cells were thawed in 37 degrees C saline and infused without incident. Hematopoietic recovery was observed, and one of the patients remains in clinical remission after 11 months of follow-up. The addition to previously developed procedures of the use of partial albumin prime, low citrate anticoagulation, and heparin allows convenient and safe collection of PBSC in extremely small children, and these PBSC are effective.

Blood Component Removal↗
PubMed1990

Contamination of peripheral blood stem cell harvests by circulating neuroblastoma cells.

Peripheral blood stem cells (PBSC) are being used as one alternative to autologous marrow rescue for patients with neuroblastoma and other solid malignancies. Some physicians prefer use of PBSC because less risk of tumor contamination is believed to exist. This hypothesis was evaluated by immunocytologic analysis of blood samples and concurrently drawn bone marrow (BM) samples and of PBSC harvests obtained from 31 patients with disseminated neuroblastoma. We found circulating neoplastic cells in 75% of specimens analyzed at diagnosis, in 36% during therapy, and in 14% of PBSC harvests. Tumor cells in blood obtained during therapy did not appear until 3 months after the time of diagnosis. Clearance of circulating neuroblastoma cells was documented after two courses of induction chemotherapy. Six of 13 patients with minimal or no BM disease had positive blood specimens. We conclude that substantial risk of tumor contamination of PB harvests exists and recommend that induction chemotherapy be administered before hematopoietic progenitor cells are collected from blood.

Adolescent↗
PubMed1990

Treatment of refractory and relapsed Hodgkin's disease: intensive chemotherapy and autologous bone marrow or peripheral blood stem cell support.

Thirty-three patients with recurrent or refractory Hodgkin's disease were treated with high-dose cyclophosphamide, BCNU, and etoposide and supported with either autologous bone marrow or peripheral blood stem cells or both. Peripheral blood stem cells were comparable to bone marrow in supporting the recovery of hematopoiesis. Twenty-five patients (76%) were in complete remission following this therapy of whom 13 have subsequently relapsed. Twelve remain alive and disease free from 10 to 47 months. The Kaplan-Meier estimate of disease-free survival at 28 months for the entire 33 patients is 32% (95% confidence interval, 13-50%). Poor outcome in six patients was associated with bone marrow involvement by Hodgkin's disease at the time of peripheral blood stem cell collection. These six patients' survival, disease-free survival, the duration of complete remission were all significantly worse than for the 27 patients who were supported with bone marrow (n = 23), peripheral blood stem cells (n = 2), or both (n = 2), and whose marrows were free of disease at the time of stem cell collection. These data demonstrate that intensive therapy with autologous transplantation can produce extended disease-free survival for some patients with advanced Hodgkin's disease and that peripheral blood stem cell support can effectively be used for hematopoietic reconstitution. However, our observations also suggest that with this preparative regimen, bone marrow involvement at the time of peripheral blood stem cell collection is predictive for a poor outcome and alternate approaches to treatment should be considered for this subset of patients.

Adolescent↗
PubMed1990

Comparison of two total body irradiation regimens in allogeneic bone marrow transplantation for acute non-lymphoblastic leukemia in first remission.

Between November 1976 and December 1987, 84 patients with newly diagnosed acute non-lymphoblastic leukemia who had achieved complete remission underwent non T-cell depleted allogeneic bone marrow transplantation from Human Leukocyte Antigen-Mixed Lymphocyte Culture (HLA-MLC) matched sibling donors. The first 36 patients (November 1976-June 1983) were prepared with cyclophosphamide, 60 mg/kg/day, IV for 2 days and single fraction total body irradiation with 750 cGy at a dose rate of 26 cGy/minute (Group I). The next 48 patients (July 1983-December 1987) were prepared with similar chemotherapy, but received hyperfractionated total body irradiation with total 1320 cGy, 165 cGy twice a day at a dose rate of 10 cGy/minute (Group II). Patient characteristics between these two groups are similar except for the significantly older age distribution in Group II. Median follow-up of Groups I and II are 8 years and 11 months and 2 years and 3 months, respectively. The Kaplan-Meier relapse-free survival, survival, and relapse rates at 3 years are 56, 58, and 19% in Group I and 69 (p = 0.22), 77 (p = 0.07), and 10% (p = 0.37) in Group II. There is no difference in the incidence of interstitial pneumonitis, viral or idiopathic, engraftment rate, or incidence of graft versus host disease (GVHD) between these two groups. The fractionated total body irradiation treated group had significantly less nausea and vomiting. Multivariate analysis shows that total body irradiation regimen is not a significant factor in regard to relapse rate, relapse-free survival, and survival.

Adolescent↗
PubMed1990

Bone marrow transplantation for advanced acute leukemia: a pilot study of high-energy total body irradiation, cyclophosphamide and continuous infusion etoposide.

Leukemic relapse following bone marrow transplantation (BMT) for acute leukemia is the most common cause of treatment failure. Because a more intensive pre-transplant preparative regimen may prevent disease recurrence we have designed a novel intensive conditioning regimen for BMT using high-energy total body irradiation (total dose 850 cGy; energy 24 MV; midplane received dose rate 26 cGy/min; day -6) followed by cyclophosphamide (dose 50 mg/kg/day; schedule 2-h infusion; days -5, -4, -3) and continuous infusion high-dose etoposide (dose 500 mg/m2/day; schedule: 22-h infusion; days -5, -4, -3). Between February 1987 and December 1988, 45 patients with advanced acute leukemia received transplants using this regimen. Twenty-five purged auto-transplants were done for B-lineage (n = 18), T-lineage (n = 6) or biphenotypic (n = 1) acute lymphoblastic leukemia, with 12 in remission and 13 in relapse at the time of transplantation. Of these, nine had non-relapse deaths and 16 have relapsed between 1 and 19 months (median 3 months) following transplantation. Of note all the T-lineage patients relapsed including two transplanted in remission and five transplanted in relapse. Nineteen patients received histocompatible allogeneic transplants and one underwent syngeneic transplantation. Of seven patients with acute lymphoblastic leukemia transplanted in refractory relapse, three have had an overt relapse, three died of interstitial pneumonitis and only one survives disease free 15 months after transplantation. Of 13 patients with acute non-lymphocytic leukemia and variants (11 who were transplanted in relapse) three died without relapse, three have relapsed and seven survive disease free from 9 to 27 months (median 20 months) after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗