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Biomedical subjects

J Lister

Publications and source records attributed to J Lister.

At least 37 records · Page 2Linked to original sources

Allogeneic peripheral blood stem cell transplant for myelodysplasia after chemotherapy for post-transplant lymphoma in a cardiac transplant recipient at 10 years.

A 32-year-old male received an allogeneic peripheral blood stem cell transplant (alloPBSCT) for myelodysplasia from his one HLA-A antigen mismatched brother. He is alive with trilineage engraftment and without active GVHD 200 days after transplant. In July 1986 he underwent orthotopic cardiac transplantation for viral cardiomyopathy and has received continuous immunosuppressive therapy. A post-transplant lymphoproliferative disorder with Hodgkin-like histopathology was diagnosed in August 1993 and was successfully treated with four cycles of MOPP chemotherapy. Due to persistent pancytopenia he underwent a bone marrow aspiration and biopsy in May 1996 which revealed monosomy 7 and morphologic changes compatible with myelodysplasia. This is the first report of a cardiac transplant recipient receiving an allogeneic hematopoietic stem cell transplant.

Adult↗

The use of counterflow centrifugal elutriation for the depletion of T cells from unrelated donor bone marrow.

Transplantation of marrow from unrelated donors is associated with an increased incidence and severity of graft-versus-host disease (GVHD). In an attempt to minimize GVHD without compromising engraftment, unrelated donor marrow was depleted of lymphocytes by counterflow centrifugal elutriation (CCE), and a fixed dose of 0.5 x 10(6) CD3+ T cells/kg, as measured in real time by flow cytometry, was added back to the graft. Patients received cyclosporine (CYA) and corticosteroids for GVHD prophylaxis and to facilitate engraftment. In the first cohort (study I), 7 patients received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) (CY) and one patient received CY (200 mg/kg) + 1260 cGy fractionated TBI. Of 6 who were evaluable for both engraftment and rejection, 4 rejected their graft. The study was terminated, and the protocol was modified (study II) by the addition of antithymocyte globulin (ATG) to the pre-BMT and post-BMT therapy. Twelve patients received CY + TBI as above plus ATG given pre-BMT and post-BMT. Ten of twelve who received ATG engrafted. Twelve patients from studies I and II were evaluable for acute GVHD. Two developed grade I acute GVHD. Two patients developed grade II acute GVHD, 2 patients developed grade III GVHD, and 1 patient developed grade IV acute GVHD. Two of three cases of acute GVHD (> grade II) occurred later than day 100 after BMT concomitant with reduction of immunosuppressive therapy. The rate of engraftment was significantly higher in study II (p = .054). In numbers of CD34+ cells infused, numbers of CFU-GM infused, and numbers of nucleated cells did not correlate with engraftment. We conclude that (a) in contrast to the results seen in recipients of marrow from HLA-matched sibling donors, the depletion of unrelated donor marrow of all but 0.5 x 10(6) CD34+ cells/kg together with CYA + corticosteroids was not sufficient to facilitate engraftment. The use of a more immunosuppressive regimen containing TBI and ATG appeared to improve engraftment. (b) The reduction of the graft T cell dose to 0.5 x 10(6) CD34+ cells/kg resulted in a higher incidence of acute GVHD than that seen in recipients of marrow from genotypically identical donors whose marrow was similarly processed.

Adolescent↗

High-dose chemotherapy and autologous stem cell support followed by posttransplantation doxorubicin as initial therapy for metastatic breast cancer.

High-dose chemotherapy is associated with a high complete response rate and possibly some survival advantage in patients with metastatic breast cancer. We designed a clinical trial consisting of a two-step high-dose chemotherapy regimen followed by posttransplantation doxorubicin as the first chemotherapy treatment for metastatic disease. Twenty-one patients with metastatic breast cancer and no previous chemotherapy for metastatic disease were treated with high-dose cyclophosphamide (Cy; 5000 mg/m2), followed by granulocyte colony-stimulating factor. Peripheral blood stem cells were collected. Subsequently, patients received Cy (6000 mg/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) (CTCb) with hematopoietic rescue. Upon recovery of hematopoietic and gastrointestinal toxicity, three cycles of doxorubicin (Dox; 60 mg/m2) were delivered. After Cy, nine patients (45%) developed neutropenic fevers. There were no episodes of bacteremia. Patients received CTCb 37 days after starting Cy and had a hospital stay of 19 days. After CTCb, the median number of days to an absolute neutrophil count >5 x 10(9)/liter was 8, and the median number of days to a platelet count >20 x 10(9)/liter was 9. Neutropenic fevers occurred in 12 patients. There were no hemorrhagic complications. Fifty-five of the 63 planned courses of Dox were delivered. The median time from peripheral blood stem cell infusion to the first Dox cycle was 38 days. The median time to the second Dox cycle was 28 days, and to the last cycle was 30 days. Three episodes of neutropenic fevers were observed. Two patients developed herpes zoster. This regimen is feasible, with acceptable toxicity.

Adult↗

A clonally distinct recurrence of Burkitt's lymphoma at 15 years.

A human immunodeficiency virus-negative male was successfully treated for two occurrences of Burkitt's lymphoma, 15 years apart. As consolidation of his second remission, he underwent high-dose chemotherapy with peripheral blood stem cell transplantation. In an effort to prove whether the second lymphoma was a relapse of the first or a second primary lymphoma, we obtained paraffin-embedded material from both lymphomas. DNA was extracted from this material and amplified by polymerase chain reaction (PCR) using consensus JH and VH region primers. Analysis of the PCR products, which mostly reflects VDJ joints, showed two sharp bands of different molecular size, proving the monoclonal nature of the lymphomas and suggesting that each had different Ig gene rearrangements. Sequencing of both PCR products showed a marked dissimilarity in nucleotide sequence in the clonally unique VDJ joint region, providing strong evidence for the separate cellular genesis of each lymphoma. These results suggest that late relapses of Burkitt's lymphoma should be examined for clonal distinctiveness. If the second lymphoma is distinct from the primary one, it might be treated as a primary lymphoma rather than as recurrent disease.

Adult↗

High-dose cyclophosphamide, carboplatin, and etoposide with autologous stem cell rescue in patients with breast cancer.

This study was designed to establish the toxicity and response rates o observed with a combination of high-dose cyclophosphamide, carboplatin, and etoposide with stem cell rescue in patients with breast carcinoma. Eligibility criteria included metastatic or locally advanced breast carcinoma ; aged < or equal to 60 years; performance status Eastern Cooperative Oncology Group (ECOG) 0-1; and creatinine clearance > or equal to 65 ml/min. Chemotherapy consisted of cyclophosphamide 25 mg/kg i.v. X 4 days, etoposide 400 mg/m(2) i.v. X 4 days, and carboplatin 375 mg/m(2) X 4 days. Bone marrow or peripheral blood stem cells were reinfused 48 h after completion of chemotherapy. Seventeen patients were treated in this study. The major toxicity was gastrointestinal (grades I and II). Fevers associated with neutropenia were observed in all the patients, but no episodes of bacteremia were documented. Hematopoietic toxicities were acceptable. No toxic deaths were observed. Six patients had chemotherapy-sensitive disease at time of transplant, nine had refractory disease, and two were untested. A response rate of 62% with 18% complete response (CR) was achieved. Two patients are free of disease at +7 and +9 months after transplantation. The combination of high-dose cyclophosphamide, carboplatin, and etoposide is well tolerated with a response rate comparable to previously reported high-dose chemotherapy regimens. However, in a poor prognostic risk group, namely patients with chemoinsensitive disease, this therapeutic approach seems to be of no advantage over standard chemotherapy.

Adult↗

Amphotericin B Lipid Complex (Abelcet) in the treatment of invasive mycoses: the North American experience.

Abelcet, or Amphotericin B lipid Complex, is unique formulation, comprising an equimolar mixture of amphotericin B complexed with two lipids. In preclinical studies, Abelcet was clearly demonstrated to be less toxic than amphotericin B desoxycholate and to be effective in models where amphotericin B was ineffective at its maximum tolerated dose. Pharmacokinetic studies in animals also showed that the concentration of Abelcet in blood is similar or reduced compared to levels seen with conventional amphotericin B, with accumulation in the liver, lungs and spleen. Phase I clinical trials determined the optimum tolerated dose of Abelcet to be 5 mg/kg d-1. Data are now available for 228 cases (including 51 paediatric cases) of invasive fungal infection treated with Abelcet in an open-label emergency-release protocol. All patients had to have failed on previous amphotericin B or other conventional antifungals, or to have unacceptable toxicity on amphotericin B, or underlying renal disease, or nephrotoxicity due to other drugs. Abelcet was administered at a dose of 5 mg/kg d-1 for 4 wk. Approximately one-third of patients had candidiasis, one-third aspergillosis and one-third other infections, including fusariosis. Of 183 cases evaluable for response, 126 (69%) had a clinical response (cure or improvement) which was mycologically confirmed in 55% (61/110 tested). Results in paediatric cases were similar to or better than those seen in the group as a whole. When comparisons were made between cases with different types of infection, underlying disease/immunosuppressive disorder, and degree of neutropenia, the response rates were very consistent from group to group. Treatment with Abelcet was well tolerated and mean serum creatinine levels actually declined during therapy, particularly in patients with pre-existing renal dysfunction.

Amphotericin B↗

Primary lymphoma of the skull presenting as multiple cranial nerve palsies.

Lymphoma presenting with isolated diffuse infiltration of the skull is exceedingly rare, with less than 20 previously reported cases. The clinical presentation of a 73-year-old female with primary lymphoma of the skull, manifesting multiple cranial nerve palsies and infiltration of the temporalis muscles is described. MRI of the head, revealed an abnormal signal from the diploic space of the call varium and skull base on both T1 and T2 weighted images, infiltration of the temporalis muscles and clivus, and diffuse meningeal enhancement encroaching on the cavernous sinus bilaterally. Biopsy of temporalis muscle and skull showed a diffuse large cell lymphoma, B-cell type. Staging workup failed to reveal any other sites of disease. Despite multiple cranial nerve palsies, there was no evidence of leptomeningeal disease on CSF examination. MRI was instrumental in demonstrating the abnormalities that lead to the diagnostic biopsy.

Aged↗

Toxicity of busulfan and cyclophosphamide (BU/CY2) in patients with hematologic malignancies.

Between July 1991 and January 1994, 52 patients with hematologic malignancies underwent BMT using BU/CY2 as conditioning regimen. Median patient age was 38 years. Eleven patients underwent autologous BMT, 22 HLA-identical allogeneic BMT, and 19 patients underwent a MUD or an allogeneic mismatched BMT. GVHD prophylaxis was with cyclosporine/methylprednisone in 26 patients; T cell depletion was used in 15 patients. VOD was observed in 7.5% of patients, IP in 12%, seizures in 4%. The overall incidence of grade II-IV acute GVHD was 35%. Delayed platelet engraftment was observed in seven of 11 patients who underwent autologous BMT. Graft failure was seen in seven of 19 (37%) patients who underwent MUD or allogeneic mismatched BMT. Six of the seven patients received T cell depletion as GVHD prophylaxis. BU/CY2 transplantation from an unrelated or family-mismatched donor with T cell depletion is associated with a high incidence of graft failure.

Adolescent↗

Inhibition of an erythroid differentiation switch by the helix-loop-helix protein Id1.

The Id proteins function as negative regulators of basic-helix-loop-helix transcription factors, which play important roles in determination of cell lineage and in tissue-specific differentiation. Down-regulation of Id1 mRNA is associated with dimethyl sulfoxide-induced terminal differentiation of mouse erythroleukemia cells. To examine the significance of Id1 down-regulation in erythroid differentiation, we generated stable mouse erythroleukemia cell lines that constitutively express a "marked" form of the murine Id1 gene. Terminal erythroid differentiation was inhibited in these lines, as indicated by a block in activation of the erythroid-specific genes alpha-globin, beta-globin, and band 3 and continued proliferation in the presence of dimethyl sulfoxide. Interestingly, this block occurred even in the presence of normal levels of the lineage-specific transcription factors GATA-1, NF-E2, and EKLF. Constitutive expression of Id1 did not interfere with DNase I hypersensitivity at site HS2 of the locus control region, expression of the erythropoietin receptor gene, or down-regulation of the endogenous Id1 or c-myc genes. The differentiation block is reversible in these lines and can be rescued by fusion with human erythroleukemia cells. These findings suggest that in vivo, Id1 functions as an antagonist of terminal erythroid differentiation.

Amino Acid Sequence↗

Autologous peripheral blood stem cell transplantation and adoptive immunotherapy with activated natural killer cells in the immediate posttransplant period.

Relapse after high-dose chemotherapy supported by peripheral blood stem cell transplantation (HDC-PBSCT) is the main cause of therapeutic failure in patients with lymphoma and breast cancer. Adoptive immunotherapy with activated natural killer (A-NK) cells and interleukin 2 might eliminate surviving residual tumor without adding to toxicity. Eleven patients with relapsed lymphoma and one with metastatic breast cancer were entered on a pilot clinical trial of HDC-PBSCT followed on day 2 after transplant by infusion of cultured autologous A-NK cells. Simultaneously, recombinant human interleukin 2 (rhIL-2) was initiated as a 4-day continuous i.v. infusion at 2 x 10(6) IU/m2/day, referred to as high-dose rhIL-2. Therapy with high-dose rhIL-2 was followed by a 90-day continuous i. v. infusion at 3 x 10(5) IU/m2/day, referred to as low-dose rhIL-2. All patients engrafted and nine completed treatment. Posttransplant days to a neutrophil count of 500/microliter and to a platelet count of 50,000/microliter were similar to comparable patients treated with HDC-PBSCT alone. Generation of A-NK cells for therapy was feasible in all patients except the three patients with Hodgkin's disease, whose cells did not proliferate in culture. Overall toxicity associated with early posttransplant transfer of A-NK cells and interleukin 2 did not differ from that observed with peripheral blood stem cell transplantation alone in comparable patients. There was early amplification of natural killer cell activity in the peripheral blood of four patients that appeared to result from the transfused A-NK cells. Adoptive transfer of A-NK cells and rhIL-2 during the pancytopenic phase after HDC-PBSCT was feasible and well tolerated, did not adversely affect engraftment, and resulted in amplified natural killer activity in the peripheral blood during the immediate posttransplantation period.

Adoptive Transfer↗

Development of the human fetal phreno-esophageal membrane and its role in the anti-reflux mechanism.

The structural development of the phreno-esophageal membrane was studied in 34 human fetuses ranging from 9-26 weeks of age. Horizontal and coronal sections of the lower esophagus, cardia, and diaphragm were stained with Victoria Blue and Gomori's aldehyde fuchsin to show elastic fibers, and with peracetic-aldehyde fuchsin to show pre-elastic, oxytalan, and elastic fibers, being the elastic elements. The membrane was found to be present between the lower esophagus and diaphragm at 9 weeks. The peracetic-aldehyde fuchsin stain showed many elastic elements in this membrane, but the elastic stain showed only a few elastic fibers under 13 weeks. There was no basic structural change of the membrane from 9 to 26 weeks except for an increasing number of fibers and no basic difference from the anatomical arrangement described in the adult with fibers running from the fascial covering of the undersurface of the diaphragm upwards to the esophageal adventitia. Three dimensional observation revealed that the abdominal part of the esophagus was fixed caudally by the posterior part of the membrane. These findings suggest the position-stabilizing function of this membrane and the developmental co-operation between the hiatal crus and the lower esophageal sphincter as an anti-reflux mechanism.

Diaphragm↗