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Biomedical subjects

J Kersey

Publications and source records attributed to J Kersey.

At least 55 records · Page 3Linked to original sources

Studies on the pathology of non-Hodgkin's lymphoma of childhood. I. The role of routine histopathology as a prognostic factor. A report from the Children's Cancer Study Group.

Between April 1977, and August 1980, the Children's Cancer Study Group (CCSG) conducted a clinical trial of childhood non-Hodgkin's lymphoma (NHL), randomizing 256 patients to one of two treatment regimens. A 4-drug regimen (regimen 1, modified cyclophosphamide, Oncorin [vincristine], methotrexate, prednisone [COMP] ) was compared with a 10-drug regimen (regimen 2, modified LSA2-L2). Using the Rappaport classification, the review pathologist diagnosed the 213 evaluable tissue specimens as follows: lymphoblastic (LC), 73; Burkitt's tumor (BT), 40; "undifferentiated" non-Burkitt's type (NB), 67; large cell or "histiocytic" lymphoma (HI), 29; and other types (OT), 4. Concurrence in classification between the review and institutional pathologists was poor when using the above four categories; however, concurrence was 88% between the review pathologist and other hematopathologists, and 99% when classifying the specimens as lymphoblastic or nonlymphoblastic. For patients with nonlocalized disease, this randomized controlled study demonstrated a new important correlation of histopathology with the effectiveness of treatment. When analyzed without stratification into lymphoblastic and nonlymphoblastic types, the two regimens showed identical relapse free survival (RFS) curves for patients with nonlocalized involvement. However, when patients were stratified according to histologic classification, regimen 2 was superior to regimen 1 for patients with lymphoblastic lymphoma, achieving 74% RFS at 30 months compared to 31% for regimen 1 (P = 0.001). Conversely, those with nonlymphoblastic types (BT, NB, HI) treated with regimen 1 had a 58% RFS at 30 months compared to 32% for those treated on regimen 2 (P = 0.01). This study demonstrates that proper, routine histopathologic classification of NHL is the best criterion for choice of therapy in children with nonlocalized involvement. As a result of this study, all patients with nonlocalized disease, diagnosed after August 1980, were no longer randomized but were assigned to the appropriate treatment regimen based on prospective review of histopathology.

Antineoplastic Combined Chemotherapy Protocols↗

Total parenteral nutrition in bone marrow transplantation: a clinical evaluation.

Bone marrow transplantation (BMT) is associated with severe metabolic stress secondary to anorexia, mucositis, enteritis, and infection. We compared nutritional parameters and clinical outcomes of 22 patients who received prophylactic total parenteral nutrition (TPN) to those of 22 controls, matched for age and diagnosis, who received nutritional support ad libitum. Over the 5-week study period, the TPN group averaged caloric intakes greater than 1.5 X basal energy expediture (BEE) per day and gained 2.5% of body weight; the control group averaged less than 0.9 X BEE and lost 3.7% of body weight. Visceral protein status as reflected by serum albumin was not different. Engraftment of donor marrow cells was 3 days earlier (p less than 0.01) in the TPN group than in the controls, despite there being no significant difference in the number of marrow cells each group received. There was no difference in the two groups' clinical outcomes; mortality, duration of hospital stay, and incidences of sepsis, graft-versus-host disease, and return of malignancy were equivalent. Thus, patients who received prophylactic TPN engrafted sooner than patients who did not; however, overall clinical outcome was unaffected by TPN. Controlled studies of prophylactic TPN are indicated for the BMT patient population.

Adolescent↗

Empirical antibacterial therapy in febrile, granulocytopenic bone marrow transplant patients.

Fifty febrile, granulocytopenic allogeneic bone marrow transplant patients receiving prophylactic trimethoprim-sulfamethoxazole were randomized to one of two empirical antibiotic regimens to determine whether a shortened course of empirical therapy was beneficial. Of the 50 patients, 25 received empirical tobramycin and ticarcillin for only 3 days, and 25 were maintained on empirical tobramycin and ticarcillin until they were afebrile and no longer granulocytopenic. Although the incidence of bacterial infections in the two groups was not statistically significantly different, almost twice as many bacterial infections were observed in the group that received the short course of empirical therapy. Furthermore, because of the high incidence of bacterial infection and clinical concerns about occult bacterial sepsis, within 2 weeks of the randomization the overall use of parenteral antibacterial agents was similar in both groups. The incidence of invasive fungal disease and the use of amphotericin B therapy were similar in both groups. The results of this study suggest that little clinical benefit is likely to be seen in bone marrow transplant patients treated with short-course empirical tobramycin and ticarcillin, despite the administration of prophylactic trimethoprim-sulfamethoxazole, and emphasize the need for new strategies to prevent infections with gram-positive and trimethoprim-sulfamethoxazole-resistant gram-negative bacteria in these patients.

Adolescent↗

Identity of immune cells in graft-versus-host disease of the skin. Analysis using monoclonal antibodies by indirect immunofluorescence.

The cellular infiltrate in skin biopsies of 9 patients with graft-versus-host disease (GVHD) has been characterized with the use of monoclonal antibodies by indirect immunofluorescence. Most infiltrating cells in dermis reacted with monoclonal antibodies which recognize T-cell antigens. A mean of 45% of all dermal cells were T11-reactive, while a smaller proportion of cells were identified by another "pan" antibody, OKT3. In all but two instances the proportion of dermal cells reactive with OKT8 exceeded the proportion reactive with OKT4. Anti-Tac, which identifies activated T cells, reacted with a variable proportion of cells. Monocytes and null cells (OKM1+) were frequently observed but were less numerous than T-lymphocytes. Infiltrates were sparsely populated with OKT6-reactive cells, and there was no difference between the number of intraepidermal cells reactive with this antibody in study subjects and normal controls. Few cells reactive with Leu 7 (large granular lymphocytes) or with anti-B-cell reagents were seen. These findings may have clinical implications for use of monoclonal antibodies for prophylaxis and treatment of GVHD.

Adolescent↗

Childhood non-Hodgkin's lymphoma. The results of a randomized therapeutic trial comparing a 4-drug regimen (COMP) with a 10-drug regimen (LSA2-L2).

Members of the Childrens Cancer Study Group treated 234 eligible patients in a randomized trial designed to study the relative effectiveness of two therapy programs for the treatment of childhood and adolescent non-Hodgkin's lymphoma. Two chemotherapeutic strategies were compared: a 4-drug regimen (COMP) and a 10-drug regimen (modified LSA2-L2). Failure-free survival for all patients was 60 per cent at 24 months. In patients with disseminated disease treatment success was influenced by both the histologic subtype of disease and the therapeutic regimen followed. The 10-drug program was more effective than the 4-drug program in patients with disseminated lymphoblastic disease (two-year failure-free survival rate, 76 vs. 26 per cent, respectively; P = 0.0002), whereas the 4-drug program was more effective than the 10-drug program in those with nonlymphoblastic disease (57 vs. 28 per cent, respectively, P = 0.008). The less toxic, more easily administered 4-drug regimen was as effective as the 10-drug regimen in patients with localized disease (89 vs. 84 per cent, respectively).

Adolescent↗

Bone marrow transplantation for non-Hodgkin's lymphoma in children and young adults. A pilot study.

Allogeneic bone marrow transplantation was performed in 10 patients with disseminated Burkitt's lymphoma or poor-prognosis T-cell lymphoblastic lymphoma. All patients received a cytoreduction regimen consisting of cyclophosphamide, cytosine arabinoside, bis-chloro-nitroso-urea, and total-body irradiation. Eight patients received marrow from HLA-matched sibling donors. One patient received marrow from a parent donor and one patient died during initial cytoreduction and did not undergo total-body irradiation or marrow infusion. Six patients had Burkitt's lymphoma stages III and IV at diagnosis, and three of the six are alive at 18, 28, and 73 months. Four patients had T-cell lymphoblastic lymphoma, stages III and IV at diagnosis, and two of the four are alive at 29 and 49 months. Overall survival in the nine patients who underwent transplantation is 56 percent by life-table analysis. Follow up for the surviving patients ranges from 18 to 73 months (median 29 months). All five survivors are at home with unmaintained remissions.

Adolescent↗

The gauze hammock sling operation in the treatment of stress incontinence.

Moir's gauze hammock sling operation for stress incontinence is described with minor modifications, and a series of 105 consecutive patients with independent follow up from 6 months to 9 years is presented. Patients were selected for operation on clinical grounds, urodynamic investigations only becoming available at the end of the series. In 48 patients the operation was a primary procedure. The outcome was determined by clinical review in 93 patients and by case note review in a further 10 with only two patients being lost to follow up. Of the 103 patients assessed, 62 were continent, 26 improved and there were 15 failures. There were two vesico-vaginal fistulas. The results compare favourably with other suprapubic operations for stress incontinence.

Female↗

Clinical usefulness of monoclonal-antibody phenotyping in childhood acute lymphoblastic leukemia.

Lymphoblasts from 59 children with non-T, non-B acute lymphoblastic leukaemia were studied with monoclonal antibodies to four cell-surface proteins. 87% of the children had lymphoblasts positive for HLA-DR, 82% for p30, 75% for p24, and 72% for CALLA. The commonest composite phenotype was HLA-DR+ p30+ CALLA+ p24+. Significant correlations were seen between expression of HLA-DR, p30, and CALLA, but not p24. p30- and CALLA phenotypes were found in patients with high white-blood-cell counts (WBC) and splenomegaly. With standard chemotherapy, disease-free survival from time of remission was shorter in p30- and CALLA- patients than in others. Splenomegaly was associated with poor disease-free survival and provided prognostic information independent of phenotype. High WBC was less significant than phenotype in predicting outcome and was not independent of phenotype.

Adolescent↗

Successful allogeneic bone-marrow transplantation for patients in the accelerated phase of chronic granulocytic leukaemia.

Nine patients underwent allogeneic bone-marrow transplantation as treatment for chronic granulocytic leukaemia (CGL) during the accelerated phase, a point in the course of the disease when it has progressed beyond the stable chronic phase but before the onset of blast crisis. After bone-marrow transplantation, haematological and cytogenetic studies showed ablation of all evidence of leukaemia, successful engraftment, and persistence of normal haemopoiesis in all patients. In one patient severe myelofibrosis and osteosclerosis disappeared after bone-marrow transplantation. Two patients have died of complications related to graft-versus-host disease (GvHD) but with no evidence of CGL. In one patient haematological and cytogenetic evidence of recurrent disease developed after bone-marrow transplantation, and she survives in chronic phase. Six patients are free of disability, do not require transfusions, possess normal marrow chromosomes, and have persistent clinical and haematological evidence of complete remission from CGL. Intervention with allogeneic bone-marrow transplantation during the accelerated phase of CGL can eradicate the disease and can provide normal haemopoiesis with acceptably low early morbidity and mortality. The long-term efficacy of bone-marrow transplantation as treatment for CGL, and the most effective timing of the transplantation with regard to the course of disease have yet to be determined.

Adult↗

Analysis of human leukemia/lymphoma cell lines with monoclonal antibodies BA-1, BA-2 and BA-3.

A panel of monoclonal antibodies (BA-1, BA-2 and BA-3) were made against the pre-B acute lymphoblastic leukemia (ALL) cell line NALM-6. BA-3 binds to the 100,000 mol. wt common ALL antigen (gp100/CALLA), BA-2 binds to a 24,000 mol, wt (p24) cell surface structure and BA-1 binds to a currently undefined antigen. These antibodies were analysed for their reactivity with 67 human leukemia/lymphoma cell lines. The cell lines studied included T ALL, non-T ALL, surface immunoglobulin+ leukemias/lymphomas, and myeloid/monocytoid leukemias. The results indicate that all three antibodies react primarily (but not exclusively) with malignant cells early in B cell development. This pattern of reactivity was similar to previous results obtained with fresh, non-cultured malignant cells. BA-1, BA-2 and BA-3 are useful tools for analysing the developmental options of normal lymphoid cells and for "cleaning up" leukemia/lymphoma cells in selected cases of autologous bone marrow transplantation.

Antibodies, Monoclonal↗

Fractionated total lymphoid irradiation as preparative immunosuppression in high risk renal transplantation: clinical and immunological studies.

Twenty-two patients at high risk to reject renal allografts have been treated with fractionated total lymphoid irradiation (FTLI) prior to transplantation of primary (2), secondary (16) or teritary (4) renal allografts. All patients undergoing retransplantation had rapidly rejected previous grafts. At 24 months following transplantation, 72% of grafts were functioning in the TLI group compared with a 38% graft function in an historical control group of recipients receiving secondary or tertiary grafts and treated with conventional immunosuppression. Important variables in determining success of transplantation following fractionated TLI include the dose of TLI, the interval from radiation to transplantation, and maintenance, post-transplant immunosuppressive therapy. Optimal results were achieved with 2500 rads delivered in 100 rad fractions followed by transplantation within two weeks, and a tapering prednisone schedule and maintenance azathioprine post-transplantation. Seventeen patients had significant complications of the radiation treatment and there was one death, prior to transplantation, associated with pneumonitis. In vitro assessment of immune function demonstrated marked peripheral T cell depletion and loss of in vitro responsiveness to mitogen and allogeneic stimulation following FTLI. The administration of donor bone marrow at the time of transplantation did not produce chimerism. The results suggest that when properly utilized FTLI can produce effective adjunctive immunosuppression for clinical transplantation.

Adolescent↗

Evolution of cultured leukemic cell lines monitored by chromosomal and immunologic analysis.

We have investigated the karyotypes and markers of B lymphocyte differentiation in two leukemic cell lines, NALM-6-B and NALM-6-MI, both derived from a patient with non-T, non-B acute lymphoblastic leukemia. Both possess characteristics of thymus-independent, bursal-equivalent (B) lymphocytes. By means of immuno-fluorescence techniques, NALM-6-B was shown to possess 47% surface membrane immunoglobulin-positive (Slg+) cells, while NALM-6-MI is surface membrane immunoglobulin-negative (Slg-), but does possess cytoplasmic immunoglobulin M (ClgM+) in more than 90% of the cells. The Slg- ClgM+ phenotype, coupled with morphologic features, is consistent with NALM-6-MI being arrested at a stage early in B-lymphocyte differentiation (a "pre-B" cell). The predominant banded chromosome karyotype of NALM-6-B is pseudodiploid with a translocation of chromosomal material from the long arm of a chromosome 5 to the short arm of a chromosome 12 (5q-/12p+) and a marker Y chromosome. NALM-6-MI possesses the same marker Y chromosome and a deletion of the long arm of chromosome 5(5q-) since in most cells material missing from chromosome 5 does not appear on the short arm of chromosome 12. Within the limits of resolution available with the banding technique, no other karyotypic differences are observed in the two cell lines. The history of the two cell lines, the karyotypic analysis, and the pattern of immunoglobulin markers indicate the possible clonal evolution of NALM-6-MI from NALM-6-B and implicate a portion of the long arm of chromosome 5 in lymphoid differentiation of these leukemic cell lines.

Adult↗