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Biomedical subjects

E Sloand

Publications and source records attributed to E Sloand.

12 recordsLinked to original sources
PubMed2003

The graft-versus-leukemia effect of nonmyeloablative stem cell allografts may not be sufficient to cure chronic myelogenous leukemia.

We treated 12 patients with chronic myelogenous leukemia (CML) with a low-intensity preparative regimen followed by allogeneic stem cell transplantation in an attempt to confer a curative graft-versus-leukemia (GVL) effect with minimum morbidity. Seven patients in first chronic phase (CP1) and five in second chronic phase (CP2) (age 15-68 years) received a nonmyeloablative conditioning regimen of fludarabine and cyclophosphamide, followed by a G-CSF-mobilized peripheral blood stem cell (PBSC) transplant from an HLA-identical sibling. Cyclosporine (CsA) was used for graft-versus-host disease (GVHD) prophylaxis. Median follow-up was 384 days. Neutrophil recovery occurred at a median of 12 days. There was no transplant-related mortality. Of the seven CP1 patients transplanted, seven achieved a stable molecular remission; two with no post-transplant intervention, three after donor lymphocytes, imatinib and interferon, and two after a myeloablative stem cell transplant. Four of five CP2 patients died in blast crisis and one survived in molecular remission. Of the 12 patients with durable engraftment, six had Grades II-IV acute GVHD; six had limited chronic GVHD. These results suggest that cytoreduction is required to optimize the curative effect of allogeneic stem cell transplantation for CML.

Adolescent↗
PubMed2000

Sustained long-term hematologic recovery despite a marked quantitative defect in the stem cell compartment of patients with aplastic anemia after immunosuppressive therapy.

Previously, we reported that patients with aplastic anemia (AA) have profoundly decreased numbers of hematopoietic progenitor and stem cells as measured in the long-term culture initiating cell (LTC-IC) assay (Blood 1996;88:1983-1991). We now present results of a long-term prospective study of LTC-IC numbers in peripheral blood (PB) and bone marrow (BM) of patients treated with antithymocyte globulin and cyclosporin A. Numbers of secondary colony forming cells (secondary CFC) in long-term bone marrow culture (LTBMC) were used to quantitate LTC-IC. BM (N = 35) and PB (N = 41) secondary CFC from both untreated severe AA patients and responders to immunosuppressive therapy who were sampled up to 6 years after initial treatment were compared. Normal controls showed 148 +/- 38 (N = 17) and 16 +/- 3 (N= 14) secondary CFC per 10(6) in BM and PB, respectively. In cross-sectional analysis, prior to therapy, AA patients showed 2.6 +/- 1 (mean +/- SD) secondary CFC/10(6) BM MNC; within the first year after initial treatment (N = 14), secondary CFC number rose modestly to 8.2 +/- 2.2/10(6) MNC, and further increased to 15.8 +/- 7 (N = 17) at 2 years and 16.2 +/- 7/10(6) MNC (N = 25) 3 years after treatment. There was no further improvement in the secondary CFC numbers at 4, 5, and > or =6 years (N = 37). Thus, while BM secondary CFC increased about 6-fold at 3 years post-therapy compared to presentation, they remained about only 10% of normal despite hematologic recovery. Similar data were obtained for PB, with approximately 4-fold increase in secondary CFC numbers within 2 years of therapy, to about 15% of normal values. We confirmed these observations in patients studied serially over a period of 4 years: initial secondary CFC were 2.35 +/- 1/10(6) BM MNC and 0.11 +/- 0.1/10(6) PB MNC improving to an average of 6 +/- 1. 2 (BM; N = 12) and 2.4 +/- 1/10(6) MNC (PB; N = 14). In many cases of partial recovery, PB counts improve but do not normalize. When we studied secondary CFC numbers only in patients who achieved complete normalization of PB counts (ANC >1,500/mm(3); platelets >10(5)/mm(3) and absolute reticulocytes >5 x 10(4)/mm(3)), BM secondary CFC were significantly higher than in patients with partial recovery; the PB secondary CFC number was modestly increased but remained below the normal values. Within the group of patients with complete recovery, there was no correlation between the secondary CFC and time after initial treatment. In addition, there also was no correlation between the secondary CFC number at presentation and the quality of hematopoietic recovery. Despite a limited expansion potential of a severely reduced stem cell pool, their numbers are sufficient to provide a long-term supply of mature blood cells. Am. J. Hematol. 65:123-131, 2000. Published 2000 Wiley-Liss, Inc.

Anemia, Aplastic↗
PubMed1999

Human G-CSF-mobilized CD34-positive peripheral blood progenitor cells can stimulate allogeneic T-cell responses: implications for graft rejection in mismatched transplantation.

To investigate mechanisms of stem cell graft rejection we studied the allo-stimulatory potential of G-CSF mobilized peripheral blood progenitor cells (PBPC). CD34+ cells were purified (>95%) in a two-step procedure using immunoaffinity columns for CD34 selection and T-depletion. The capacity of CD34+ cells to stimulate allogeneic T-cell responses was compared with other cells from the same individual. CD34+ cells induced potent proliferative responses at stimulator:responder ratios of 1:20, but were approximately 50-fold less efficient compared to dendritic cells. Furthermore, CD34+ cells primed responses from partially matched allogeneic T cells in bulk cultures. Dual-colour flow cytometry showed that the co-stimulatory molecules B7.1, CD40 and ICAM-1 were absent on resting CD34-positive progenitor cells, but were induced during incubation with allogeneic lymphocytes due to a cytokine-mediated effect. Up-regulation of accessory molecules on CD34+ cells was reproduced by incubation with interferon-gamma or GM-CSF which enhanced the allo-stimulatory activity of CD34+ cells. Blocking studies with inhibitory antibodies suggested co-stimulatory functions for B7.2, ICAM-3, CD40 and LFA-3. CD34+ cells were more efficient in inducing allogeneic T-cell responses when compared to the unprocessed leukapheresis products. The reduced allo-stimulatory ability of G-CSF mobilized PBPC could be explained by the presence of CD3+ 4+ and CD3+ 8+ lymphocytes with suppressor activity. We conclude that current methods of stem cell selection for transplantation do not avoid allosensitization of the recipient and that further graft manipulation with add-back of lymphocytes or selection of subsets of CD34+ cells with reduced allo-stimulatory ability may reduce graft rejection.

Antibodies, Blocking↗
PubMed1995

Platelet membrane glycoproteins and microvesicles in blood from postoperative salvage: a study in cardiac bypass patients.

BACKGROUND: Transfusion of blood collected by intraoperative and postoperative salvage systems has been linked to the development of thrombocytopenia and disseminated intravascular coagulation. Although functional defects have been reported in platelets from unwashed salvaged blood, platelet membrane glycoprotein (GP) composition, a potentially important determinant of function and survival, has not been studied. STUDY DESIGN AND METHODS: Platelets from 22 patients whose blood was salvaged at the completion of surgery were analyzed and compared to platelets obtained from the venous blood from the same patient. Platelet membranes were stained with fluorescein isothiocyanate-conjugated CD41a monoclonal antibody (anti-GPIIb/IIIa) to identify platelets, a phycoerythrin-conjugated monoclonal antibody, CD62 (anti-P-selectin) to identify activated platelets, and CD42b (anti-GPIb) or anti-GPIb/IX to assess GPIb. Samples were analyzed with a flow cytometer using software. RESULTS: Platelets obtained from salvaged blood demonstrated lower GPIb expression (CD42b and GPIb/IX monoclonal antibody binding), higher P-selectin expression, and greater numbers of platelet-derived microvesicles. CONCLUSION: The clinical significance of transfusing blood containing activated platelets and microvesicles merits investigation.

Blood Platelets↗
PubMed1995

A novel hereditary macrothrombocytopenia.

PURPOSE: A family is described in which macrothrombocytopenia and hearing loss are transmitted in an autosomal-dominant fashion. PATIENTS AND METHODS: Several members of the family were studied extensively. Review of blood smears, coagulation studies, platelet function testing, and electron microscopy were performed. Platelet membrane glycoproteins were examined using flourescein-conjugated antibodies and flow cytometry. RESULTS: Platelet counts ranged from 50,000 to 123,000/microliters. Both mean platelet diameter and volume were increased. No leukocyte inclusions were noted by light or electron microscopy. Platelet aggregation was normal with adenosine diphosphate (ADP), collagen, and ristocetin but diminished with epinephrine and arachidonic acid. Flow cytometry showed normal platelet membrane glycoproteins and the unusual expression of glycophorin A on 40-60% of the giant platelets. CONCLUSIONS: This family's syndrome of macrothrombocytopenia and late-onset hearing loss appears to represent a novel giant platelet disorder. The expression of glycophorin A suggests disordered megakaryocytopoiesis with the early release of immature platelets.

Adult↗
PubMed1994

Transfusion of blood components to persons infected with human immunodeficiency virus type 1: relationship to opportunistic infection.

BACKGROUND: Although a recent study reported shorter survivals in human immunodeficiency virus type 1 (HIV-1)-infected patients who received transfusions, no study has analyzed the relationship in such patients between the frequency of opportunistic infection and transfusion. STUDY DESIGN AND METHODS: Records of 196 HIV-1-infected subjects with CD4 lymphocyte counts below 250 cells per mm3 were reviewed to determine if there were more opportunistic infections in patients who previously received transfusions than in those who received no transfusions. The decline in CD4 cells was also compared, and the frequency of transfusion reactions and red cell alloantibodies was assessed. RESULTS: The frequency of cytomegalovirus (CMV), wasting, and bacterial infections (p < 0.01), but not the frequency of Pneumocystis carinii pneumonia (PCP) (p > 0.2), was significantly increased in the patients who had previously received transfusions, and this effect was independent of CD4 count, race, or risk factor. The frequency of CMV infection, but not of PCP, was also related to the number of units of blood received (p < 0.01). Significant bacterial infections occurred primarily in persons with CMV infection, of whom there were more in the transfusion cohort. When analyzed separately in the group of patients without CMV infection, the frequency of bacterial infection was unrelated to transfusion. The death rate in those who received transfusions was also greater than that in patients who had never received a transfusion. None of the 130 patients who received red cell transfusions developed red cell alloantibodies. CONCLUSION: The higher incidence of certain infectious complications in HIV-1-infected patients who received transfusions indicates that the relationship of transfusion to virus activation in patients with acquired immunodeficiency syndrome and the potential benefits of modifying the preparation of blood components should be investigated further.

AIDS-Related Opportunistic Infections↗
PubMed1993

Chemotherapy for patients with pulmonary Kaposi's sarcoma: benefit of filgrastim (G-CSF) in supporting dose administration.

Kaposi's sarcoma (KS) is common in individuals infected with the human immunodeficiency virus (HIV-1). Although KS is frequently indolent, it can also be aggressive and life-threatening, especially in patients with pulmonary involvement (PKS), who have poor survival rates when untreated. In an effort to develop treatment regimens for PKS that would prolong life or reduce clinical symptoms, we used combination chemotherapy to treat 18 patients who had AIDS and PKS; 13 (72%) of them had a history of previous opportunistic infections. Doxorubicin, bleomycin, vinblastine, vincristine, actinomycin D, and dacarbazine were used in 3-week cycles with concomitant zidovudine, zalcitabine (dideoxycytidine), or didanocine (dideoxyinosine). Antiviral therapy was continued with chemotherapy. A partial or complete response to chemotherapy was obtained in 15 of the 18 patients (83%), as characterized by clearing of infiltrates on chest films and resolution of dyspnea and cough. Only 2 patients had opportunistic infections during treatment. Median survival was 9 months; patients who received dose reductions in less than three cycles of chemotherapy survived more than 1 year. Most deaths were related to unresponsive PKS. These results indicate that patients with symptomatic PKS can be safely and effectively treated with combination chemotherapy while receiving myelosuppressive drugs such as zidovudine. Such patients receive substantial relief from dyspnea and cough. Survival for treated patients exceeds survival for untreated historical controls.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

The challenge of Pneumocystis carinii culture.

Published and unpublished data on the cultivation of P. carinii were reviewed by a panel of investigators convened by the National Institutes of Health. Although several cell culture systems allow propagation of P. carinii for a limited time with modest rates of replication, these have not proved adequate for isolation of P. carinii in sufficient quantity to explore important basic biological investigation. Attempts at cell-free culture have yielded only transient proliferation. Because much of the unsuccessful work on cultivation of the organism has been unpublished, the panel agreed that these data may be useful to other investigators in designing experimental strategies for cultivation. Therefore, the purpose of this report is to make available this information to researchers, lest others unknowingly repeat unsuccessful methods. It is hoped that by documenting the history and the complexities of Pneumocystis culture, renewed interest and efforts will be directed toward this fundamental scientific challenge.

Animals↗
PubMedDate not supplied

Pediatric and adolescent breast health.

The incidence of serious breast pathology in children and adolescents is low. Despite this, children, adolescents, and their parents come to the primary care provider with many breast-related concerns. Tanner staging is a good predictor of ensuing physical sexual development and can be used as a tool to reassure the pubertal girl that she is normal. Variations such as polythelia, premature thelarche, gynecomastia, nipple irritation from exercise, and nipple piercing and tattooing can be managed with education and reassurance. Whereas breast cancer is extremely rare in adolescents, evaluation with ultrasonography may be indicated. The primary care provider plays a central role in educating young girls and adolescents about healthy breast practices such as avoidance of alcohol and cigarette smoking, exercise, low-fat diet, breast self-examination, and avoidance of piercing and tattooing.

Adolescent↗