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Biomedical subjects

A Kessinger

Publications and source records attributed to A Kessinger.

At least 37 records · Page 2Linked to original sources
PubMed2000

Filgrastim as an alternative to donor leukocyte infusion for relapse after allogeneic stem-cell transplantation.

PURPOSE: Donor leukocyte infusion (DLI) effectively treats relapse after allogeneic stem-cell transplantation (alloSCT), but the response may require several months and may be associated with significant toxicity. Filgrastim has also been observed to effectively treat leukemic relapse after alloSCT. A retrospective analysis was performed to determine the effectiveness of filgrastim in treating relapses after alloSCT. PATIENTS AND METHODS: Fourteen patients with hematologic malignancies were treated with filgrastim at relapse after alloSCT. Filgrastim was given at 5 mcg/kg/d subcutaneously for 21 consecutive days. Response was evaluated at 7 days after completion of filgrastim. Immunosuppressants, if present, were rapidly tapered to complete discontinuation at the time of relapse. RESULTS: Three patients were not assessable for response because additional therapy was necessary before completion of filgrastim. Six patients (43%) achieved a complete response on an intent-to-treat basis. When response was evaluated based on relapse type, three of four cytogenetic relapses, two of three morphologic relapses, and one of four hematologic relapses achieved a complete remission. Two responses were observed in patients who were completely off of any immunosuppression at the time of relapse. Six patients developed chronic graft-versus-host disease. The event-free and overall survival rates for all 14 patients are 43% and 73%, respectively. CONCLUSION: The use of filgrastim with rapid discontinuation of immunosuppression results in response rates that are similar to results using DLI. Filgrastim could be considered as an alternative or an adjunct to DLI for relapses after alloSCT.

Adult↗
PubMed2000

Antitumor therapeutic potential of activated human umbilical cord blood cells against leukemia and breast cancer.

In this study, in vitro and in vivo antitumor effects of mononuclear cells from human umbilical cord blood cells (UCBCs) and peripheral blood stem cells (PBCs) harvest obtained by leukapheresis were compared. Interleukin 2 (IL-2)-activated mononuclear cells from UCBCs showed increased cytotoxicity against K562 and Raji hematopoietic malignant cells compared with PBCs (P < 0.05). After IL-2 activation, both UCBCs and PBCs showed significant cytotoxicity against MDA-231 human breast cancer cells. The UCBC population involved in this antitumor activity appeared to be CD56+ natural killer precursors. The cytotoxicity of UCBCs was inhibited in the absence of Ca2+ (P < 0.05), supporting a perforin/granzyme-mediated target of cell lysis. In addition, antibodies to Fas ligand blocked cytotoxic activity, suggesting that some of the antitumor cytotoxicity was Fas ligand mediated. In vivo antitumor effects of UCBCs and PBCs were studied using a human leukemic cell-bearing severe combined immunodeficient mouse model. There was a significant increase in the survival of K562 leukemia-bearing mice that also received 5 million in vitro IL-2-activated UCBCs or PBCs i.v. on days 3 and day 5 after tumor transplantation compared with untreated mice (P < 0.01). Similar antitumor cytotoxicity of UCBCs and PBCs was also observed against MDA-231 human breast cancer grown in severe combined immunodeficient mice (P < 0.01). These studies suggest that IL-2-activated UCBCs may be a useful source of cellular therapy for patients with hematological malignancies and breast cancer.

Animals↗
PubMed1999

Cortical blindness and seizures in a patient receiving FK506 after bone marrow transplantation.

A 54-year-old woman with a myelodysplastic syndrome treated with high-dose chemotherapy and an allogenic bone marrow transplant developed acute cortical blindness while receiving tacrolimus (FK506). MRI showed white matter abnormalities. After discontinuation of FK506, the patient's vision returned within 8 days. FK506 neurotoxicity is similar to cyclosporine neurotoxicity and can occur in allogenic bone marrow transplant patients treated with FK506.

Blindness, Cortical↗
PubMed1999

Costs of care associated with high-dose therapy and autologous transplantation for non-Hodgkin's lymphoma: results from the University of Nebraska Medical Center 1989 to 1995.

The purpose of this paper was to (1) comprehensively analyze transplant-related costs for predicted temporal cost shifting and (2) to evaluate whether previous findings of decreasing costs of care persisted using a cost analysis of 353 NHL patients who received autologous stem cell transplantation (SCT) at the University of Nebraska Medical Center. All transplant-related costs between the patient's initial consult and program dismissal were obtained and inflated to constant 1995 dollars. Homogeneous resources were categorized into six cost-drivers and subdivided into outpatient, transplant, and additional inpatient time periods in order to evaluate resource utilization and cost shifting patterns. Between 1989 and 1991 both the average length of stay and comprehensive costs decreased 4.9 days and 14%, respectively. By 1995 additional decreases of 25.7 days and 51% led to an overall 7 year cost decline of 65%. Percent contributions of the six cost-drivers remained similar demonstrating uniformed suppression in transplant-related resource consumption. In contrast, the timing of resource utilization changed dramatically, with transplant hospitalization costs accounting for 83% of the overall costs in 1989, 71% by 1992, and only 45% in 1995, while total outpatient's contribution was 14%, 26% and 49%. Before 1991 ebbing costs were likely related to the development of new technologies such as hematopoietic growth factors and peripheral SCT, while the three-fold larger improvement in costs reported by 1995 are presumably associated with learning curve effects such as organizational changes, increased use of coordinated outpatient facilities, and the more cost-effective use of laboratory tests and pharmaceuticals.

Adolescent↗
PubMed1999

Limited stage I and II follicular non-Hodgkin's lymphoma: the Nebraska Lymphoma Study Group experience.

The purpose of this study was to evaluate the outcome and prognostic factors of patients with limited stage follicular non-Hodgkin's lymphoma treated prospectively by the Nebraska Lymphoma Study Group (NLSG). Forty previously untreated patients, median age 64 years, with limited stage follicular lymphoma were prospectively treated according to the protocols of the NLSG between January 1980 and December 1990. The follicular large cell type represents 75% of the cases, and 14 of the biopsies also had a diffuse component (composite lymphoma). The initial treatment was radiation therapy (RT) to the involved field in 15 patients, anthracycline-containing combination chemotherapy (CT) in 20, and combined RT and CT in 5. Thirty-seven patients (92.5%) achieved a complete remission (CR). The median follow-up is 120 months (range, 20 to 214). Of the 37 patients achieving a CR, 7 patients are alive in first CR, one died due to sepsis, another because of a myeloproliferative disorder at 77 months following chemotherapy, 6 died because of unrelated causes in first CR. Twenty-two patients relapsed between 1 to 128 months following a CR. The estimated 10-year event-free survival is 21% (95% CI: 7 to 35). Two patients received no or palliative therapy after relapse and both died of progressive disease. Nineteen patients received salvage therapy and 15 achieved a second remission. The median survival after first relapse is 55 months. The estimated 10-year overall survival is 44% (95% CI: 28 to 60). Various factors including sex, histologic subtype, stage, and degree of follicularity do not influence the overall survival or event-free survival. CT with or without RT resulted in a better trend for 10-year event-free survival in stage IA patients compared to RT alone but estimated 10-year overall survival is no different. The overall survival is worse in the > or = 60 age group but this difference is not evident if data is adjusted for cause specific death. In conclusion, limited stage follicular lymphoma has an excellent initial response to radiation therapy or chemotherapy; however the recurrence rate is high and cure is limited.

Adult↗
PubMed1998

Mobilization of blood stem cells.

Deliberately increasing the number of hematopoietic stem and progenitor cells in the circulation allows faster and more efficient collection of sufficient cells for transplantation in both the allogeneic and autologous settings. These mobilized stem cells, when transplanted, provide quicker hematopoietic recovery for the patient than do nonmobilized blood stem cells or steady-state marrow-derived stem cells. Currently used clinical procedures to produce stem cell mobilization include administration of G-CSF or GM-CSF, either as single agents or in combination with myelosuppressive chemotherapy. Some autologous blood stem cell donors exhibit indifference to currently applied mobilization therapies. This failure to mobilize has been associated with prior stem cell toxic therapy, e.g., radiation therapy and chemotherapy, but the association is incomplete. The observation that occasional normal donors have failed to respond to mobilization therapy indicates that factors other than stem cell damage could also be involved. Recently, a murine model has provided evidence that a circulating factor inhibits mobilization in some settings. Preliminary investigations have suggested that a circulating factor may inhibit mobilization of human hematopoietic progenitor cells in some instances. Studies to identify this factor(s) are underway. The mechanisms of blood stem cell mobilization are still poorly understood and there continues to be the potential to improve this process.

Animals↗
PubMed1998

High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

BACKGROUND: High-dose therapy followed by autologous stem-cell transplantation (autoSCT) induces complete remissions in the majority of patients with advanced B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma (B-CLL). However, the long-term utility of this therapy for B-CLL is unknown. PATIENTS AND METHODS: Sixteen previously treated patients with B-CLL were transplanted using autologous blood (n = 13) or bone marrow (n = 3). The median age of the patients was 49 f1p4s (range 44-60 years), and the median number of prior chemotherapy regimens was two. Patients were eligible for transplantation if they had chemosensitive disease and no morphologic evidence of malignant cells in the graft. Preparative regimens included cyclophosphamide and total-body-irradiation, with or without cytarabine, or BEAC. RESULTS: All patients engrafted and achieved a complete remission posttransplant. Ten patients were alive at a median of 41 months (range 22-125 months), and five were disease-free. Eight patients have relapsed and six have died (three from progressive malignancy). The projected three-year overall survival, failure-free survival and relapse rates were 68%, 37%, and 56%, respectively. CONCLUSIONS: AutoSCT for advanced B-CLL is associated with a high relapse rate. Whether this therapy can prolong life or produce cures is uncertain.

Adult↗
PubMed1998

Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies.

Forty-one patients were studied at set times after allogeneic blood stem cell transplantation (alloBSCT) for recovery of lymphocyte numbers and function. Cells were mobilized with G-CSF from HLA-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate; G-CSF was administered post-transplant. Median time to absolute lymphocyte count (ALC) >500/microl was 17 days vs 41 and 49 days in historical alloBMT patients with G-CSF (n = 23) or no cytokine (n = 29) post-transplant, respectively (P < 0.0001). CD4/CD8+ ratio was 1.9 on day 28 after alloBSCT, then gradually declined to 0.8 at 1 year due to more rapid CD8+ cell recovery. Mean phytohemagglutinin-induced T cell responses were lower than normal on day +28 (P < 0.05), then tended to recover towards normal values. Natural-killer cytotoxicity remained low from day +28 to 1 year post-alloBSCT, but considerable lymphokine-activated killer cytotoxicity was induced from cells already obtained on day +28. Faster lymphocyte recovery correlated with better survival in alloBSCT patients (median follow-up 287 days, P = 0.002), ALC recovery was not affected by acute GVHD, CMV infections or doses of infused cells. ALC recovery did not correlate with survival in either historical alloBMT group. These data suggest that after alloBSCT lymphocyte reconstitution is faster than after alloBMT, and that quicker lymphocyte recovery predicts better survival in the alloBSCT setting.

Adult↗
PubMed1998

Increased platelet transfusion requirement is associated with multiple organ dysfunctions in patients undergoing hematopoietic stem cell transplantation.

Organ dysfunction following hematopoietic stem cell transplantation (HSCT) may be a manifestation of a systemic inflammatory response. We speculate that part of the platelet transfusion requirement in HSCT patients results from this systemic inflammatory response, and increased transfusion requirement would be associated with, or precede, organ dysfunction. We studied 199 adults undergoing autologous (n=173) or allogeneic (n=26) HSCT. Patients with CNS (P=0.008) or pulmonary (P=0.002) dysfunction, or with VOD (P=0.05) received a higher mean number of platelet transfusions per week than patients who did not have these dysfunctions. Furthermore, a higher number of platelet transfusions during any 1 week period was significantly associated with development of pulmonary (P=0.0002) or renal (P < 0.0001) dysfunction in the following week. This predictive value was strongest early in the HSCT course, but remained significant over all 4 weeks. In multivariate analysis the number of platelet transfusions during the previous week was independently predictive for development of pulmonary dysfunction in week 2 (P=0.01) and week 3 (P=0.055). We believe that occurrence of increased platelet transfusion requirement prior to onset of dysfunction is consistent with the concept that an antecedent inflammatory response results in both platelet consumption and various organ dysfunctions. Increased platelet transfusion requirement may act as an early marker of subsequent organ dysfunction. Additionally, there may be a direct role of platelets in the development and progression of organ dysfunction in HSCT patients.

Adolescent↗
PubMed1998

A prospective randomized double-blind trial of antithrombin III concentrate in the treatment of multiple-organ dysfunction syndrome during hematopoietic stem cell transplantation.

Many of the complications of high-dose therapy with hematopoietic stem cells are caused by or lead to the multiple-organ dysfunction syndrome (MODS). In hematopoietic stem cell transplantation (HSCT), acquired antithrombin III (ATIII) deficiency is independently associated with MODS to the exclusion of transplant type, preparative regimen, and bacteremia. In experimental settings, replacement of ATIII can ameliorate the severity of MODS that develops in response to a variety of pathologic stimuli, suggesting that ATIII supplementation might improve the clinical course of MODS in patients undergoing HSCT. We performed a study to determine if ATIII can improve the morbidity of MODS in HSCT. Forty-nine patients undergoing HSCT, who developed pulmonary dysfunction (oxygen saturation of <90%), central nervous system dysfunction (drop of >4 points in the mini-mental status exam), or hepatic dysfunction (bilirubin >34 micromol/L [2.0 mg%], weight gain of >5% over baseline, and abdominal pain, possibly of hepatic origin) with a concomitant ATIII activity of <84% were double-blind randomized to receive ATIII concentrate, 70 units/kg within 24 hours of recognition of initial organ dysfunction followed by 50 units/kg 8, 16, 48, and 72 hours later, or albumin placebo. The group randomized to ATIII had a lower severity-of-illness score (15.7 +/- 19.2 vs. 28.6 +/- 25.2, p = 0.03), shorter duration of hospitalization (14.9 +/- 16.7 vs. 25.7 /- 17.9 days, p = 0.03), and lower hospital charges ($138,700 +/- $23,500 vs. $206,400 +/- $34,000). ATIII concentrate was associated with improved morbidity of MODS in patients undergoing HSCT when given early in the evolution of the syndrome.

Adult↗
PubMed1998

Concurrent partial body radiation prevents cytokine mobilization of blood progenitor cells: an effect mediated by a circulating factor.

Mobilization of stem and progenitor cells into blood, which facilitates the collection of blood-derived autograft and allograft products, can be accomplished with administration of myelosuppressive chemotherapy, hematopoietic growth factors, or both. Autologous donor indifference to mobilization attempts has been correlated with prior administration of chemotherapy and radiation therapy. To investigate whether concurrent administration of radiation therapy inhibits mobilization, five daily injections of a potent combination of mobilizing cytokines, 500 U/kg erythropoietin (EPO) plus 15 microg/kg G-CSF, were administered each morning to Balb/c mice. Each afternoon, a 2 Gy fraction of Co-60 radiation was administered to either the lower limb or the upper or lower hemibody. Each day, mice were necropsied, and blood stem cell mobilization was determined by assaying the number of hematopoietic colony-forming cells in the blood and in the spleen. Unirradiated cytokine-injected mice showed a significant mobilization effect evident as increased colony-forming cells in blood and spleen compared with saline-injected unirradiated controls. The irradiated mice showed markedly inhibited or absent mobilization regardless of the part of the body irradiated. To investigate the mechanism of radiation-induced mobilization inhibition, heparinized plasma was obtained from mice whose lower bodies were irradiated with 2 Gy 18 h previously, and 0.5 ml was injected i.v. into intact mice 10 min before they received 15 microg/kg G-CSF and 500 U/kg EPO. Unlike mice that received G-CSF + EPO only and showed mobilization of progenitors from marrow to spleen, recipients of plasma from irradiated mice before and after cytokine administration showed significantly reduced mobilization of progenitors. Thus, radiation-induced inhibition of stem cell mobilization is mediated by an unidentified circulating factor.

Animals↗
PubMed1998

Consensus conference on high-dose therapy with hematopoietic stem cell transplantation in diffuse large-cell lymphoma. Type of cells, optimal mobilization of stem cells--positive and negative selection.

Stem cell transplantation has played a role in the management of diffuse large-cell lymphoma for decades. The optimal source of the stem cells and the proper composition of the cellular graft product has not been defined. The field is changing rapidly and the future is likely to hold improvements and requirements that will further benefit the patient!

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Effect of follicularity on autologous transplantation for large-cell non-Hodgkin's lymphoma.

PURPOSE: This study evaluated the outcomes of patients who received high-dose chemotherapy (HDC) and autologous hematopoietic stem-cell transplantation (ASCT) for large-cell non-Hodgkin's lymphoma (NHL) and the effect of a follicular versus a diffuse histology. PATIENTS AND METHODS: The prognostic factors in 289 patients who underwent HDC and ASCT for large-cell NHL between May 1983 and December 1996 were analyzed. RESULTS: With a median follow-up duration of 24 months for surviving patients (range, 3 to 131 months), 112 of 289 (39%) were alive and 82 of 289 (28%) were failure-free. In a multivariate analysis, the factors associated with a poorer failure-free survival (FFS) included a lactic dehydrogenase (LDH) level greater than normal (P < .0001), three or more prior chemotherapy regimens received (P < .01), a mass > or = 10 cm at transplant (P < .01), and diffuse histology at the time of transplant (P = .026). Patients who received HDC and ASCT for large-cell NHL in the good-prognosis category (normal LDH, < three prior chemotherapy regimens, no large mass, and not chemotherapy-resistant) had a 5-year survival rate of 45%. Within the good-prognosis group, patients with diffuse large-cell NHL had a 5-year survival rate of 42% compared with 58% for patients with follicular large-cell (FLC) lymphoma (P = .05). CONCLUSION: Good-prognosis patients with FLC histology who receive HDC and ASCT have an improved survival compared with good-prognosis patients with a diffuse large-cell histology.

Adolescent↗
PubMed1998

Antitumor activity of human umbilical cord blood cells: A comparative analysis with peripheral blood and bone marrow cells.

Although the hematopoietic reconstituting ability of human umbilical cord blood cells (UCBC) is well documented, their antitumor cytotoxic potential has not been well studied. Therefore, UCBC were compared to normal peripheral blood stem cells (PBSC) and bone marrow (BM) stem cell harvests for cytomorphology, antitumor cytotoxic activity before and after ex vivo cytokine manipulation, response to T and B cell mitogens, expression of adhesion molecules and immunophenotypes using flow cytometry, cytokine production and in vivo antitumor activity. BM and PBSC, but not UCBC, did not form cellular clusters in culture. More cytotoxic granules were present in the cytoplasm of UCBC than PBSC following activation in vitro. Ex vivo manipulation of UCBC with cytokines produced more cytotoxicity to K562 and Raji tumor cells than PBSC or BM (p<0.001). Most cytotoxic cells in UCBC cultures were T lymphocytes, and a correlation existed between the number of CD56+ cells and cytotoxicity levels, particularly after in vitro activation with interleukin-2. No significant difference in adhesion molecule expression was noted among UCBC, PBSC and BM cells. However, there was a significantly decreased expression of CD54 molecules (ICAM) on UCBC compared to PBSC (p<0.05). IL-2 activated UCBC showed significant antitumor effects against K562 leukemic cells grown in SCID mice. Thus UCBC contained more antitumor effector cells and precursors than cells from marrow or peripheral blood cells which might be capable of providing a therapeutic effect.

Animals↗
PubMed1998

Cell adhesion molecule expression on CD34+ cells in grafts and time to myeloid and platelet recovery after autologous stem cell transplantation.

The relationship between cell adhesion receptor expression on CD34+ cells in stem cell grafts and the time to neutrophil and platelet recovery after autologous stem cell transplantation (ASCT [n = 25]) was studied with granulocyte/monocyte-colony stimulating factor (GM-CSF)-mobilized peripheral blood stem cells (PBSCs) and steady-state bone marrow (BM) harvests. Cell adhesion receptor expression was analyzed using flow cytometry after CD34+ cell enrichment. Significantly higher expression of L-selectin and CD44, and significantly lower expression of VLA-4, LFA-1, ICAM-1, Sialyl Lewis(x), Sialyl Lewis(A), and Thy-1 were observed on PBSCs compared with BM CD34+ cells. The log of the number of reinfused CD34+ cells, colony forming units granulocyte/macrophage (CFU-GM), and CD34+ cells coexpressing VLA-4, VLA-5, LAF-1, Mac-1, LFA-3, or CD38 but not ICAM-1, Sialyl Lewis(x), Sialyl Lewis(A), or Thy-1 correlated with the time required to reach an absolute neutrophil count (ANC) of > or =0.5 x 10(9)/L. In addition, the log of the number of CD34+ L-selectin+ and CD34+CD44+ cells reinfused after ASCT correlated better with the time required to reach an ANC of > or =0.5 x 10(9)/L than did the log of the number of CD34+ cells or CFU-GM reinfused. The log of the number of reinfused CD34+ cells, CFU-GM, and CD34+ cells coexpressing CD44, L-selectin, VLA-5 Mac-1, or CD38, but not VLA-4, LAF-1, ICAM-1, LAF-3, Sialyl Lewis(X), Sialyl Lewis(A), or Thy-1, correlated with the time required to reach a platelet count of >20 x 10(9)/L. Thus, L-selectin or CD44 may play an important role in the homing of progenitors after ASCT. In addition, the higher proportion of CD34+L-selectin+ or CD34+CD44+ cells in leukapheresis products may provide one explanation for the more rapid hematologic reconstitution observed after PBSC transplantation.

Adult↗
PubMed1997

Normal saline versus heparin flush for maintaining central venous catheter patency during apheresis collection of peripheral blood stem cells (PBSC).

Thrombotic occlusion is frequently a complication of central venous catheters (CVCs). The original designers and producers of CVCs recommended heparin flush regimens to prevent thrombosis and maintain patency. This has become standard practice although no studies have demonstrated a relationship between heparin flushing and reduction of catheter thrombosis. Many consider the routine use of heparin flushing innocuous. However, serious complications including drug interactions and heparin induced thrombocytopenia and thrombosis syndrome (HITS) have been reported in association with heparin flushing. Numerous studies comparing heparin to saline flushing in peripheral devices suggest equal rates of thrombotic occlusions. The purpose of this study was to examine the incidence of thrombotic occlusions in CVCs using heparin compared to saline flushing. The study involved 78 cancer patients undergoing apheresis collection for peripheral blood stem cells; 29 received saline flushes and 49 received heparin (100 U/ml of saline) flushes. Study endpoints included slow apheresis flow rate (< 50 ml/min), urokinase use for thrombolysis, and radiographic evidence of catheter thrombosis. No significant differences were found for any endpoint between the two groups. These findings suggest saline may be as effective as heparin for maintaining patency of CVCs.

Adult↗