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Biomedical subjects

A Kessinger

Publications and source records attributed to A Kessinger.

At least 109 records · Page 6Linked to original sources
PubMed1992

Significance of detection of occult non-Hodgkin's lymphoma in histologically uninvolved bone marrow by a culture technique.

Prolonged disease-free survival of patients with recurrent or resistant non-Hodgkin's lymphoma (NHL) has been achieved with high-dose therapy followed by autologous bone marrow transplantation (ABMT). A concern with the use of ABMT is that the marrow that is reinfused may contain undetected NHL cells with the potential to reestablish metastatic disease in the recipient. Using a culture technique that is sensitive for detecting occult lymphoma cells in BM, we analyzed histologically normal marrow harvests from 59 consecutive patients with intermediate- or high-grade NHL who were candidates for high-dose therapy and ABMT. The culture results indicated that 22 of the patients had occult lymphoma in their marrow. Forty-three patients underwent high-dose therapy followed by ABMT. Twenty-four achieved a complete clinical remission. Those with occult lymphoma in their harvests (11 patients) continued to relapse for up to 3 years, whereas no relapses were observed beyond 8 months in 13 patients receiving marrow that did not contain detectable lymphoma cells using the culture technique. The relapses in the patients who achieved a complete remission occurred at sites of prior bulky disease rather than at new sites, suggesting that the ability to detect occult lymphoma cells in marrow is a marker of biologic aggressiveness and/or resistance to therapy, or that the reinfused cells could only grow in previously involved sites. The detection of lymphoma cells in marrow used for ABMT is an important adverse prognostic factor, and appears to be independent of other clinical predictors of outcome such as sensitivity or resistance of disease to prior chemotherapy.

Adolescent↗
PubMed1992

Long-term sequelae of autologous bone marrow or peripheral stem cell transplantation for lymphoid malignancies.

The study was made to evaluate the long-term physical and psychosocial changes after high-dose therapy and autologous bone marrow or peripheral stem transplantation for recurrent lymphoid malignancies. Patients who had undergone high dose therapy and autologous bone marrow or peripheral stem cell transplantation for recurrent lymphoid malignancies at least 1 year previously were contacted by phone interview regarding their status after the transplant. The patients' comments were confirmed by checking medical records when possible. Fifty patients who had undergone transplantation at the University of Nebraska Medical Center at least 1 year before the interview were available for interview and willing to answer questions. After transplant, many patients noticed temporary changes in their appearance, which usually returned to normal within 1 year. Few patients reported remarkable cardiovascular, gastrointestinal, or pulmonary changes after transplantation. However, up to one-third of the patients reported changes in sexual function or desire. The most common infectious problem after transplant was Herpes zoster, which occurred in 25% of the patients. Overall, the patients had a positive outlook after high-dose therapy and transplantation, with most being able to return to work and enjoy a normal life style. Ninety-six percent of the patients stated that they would be willing to undergo high-dose therapy and transplantation again under the same circumstances.

Body Image↗
PubMed1992

High-dose hydroxyurea in autologous bone marrow transplantation: a promising "new" agent.

Hydroxyurea is an antineoplastic drug with a broad spectrum of clinical activity and minimal nonhematopoietic toxicity. It potentiates the cytotoxicity of alkylating agents and topoisomerase II active drugs in vitro and in vivo. It is not susceptible to alkylating agent-specific or multidrug-type resistance. We have therefore added high-dose oral hydroxyurea to widely used autologous bone marrow transplantation combination chemotherapy regimens for large cell lymphoma and metastatic breast cancer. Seventeen patients with primary-refractory or refractory-relapse large cell lymphoma received oral hydroxyurea (1.5 g/m2 every 6 hours for 12 doses) added to carmustine/cyclophosphamide/etoposide (BCV). Twelve patients with metastatic breast cancer received the same dose oral hydroxyurea added to cyclophosphamide and thiotepa. Mucositis severe enough to require parenteral narcotics was seen in over half of the patients, but none required intubation for airway maintenance. A thrombotic thrombocytopenic purpura-like hemorrhagic syndrome occurred in six patients and was fatal for three. With the BCV/hydroxyurea regimen, this syndrome was seen with the same frequency as with BCV alone. Death from rapidly progressive disease or toxicity occurred in seven of 29 patients (24%). For patients with 6 months' minimum follow-up, four of 12 (33%) of the metastatic breast cancer patients remain in complete response (median follow-up, 15 months), and four of 17 (24%) refractory large cell lymphoma patients remain in complete response (median follow-up, 10 months). High-dose hydroxyurea may increase the effectiveness of standard autologous bone marrow transplantation regimens without substantially increasing toxicity.

Administration, Oral↗
PubMed1991

High-dose cyclophosphamide, carmustine, and etoposide followed by autologous peripheral stem cell transplantation for patients with relapsed Hodgkin's disease.

Between February 1986 and March 1990, 56 patients with relapsed Hodgkin's disease treated with high-dose cyclophosphamide, carmustine, and etoposide (CBV) received an autologous peripheral stem cell transplantation (PSCT) rather than an autologous bone marrow transplantation (ABMT) because each patient had a marrow abnormality, either hypocellularity or tumor involvement. At least 6.5 x 10(8) [corrected] mononuclear cells/kg patient weight were collected from the peripheral blood of each patient, cyropreserved, and returned intravenously following CBV administration. Three patients had an early death 2, 22, and 25 days after PSCT. The actuarial event-free survival for these 56 patients at 3 years was 37% and was at least as good as that reported for relapsed Hodgkin's disease patients treated with CBV and ABMT. The 30 patients who had no marrow metastases at the time of PSC harvesting had an actuarial event-free survival of 47%, while those 26 patients with marrow metastases had a significantly different actuarial event-free survival of 27% (P = .02). CBV and PSCT for patients with relapsed Hodgkin's diseases who have marrow hypocellularity in traditional harvest sites or histopathologic evidence of BM metastases can result in long-term event-free survival.

Adult↗
PubMed1991

Autologous bone marrow transplantation for patients with relapsed Hodgkin's disease.

PURPOSE: High-dose therapy and autologous bone marrow transplantation (ABMT) are being increasingly utilized for the management of patients with relapsed Hodgkin's disease. Because patients with relapsed Hodgkin's disease often initially respond to salvage chemotherapy regimens, ABMT is frequently delayed until late in the course of the disease. The optimal timing for ABMT has not been identified. The purpose of this study was to determine the value of ABMT earlier in the course of Hodgkin's disease. PATIENTS AND METHODS: We treated 70 patients between October 1984 and October 1988 with high-dose cyclophosphamide, carmustine, and etoposide, followed by infusion of previously cryopreserved autologous bone marrow, and analyzed the results to determine the impact of timing of ABMT on treatment outcome. One (17 patients), two (24 patients), or three or more (29 patients) chemotherapy regimens had failed in patients before ABMT. RESULTS: The results for all 70 patients included a complete remission rate of 59%, an early death rate of 11%, a 4-year survival of 47%, and 27% of all treated patients alive and in complete remission at 4 years. The median follow-up for patients remaining in complete remission is 56 months (range 26 to 73 months). The frequency of achieving a complete remission was higher in patients in whom fewer regimens had failed before ABMT (i.e., 82% versus 58% versus 45%, p = 0.02), as was the 4-year disease-free survival (i.e., 44% versus 33% versus 21%, p = 0.04). CONCLUSION: ABMT is a more effective therapy when used early for patients with relapsed Hodgkin's disease.

Adolescent↗
PubMed1991

Thrombotic complications of silicone rubber catheters during autologous marrow and peripheral stem cell transplantation: prospective comparison of Hickman and Groshong catheters.

Thrombosis is common after placement of silicone rubber subclavian vein catheters in patients with malignancy receiving conventional doses of chemotherapy. To determine the incidence of this complication in marrow transplant patients and the effect of different catheter designs on thrombosis rates, patients were randomized to receive either open-ended Hickman catheters or valve-ended Groshong catheters for venous access during the transplantation procedure. A total of 35 catheters were placed, of which 23 were double-lumen (11 Groshong and 12 Hickman) and 12 were single-lumen (six Groshong and six Hickman). Arm venograms were performed on all patients at the time of hematopoietic recovery or occurrence of symptoms of subclavian vein thrombosis. There were 10 cases of total subclavian vein thrombosis (three were symptomatic) and 12 cases of asymptomatic non-occlusive mural thrombi. Only 13 normal veins were found. There was no difference in thrombosis rate between the Hickman and Groshong catheters. Double lumen catheters tended to be more likely to cause total venous occlusion (nine of 23) than single lumen catheters (one of 12) (p = 0.06, Fisher's exact test). We conclude that subclavian vein thrombosis is a common occurrence after placement of silicone rubber catheters for venous access during marrow transplantation. Most cases are asymptomatic. Groshong catheters are just as likely to cause this complication as Hickman catheters.

Bone Marrow Transplantation↗
PubMed1991

The use of recombinant human granulocyte-macrophage colony stimulating factor for the treatment of delayed engraftment following high dose therapy and autologous hematopoietic stem cell transplantation for lymphoid malignancies.

To test the value of recombinant human granulocyte-macrophage colony stimulating factor for the treatment of delayed engraftment following high dose therapy and autologous hematopoietic stem cell transplantation, we enrolled 12 patients with recurrent non-Hodgkin's lymphoma or Hodgkin's disease having an absolute granulocyte count less than 150 x 10(6)/l on day 30 after autologous hematopoietic stem cell infusion in an open-label, nonrandomized study. These patients were compared to 21 similar historical control patients who were not treated with colony stimulating factor. Overall, the patients treated with granulocyte-macrophage colony stimulating factor had a mean absolute granulocyte count of 704 x 10(6)/l on day 44 after stem cell infusion compared to a mean absolute granulocyte count of 408 x 10(6)/l in historical controls (p = 0.008). The number of documented bacterial and fungal infections occurring after day 30 (9 vs 0, p = 0.01) was significantly reduced in the study group. The toxicity attributed to the granulocyte-macrophage colony stimulating factor was minimal with only one patient experiencing chills. Recombinant human granulocyte-macrophage colony stimulating factor appears to be effective for the treatment of delayed engraftment following high-dose therapy and autologous hematopoietic transplantation for lymphoid malignancies, with most patients having accelerated granulocytic recovery and a reduced incidence of infections.

Adolescent↗
PubMed1991

Catheter-related thrombosis in patients with refractory lymphoma undergoing autologous stem cell transplantation.

Long-term indwelling central venous catheters have eased the administration of drugs, blood products, and hyperalimentation to patients with cancer. However, their use is associated with thrombotic complications. We report here on the thrombotic complications prospectively observed in 46 patients with refractory lymphoma (22 Hodgkin's disease, 24 non-Hodgkin's lymphoma) who had placement of one or more catheters in preparation for autologous stem cell transplantation (ASCT). Thrombosis of 26 catheters in 19 patients was observed. Specific abnormalities of hemostasis were equally common in patients who developed thrombosis and in those who did not. Thrombotic complications were more common in patients with Hodgkin's disease (13/22) than in patients with non-Hodgkin's lymphoma (6/24, p = 0.04). Although more patients with Hodgkin's disease had received prior splenectomy and/or irradiation to the area involved by thrombosis than patients with non-Hodgkin's lymphoma, the incidence of splenectomy and irradiation was similar for patients with Hodgkin's disease who developed thrombosis and those who did not. Therefore, although the etiology remains unexplained, patients with Hodgkin's disease undergoing intensive chemotherapy and ASCT appear to have a higher incidence of catheter-related thrombosis than patients with non-Hodgkin's lymphoma undergoing similar therapy.

Adult↗
PubMed1991

High-dose therapy and autologous peripheral stem cell transplantation for patients with bone marrow metastases and relapsed lymphoma: an alternative to bone marrow purging.

Throughout a 4-year period, we reinfused autologous peripheral stem cells rather than purged autologous bone marrow following high-dose therapy to 57 patients with relapsed lymphoma and bone marrow metastases. Approximately 7 x 10(8) circulating mononuclear cells/kg patient weight were collected for each patient with 6-19 4-h apheresis procedures while hemopoiesis was unperturbed. Following collection, the cells were cryopreserved. Administration of high-dose therapy, which included either combination chemotherapy or combination chemotherapy plus total body irradiation, was followed by i.v. administration of the thawed autologous stem cells. The rate of hemopoietic recovery varied with the specific high-dose therapy administered. Sixty-two percent of 50 evaluable patients had a clinical complete response. The actuarial event-free survival for these patients 4 years after transplantation was 30%, and the projected survival at 4 years was 51%. Patients with relapsed lymphoma and bone marrow metastases who receive high dose therapy followed by peripheral stem cell transplantation can experience long-term event-free survival. Whether similar patients would fare as well with the same high-dose therapy followed by a purged autologous bone marrow transplantation would require a randomized prospective study.

Adult↗
PubMed1991

Addition of peripheral blood stem cells collected without mobilization techniques to transplanted autologous bone marrow did not hasten marrow recovery following myeloablative therapy.

A randomized prospective trial was conducted to determine if the addition of cryopreserved autologous peripheral blood stem cells (PBSC) collected without mobilization techniques to autologous cryopreserved bone marrow for patients receiving an autologous bone marrow transplant (ABMT) affected the time to marrow function recovery. Thirty-five evaluable patients with various malignancies were studied. Sixteen received PBSC + ABMT and 19 received ABMT alone. The PBSC were collected with 4 h leukapheresis procedures on 3 consecutive days. No manipulations to increase the number of circulating stem cells were used during the collections. The median time to recover 0.5 x 10(9)/l circulating granulocytes was 20 days after transplantation in the ABMT group and 27 days in the PBSC + ABMT group (p = 0.12). The median time to recover 20 x 10(9)/l platelets was 22 days after transplantation in the ABMT group and more than 27 days in the PBSC + ABMT group (p = 0.29). The day of discharge from the hospital was earlier for the ABMT group (median 29 days) than the PBSC + ABMT group (median 35 days, p = 0.03). We did not find that the addition of non-mobilized PBSC to infused autologous marrow accelerates marrow recovery.

Adolescent↗
PubMed1991

High frequency of antithrombin 3 and protein C deficiency following autologous bone marrow transplantation for lymphoma.

To investigate the possibility that a hypercoagulable state develops during autologous bone marrow transplantation (BMT), we measured levels of circulating natural anticoagulants and fibrinolytic proteins before and weekly during the hospital course of 18 patients undergoing autologous BMT for Hodgkin's and non-Hodgkin's lymphoma. Patients received either weekly (standard dose group) or daily (high dose group) vitamin K supplements with their total parenteral nutrition. By day 14 there had been a significant drop in protein C activity (mean of 95% of normal to 52%), protein C antigen (mean of 105% of normal to 70%), and antithrombin 3 activity (111% of normal to 83%), and an increase in fibrinogen (471-621 mg/dl) and tissue plasminogen activator (6.9-13.8 ng/ml). No changes were seen in free or total protein S, plasminogen activator inhibitor, prothrombin time or partial thromboplastin time. The decreases in protein C and antithrombin 3 persisted through day 28 after transplantation. The drop in protein C correlated strongly with decrease in serum albumin, suggesting impaired synthesis of these proteins by the liver. No differences were seen in any of these parameters between the standard and high dose groups. Deficiencies in anticoagulant proteins antithrombin 3 and protein C and a rise in fibrinogen without a concomitant improvement in fibrinolytic variables create a potentially hypercoagulable state which may contribute to the thrombotic complications of autologous BMT.

Adult↗
PubMed1991

Prothrombotic hemostatic abnormalities in patients with refractory malignant lymphoma presenting for autologous stem cell transplantation.

Forty-six patients with refractory malignant lymphoma (Hodgkin's and non-Hodgkin's) admitted for autologous marrow or peripheral blood stem cell transplantation (ASCT) were evaluated for the presence of hemostatic abnormalities known to be associated with a hypercoagulable state in other patient populations. All patients had received numerous chemotherapeutic agents in the past and often radiation therapy as well. Hemostatic abnormalities were found to be common in these patients. The most frequent finding was hyperfibrinogenemia, present in 35% of patients. Decreased protein C activity was present in 32% of patients. Protein C antigen was low in only one individual and protein S was normal or increased in all patients. Low levels of antithrombin III were present in 16%. Plasminogen activator inhibitor was elevated in 20%. Anticardiolipin antibodies were present in 29% of patients; other evidence of a lupus anticoagulant was present in only eight patients. The frequency of each hemostatic abnormality was similar for patients with Hodgkin's disease (HD) and those with non-Hodgkin's lymphoma (NHL) despite the fact that significantly more patients with HD had received irradiation and/or previous splenectomy than patients with NHL. We conclude that multiple prothrombotic abnormalities of hemostasis are present in patients with refractory lymphoma referred for ASCT. Whether these are the result of lymphoma or the result of therapy cannot be determined from this study.

Adult↗