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Biomedical subjects

A Kessinger

Publications and source records attributed to A Kessinger.

At least 91 records · Page 5Linked to original sources
PubMed1994

High-dose cyclophosphamide, thiotepa and hydroxyurea with autologous hematopoietic stem cell rescue: an effective consolidation chemotherapy regimen for early metastatic breast cancer.

Phase I and II trials have demonstrated that high-dose chemotherapy with autologous hematopoietic stem cell rescue is effective 'consolidation' chemotherapy for patients with responding metastatic breast cancer. In this study 26 women with metastatic breast cancer responding to lower dose combination chemotherapy were treated with 18 g/m2 of hydroxyurea added to the widely used combination of cyclophosphamide (CY) 6 g/m2 and thiotepa 600 mg/m2. Hematopoietic stem cell support was provided in the form of previously collected cryopreserved marrow or peripheral blood stem cells if there were malignant cells in the marrow. The patients ranged in age from 25 to 51 years with a median of 43 years. Three patients (12%) died of toxicity, one from Candida pneumonia and the other two from pulmonary and central nervous system bleeding secondary to platelet consumption associated with high fever and renal dysfunction, a syndrome we have seen with approximately the same frequency as a complication of other 'marrow transplant level' chemotherapy. The 1 and 2 year progression-free survivals are projected to be 42% and 27%, respectively. Patients in complete remission or with only residual radiographic abnormalities in bone prior to this therapy had 67% and 58% 1 and 2 year progression-free survival probabilities. High-dose hydroxyurea can safely be added to the CY and thiotepa combination.

Adult↗
PubMed1993

Is blood or bone marrow better?

Hematopoiesis that has been ablated with high-dose radiation-chemotherapy can be restored with either autologous peripheral stem cell transplantation (PSCT) or autologous bone marrow transplantation (ABMT). Characteristics unique to either type of transplant make one preferable to the other in certain clinical situations. When marrow metastases preclude ABMT, blood provides a suitable source of precursors for autografting. Peripheral cells are more time consuming to collect and more labor intensive to process and store. The peripheral autograft product can be manipulated with mobilization techniques (chemotherapy and/or cytokines) to provide more rapid recovery of granulocytes and perhaps red cells and platelets, while transplantation of manipulated marrow autografts has not yet been reported. Further advances in both ABMT and PSCT will provide additional opportunities to improve the outcome of patients treated with high-dose therapy.

Antineoplastic Agents↗
PubMed1993

Nosocomial invasive aspergillosis in lymphoma patients treated with bone marrow or peripheral stem cell transplants.

OBJECTIVES: To determine the prevalence of aspergillosis in lymphoma patients housed in a protective environment while undergoing a bone marrow transplant or peripheral stem cell transplant and its relation to lymphoma type, type of transplant, period of neutropenia, method of diagnosis, species of Aspergillus, and the use of empiric amphotericin B. DESIGN: Clinical, autopsy, and microbiology records were reviewed retrospectively to determine the presence or absence of invasive aspergillosis. All positive specimens underwent further review to determine parameters outlined above. SETTING: The review took place at the University of Nebraska Medical Center with lymphoma patients housed in the oncology/hematology special care unit, which consists of 30 single-patient rooms under positive pressure with high-efficiency particulate air filtration. PATIENTS: 417 lymphoma patients admitted to the oncology/hematology special care unit who underwent 427 courses of high-dose chemotherapy with or without total body irradiation followed by a stem cell rescue. RESULTS: Twenty-two cases (5.2%) of nosocomial invasive aspergillosis (14 caused by Aspergillus flavus, 2 by Aspergillus terreus, 2 by Aspergillus fumigatus, and 4 by characteristic histology) were diagnosed. The prevalence of disease according to transplant was 8.7% for allogeneic bone marrow transplant (2/23 treatments), 5.6% for autologous peripheral stem cell transplant (9/161), and 4.5% for autologous bone marrow transplant (11/243). Fifteen patients were presumptively diagnosed prior to death (68.2%) most commonly by histologic examination of skin biopsies. All 22 patients received amphotericin B therapy, 17 prior to aspergillosis diagnosis, and 7 (31.8%) survived. No patient with disseminated disease survived. CONCLUSIONS: Even when housing lymphoma patients undergoing myeloablative therapy in a protective environment containing high-efficiency particulate air filtration, there was a risk of developing aspergillosis. These data also showed that antemortem diagnosis with aggressive amphotericin B therapy was most effective in the management of infected lymphoma patients when engraftment occurred and the disease did not become disseminated.

Amphotericin B↗
PubMed1993

Systemic administration of a phosphorothioate oligonucleotide with a sequence complementary to p53 for acute myelogenous leukemia and myelodysplastic syndrome: initial results of a phase I trial.

A synthetic phosphorothioate oligonucleotide was administered systemically to five patients with either relapsed or refractory acute myelogenous leukemia (AML), or myelodysplastic syndrome (MDS). Patients received a 10-day continuous intravenous infusion of this compound, which is complementary to p53 mRNA. No major toxicity attributable to a dose of 0.05 mg/kg/hr was observed. A range of approximately 9 to 18% of the administered dose was recovered in the urine as intact oligonucleotide. Evaluation of malignant cells recovered from bone marrow and peripheral blood at intervals before, during, and after treatment reveals no enhanced growth potential following oligonucleotide administration. Hence, a phosphorothioate oligonucleotide complementary to p53 mRNA can be administered at this dose level to humans without major toxicity. Higher doses need to be evaluated for toxicity and potential clinical efficacy.

Adolescent↗
PubMed1993

Peripheral stem cell transplantation in non-Hodgkin's lymphoma patients.

Transplantation of circulating progenitor/stem cells collected before and stored during administration of marrow-ablative antitumor therapy has restored sustained hematopoiesis for patients with a variety of malignancies. One of the most common diseases so treated is refractory or relapsed non-Hodgkin's lymphoma (NHL). Autologous peripheral stem cell transplantation (PSCT) often has been used rather than autologous bone marrow transplantation (ABMT) because NHL commonly involves the bone marrow, and because, in some situations, PSCT provides earlier engraftment than ABMT. Between July 1986 and September 1992, 170 adult patients with refractory or relapsed NHL were treated with high-dose therapy and PSCT at the University of Nebraska Medical Center (UNMC). With a median follow-up of 469 days for the evaluable survivors, the actuarial progression-free survival for 167 patients at 6 years after PSCT was 30%. High-dose therapy and PSCT for NHL patients has resulted in long-term progression-free survival and probably cure for some patients. The role of PSCT in this disease continues to evolve.

Actuarial Analysis↗
PubMed1993

High dose chemotherapy followed by autologous hematopoietic rescue in Hodgkin's disease: long-term follow-up in 128 patients.

BACKGROUND: There is little long-term follow-up information after autologous transplantation for Hodgkin's disease. We evaluated the influence of various prognostic factors and examined the outcome in 128 such patients. PATIENTS AND METHODS: Patients received high dose cyclophosphamide, carmustine, and etoposide followed by autologous hematopoietic rescue. RESULTS: Patients have been observed between 50-130 months (median 77 months) following transplantation. Overall survival at four years is estimated as 45 percent, and failure-free survival as 25 percent. The best results were seen in patients with a good performance status, who had failed at most one prior chemotherapy regimen. Failure-free survival at four years is estimated as 53 percent for this group. Relapses more than 24 months after transplantation were seen in 11 patients. Five patients developed myelodysplastic syndromes. Three patients became pregnant after the transplant. CONCLUSIONS: Prolonged failure-free survival may be observed following high dose chemotherapy and autologous hematopoietic rescue in patients with Hodgkin's disease. Superior results were seen in patients without extensive prior chemotherapy and in those with a good performance status. Late relapses and deaths from secondary myelodysplastic syndromes mandate prolonged follow-up after autologous transplantation for Hodgkin's disease.

Adolescent↗
PubMed1993

High-dose chemotherapy and autologous hematopoietic stem-cell transplantation for aggressive non-Hodgkin's lymphoma.

PURPOSE: To evaluate clinical and tumor characteristics in patients receiving high-dose chemotherapy and autologous peripheral stem-cell transplantation (PSCT) or bone marrow transplantation (ABMT) for relapsed or primary refractory non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: One hundred fifty-eight patients with NHL received high-dose chemotherapy and ABMT or PSCT. A multivariate analysis of characteristics was performed for comparison of the long-term failure-free survival (FFS) rate. RESULTS: Using a multivariate analysis, a prognostic model was constructed with patients in the good-prognosis group being those without a mass > or = 10 cm at the time of transplant, and no more than one of the following characteristics: three or more prior chemotherapy regimens, lactate dehydrogenase (LDH) level above normal, and chemotherapy resistance. Patients in the poor-prognosis group had a mass > or = 10 cm, or two of the other characteristics noted. The poor-prognosis group had a 3-year FFS rate of 10%, compared with a 45% 3-year FFS in the good-prognosis group (P < .001). Within the prognostic groups, there was no difference in the 3-year FFS rate of the poor-prognosis patients who received ABMT versus PSCT (10% v 12%; not significant). However, in the good-prognosis group, patients who received ABMT had a 3-year FFS rate of 32%, compared with 70% for those who received PSCT (P < .008). CONCLUSION: This prognostic model can identify patients with good and poor prognoses following high-dose chemotherapy and ABMT or PSCT for aggressive NHL. In good-prognosis patients, those who received PSCT had a superior FFS rate.

Adolescent↗
PubMed1993

Mesna compared with continuous bladder irrigation as uroprotection during high-dose chemotherapy and transplantation: a randomized trial.

PURPOSE: To compare the use of intravenous (IV) hydration plus either continuous bladder irrigation or mesna for the prevention of hemorrhagic cystitis in the bone marrow transplant setting. PATIENTS AND METHODS: Two hundred patients were prospectively randomized to receive either continuous bladder irrigation with 200 mL/h of normal saline, or continuous infusion mesna at 100% of the cyclophosphamide dose. RESULTS: The overall incidence of hematuria of any grade was significantly higher in the bladder-irrigation group (76%) compared with the mesna group (53%) (P = .007). However, the incidence of grade III and IV hematuria was the same in both groups (18%; P = NS). Moderate or severe discomfort or bladder spasms were reported in 84% of the patients who received bladder irrigation, compared with 2% of the patients who received mesna prophylaxis (P < .0001). Urinary tract infections (UTIs) were documented in 27% of the patients in the bladder-irrigation group, compared with 14% of the patients in the mesna group (P = .03). CONCLUSION: Both continuous bladder irrigation and mesna were equally effective in preventing severe hemorrhagic cystitis associated with high-dose cyclophosphamide and bone marrow transplantation. However, the use of mesna was associated with significantly less discomfort and a lower incidence of UTIs.

Adult↗
PubMed1993

Granulocyte macrophage colony stimulating factor: high incidence of apheresis catheter thrombosis during peripheral stem cell collection.

Granulocyte-macrophage colony stimulating factor (GM-CSF) has been used to augment circulating hemopoietic stem cells in the peripheral blood and promote efficient peripheral stem cell (PSC) collection. Anecdotal reports indicate that GM-CSF may contribute to apheresis catheter dysfunction during PSC collection. We prospectively evaluated thrombotic occlusion rate of inferior vena cava (IVC) catheters following introduction of GM-CSF compared with a control group who underwent PSC collection prior to introduction of GM-CSF. Both groups were given aspirin (325 mg daily). The active treatment group was given GM-CSF (starting dose 250 micrograms/m2/day) as continuous infusion via the IVC catheter. The rate of thrombotically occluded catheters increased from 1/29 (3%) to 20/37 (54%) (p < 0.0001). Thrombi developing during GM-CSF therapy were unusual as 25/36 (69%) occlusions cleared with mechanical clot aspiration and did not require lytic agents.

Aspirin↗
PubMed1993

The use of peripheral stem cell support of high-dose chemotherapy.

Blood-derived stem cells are a functionally equivalent alternative to marrow-derived stem cells when autotransplanted to restore hematopoiesis that has been iatrogenically ablated. This alternate source of stem cells is particularly useful for patients who are candidates for marrow-ablative therapy and who also have bone marrow abnormalities that make it an unsuitable product for transplantation. When autologous blood-derived stem cells that were collected while their numbers were deliberately expanded in the circulation (mobilized) are transplanted, the resultant recovery of marrow function is very rapid. Because autologous bone marrow transplantation alone cannot result in hematopoietic recovery that is as rapid, peripheral stem cells have been preferred to bone marrow for autografting in some patients. This early recovery involves not only granulocytes but also platelets and red cells. Currently available cytokines administered at the time of ABMT usually facilitate only rapid granulocyte recovery. Emerging studies indicate that other consequential benefits of peripheral stem cell infusion that have not yet been fully recognized may exist. If, ultimately, techniques are developed that produce optimal stem cell mobilization for every eligible patient, then perhaps peripheral stem cell collections can be completed in 1 to 2 days. These cells could be used to minimize or ameliorate the hematopoietic toxicity associated with myelotoxic therapy. Perhaps then the technique eventually will become a routine adjunct to chemotherapy administration.

Antineoplastic Agents↗
PubMed1993

Utilization of peripheral blood stem cells in autotransplantation.

Autologous blood-derived hematopoietic progenitors can be used like autologous bone marrow to restore hematopoiesis following marrow ablative therapy. Peripheral stem cell transplantation (PSCT) is preferable to autologous bone marrow transplantation (ABMT) if autologous marrow is not suitable for use as a graft product. Generally, this unsuitability results from marrow hypocellularity or metastatic disease. PSCT also has an advantage over ABMT in that it often restores marrow function more rapidly.

Blood Preservation↗
PubMed1993

Protein C deficiency following hematopoietic stem cell transplantation: optimization of intravenous vitamin K dose.

Patients undergoing hematopoietic stem cell transplantation (HSCT) are dependent on i.v. vitamin K supplementation to prevent deficiency. Vitamin K deficiency may contribute to the development of a hypercoagulable state by limiting hepatic synthesis of fully functional carboxylated anticoagulant protein C (PC). The ratio of PC antigen (CAg) to PC measured in a clot-based functional assay (CFx) reflects the degree to which PC is carboxylated. The 133 patients undergoing HSCT received vitamin K 10 mg per week (low dose, 101 patients) or 5 mg per day (high dose, 32 patients) i.v. as their sole exogenous source of vitamin K. CAg and CFx were assayed before HSCT preparative regimen and again 14 days later. CAg and CFx fell significantly in both groups from day 0 to day 14 but there were no differences between the low-dose and high-dose vitamin K groups. For both groups, CAg correlated strongly with CFx at day 14 (p = 0.0001). At day 14, the CAg/CFx ratio for the low-dose group was significantly greater than for the high-dose group (1.26 +/- 0.4 vs 1.09 +/- 0.1, p < 0.0002), suggesting that low-dose patients had a higher proportion of incompletely carboxylated PC. The CAg/CFx ratio at day 14 correlated with serum albumin for the high-dose group (p = 0.05), but not the low-dose group (p = 0.09), suggesting that the change in ratio in the low-dose group was not simply due to a lack of protein synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens↗
PubMed1993

High-dose chemotherapy and autologous transplant with peripheral-blood stem cells.

The use of high-dose chemotherapy with autologous bone marrow transplantation has expanded over the last decade; however, patients who have tumor involvement in their bone marrow or who have received previous pelvic irradiation are frequently excluded from consideration for this therapy due to the inability to harvest an adequate rescue product. The ability to collect autologous peripheral-blood progenitors has allowed the expansion of this therapy to these two patient populations. Also, as experience using peripheral-blood progenitors has grown, it has become apparent that in some patient populations, engraftment times may be significantly shortened by their use, either alone or in combination with autologous bone marrow. This type of hematopoietic rescue following high-dose chemotherapy has now been used in a number of studies for the treatment of a variety of malignancies. Various mobilization and cell selection techniques are currently being evaluated for further refinement of this technique.

Antineoplastic Agents↗
PubMed1992

Progressive disease after high-dose therapy and autologous transplantation for lymphoid malignancy: clinical course and patient follow-up.

Of 364 patients with lymphoid malignancy who underwent high-dose therapy with autologous bone marrow transplantation (ABMT) or peripheral stem cell transplantation (PSCT), 169 patients have had progressive disease after the procedure. The median survival from the time of relapse for patients with Hodgkin's disease (HD) who progressed after the transplant was 10.5 months. This compares with a median survival of 3 months for relapsed non-Hodgkin's lymphoma (NHL) patients (P = .0036). After failing transplantation, 56 patients were treated with further chemotherapy, 35 with involved field irradiation therapy, and 18 patients were treated with combination chemotherapy and irradiation. Seven patients received biologic therapy and seven patients underwent a second bone marrow transplant. The remainder of the patients were believed to be too ill for further therapy or chose not to receive further treatment for their recurrent lymphoid malignancy. Sixty of the 169 patients with progressive disease after the transplant are still alive; however, only 18 patients are alive off therapy without evidence of active disease after their relapse. Ten of the 18 patients are still less than 12 months past their posttransplant salvage therapy and are at high-risk for relapse. Five patients are progression free at 15 to 36 months after their posttransplant relapse. Only three patients (two NHL and one HD) treated with other modalities after autologous transplant failure are alive without evidence of disease and have been observed at least 4 years postrelapse. Although a few patients will have a durable response to subsequent therapy, the majority of patients who have progressive disease after an autologous transplant for lymphoid malignancy will succumb to recurrent disease within a short period of time.

Adult↗