Biomedical subjects

T Gooley

Publications and source records attributed to T Gooley.

81 records · Page 5Linked to original sources

PubMed1995

Tacrolimus (FK506) alone or in combination with methotrexate or methylprednisolone for the prevention of acute graft-versus-host disease after marrow transplantation from HLA-matched siblings: a single-center study.

The pharmacokinetics, safety, and efficacy in marrow transplantation of FK506-based immunosuppression for graft-versus-host disease (GVHD) prophylaxis was evaluated in an open label pilot study of 18 patients. Patients more than 12 years of age (median, 35 years; range, 15 to 50 years) with advanced hematologic malignancies receiving HLA-matched sibling marrow grafts were randomized to receive FK506 alone, FK506 and methotrexate (MTX), or FK506 and methyl-prednisolone. Of 17 evaluable patients, all had evidence of sustained marrow engraftment. The median time to an absolute neutrophil count of greater than 500/microL was 15 days for patients receiving FK506 alone or FK506 plus methylprednisolone and 23 days for FK506 plus short MTX. Pharmacokinetic studies did not show any significant difference in clearance of FK506 when administered alone or in combination with methylprednisolone or MTX. The mean bioavailability after oral administration in these same three groups was 0.49 +/- 0.1, 0.27 +/- 0.12, and 0.16 +/- 0.08, respectively (P = .003). The decrease in bioavailability may have resulted from an exacerbation of radiation-induced gastroenteritis by MTX. The most significant adverse effect associated with the administration of FK506 was nephrotoxicity, which occurred in 14 of 18 patients (78%). The mean glomerular filtration rate, determined by clearance of (99MTc)DTPA, decreased to 56% (+/- 18%) of the pretransplant baseline level by week 8 (P = .002). Eight of 18 patients (44%) developed grades II-IV acute GVHD, predominantly of the skin and gastrointestinal tract. The actuarial probability of transplant-related mortality during the first 100 days was 24%. The actuarial probability of 1-year disease-free survival was 39%. In conclusion, although bioavailability of FK506 may be affected in patients receiving MTX, this study suggests that FK506 may have a role in the management of patients after allogeneic marrow transplantation.

Administration, Oral↗

PubMed1995

Polymerase chain reaction detection of the BCR-ABL fusion transcript after allogeneic marrow transplantation for chronic myeloid leukemia: results and implications in 346 patients.

We studied 346 patients after bone marrow transplantation (BMT) for chronic myeloid leukemia (CML) for the presence of the bcr-abl transcript detected by the polymerase chain reaction (PCR) to understand the frequency and implication of a positive test. A total of 634 samples of BM and/or peripheral blood were obtained for PCR analysis between 3 and 192 months after BMT. A positive PCR test at 3 months post-BMT was not statistically significantly associated with an increased risk of relapse compared with PCR-negative patients. However, a positive PCR assay at 6 months and beyond was highly associated with subsequent relapse. The Kaplan-Meier estimate of relapse for patients testing PCR-positive at 6 to 12 months was 42% versus 3% for PCR-negative patients (P < .0001). The Kaplan-Meier estimate of survival at 4 years for the PCR-positive patients was 74% compared with 83% for the PCR-negative group (P = .002). Multivariable analysis indicated that a PCR-positive result at 6 to 12 months post-BMT, the type of BMT donor (allogeneic matched donor v mismatched or unrelated), and the presence of acute GVHD were independent risk factors for subsequent relapse. The relative risk (RR) for relapse for patients PCR-positive at 6 to 12 months post-BMT was 26.1 (95% confidence interval, 8.9 to 76.1, P < .0001). The outcome of long-term patients (> 36 months post-BMT) who tested PCR-positive was much better, as 15 of 59 (25%) tested positive for bcr-abl, but only one patient relapsed. There was a 91% concordance between PCR tests of simultaneously obtained BM and peripheral blood. These analyses show that the PCR assay of the bcr-abl fusion transcript 6 to 12 months post-BMT is an independent predictor of subsequent relapse which provides an opportunity for early therapeutic intervention.

Adolescent↗

PubMed1995

Utility of transvenous liver biopsies and wedged hepatic venous pressure measurements in sixty marrow transplant recipients.

Sixty marrow transplant recipients with liver dysfunction underwent transvenous liver biopsy and measurement of the hepatic venous pressure gradient. Biopsies were done on 29 patients using a Cook needle inserted through the jugular vein, on 30 patients through the femoral vein with a Mansfield biopsy forceps, and on 1 patient using both instruments. The average number of evaluable portal spaces was 4.0 for aggregated Cook needle specimens and 5.2 for Mansfield forceps specimens. The average number of central venules was 2.6 for Cook needle specimens and 3.5 for Mansfield specimens. Tissue obtained with the Mansfield forceps had crush artifact, especially along the edges, making assessment of bile ducts more difficult than in Cook needle specimens. Liver histology aided management in 53/60 patients by confirming the clinical diagnosis in 24 (40%) and by providing additional diagnoses in 29 (48%). Hepatic venous pressure gradient > 10 mmHg correlated with a histologic diagnosis of veno-occlusive disease (P = 0.001); this gradient value provided 91% specificity and 86% positive predictive value. Eleven patients had bleeding complications, 9 after Cook needle biopsy and 2 after Mansfield forceps biopsy. There were 3 procedure-related deaths, 2 from intraperitoneal bleeding after Cook needle biopsy and 1 from femoral vein bleeding after Mansfield biopsy. We conclude that transvenous liver biopsy and pressure measurements provide useful diagnostic information in marrow transplant patients with liver disease. In our hands, the Mansfield forceps was associated with a lower risk of intra-abdominal bleeding and capsular perforation of the liver while providing adequate histology for diagnosis. Hepatic venous pressure gradients > 10 mmHg were highly specific for a diagnosis of veno-occlusive disease in this patient population.

Biopsy↗

PubMed1995

Factors that influence collection and engraftment of autologous peripheral-blood stem cells.

PURPOSE: To analyze factors that affect the collection of peripheral-blood stem cells (PBSC) before transplant and the tempo of engraftment after transplant. PATIENTS AND METHODS: A consecutive series of 243 patients with breast cancer (n = 87), malignant lymphoma (n = 90), multiple myeloma (n = 32), or other malignancies (n = 34) had PBSC collected following stimulation with colony-stimulating factors (CSFs) or after chemotherapy followed by CSF. Infusion of PBSC was performed following myeloablative chemotherapy with chemotherapy with or without total-body irradiation (TBI). Postinfusion CSFs were administered to 72 patients. An analysis of factors that influence CD34+ cell yield was performed by linear regression. Cox regression analysis was used to determine factors that affect the kinetics of granulocyte and platelet recovery following infusion of PBSC. RESULTS: Mobilization with chemotherapy followed by CSF, a diagnosis of breast cancer, absence of marrow disease, no prior history of radiation therapy, and fewer cycles of conventional-dose chemotherapy were associated with a higher average daily yield of CD34+ cells. In the multivariate analysis, the CD34 content of infused cells and the use of a posttransplant CSF influenced neutrophil recovery after infusion of PBSC. CD34 content was also important for predicting platelet recovery. The use of postinfusion CSF was associated with a significant delay in platelet recovery in patients who received less than 5.0 x 10(6) CD34+ cells/kg, but there was no discernable effect in patients who received greater than 5.0 x 10(6) CD34+ cells/kg. CONCLUSION: Disease status and prior treatment influence the ability to mobilize PBSC. CD34 cell dose is an important predictor of engraftment kinetics after PBSC transplant, regardless of disease or mobilization technique. The use of postinfusion CSF improves neutrophil recovery, but at low CD34 doses can delay platelet recovery.

Adolescent↗

PubMed1995

Influence of total nucleated cell dose from marrow harvests on outcome in patients with acute myelogenous leukemia undergoing autologous transplantation.

This retrospective study was conducted to determine whether the total number of nucleated cells (TNC)/kg collected at marrow harvest was associated with outcome in 151 patients with acute myelogenous leukemia (AML) who received an autologous purged (n = 67) or non-purged (n = 84) marrow transplant. At the time of transplant 33 patients were in first complete remission (CR), 47 in second CR, 54 in first relapse and 17 beyond second CR. Ninety patients received busulfan (BU) 16 mg/kg and cyclophosphamide (CY) 120 or 200 mg/kg, 51 patients received CY 120 mg/kg and total body irradiation (TBI) 12-15.75 Gy and 10 patients received BU 8 mg/kg, CY 60 mg/kg and TBI 12 Gy as conditioning regimens. Patients whose marrow harvest yielded < 2 x 10(8) TNC/kg did not undergo purging with 4-hydroperoxycyclophosphamide (4HC). This group of patients (n = 28) had a 100 day mortality of 50% and only 54% achieved a granulocyte levels of > 0.5 x 10(9)/l and 29% achieved platelet transfusion independence. Patients whose marrow harvest yielded 2-4 x 10(8) TNC/kg and did not undergo marrow purging had a 20% mortality by day 100, 91% recovered granulocytes to > 0.5 x 10(9)/l and 61% became platelet independent. Patients whose marrow harvest yielded 2-4 x 10(8) TNC/kg and underwent marrow purging with 4HC had a 50% mortality by day 100 and 58% achieved a granulocyte levels of > 0.5 x 10(9)/l and 42% became platelet transfusion independent.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1995

Polymerase chain reaction-based detection of minimal residual disease in acute lymphoblastic leukemia predicts relapse after allogeneic BMT.

We studied 20 patients who had received allogeneic bone marrow transplants for acute lymphoblastic leukemia. Using the polymerase chain reaction (PCR), we examined them for the presence of immunoglobulin heavy chain variable-diversity-junctional (IgH V-D-J) gene rearrangements as a marker of minimal residual disease (MRD). Seventeen of the patients were transplanted in relapse or for primary refractory disease, and three were transplanted in "high risk" remission. Thirteen patients had at least one positive PCR assay for MRD in the first 100 days after transplant; two died of nonleukemic causes, while all the remaining 11 relapsed. Seven patients had all negative PCR assays; two died of nonleukemic causes, four remain alive and well, and one patient with consistently negative PCR assays relapsed 47 days after his last negative test. Considering PCR status as a time-dependent covariate, the relative risk of relapse for PCR-positive patients compared to PCR-negative patients is 6.4 (p = 0.0067; 95% CI, 1.6-24.4), and the relative risk of relapse or death is 4.8 (p = 0.0052; 95% CI, 1.6-14.2). The Kaplan-Meier estimate of relapse at 1 year for PCR-positive patients is 100% compared to 33% for PCR-negative patients. The estimate for disease-free survival at 1 year for PCR-positive patients is 0% compared to 44% at 3 years for the PCR-negative group. The PCR assay for MRD appears to be a sensitive and specific test, identifying patients at high risk of relapse following allogeneic BMT who might benefit from further therapeutic interventions.

Adolescent↗

PubMed1994

Peripheral blood stem cells (PBSCs) collected after recombinant granulocyte colony stimulating factor (rhG-CSF): an analysis of factors correlating with the tempo of engraftment after transplantation.

Factors affecting mobilization and engraftment were analysed in 54 patients undergoing transplant using autologous PBSCs mobilized with high-dose recombinant granulocyte stimulating factor (rhG-CSF). Patients received 5-7 d of rhG-CSF, 16 micrograms/kg/d, administered subcutaneously. PBSCs were harvested by leukapheresis using automated continuous-flow blood cell separators beginning on day 4 of rhG-CSF, processing 10 litres of whole blood, for 2-6 consecutive days. Transplants were performed for the following diseases: breast cancer (n = 22), non-Hodgkin's lymphoma (n = 18), multiple myeloma (n = 7) and other (n = 7). Engraftment was rapid with patients reaching a neutrophil count of 1 x 10(9)/l a median of 12 d (range 9-22) after transplant. Platelets > 20 x 10(9)/l independent of transfusion support were achieved a median of day 10 (range 7-60) after infusion. Multiple factors potentially influencing engraftment were examined using a Cox regression model. The number of CD34+ cells per kg was highly correlated with the time to achievement of granulocyte and platelet recovery (P < 0.012, 0.0001). The use of a post-infusion growth factor and a radiation preparative regimen was important for neutrophil recovery, and a diagnosis of breast cancer was important for platelet recovery. In an analysis by linear regression of the logarithm of CD34+ cells collected, lower age, marrow without disease, no prior radiation, and lower number of prior chemotherapy regimens, were important factors influencing larger numbers of CD34+ cells in collections.

Adolescent↗

PubMed1994

Phase I study of high-dose busulfan, melphalan and thiotepa with autologous stem cell support in patients with refractory malignancies.

The purpose of this study was to determine the maximal tolerated dose of thiotepa administered with busulfan 12 mg/kg and melphalan 100 mg/m2 followed by autologous stem cell transplantation in patients with refractory malignancies. Twenty-eight patients with refractory malignancies received high-dose busulfan 12 mg/kg, melphalan 100 mg/m2 and escalating doses of thiotepa 450-550 mg/m2 followed by infusion of cryopreserved autologous peripheral blood stem cells (n = 26) or marrow (n = 2). The maximum tolerated dose was determined to be busulfan 12 mg/kg, melphalan 100 mg/m2 and thiotepa 500 mg/m2. Two of three patients receiving thiotepa 550 mg/m2 experienced grade 3 colitis. Twenty patients were enrolled at the maximum tolerated dose and the incidence of grade 3-4 regimen-related toxicity and mortality was 10% and 5%, respectively. Ninety-five per cent of patients experienced grade 1-2 mucositis, 50% grade 1-2 gastrointestinal toxicity, 35% grade I hepatic toxicity and 20% experienced grade 1-2 skin toxicity. The median time to achieve a granulocyte count of 0.5 x 10(9)/I was 10 days (range 8-20 days) and platelet transfusion independence was 10 days (range 1-26 days). Five of ten patients with stage 4 refractory breast cancer achieved a complete and two a partial remission with a complete response rate of 50% and a overall response rate of 70%. In conclusion, busulfan, melphalan and thiotepa can be administered in high doses with tolerable mucositis as the major side-effect. This combination has significant activity in patients with breast cancer, and phase II studies in patients with breast cancer and other chemotherapy sensitive malignancies are warranted.

Adolescent↗

PubMed1993

Molecular detection of residual lymphoma cells in peripheral blood stem cell harvests and following autologous transplantation.

Twenty-seven patients with non-Hodgkin's lymphoma (NHL) have undergone peripheral blood stem cell (PBSC) harvesting for autologous transplantation (Tx). A molecular marker was found at presentation in 23/27 patients. Immunoglobulin heavy chain (IgH) or T cell receptor beta (TCR beta) rearrangements were detected by Southern blotting or the polymerase chain reaction (PCR) in 13 patients; PCR detected the bcl-2/JH fusion in 10 patients. Fifteen autologous PBSC transplants have been performed in 11 patients. In 5/11 patients, the marker was present in at least one PBSC collection (in four patients, every PBSC collection was positive). Survival data are available for nine patients (two early deaths); three patients relapsed and died (221 - 930 d), one is alive and in relapse (354 + d) and five are alive and in complete remission (330 - 1290 + d). These findings suggest that tumour cell contamination of PBSC harvests is not uncommon. Whether these cells are clonogenic and contribute to disease relapse remains to be elucidated. The presence of residual disease at the time of transplantation and the reappearance (or persistence) of marker positive cells post-transplantation both appear to be poor prognostic factors for disease-free survival.

Adult↗