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Biomedical subjects

D D Hurd

Publications and source records attributed to D D Hurd.

At least 37 records · Page 2Linked to original sources
PubMed1995

Randomized, comparative study of high-dose (with autologous bone marrow support) versus low-dose cyclophosphamide, cisplatin, and carmustine as consolidation to adjuvant cyclophosphamide, doxorubicin, and fluorouracil for patients with operable stage II or III breast cancer involving 10 or more axillary lymph nodes (CALGB Protocol 9082). Cancer and Leukemia Group B.

The prognosis for patients with primary breast cancer involving multiple axillary lymph nodes is poor. Only about 30% of patients remain disease-free at 5 years from diagnosis despite surgery, conventional-dose chemotherapy, and radiation therapy. In nonrandomized studies, the use of high-dose chemotherapy as consolidation therapy after standard-dose induction chemotherapy has resulted in an apparent improvement in disease-free survival rates to over 70%. These results have prompted the National Cancer Institute to sponsor large-scale, multicenter, randomized comparative trials of this strategy. This Intergroup Study (Cancer and Leukemia Group B 9082, Southwest Oncology Group 9114, and National Cancer Institute of Canada MA13) compares two treatment strategies in women with primary breast cancer involving 10 or more axillary lymph nodes. Arms A and B are identical in the use of four cycles of conventional therapy with cyclophosphamide and doxorubicin and fluorouracil, radiation therapy, and tamoxifen. The only difference between the two arms is the dose intensity of the cyclophosphamide, cisplatin, and carmustine given following conventional adjuvant treatment. Arm A dictates bone marrow, peripheral blood stem cell, and hematopoietic growth factor support and frequently requires a prolonged hospital stay with high resource utilization. Arm B, with its less dose-intensive therapy, requires considerably less support to apply the treatment. Because of the high cost of this therapy and the requirement for technology-intensive support, there has been considerable interest in economic outcome assessments.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Reactivation toxoplasmic retinochoroiditis in patients undergoing bone marrow transplantation: is there a role for chemoprophylaxis?

The objective of this study was to report the occurrence of reactivation ocular toxoplasmosis in bone marrow transplant (BMT) recipients and to propose guidelines for identification and chemoprophylaxis of high-risk patients. The study design was a series of cases from the tertiary care university hospital which has an active BMT program. The patients were two recipients of autologous BMTs with past histories of toxoplasma retinochoroiditis who developed symptomatic reactivation of ocular toxoplasmosis as documented by formal opthalmologic examination in the early post-transplant period. Opthalmoscopic examinations in the two patients with non-Hodgkin's lymphoma who received autologous transplants and then developed decreased visual acuity in the first week after transplant revealed recurrent retinochoroiditis adjacent to old toxoplasma lesions. Pre-transplant eye examinations in both patients had demonstrated only inactive chorioretinal scars. Therapy with sulfadiazine, pyrimethamine and prednisone ultimately led to resolution of retinitis in both patients. BMT recipients who are seropositive for antibody to T. gondii and have findings consistent with previous toxoplasma retinochoroiditis on pre-transplant ophthalmologic examination appear to be at risk for reactivation of ocular toxoplasmosis in the early post-transplant period and may warrant preventive chemoprophylaxis for toxoplasmosis.

Animals↗
PubMed1995

Phase I study of continuous infusion 6-thioguanine in patients with acute leukemia.

6-Thioguanine (6-TG) was administered as a continuous i.v. infusion for 7 days to 24 patients with relapsed or refractory acute leukemia or in the blast phase of chronic granulocytic leukemia. The daily dose of 6-TG was escalated from 37.5 mg/m2 to 160 mg/m2. Stomatitis was dose-related and dose-limiting with a maximum tolerated dose of 120 mg/m2 daily. Cutaneous reactions were dose-related but not dose-limiting. The recommended dose for phase II trials in acute leukemia is 120 mg/m2 per day as a continuous infusion for 7 days. There were two complete and four partial remissions among all patients. At the suggested phase II dose of 120 mg/m2 there were two complete remissions and one partial remission in five evaluable patients.

Acute Disease↗
PubMed1994

Prognostic factors for therapeutic outcome of diffuse small non-cleaved cell lymphoma in adults.

Most reports of prognosis and therapy in diffuse small non-cleaved cell lymphoma (DSNCL), an aggressive high-grade non-Hodgkin's lymphoma (NHL) which appears to be of two histopathologic subtypes, have included predominantly a pediatric population and very few adults. We studied 20 newly diagnosed, previously untreated adults with DSNCL. Three patients had Ann Arbor Stage I disease, five Stage II, and 12 Stage IV. Bone marrow involvement was present in seven of 20 (35%) patients; no patient had central nervous system involvement at diagnosis. Clonal chromosomal abnormalities were found on cytogenetic analysis of all 12 cases studied. Ten patients had specific recurring translocations, including t(8;14) (q23;q32) (five patients), t(14;18) (q32;q21) (four patients), and t(2;8) (p12;q24) (one patient). Induction chemotherapy with the COMP regimen (cyclophosphamide, vincristine, methotrexate, and prednisone) or a variant schedule of the same drugs resulted in complete remission for 13 patients (65%), and partial remission for 5 patients (25%). Clinical characteristics predictive of a favorable response to induction therapy included Stage I or II disease, a normal lactic dehydrogenase (LDH), and performance status (PS) of 0 or 1. Remission duration ranged from two to 125+ (median 37+) months. Survival ranged from one to 126+ (median 23) months; ten patients (50%) remain alive, nine with no active disease. Factors predictive of longer survival included achievement of a complete remission with induction therapy, a normal LDH, and PS 0 or 1. As in children with DSNCL, long-term disease-free survival may be achieved in adults with combination chemotherapy.

Adolescent↗
PubMed1994

Hemorrhagic cystitis in bone marrow transplantation.

OBJECTIVES: Patients undergoing bone marrow transplantation are at risk for hemorrhagic cystitis despite appropriate preventive measures. This complication could have an impact on patient survival and other outcome variables. METHODS: A retrospective study of patients subjected to bone marrow transplantation was conducted to determine risk factors for hemorrhagic cystitis and evaluate the impact of hemorrhagic cystitis on certain outcome variables. Patients who experienced hemorrhagic cystitis received various forms of therapy, at the discretion of the treating physician. RESULTS: Hemorrhagic cystitis occurred more frequently in younger patients and those undergoing allogeneic transplantation. The occurrence of hemorrhagic cystitis was associated with increased hospital costs, length of hospitalization, and mortality. Gender, race, type of malignancy, other pretransplantation comorbidity, and the occurrence of other peritransplantation complications were not associated with occurrence of hemorrhagic cystitis. CONCLUSIONS: Hemorrhagic cystitis is a significant complication of bone marrow transplantation, which influences economic and survival outcome. Since the number of bone marrow transplants being performed is increasing, urologists should be prepared to play an active role in treating patients who experience this complication.

Adolescent↗
PubMed1993

Processing forms used in the bone marrow transplantation laboratory: toward standardization.

We developed a set of one-page data forms for each procedure that is used in the different types of bone marrow transplant processing performed in our laboratory. In this paper we duplicate this set of forms and illustrate how they can be "mixed and matched" to accommodate the type of processing that is being carried out on a particular day. Finally, we describe the benefits that we have gained from using this system and suggest interlab advantages to adopting such a system.

Bone Marrow Transplantation↗
PubMed1991

Early herpes zoster infection in adult patients with Hodgkin's disease undergoing autologous bone marrow transplant.

The incidence of varicella-zoster-virus infection/reactivation in adult patients with Hodgkin's disease undergoing autologous bone marrow transplantation (BMT) at the University of Minnesota Hospital and Clinic was determined. Seven of 28 evaluable patients (25%) developed varicella-zoster infections in the first 150 days post-transplant. Two additional patients developed zoster after day 150 for a total incidence of 32%. We evaluated analysed risk factors to determine if there were any characteristics that could identify patients at risk for zoster early (less than 150 days) in their post-transplant course. Sex, age, prior radiation, and lack of immunity as determined by viral antibody titers were not associated with an increased incidence. Ten of the 28 patients had a history of zoster at some time after the diagnosis of Hodgkin's disease. Six of these 10 patients (60%) again developed zoster post-transplant. This compared to only one episode of varicella-zoster post-transplant among the 18 patients without a history of zoster following the diagnosis of Hodgkin's disease (p less than 0.01, Fisher's exact). We conclude that a prior history of zoster any time after diagnosis of Hodgkin's disease is strongly associated with developing zoster in the first 150 days after autologous BMT.

Adolescent↗
PubMed1990

Prognostic factors at relapse for adults with acute myeloid leukemia.

To identify prognostic factors for patients with acute myeloid leukemia in first relapse we have analyzed the courses of 57 patients undergoing intensive reinduction therapy. The median duration of first remission was 9 months. A second complete remission was achieved by 31 patients (54%). The median duration of second remission was 5 months (range 1-142 + months). Two patients are still disease-free with 42 months and 142 months follow-up. Clinical, laboratory, and treatment variables at the time of original diagnosis and at relapse were examined for possible associations with the outcome of reinduction chemotherapy. Only duration of first remission consistently correlated with ability to achieve a second remission, second remission duration, and overall survival from reinduction. The second complete remission rate was 69% for those with a first remission longer than 9 months but only 39% for those with a first remission less than 9 months (P less than 0.05). The patients with longer first remissions also had longer second remissions (8 months median vs. 4 months, P = 0.02) and a longer median survival following reinduction chemotherapy (8 months vs. 5 months, P = 0.02). We conclude that the duration of a patient's first remission should be considered a useful prognostic factor both in treatment planning and in the interpretation of clinical trials of patients in relapse.

Antineoplastic Agents↗
PubMed1990

Sequential karyotypes in non-Hodgkin lymphoma: their nature and significance.

The examination of sequential karyotypes in hematologic disorders has demonstrated that karyotypic changes are often associated with concurrent changes in clinical behavior. Acquired abnormalities that recur among different patients may also suggest genomic areas important to tumor progression. We therefore examined sequential karyotypes in 21 patients with non-Hodgkin lymphoma (NHL). Sixteen of the 21 karyotypes demonstrated changes, including the majority of 6 small lymphocytic, 11 follicular, and 4 intermediate and high-grade diffuse lymphomas. The t(14;18)(q32;q21) occurred in ten initial karyotypes was retained in all cases. The band most frequently affected by newly acquired abnormalities was 14q32 (n = 5); chromosomes 1 and 2 (n = 5, each), and the 17p arm (n = 4) were also commonly affected. The acquired deletion of all or part of 17p appeared to be associated with a poor prognosis. Histologic transformation and karyotypic change did not correlate. This study of sequential karyotypes in NHL 1) confirms the primary importance of the t(14;18), 2) suggests that the 14q32 band is involved frequently in both primary and secondary cytogenetic events, and 3) suggests other genomic regions of potential significance to progression.

Adult↗
PubMed1990

Treatment of refractory and relapsed Hodgkin's disease: intensive chemotherapy and autologous bone marrow or peripheral blood stem cell support.

Thirty-three patients with recurrent or refractory Hodgkin's disease were treated with high-dose cyclophosphamide, BCNU, and etoposide and supported with either autologous bone marrow or peripheral blood stem cells or both. Peripheral blood stem cells were comparable to bone marrow in supporting the recovery of hematopoiesis. Twenty-five patients (76%) were in complete remission following this therapy of whom 13 have subsequently relapsed. Twelve remain alive and disease free from 10 to 47 months. The Kaplan-Meier estimate of disease-free survival at 28 months for the entire 33 patients is 32% (95% confidence interval, 13-50%). Poor outcome in six patients was associated with bone marrow involvement by Hodgkin's disease at the time of peripheral blood stem cell collection. These six patients' survival, disease-free survival, the duration of complete remission were all significantly worse than for the 27 patients who were supported with bone marrow (n = 23), peripheral blood stem cells (n = 2), or both (n = 2), and whose marrows were free of disease at the time of stem cell collection. These data demonstrate that intensive therapy with autologous transplantation can produce extended disease-free survival for some patients with advanced Hodgkin's disease and that peripheral blood stem cell support can effectively be used for hematopoietic reconstitution. However, our observations also suggest that with this preparative regimen, bone marrow involvement at the time of peripheral blood stem cell collection is predictive for a poor outcome and alternate approaches to treatment should be considered for this subset of patients.

Adolescent↗
PubMed1989

Peripheral blood stem cell collection and use in Hodgkin's disease. Comparison with marrow in autologous transplantation.

Hematopoietic progenitor cells can be collected from blood by cytapheresis; the clinical use of these cells may offer such advantages over marrow as the avoidance of general anesthesia, collection on an outpatient basis, and use when marrow is involved with malignancy. Since Hodgkin's disease rarely spreads hematogenously, postchemotherapy marrow transplantation with autologous peripheral blood stem cells (PBSCs) was compared to that with marrow transplantation in patients with this disorder. Seven patients were treated with PBSCs and 19 with marrow. Five to nine collections of PBSC were performed per patient. There was a rebound increase in circulating committed progenitors when PBSC were collected during the marrow rebound after cyclic chemotherapy. After intensification and cellular rescue, quicker recovery of circulating white cells (p less than 0.05) and a shorter hospital stay (not significant) were seen in the PBSC patients than in those treated with autologous marrow. There was no difference in the duration of red cell or platelet transfusion required after transplant. Of six patients whose marrows were previously involved by Hodgkin's, recurrent or progressive disease has occurred in five. PBSC may be a viable alternative to marrow in selected patients.

Blood Component Removal↗
PubMed1988

Treatment of refractory lymphoma with methotrexate, VM-26 (teniposide), procarbazine, and dexamethasone: Cancer and Leukemia Group B study 7902.

Seventy-eight individuals previously treated with chemotherapy for non-Hodgkin's lymphoma were enrolled in a phase II pilot study employing methotrexate 100 mg/M2 iv (day 1), calcium leucovorin 10 mg/M2 iv and/or po q6h (days 2-4), VM-26 (teniposide) 100 mg/M2 iv (days 2 and 9), procarbazine 100 mg/M2 po (days 2-15), and dexamethasone 15 mg/M2po (days 2-8) (MV26PD). Thirty percent of the 78 patients treated had a response to therapy (8% complete, 22% partial). Twenty-four percent of patients with diffuse histiocytic (large cell) lymphoma had a response (12% complete, 12% partial). The estimated failure-free survival was 41% at 3 months and the median survival (death from any cause) was 4.5 months for the entire cohort. Two individuals, including one individual with diffuse histiocytic lymphoma, remain in a complete response for over 900 days. Significant hematologic toxicity and infectious complications were seen in this heavily pretreated group of patients. MV26PD represents an active combination of agents for the treatment of non-Hodgkin's lymphoma. The optimal dosing for MV26PD remains to be determined.

Adult↗
PubMed1988

Autologous bone marrow transplantation in non-Hodgkin's lymphoma: monoclonal antibodies plus complement for ex vivo marrow treatment.

PURPOSE: Patients with non-Hodgkin's lymphoma who fail to achieve a complete remission or who relapse are rarely cured with conventional therapies. For this group of patients, intensive therapy and bone marrow rescue may be curative. Our goal was to assess the effects of autologous transplantation in patients with B-cell lymphomas and a poor prognosis. To avoid occult or overt contamination with lymphoma, monoclonal antibodies BA-1, BA-2, and BA-3 were used for ex vivo marrow treatment. PATIENTS AND METHODS: Seventeen patients underwent intensive therapy and autologous bone marrow transplant using the aforementioned marrow. Ten of the 17 patients (Group I) had disease that was in complete or partial remission. The other seven patients either had disease that was not responsive to treatment or had bone marrow transplant as their initial therapy at relapse. RESULTS: The ex vivo treatment did not adversely affect engraftment. For those patients who could be evaluated, the median time to white cell engraftment was 24 days; the median durations of red cell and platelet support were 24 and 29 days, respectively. Eleven of the 17 patients had complete remissions at the evaluation 28 days after transplant. Three patients subsequently experienced a relapse, three died while their disease was in complete remission, and five are alive and disease-free 405 to 1,674 days after transplant. Group I patients had an estimated 40 percent disease-free survival rate at three years compared with 0 percent for Group II patients (p less than 0.01). CONCLUSION: Our data support autologous bone marrow transplantation as an important treatment modality for the non-Hodgkin's lymphomas. With the current preparative regimens available, however, its use should be limited to patients with disease that is still responding to conventional therapies.

Adolescent↗
PubMed1988

Cytogenetic abnormalities predict clinical outcome in non-Hodgkin lymphoma.

Tumor cytogenetic analysis was done for 68 patients with newly diagnosed non-Hodgkin lymphoma, and recurring cytogenetic abnormalities were correlated with achievement of complete remission, duration of complete remission, and survival. Among all patients, the presence of normal metaphases in tumor material was associated with a higher complete remission rate and longer survival. However, the duration of complete remission did not correlate with the presence or absence of chromosomal changes. Among patients with follicular lymphomas, the presence of normal metaphases in the tumor material was again associated with a higher rate of complete remission and with longer survival. Patients with structural abnormalities of chromosome 17 had a shorter survival than patients without these abnormalities. Among the patients with diffuse large-cell and immunoblastic lymphomas, those with breaks in the short arm of chromosome 2 had a longer survival than those without these breaks. We conclude that chromosomal abnormalities are predictive of clinical outcome in malignant lymphoma.

Adolescent↗
PubMed1988

Allogeneic bone marrow transplantation for acute nonlymphocytic leukemia in first remission.

Seventy-three patients with acute nonlymphocytic leukemia in first complete remission (CR) have received allogeneic bone marrow transplantation (BMT) with non-T-lymphocyte-depleted marrow obtained from matched sibling donors. The first 36 patients received a preparative regimen consisting of cyclophosphamide, 60 mg/kg/d (days -6 and -5), and 750 cGy single-dose total-body irradiation (TBI) (day -1). Subsequently, 37 patients received cyclophosphamide 60 mg/kg/d (days -6 and -5), and 165 cGy fractionated TBI administered twice daily for a total dose of 1,320 cGy (days -4, -3, -2, and -1). Survivors have been followed from 9 to 124 months (median, 40 months). The 61% (95% confidence interval [CI], 45% to 77%) projected disease-free survival (DFS) of 41 children less than 18 years old does not differ significantly from the 62% (95% CI, 49% to 73%) projected DFS of 32 adults at 84 months (P = .89). Similarly, the 15% (95% CI, 1% to 29%) projected relapse rate seen in children does not differ from the 9% (95% CI, 0% to 21%) seen in adults (P = .69). Multivariate Cox regression analysis of presenting features demonstrates that a presenting WBC count greater than 20,000/m3 is associated with decreased DFS (P = .01). When compared with other French-American-British (FAB) subtypes, presentation with FAB M4 or M5 morphology is significantly associated with relapse in multivariate analysis (P = .014). Other presenting features such as preparation with single-dose or fractionated TBI, interval from diagnosis to CR or CR to BMT, donor or recipient sex, and donor or recipient cytomegalovirus serology do not correlate independently with either DFS or relapse. When included in the stepwise multivariate analysis of presenting patient features, two posttransplant events, development of grades 2 to 4 acute graft-v-host disease (GVHD) (P less than .03) and development of interstitial pneumonitis (P less than .001), also correlate independently with poor DFS. Allogeneic BMT provides equivalent, prolonged DFS in both children and young adults when performed in first CR and should be considered the therapy of choice for all first CR patients under 45 years of age with a suitable donor. Continued efforts to prevent and treat acute GVHD and pneumonitis as well as efforts designed to prevent relapse in patients presenting with FAB M4 and M5 morphology should further improve outcome.

Age Factors↗