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Biomedical subjects

E C Reed

Publications and source records attributed to E C Reed.

At least 19 recordsLinked to original sources

NCCN Practice Guidelines for Breast Cancer.

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. In many situations, the patient and physician have the responsibility to jointly explore and ultimately select the most appropriate option from among the available alternatives. With rare exception, the evaluation, treatment, and follow-up recommendations contained within these guidelines were based largely on the results of past and present clinical trials. However, there is not a single clinical situation in which the treatment of breast cancer has been optimized with respect to either maximizing cure or minimizing toxicity and disfigurement. Therefore, patient and physician participation in prospective clinical trials allows patients not only to receive state-of-the-art cancer treatment but also to contribute to the improvement of treatment of future patients.

Breast Neoplasms↗

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↗

Invasive pulmonary aspergillosis due to Aspergillus terreus: 12-year experience and review of the literature.

A 12-year retrospective analysis was done to identify and evaluate in detail cases of invasive pulmonary aspergillosis (IPA) caused by Aspergillus terreus. We identified 13 A. terreus infections among 133 total cases of confirmed invasive aspergillosis; 11 were IPA and 2 were primary peritoneal infections. Of the 11 patients with IPA, 7 developed neutropenia during hospitalization, and the remaining four were receiving immunosuppressive agents. Ten patients with IPA died; one liver transplantation patient without neutropenia survived after treatment with amphotericin B, itraconazole, and a pulmonary lobectomy. Six patients developed disseminated disease, with the heart the most common extrapulmonary site identified (four patients). These cases demonstrate that IPA caused by A. terreus rapidly progresses in immunocompromised patients receiving amphotericin B and illustrate the need for sensitive diagnostic tests and more effective antifungal agents.

Antifungal Agents↗

Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies.

PURPOSE: To compare hematopoietic recovery, duration of hospitalization, and 100-day survival in patients who received allogeneic-blood stem cells (BSC) or conventional allogeneic bone marrow transplantation (BMT). PATIENTS AND METHODS: From December 1994 to August 1995, 21 patients participated in a phase II study of allogeneic BSC transplantation. Cells mobilized with granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human leukocyte antigen (HLA)-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate. G-CSF (10 micrograms/kg/d) was administered posttransplant. The outcomes were compared with 22 identically treated historical patients who received allogeneic BMT. RESULTS: The median infused CD34+ cell and granulocyte-macrophage colony-forming unit (CFU-GM) content were 7.73 x 10(4)/kg and 41.6 x 10(4)/kg, respectively. The median time to a neutrophil count greater than 500/ microL was 11 days after BSC and 16.5 days after BMT (P = .0003). A trend toward faster platelet and RBC recovery after BSC was observed. BSC patients received fewer platelet transfusions: 10 versus 19 (P = .015). The median length of hospitalization was shorter after BSC transplantation: 25 versus 31.5 days (P = .0243). The 100-day survival rates were similar: 83% after BSC and 75% after BMT (P = .3585). The incidence of acute GVHD grade II to IV was 57% and 45% for BSC and BMT, respectively (P = .4654). CONCLUSION: In comparison to BMT, allogeneic BSC transplantation may result in faster hematopoietic recovery, shorter hospital stay, and similar early survival. Whether allogeneic BSC are superior to bone marrow needs to be determined in randomized trials.

Adult↗

Immunologic attributes of cytokine mobilized peripheral blood stem cells and recovery following transplantation.

The immunologic attributes of cytokine mobilized peripheral blood stem cell (PSC) products (n = 52) and the resulting reconstitution of the hematopoietic and immunologic system following autologous transplantation were examined in a consecutive population of non-Hodgkin lymphoma (NHL), or solid tumor patients at the University of Nebraska Medical Center. Granulocyte-monocyte colony stimulating factor (GM-CSF)-mobilized PSC products had a high frequency of monocytes (31%) and bands (15%) as compared to normal peripheral blood (PB) cells. The phenotypic analysis of the mobilized PSC product revealed that they had normal levels of CD4+ cells, an increased frequency of CD8+ cells and a corresponding decrease in the CD4+:CD8+ cell ratio as compared to the peripheral blood leukocytes (PBL) of normal individuals. PSC products also had an increase in CD34+ cells as compared to PB. Natural killer (NK) and T cell activity in the PSC products were also lower than that observed in PB. Post-transplantation there was an accelerated reconstitution of NK-cell function in the PB as compared to T cell function (PHA (phytohemagglutinin) mitogenesis) which did not return to normal by day 100 post-transplantation. We also report for the first time high levels of an irradiation resistant suppressor cell activity in the PSC product and in the PB post-transplantation. There was also a concomitant increase in CD4-, CD8-, TCR alpha/beta+ cells (phenotypic homolog of 'natural suppressor' (NS) cells) in the PB post-transplantation. The number of months of prior chemotherapy correlated with PHA response but the NS activity and frequency of CD4-, CD8- and TCR alpha/beta+ cells did not. Further, cytokine mobilization and apheresis appears to contribute to the loss of PHA responsiveness and the increased levels of suppressor cell activity.

Antigens, CD34↗

Use of continuous infusion granulocyte-macrophage colony-stimulating factor alone or followed by granulocyte colony-stimulating factor to enhance engraftment following high-dose chemotherapy and autologous bone marrow transplantation for lymphoid malignancies.

We evaluated the differences in engraftment and toxicities post-autologous transplant using granulocyte-macrophage colony stimulating factor (GM-CSF) as a continuous infusion either alone or in a sequential manner with granulocyte colony-stimulating factor (G-CSF). Patients receiving high-dose chemotherapy and autologous bone marrow transplantation (ABMT) for lymphoid malignancies participated in two phase II trials evaluating either continuous infusion GM-CSF (GM-CSF (CI)) or continuous infusion GM-CSF followed by sequential G-CSF (GM-CSF/G-CSF) administered post-ABMT. These patients were compared to similar historical control patients receiving GM-CSF administered as a 2-h intravenous (i.v.) infusion (GM-CSF (2-h)). Patients receiving GM-CSF (CI) and GM-CSF/G-CSF had a median day to reach an absolute neutrophil count of 500/microliter post-ABMT of 12 and 11 days, respectively. This compared to a median day of 22 in the GM-CSF (2-h) historical control patients. The median day to platelet independence was 18, 18 and 30 days, respectively. The incidence of toxicities such as incidence of infection, pleural effusions, and rash did not differ greatly between the groups. We conclude that the use of continuous infusion GM-CSF either alone or sequentially with G-CSF produced improved engraftment times compared to historical control patients treated with GM-CSF as a 2-h i.v. infusion. The toxicities at a reduced dose of 125 micrograms/m2 given as a continuous infusion appear to be similar to those seen in patients receiving GM-CSF as a 2-h infusion.

Adult↗

Immunologic phenotype and function in human bone marrow, blood stem cells and umbilical cord blood.

The T cell-mediated antineoplastic activity observed following allogeneic transplantation and the suggestion of improved therapeutic efficacy by autologous peripheral stem cell transplantation (PSCT) as compared to autologous bone marrow transplantation (ABMT) for non-Hodgkin's lymphoma (NHL) stimulated our interest in the immunologic competence of stem cell products. We report the immune phenotype and function of normal peripheral blood (PB) cells, bone marrow (BM) cells from normal donors and cancer bearing patients, GM-CSF-mobilized and apheresed blood mononuclear cells from NHL patients, unmobilized apheresed mononuclear cells from normal volunteers and umbilical cord blood (CB). The analyses include three-color fluorescent cytometry of the major hematologic and immunologic phenotypes as well as natural killer (NK) activity, natural suppressor (NS) activity, and phytohemagglutinin (PHA) and pokeweed (PWM) mitogenesis. These studies demonstrated an increased frequency of T cells in apheresis products as compared to BM and CB products. Specifically, the mobilized PSC had significant increases in CD3+, CD4+, CD45RO+ and CD56+ cells relative to BM cells. In addition, the frequency of TCR gamma/delta + cells in all the stem cell products, with the exception of CB, were also increased compared to normal peripheral blood leukocytes (PBL). However, all the stem cell products had a significant depression in T (PHA mitogenesis) and B (PWM mitogenesis) cell function. The depression in immune cell functionality, in the PSC products was perhaps due to the high frequency of monocytes which appeared to be increased due to both mobilization and apheresis. The frequency of the NK cell phenotype (CD56) but not function was increased in the mobilized PSC products, while the NK cell function in the BM products from cancer patients but not normal donors was depressed as compared to normal PBL. In summary, there are significant differences in the cellular phenotypes and immunologic competence among the various stem cell products with potential therapeutic implications.

Bone Marrow↗

Systemic adjuvant therapy for breast cancer.

The benefits of adjuvant systemic therapy in the treatment of early breast cancer are well established. However, many questions remain regarding the appropriate selection of patients and regimens, duration of treatment, timing or sequencing of treatment as well as the role of high-dose chemotherapy or new active drugs such as paclitaxel. Future answers will only come through continued participation in carefully designed clinical research.

Adult↗

Multiple organ dysfunction syndrome in bone marrow transplantation.

OBJECTIVE: To define the frequency and outcome of organ dysfunction in bone marrow transplantation (BMT) and to determine if patients with organ dysfunction have lower levels of protein C (PC) and/or antithrombin III (ATIII) than those without organ dysfunction. DESIGN: Inception cohort of patients undergoing BMT, followed for 28 days, until hospital dismissal, or until death. SETTING: Bone marrow transplant department of a university hospital. PATIENTS: A total of 199 consecutive patients admitted for BMT. INTERVENTIONS: Standard supportive care was given to all patients. MAIN OUTCOME MEASURES: Definitions of organ dysfunction were arrived at prior to beginning the study. They include pulmonary, central nervous system (CNS), hepatic, and renal dysfunction. Protein C and ATIII levels were measured prior to beginning the preparative regimen and weekly thereafter. RESULTS: Single organ dysfunction, manifesting as pulmonary, CNS, or hepatic dysfunction, occurred in 93 (48.5%) of the 199 patients and was a strong predictor of multiple organ dysfunction syndrome (MODS) and death. Death occurred in 14 (7.0%) of the patients. Cause of death was precisely identified in only four patients. Low levels of either PC or ATIII were associated with death and pulmonary, CNS, and hepatic dysfunction. Multivariate analysis showed ATIII and PC levels were associated with single organ dysfunction independent of the type of transplant, the type of preparative regimen, and the presence of bacteremia. CONCLUSIONS: Single organ dysfunction during BMT is a marker for a systemic abnormality that has a high likelihood of progressing to MODS, similar to that seen in other critically ill patient populations. MODS is the leading cause of death in series of BMT patients. Low levels of ATIII and PC are markers of and may be involved in the pathogenesis of MODS in BMT.

Adolescent↗

Pulmonary resection for invasive Aspergillus infections in immunocompromised patients.

Standard antifungal medical therapy of invasive pulmonary aspergillosis that occurs in immunocompromised patients with hematologic diseases with neutropenia or in liver transplant recipients results in less than a 5% survival. In view of these dismal mortality rates, we adopted an aggressive approach with resection of the involved area of lung along with systemic antifungal therapy when localized invasive pulmonary aspergillosis developed in these patients. Between January 1987 and December 1993, 14 patients with hematologic diseases and 2 liver transplant recipients underwent resection of acute localized pulmonary masses suggestive of invasive pulmonary aspergillosis a median of 7.5 days (range 1 to 45 days) after the diagnosis was clinically suggested and confirmed by chest computed tomographic scans. Operative procedures done included two pneumonectomies, one bilobectomy with limited thoracoplasty, nine lobectomies, and five wedge resections (one patient with hematologic disease had two procedures). All patients were treated before and after the operation with antifungal agents. Nine (64%) of 14 patients with hematologic disease and 2 (100%) of 2 liver transplant recipients survived the hospitalization with no evidence of recurrent Aspergillus infection after a median 8 months of follow-up (range 3 to 82 months). The five hospital deaths (all patients with hematologic diseases) occurred a median of 20 days after operation from diffuse alveolar hemorrhage in three, graft-versus-host disease in one, and multiple organ system failure with presumed disseminated Aspergillus infection in one. Four of the five deaths were in patients with allogeneic bone marrow transplants. Two of the three patients requiring resection of multiple foci of infection died, as did the only patient who was preoperatively ventilator dependent. In immunocompromised patients with hematologic diseases or liver transplantation with invasive pulmonary aspergillosis, early pulmonary resection should be strongly considered when the characteristic clinical and radiographic pictures appear.

Adult↗

Comparison of subcutaneous and intravenous administration of recombinant human granulocyte-macrophage colony-stimulating factor for peripheral blood stem cell mobilization.

In an effort to determine whether subcutaneous or continuous intravenous infusion administration of rhGM-CSF results in better hematopoietic progenitor mobilization, the findings of two sequential clinical trials were reviewed. Patients who had received prior chemotherapy for leukemia, lymphoma, multiple myeloma, breast cancer, or other solid tumors and were candidates for high-dose therapy received rhGM-CSF, 250 micrograms/m2/day, either as a continuous intravenous infusion (trial 1) or subcutaneously (trial 2) for stem cell mobilization. At least five apheresis collection procedures were performed to collect a target number of 6.5 x 10(8) mononuclear cells (MNC)/kg. For the 37 patients in trial 1, the collections contained a median of 7.99 x 10(8) MNC/L (range 6.42-21.36) and a median of 5.27 x 10(4) CFU-GM/kg (range 0.28-19.35). In trial 1, 25 patients were autografted with their cells and recovered 0.5 x 10(9) granulocytes/L at a median of 12 days (range 6-16). For the 33 patients in trial 2, the autograft product contained a median of 7.63 x 10(8) MNC/kg (range 6.51-22.66) and 6.31 x 10(4) CFU-GM/kg (range 0.06-60.4). In trial 2, 25 patients were autografted. The median time to reach 0.5 x 10(9) granulocytes/L was 11 days (range 9-26). All patients received rhGM-CSF after peripheral stem cell transplant. No significant differences in the collected products or the time to hematopoietic recovery was found between the two trials (p > 0.05). The mobilization effects of subcutaneous rhGM-CSF in these pretreated patients were similar to those of intravenous rhGM-CSF.

Adult↗

Invasive infection due to Candida krusei in immunocompromised patients not treated with fluconazole.

Candida krusei is a cause of invasive candidiasis (IC), with numerous cases reported among leukemia patients after bone marrow transplantation and treatment with fluconazole. The relation between fluconazole therapy and IC remains controversial. In a retrospective review covering 5 years, we identified 203 cases of IC, 71 (35%) of which were due to non-albicans species. Eight cases were caused by C. krusei: four of the patients involved had leukemia, two had breast cancer, one had end-stage liver disease, and one had undergone abdominal trauma. None of these patients received fluconazole. Surveillance cultures detected colonization with C. krusei before the onset of symptoms in seven cases. The median time from colonization to IC diagnosis was 10 days. Of six patients with neutropenia, five were neutropenic at IC diagnosis. Concomitant infections were common; four patients had both bacteremia and invasive aspergillosis. C. krusei was considered the immediate cause of five of the seven deaths among this group of patients. These eight cases extend the range of immunocompromised conditions in which IC caused by C. krusei develops in the absence of fluconazole therapy.

Abdominal Injuries↗

Erythropoietin for mobilization of circulating progenitor cells in patients with previously treated relapsed malignancies.

A trial to determine the usefulness of recombinant human erythropoietin (rhEpo) as a mobilizing cytokine for patients with previously treated relapsed malignancies was performed. An initial peripheral stem cell apheresis collection was conducted during steady-state hematopoiesis for each patient to provide baseline data. rhEpo, 200 U/kg/day, was administered subcutaneously until the last apheresis procedure was completed. Immediately after the fourth daily dose of Epo, apheresis procedures were resumed and continued beyond five collections, when necessary, to accrue a total of 6.5 x 10(8) mononuclear cells (MNCs)/kg. Eight female and four male patients (median age = 44 years) were evaluated. Five to 14 (median = 8) apheresis procedures were performed for each patient. Toxicity attributable to Epo administration was negligible. Mobilization effects, as determined by an increase in the number of colony-forming units granulocyte/macrophage (CFU-GM) and burst-forming units-erythroid (BFU-E) in the apheresis products after Epo administration, were observed in all patients. Nine patients received high-dose chemotherapy and Epo-mobilized peripheral stem cell transplantation (PSCT). Beginning the day of the transplant, GM-CSF was administered until neutrophil recovery was satisfactory. The median time to recover 0.5 x 10(9)/L granulocytes was 16 days after PSCT. Epo appears to have mobilization properties. Further studies are needed to determine the clinical usefulness of Epo as a mobilizing cytokine. The addition of Epo to other mobilizing cytokines may provide increased effectiveness without adding toxicity.

Adult↗

High-dose therapy and peripheral blood progenitor cell transplantation: effects of recombinant human granulocyte-macrophage colony-stimulating factor on the autograft.

Between June 1989 and June 1992, 144 patients participated in sequential clinical trials using peripheral blood progenitor cells (PBC) as their sole source of hematopoietic rescue following high-dose chemotherapy. All patients had received prior extensive combination chemotherapy and had marrow defects that precluded autologous bone marrow transplantation (ABMT). PBC were collected according to a single apheresis protocol. The initial 86 patients (group 1) had PBC collected without mobilization. Beginning in April 1991, PBC were mobilized solely with recombinant human granulocyte-macrophage colony-stimulating factor (rHuGM-CSF). Thirty-four patients (group 2) received rHuGM-CSF at a dose of 125 micrograms/m2/d by continuous intravenous infusion, and 24 patients (group 3) received rHuGM-CSF at a dose of 250 micrograms/m2/d by continuous intravenous infusion. Patients underwent at least six aphereses and had a minimum of 6.5 x 10(8) mononuclear cells (MNC)/kg collected. Cytokines were not routinely administered immediately after transplantation. A median of nine aphereses were required to collect PBC in group 1 and seven aphereses for groups 2 and 3 (P = .03). The time required to recover 0.5 x 10(9)/L granulocytes after transplant was significantly shorter (P = .0004) for the mobilized groups; the median time to recovery was 26 days for group 1, 23 days for group 2, and 18 days for group 3. Transplantation of PBC mobilized with rHuGM-CSF resulted in a shorter time to platelet (P = .04) and red blood cell (P = .01) transfusion independence. Mobilization with rHuGM-CSF alone resulted in efficient collection of PBC, that provided rapid and sustained restoration of hematopoietic function following high-dose chemotherapy. Mobilization of PBC with rHuGM-CSF alone is an effective method for patients who have received prior chemotherapy and have bone marrow abnormalities.

Adolescent↗

Corticosteroids as adjunctive therapy for diffuse alveolar hemorrhage associated with bone marrow transplantation. University of Nebraska Medical Center Bone Marrow Transplant Group.

BACKGROUND: Diffuse alveolar hemorrhage is a frequent complication of treating malignancies with high-dose chemotherapy and bone marrow transplantation and is associated with very high mortality. This disorder's association with pulmonary inflammation, its coincidence with marrow recovery, and the usefulness of corticosteroids for treating other pulmonary hemorrhage syndromes provided the rationale for this study. METHODS: We retrospectively studied 65 episodes of diffuse alveolar hemorrhage that has occurred in 63 of 603 consecutively treated patients who had undergone high-dose chemotherapy with bone marrow transplantation. Patients were divided into three groups according to the therapy they had received for diffuse alveolar hemorrhage: supportive therapy alone (n = 12); low-dose corticosteroids (30 mg or less of methylprednisolone or its equivalent; n = 10); and high-dose corticosteroids (more than 30 mg methylprednisolone or its equivalent; n = 43). The primary outcome measures were overall survival and survival to hospital discharge, occurrence of respiratory failure requiring intubation, and development of infections subsequent to the diagnosis of diffuse alveolar hemorrhage. RESULTS: Overall survival at the end of the follow-up period was significantly higher for the high-dose corticosteroid group compared with the supportive therapy group (P = 0.005); however, treatment with low-dose steroids did not increase survival over supportive therapy alone (P = 0.198). In addition, survival to discharge was significantly increased for the high-dose group compared with the other two groups combined (33% versus 9.1%, P = 0.038). Respiratory failure after the diagnosis of diffuse alveolar hemorrhage developed in only 12 of the 22 unintubated patients in the high-dose group compared with 9 of the 10 initially unintubated patients in the other two groups (P = 0.056). Although the incidence of infections was high (40%) subsequent to diffuse alveolar hemorrhage, neither high-dose nor low-dose corticosteroid treatment significantly increased the risk of infections (P > 0.4, all comparisons). CONCLUSIONS: In this study, high-dose corticosteroid therapy for diffuse alveolar hemorrhage related to bone marrow transplantation was associated with improved total survival and survival to hospital discharge, and decreased development of respiratory failure in these patients. These results suggest the therapy is beneficial, and further prospective studies are warranted to verify the effectiveness of the treatment.

Adult↗

Airborne fungal spore monitoring in a protective environment during hospital construction, and correlation with an outbreak of invasive aspergillosis.

OBJECTIVE: Evaluate aerobiological monitoring for fungal spores during hospital construction and correlate results with an outbreak of invasive aspergillosis (IA). DESIGN: Prospective air sampling for molds was done using the gravity air-settling plate (GASP) method. SETTING: A university medical center special care unit consisting of single-patient rooms with high-efficiency particulate air filtration under positive pressure. PATIENTS: Five neutropenic patients who subsequently developed IA. RESULTS: Four of the five patients with IA were housed in rooms adjacent to a construction staging area. Aerobiological monitoring detected an increase in the number of airborne fungal spores including Aspergillus species in these rooms; however, increased counts preceded IA diagnosis by 1 to 7 days in only three of the five patients. Swab cultures of the exhaust vents within each room confirmed results from air-settling plates. Follow-up monitoring, using the GASP method, demonstrated that control procedures were effective in reducing air mold contamination. CONCLUSION: The GASP method, although able to demonstrate that infection control measures reduced mold contamination of the air, was insensitive to detect levels of mold contaminates in time to prevent IA.

Air Microbiology↗

Incidence and characterization of secondary myelodysplastic syndrome and acute myelogenous leukemia following high-dose chemoradiotherapy and autologous stem-cell transplantation for lymphoid malignancies.

PURPOSE: To analyze the risk of developing myelodysplastic syndrome (MDS) or acute myelogenous leukemia (AML) following autologous bone marrow transplantation (ABMT) or peripheral stem-cell transplantation (PSCT) and to determine the impact on failure-free survival (FFS). PATIENTS AND METHODS: Patients underwent ABMT or PSCT for the treatment of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) at the University of Nebraska Medical Center. For those patients who went on to develop MDS/AML, controls were selected and a case-control-within-a-cohort study undertaken. RESULTS: Twelve patients developed MDS or AML a median of 44 months following ABMT/PSCT. The cumulative incidence (P = .42) and the conditional probability (P = .32) of MDS/AML were not statistically different between HD and NHL patients. Age greater than 40 years at the time of transplant (P = .05) and receipt of a total-body irradiation (TBI)-containing regimen (P = .06) were predictive for developing MDS/AML in patients with NHL. CONCLUSION: There is an increased risk of MDS/AML following ABMT/PSCT for lymphoid malignancies. NHL patients age > or = 40 years at the time of transplant and who received TBI are at greatest risk.

Adult↗

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↗