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F R Dunphy

Publications and source records attributed to F R Dunphy.

32 records · Page 2Linked to original sources
PubMed1994

High-dose therapy with stem cell support in solid tumors.

We describe some issues of ongoing studies and results in metastatic and high-risk breast cancer. Caution should be used to not over interpret the outcomes of these data given the patient selection. In other tumors with lesser developed studies, such as with ovarian cancer, non seminomatous germ cell tumors (NSGC), childhood sarcoma, melanoma and limited small cell carcinoma, promising outcomes in small phase II studies are identified and proposed or potential studies comparing high-dose therapy to conventional are outlined. High-dose therapy with either peripheral blood stem cell support (PBSC) or autologous bone marrow transplantation (ABMT) in Phase II studies on a diverse array of solid tumors shows exciting promise of long-term, disease-free survival. Comparative studies in early-stage patients are urgently needed to confirm these outcomes.

Breast Neoplasms↗
PubMed1994

Auer rod-like inclusions in adult common acute lymphoblastic leukemia.

We report a case of adult common acute lymphoblastic leukemia, defined by enzyme histochemistry and immunophenotypic analysis, which had rod-shaped cytoplasmic inclusions that on Wright's-stained peripheral blood smear resembled Auer rods. Electron microscopic analysis of a buffy coat preparation revealed that the inclusions were not characteristic of Auer rods, but rather that they were composed of concentric lamellar structures with no limiting membrane and were closely associated with the nuclear membrane. Therefore, the presence of Auer rod-like inclusions in blasts on a Wright's-stained peripheral blood smear does not preclude a diagnosis of acute lymphoblastic leukemia.

Adult↗
PubMed1994

Randomized study of growth factors post-peripheral-blood stem-cell transplant: neutrophil recovery is improved with modest clinical benefit.

PURPOSE: To evaluate the clinical value of growth factors (GFs) with peripheral-blood stem cells (PBSC) collected following mobilization with GFs, we randomized patients to receive or not to receive GFs following transplant. PATIENTS AND METHODS: Thirty-seven patients were apheresed after receiving the combination of granulocyte colony-stimulating factor (G-CSF) with granulocyte-macrophage colony-stimulating factor (GM-CSF) at doses of 10 micrograms/kg/d and 5 micrograms/kg/d, respectively, for 6 days before apheresis and during a median of 4 days of collections. One day after the infusion of autologous marrow and PBSC, patients were randomly assigned to receive no GFs or a combination of G-CSF (7.5 micrograms/kg/d) and GM-CSF (2.5 micrograms/kg/d), both as a 2-hour intravenous (i.v.) infusion twice per day until the neutrophil count was greater than 1,500/microL. RESULTS: The median days to recovery to an absolute neutrophil count (ANC) of 100/microL (9 v 11.5, P = .0005), 500/microL (10 v 16, P = .0004), or 1,000/microL (12 v 21, P = .0008) was shortened with the use of GFs, post-PBSC infusion. In addition, the duration of hospitalization was shorter (19 v 21 days, P = .0112) in the arm receiving GFs post-PBSC infusion. There was no significant difference between the two study arms in the duration of fever, documented septic episodes, or RBC or platelet transfusion requirements. CONCLUSION: Despite faster neutrophil recovery and shortened duration of hospitalization with GFs administered after PBSC transplantation, the measured clinical variables of febrile days, septic episodes, and transfusion requirements were similar between the study arms. The use of GFs post-PBSC transfusion is associated with a modest clinical benefit.

Adult↗
PubMed1994

Gastrointestinal disease in patients receiving salvage chemotherapy or bone marrow transplantation.

Thirty-three patients receiving either salvage chemotherapy or bone marrow transplantation with potential surgical illness related to gastrointestinal symptoms were identified. Sixty-nine percent of patients received salvage chemotherapy for either hematological (61%) or visceral malignancies (39%). Twenty-one percent of patients had a previous bone marrow transplant. Twenty-two (66%) had an absolute neutrophil count less than 10(3)/mm3. Ulcerative foregut disease (51%) and perianal disease (21%) were the most common disease entities identified. Esophagogastroduodenoscopy (79%) and anorectal examination under anesthesia (21%) provided the greatest diagnostic yield. The mean hospitalization was 21 days. Surgery was performed in 21% of patients, but was seldom required for abdominal pain or intestinal bleeding. Perianal disease was often chronic and required multiple operative procedures. Overall, a 27% mortality was found. Gastrointestinal disease in patients receiving salvage chemotherapy or bone marrow transplantation is usually manifested by bleeding and localized to the proximal gut, or related to perianal disease.

Antineoplastic Agents↗
PubMed1993

Tandem transplants in solid tumors: marrow versus peripheral stem cell transplant: peripheral blood cells as now practiced are not the whole answer.

We have performed sequential studies examining the modification of hematopoietic toxicity after the administration of high-dose cyclophosphamide, etoposide, and cisplatin (CVP). The sequential studies include a comparison of the influence of autologous bone marrow transplantation (ABMT) on hematopoietic recovery after CVP, with or without growth factors. These studies demonstrate a significant shortening of the duration of neutropenia with ABMT, but minimal impact on the number of infectious episodes, when compared to those not receiving ABMT. The addition of mobilized peripheral blood stem cells (PBSC) to ABMT followed by growth factor was found to enhance platelet recovery, but did not significantly further reduce the period of absolute neutropenia. Subsequent studies show that similar early hematopoietic recovery can be achieved by use of peripheral blood stem cells alone, pheresed following several days of subcutaneous administration of recombinant growth factors, but neutrophil recovery is more rapid with use of growth factor after PBSC infusion. Using the product of two phereses for each cycle of recovery appears to result in similar rates of hematopoietic engraftment after each cycle of CVP. In conclusion, the use of peripheral blood stem cells alone following sequential high dose CVP is associated with rapid neutrophil and platelet recovery. Caution should be exercised when using PBSC alone after high dose therapy, due to the lack of platelet recovery in some instances, which can be overcome by reinfusion of backup marrow. Thus, studies evaluating the role of PBSC after high dose therapy should continue.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Influence of mobilized peripheral blood cells on the hematopoietic recovery by autologous marrow and recombinant human granulocyte-macrophage colony-stimulating factor after high-dose cyclophosphamide, etoposide, and cisplatin.

Peripheral blood cells (PBC) can hasten hematopoietic recovery after high-dose chemotherapy. To determine if PBC apheresed after mobilization further enhance hematopoietic recovery over that achieved with autologous bone marrow (ABM) and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), 14 patients with metastatic solid tumors were supported by ABM and rhGM-CSF during the first course of high doses of cyclophosphamide, etoposide, and cisplatin (CVP) and 11 of these 14 patients by mobilized PBC with ABM and rhGM-CSF during the second CVP. Each patient served as his or her own control. Identical doses of CVP were administered in both courses: cyclophosphamide 5.25 g/m2, etoposide 1,200 mg/m2, and cisplatin 165 to 180 mg/m2. PBC were collected on day 10 after mobilization with cyclophosphamide (3 g/m2) intravenously (IV) on day 1, doxorubicin (50 mg/m2) as a continuous IV infusion over 48 hours starting day 2, and rhGM-CSF as a daily 4-hour IV infusion starting day 4 at 0.6 mg/m2 for 14 days. Comparing recovery in the 11 patients to receive two cycles of therapy, the median days to an absolute neutrophil count of 0.1 x 10(9)/L and 0.5 x 10(9)/L were not statistically significant between the two courses; neither was there a difference in the incidence of fever and bacteremia. The median number of days to platelet count of 0.02 x 10(12)/L unmaintained by platelet transfusion was 20 from marrow infusion for course 1 and 16 for course 2 (P = .059). The median number of days to a platelet count of 0.05 x 10(12)/L was significantly shortened: 24 and 19 days for courses 1 and 2, respectively (P = .045). Patients who received PBC required fewer number of platelet transfusions. Extramedullary toxicities were not different between the groups. Our finding of enhanced early recovery of platelets and reduced platelet transfusion requirement is in concordance with other studies.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Autologous bone marrow transplantation in solid tumors.

Recent studies in autologous bone marrow or peripheral blood transplantation in solid tumors are discussed. The toxicity and activity of high-dose cisplatin or carboplatin combined with etoposide and other drugs are described. The results of trials in nonseminomatous germ cell tumors, neuroblastoma, ovarian cancer, and brain tumors are detailed and discussed. The impressive antitumor activities noted in certain subgroups should lead to an early application of these strategies before drug resistance becomes prevalent.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Impact of autologous bone marrow infusion on hematopoietic recovery after high-dose cyclophosphamide, etoposide, and cisplatin.

Because of potential tumor contamination and inadequacy of current purging technique of bone marrow in patients with solid tumors, we investigated an alternative approach to high-dose therapy without autologous bone marrow (ABM) infusion. Three levels of nonmyeloablative doses of cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 165 mg/m2 (CVP) were administered to patients with metastatic solid tumors. Patients were randomized to ABM (n = 46) or no-ABM (NABM) (n = 46) infusion after CVP to study the impact of ABM on hematopoietic recovery, morbidity, and mortality. All patients had ABM harvested, underwent conventional chemotherapy, and then received CVP. Seventy-three patients received two courses of similar doses. The following were the median days to absolute neutrophil count (ANC) of 0.1 x 10(9)/L: for the ABM arm, 19, 21, and 19 and for the NABM arm, 23, 20, and 21 at levels 1, 2, and 3, respectively, during course 1 (P = .01, .80, and .01, respectively). During course 2, ANCs to 0.1 x 10(9)/L and 0.5 x 10(9)/L were attained significantly faster at levels 1 and 3 in the ABM arm. ANC to 1.0 x 10(9)/L was comparable in both arms. Incidence of infection and duration of fever were similar in both arms. Although mortality and the incidence of delayed hematopoietic recovery were more frequent in the NABM arm, this was not statistically significant. Platelet recovery was consistently prolonged in course 2 in both arms, with demonstrable benefit of ABM in course 2 when dose levels were collectively considered. We conclude that (1) ABM enhanced recovery of ANC to 0.1 x 10(9)/L; (2) ABM did not decrease the incidence of infections and the duration of fever; and (3) CVP can be safely given without ABM to carefully selected patients.

Adult↗
PubMed1990

Treatment of estrogen receptor-negative or hormonally refractory breast cancer with double high-dose chemotherapy intensification and bone marrow support.

We have used high-dose therapy followed by randomization to receive or not receive autologous bone marrow infusion in 58 stage IV breast cancer patients (all were estrogen receptor-negative [ER-] or primary hormonal refractory). Patients received a median of four courses of induction chemotherapy and if stable or responding received two courses of intensive therapy with cyclophosphamide 4.5 to 5.25 g/m2, etoposide 750 to 1,200 mg/m2, and cisplatin 120 to 180 mg/m2 (CVP). The complete remission (CR) rate after completion of the induction and intensive phases was 55%. Median progression-free interval from induction is 57 weeks with a projected 2-year progression-free survival of approximately 25%. Six of seven patients followed for greater than 2 years are still progression-free. Three favorable features predicted for improved progression-free survival are the following: (1) absent liver involvement, (2) absent soft tissue involvement, and (3) less than or equal to two disease sites (P values of .001, .013, and .048, respectively). Hormonal and menopausal status did not predict for progression-free survival. Major toxicities were infectious secondary to neutropenia, with a 93% incidence of fever and a 38% incidence of sepsis. The treatment-related mortality rate was 9%, with three infectious, one coronary, and one late hemorrhage-related death of unknown cause. Longer follow-up is still needed to truly evaluate the possibility of long-term disease-free survival, but further studies of this approach to high-dose intensification in poor prognostic groups of stage IV breast cancer appear warranted.

Adult↗
PubMed1990

Methylprednisolone, cyclosporine and methotrexate for prophylaxis of acute graft-versus-host disease.

Twenty-four patients were given the combination of methylprednisolone 100 mg i.v. on day 0, cyclosporine 2 mg/kg i.v. every 12 h starting on day -3 and methotrexate 5 mg/m2 on days 1, 3, and 6, then 10 mg/m2 on days 11 and 18 after allogeneic bone marrow transplantation for hematological malignancies for the prophylaxis of acute graft-versus-host disease. (GVHD). Methylprednisolone was given prior to the marrow infusion for its lympholytic effect. The methotrexate dose on days 1, 3, and 6 was half of that given in other studies to decrease the early toxicities. The outcome of this group is compared with patients transplanted before 1988 and given methotrexate alone, methotrexate with prednisone, or cyclosporine alone. There is no difference in relapse and survival between the groups at this time. The rate of engraftment and incidence of mucositis with the combination is not significantly different from the cyclosporine group. No patient developed greater than grade II acute GVHD with the combination. The probability of grade II or higher acute GVHD with the combination (14%) is significantly less than methotrexate, with or without prednisone or cyclosporine alone.

Adolescent↗
PubMedDate not supplied

Changes in quality-of-life scores in a population of patients treated for squamous cell carcinoma of the head and neck.

BACKGROUND: Quality of life levels fluctuate depending on treatment type and at various points throughout treatment. In patients with advanced head and neck cancer, quality of life is thought to be treatment dependent. The purpose of this study is to compare levels of patients self-reported quality of life across treatment. PATIENTS AND METHODS: Preliminary data presented here are based on 24 patients enrolled so far in an experimental organ-preservation protocol. The two treatment groups consist of one group treated with chemotherapy (paclitaxel and carboplatin) followed by radiation therapy and the second group which is treated with chemotherapy (paclitaxel and carboplatin) followed by surgery and postoperative radiation. Data is collected pretreatment and at uniform points throughout the course of treatment. RESULTS: Preliminary results suggest that quality of life is significantly higher in the nonsurgical group than in the surgical group at the last treatment point reported. Social distress/avoidance is also lower in the nonsurgical group. Because of the small number of patients represented in this study, results should be interpreted with caution and should be viewed as descriptive at this juncture. CONCLUSION: Quality of life seems to be preserved in patients who experience less invasive and disfiguring treatment, and who also have compromised eating and communication abilities. Data collection in this study is ongoing.

Antineoplastic Combined Chemotherapy Protocols↗
PubMedDate not supplied

Correlation of fine needle aspiration biopsy and fluoride-18 fluorodeoxyglucose positron emission tomography in the assessment of locally recurrent and metastatic head and neck neoplasia.

OBJECTIVE: Patients with primary head and neck neoplasia can present during follow-up with suspected recurrence, and both fine needle aspiration biopsy (FNAB) and fluoride-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan are available methodologies for evaluating these patients. Our objective was to retrospectively correlate patients who underwent both FNAB and FDG-PET scan in order to assess the possibility of recurrent neoplasia. STUDY DESIGN: The cytopathology files at Saint Louis University Health Sciences Center were retrospectively searched for patients with known primary head and neck malignancies beginning in 1995. Suspected recurrence and local metastases evaluated by both FNAB and FDG-PET scan were correlated. RESULTS: Twenty-eight patients received a combined total of 37 FNABs with concurrent FDG-PET scans. The majority of patients had primary oropharyngeal squamous cell carcinoma with intermixed, single cases of other primary head and neck neoplasms. Thirty of the 32 aspirates with recurrent or locally metastatic disease had combined positive findings by both FNAB and FDG-PET scan, yielding a sensitivity of 94%. One nonspecific and one negative FDG-PET scan came from a patient who had disease confirmed by FNAB. Five patients had negative findings by both methods that were supported by the subsequent clinical course. CONCLUSION: FNAB can provide confirmatory evidence of disease in a clinically suspicious abnormality with nonspecific FDG-PET results. FNAB and FDG-PET are highly sensitive for tumors in cases of clinically suspected recurrence and locally metastatic disease.

Biopsy, Needle↗