High-dose chemotherapy and autologous stem cell transplantation for breast cancer.
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Antineoplastic Agents↗
Biomedical subjects
C H Weaver
Publications and source records attributed to C H Weaver.
High-dose cyclophosphamide, carmustine, and etoposide followed by allogeneic bone marrow transplantation in patients with lymphoid malignancies who had received prior dose-limiting radiation therapy.
PURPOSE: To evaluate a high-dose chemotherapy regimen without total-body irradiation (TBI) followed by allogeneic (allo) bone marrow transplantation (BMT) in patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. PATIENTS AND METHODS: Fifty-six patients with non-Hodgkin's lymphoma (NHL, n = 26), Hodgkin's disease (HD, n = 17), or acute lymphoblastic leukemia (ALL, n = 13) with a history of previous radiation therapy were treated with cyclophosphamide (7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2; CBV) followed by allo BMT. RESULTS: Nine of 56 patients are alive and disease-free a median of 1,091 (range, 512 to 1,784) days post-transplant. The probabilities of transplant-related mortality, relapse, and event-free survival at 2 years for the entire group of 56 patients were .62, .59, and .17, respectively. Patients who received 600 mg/m2 of carmustine had a higher incidence of grade 3 or 4 regimen-related toxicities (RRTs) (14 of 22) than did patients who received 300 mg/m2 (12 of 33; P < .04), whereas there was no difference in relapse (.34 and .53, respectively, P = .73). Fourteen of 16 patients who received allo BMT for advanced disease (n = 12) or less-advanced disease (n = 4) but who were also eligible for auto BMT relapsed (n = 4) or died of transplant-related complications (n = 10). CONCLUSIONS: Allo BMT following a high-dose CBV regimen resulted in long-term disease-free survival in 17% of patients with lymphoid malignancies who had received prior dose-limiting radiotherapy. A high incidence of transplant-related complications, especially fatal idiopathic pneumonia syndrome (IPS) and a high relapse rate limited success. Morbidity and mortality associated with carmustine 600 mg/m2 were high and were not associated with a decrease in relapse. The number of patients in this study eligible for either allo or auto BMT was limited and precluded meaningful analysis of relative effectiveness.
Adolescent↗
Rapid engraftment after autologous transplantation utilizing marrow and recombinant granulocyte colony-stimulating factor-mobilized peripheral blood stem cells in patients with acute myelogenous leukemia.
This study was performed to determine whether peripheral blood stem cells (PBSCs) mobilized with recombinant granulocyte-colony stimulating factor (rhG-CSF) increase the tempo of granulocyte and platelet recovery when added to marrow in patients with acute myelogenous leukemia (AML) undergoing autologous bone marrow transplantation (BMT). Twenty six patients with AML had bone marrow harvested in first (n = 16) or second (n = 10) complete remission (CR) and cryopreserved. Patients received rhG-CSF alone (n = 20) or rhG-CSF following chemotherapy (n = 6). PBSCs were collected from 24 of the 26 patients a median of 7 (range 3-2130) days after marrow harvest. Two patients presumed to be in second CR did not have PBSCs collected because of early relapse. Fourteen patients in first CR (n = 3), second CR (n = 8) or first relapse (n = 3) proceeded to autologous BMT utilizing marrow + rhG-CSF-mobilized PBSCs. Engraftment parameters were compared with a historical group of 158 patients with AML who had received purged (n = 67) or unpurged (n = 91) autologous BMT without PBSCs. The median number of peripheral blood total nucleated and CD34+ cells collected from 24 patients was 19.55 x 10(8)/kg (range 1.83-54.83) and 5.59 x 10(6)/kg (1.23-34.79), respectively. All patients transplanted achieved a granulocyte level of > 0.5 x 10(9)/l with a median of 13 days (range 11-27 days) and platelets to 20 x 10(9)/l median 14 days (range 9-83 days).(ABSTRACT TRUNCATED AT 250 WORDS)
Acute Disease↗
Immunocytochemical analysis of tumor cells in pre- and post-culture peripheral blood progenitor cell collections from breast cancer patients.
We examined peripheral blood progenitor cell (PBPC) collections and CD(34+)-selected fractions cultured in PIXY321, a fusion protein comprising analog interleukin-3 (IL-3) and granulocyte-macrophage colony-stimulating factor (GM-CSF) domains, for the presence of contaminating tumor cells from 14 patients with advanced-stage breast cancer. Five of the 14 (36%) pre-culture PBPC specimens contained immunocyto-chemically (ICC)-detectable tumor cells using two different cocktails of monoclonal antibodies (mAbs). After 10 days in culture with PIXY321, the CD(34+)-selected fractions showed a median 23.6-fold expansion of hematopoietic cells. No ICC-positive tumor cells were detected in any post-culture specimens. We conclude that in vitro expansion of CD(34+)-selected PBPCs with PIXY321 can expand hematopoietic cell populations apparently without risk of expanding contaminating breast cancer cell populations.
Antibodies, Monoclonal↗
High-dose fractionated total-body irradiation, etoposide, and cyclophosphamide followed by autologous stem-cell support in patients with malignant lymphoma.
PURPOSE: To evaluate a high-dose treatment regimen of fractionated total-body irradiation (TBI), etoposide, and cyclophosphamide (Cy) followed by autologous stem-cell transplantation (ASCT) in patients with malignant lymphoma. PATIENTS AND METHODS: Fifty-three patients with non-Hodgkin's lymphoma (NHL; n = 43) or Hodgkin's disease (HD; n = 10) received 12.0 Gy of fractionated TBI, etoposide 60 mg/kg, and Cy 100 mg/kg followed by infusion of autologous hematopoietic stem cells. RESULTS: Thirty-one of 53 patients are alive a median of 643 (range, 177 to 1,144) days after transplant. The 2 year Kaplan-Meier (K-M) estimates of survival, event-free survival (EFS), and relapse for all 53 patients were 54%, 45%, and 43%, respectively. Sixteen of 24 patients with less advanced disease and 10 of 29 patients with more advanced disease survive free of disease for K-M estimates of EFS of 61% and 31%, respectively (P = .006). The K-M estimates of relapse were 34% for patients with less advanced disease and 53% (P = .05) for patients with more advanced disease. The K-M estimates of dying from causes other than relapse were 8% in patients with less versus 25% in patients with more advanced disease (P = .09). CONCLUSION: These data indicate that approximately 60% of patients transplanted early after failure of initial therapy for malignant lymphoma are projected to be disease-free more than 2 years after treatment with fractionated TBI, etoposide, and Cy and infusion of autologous hematopoietic stem cells. The transplant-related mortality rate is low and relapse is the main cause of treatment failure in patients with less advanced disease. For patients with more advanced disease, the K-M estimates of both transplant-related deaths (25%) and relapse (53%) remain major problems.
Adolescent↗
Lymphocyte content in peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor.
The effects of rhG-CSF on peripheral blood lymphocytes and lymphocyte populations in the apheresis product has been determined in 13 individuals (11 autografts and 2 normal donors) who had peripheral blood mononuclear cells (PBMCs) collected on days 3, 4, and 5 of administration of rhG-CSF 16 micrograms/kg/day x 5 days. The absolute number of CD34+ cells increased 9 and 25-fold from pretreatment levels after 4 and 5 days of rhG-CSF, respectively. All patients demonstrated an increase in CD3, CD4, CD8, CD19 and CD20 lymphocytes after 3 days of rhG-CSF with T lymphocytes increasing 1.5-2.0 times baseline by day 3 or rhG-CSF administration. All lymphocyte phenotypes returned to below pretreatment levels on days 4 and 5 of rhG-CSF administration. The ratio of CD4/CD8 lymphocytes was not affected by rhG-CSF. Collection of PBMCs on 3 consecutive days yielded a mean of 8.77 x 10(8) CD34 cells, 14.03 x 10(10) total nucleated cells and 3.17 x 10(10) CD3 lymphocytes. These data suggest that rhG-CSF mobilized PBMCs have approximately one log more T cells than marrow and the effect of rhG-CSF on the quantity and phenotype of lymphocytes is minimal. Strategies for coping with an increased incidence of GVHD, if it occurs, could include the utilization of both methotrexate and cyclosporine as immunoprophylaxis, selective T cell depletion or CD34 positive selection.
Adolescent↗
Effect of graft-versus-host disease prophylaxis on relapse in patients transplanted for acute myeloid leukemia.
Between November 1978 and September 1988, 184 patients with acute myeloid leukemia in first remission received marrow transplants from HLA-identical siblings after conditioning with 120 mg/kg of cyclophosphamide and 12.0 Gy fractionated total body irradiation. Patients received either cyclosporine (CYA, n = 59), methotrexate (MTX, n = 82), or MTX + CYA (n = 43 as graft-versus-host disease (GVHD) prophylaxis. The probabilities of grades II-IV acute GVHD after CYA, MTX or MTX+CYA were 0.43, 0.48 and 0.28, respectively (p = 0.06). The probability of non-relapse mortality was 0.53, 0.50 and 0.42 at 4 years in patients treated with CYA, MTX, or MTX + CYA, respectively. The probability of relapse was 0.24 in patients receiving CYA, 0.24 in patients receiving MTX and 0.44 in patients receiving MTX + CYA (p = 0.02). The probability of survival at 4 years was 0.54 with CYA, 0.51 with MTX and 0.45 with MTX + CYA. A multivariate analysis of risk factors for relapse examined age, WBC at diagnosis, blast count at diagnosis, percentage of marrow blasts, FAB subtype, the number of remission induction courses to achieve a remission, maintenance therapy, consolidation therapy, marrow cell dose, donor-recipient sex, GVHD prophylaxis regimen and isolation and decontamination in laminar airflow rooms. GVHD prophylaxis with MTX + CYA was independently significantly associated with an increased risk of relapse (relative risk 2.25, p = 0.01). Acute GVHD was associated with increased non-relapse mortality (RR = 3.58, p < 0.0001). The administration of MTX + CYA did not adversely affect survival because patients receiving this regimen experienced less mortality from causes other than relapse when compared with patients receiving either CYA or MTX alone.
Adolescent↗
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↗
Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor.
Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.
Adult↗
Follow-up report on the outcome of patients relapsing after autologous marrow transplantation for malignant lymphoma.
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Bone Marrow Transplantation↗
High-dose cyclophosphamide, carmustine, and etoposide followed by autologous bone marrow transplantation in patients with lymphoid malignancies who have received dose-limiting radiation therapy.
PURPOSE: To evaluate high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) in patients with lymphoid malignancy who had received prior radiation therapy. PATIENTS AND METHODS: Fifty-seven patients with non-Hodgkin's lymphoma (NHL; n = 23), Hodgkin's disease (HD, n = 32), or acute lymphoblastic leukemia (ALL; n = 2) with a history of previous radiation therapy were treated with cyclophosphamide (Cy; 7.2 g/m2), carmustine (300 mg/m2 or 600 mg/m2), and etoposide (2,400 mg/m2) (CBV) followed by ABMT. RESULTS: The projected 2-year probabilities of survival, event-free survival (EFS), and relapse were .31, .24, and .76, respectively. For patients with intermediate- and high-grade lymphoma and HD the probabilities were .27, .10, and .14 for EFS and .57, .90, and .77 for relapse. The probability of nonrelapse mortality in the first 100 days post-ABMT was 33%. Idiopathic pneumonia syndrome (IPS) was observed in no patients who received carmustine 300 mg/m2 and 23% of patients who received carmustine 600 mg/m2 (P = .05). Eight-three percent of patients who received mediastinal radiation therapy less than 3 months before transplant developed IPS, compared with 13% who received radiation therapy more than 3 months before transplant (P = .001). CONCLUSION: ABMT following high-dose CBV resulted in long-term disease-free survival in 25% of patients with lymphoid malignancies who had previously received dose-limiting radiation therapy. Fatal IPS and a high relapse rate were major factors limiting successful outcome following ABMT. The morbidity and mortality rates associated with the administration of carmustine 600 mg/m2 were prohibitively high, especially in patients who received mediastinal radiation immediately before ABMT, and were not associated with a decrease in post-ABMT relapse.
Adolescent↗
The effectiveness of single-dose metronidazole therapy for patients and their partners with bacterial vaginosis.
A randomized, placebo-controlled, double-blind clinical trial was performed to test the hypothesis that a 2-g single dose of metronidazole for male partners of women with bacterial vaginosis was more effective than placebo in improving cure rate and decreasing recurrence rate. In addition, the effectiveness of a 2-g single dose of metronidazole was compared with a seven-day course of 500 mg of metronidazole twice a day in patients with bacterial vaginosis. Statistically significant benefits of partner treatment were noted in the initial cure rate by Gram-stained smear criteria (P less than .01) and in percentage of women with symptoms eight weeks after initiating therapy (P less than .05). The seven-day course of metronidazole was superior to the single-dose regimen in the percentage of patients with clue cells and the percentage of patients with a positive "sniff" test at the first follow-up visit; however, differences in the initial cure rate assessed by clinical criteria and Gram-stained smear criteria were not statistically significant between the two patient treatment regimens. Recurrence rates by Gram-stained smear criteria between patient and partner treatment groups at five and eight weeks after initiation of treatment were also not significantly different between the two patient regimens. Single-dose metronidazole treatment of the sexual partner of women with bacterial vaginosis improves initial bacterial vaginosis cure rates. The seven-day course of metronidazole was not found by statistical analysis to be significantly superior to single-dose therapy when considering initial cure rates by clinical or Gram-stained smear criteria or recurrence rates.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Bacterial vaginosis.
Bacterial vaginosis (nonspecific vaginitis) is a polymicrobial, superficial vaginal infection caused by an increase in anaerobic organisms and a concomitant decrease in lactobacilli. Gardnerella vaginalis, once thought to be the sole etiologic agent, is probably one of several endogenous members of the vaginal flora that overgrow in women with bacterial vaginosis. Whether the growth of anaerobes or a primary decrease in lactobacilli is the initial pathogenic event remains unclear. Epidemiological studies have revealed that current or previous infections caused by Trichomonas organisms, increased sexual activity, and intrauterine device use are risk factors for this condition. Studies have indicated that bacterial vaginosis, previously thought to be a benign illness, is associated with some morbidity in pregnant women. Symptoms remain unreliable in the diagnosis of bacterial vaginosis. Diagnostic efficacy is best achieved by utilizing clinical signs. Assessment of cure is best accomplished by Gram stain, not clinical criteria. Metronidazole, 500 mg orally for seven days, remains the treatment of choice; however, a 2-g single dose of metronidazole represents a reasonable alternative if cost and compliance issues predominate in a clinical situation. Although a recent study supports the contention that treatment of the male sexual partner of women with bacterial vaginosis is effective, a general recommendation cannot be made with confidence on the issue of sexual partner treatment until other supporting work is done.
Bacterial Infections↗
Continuing education for emerging professions.
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Education, Continuing↗