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Biomedical subjects

F B Petersen

Publications and source records attributed to F B Petersen.

At least 37 records · Page 2Linked to original sources
PubMed1993

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↗
PubMed1993

Autologous marrow transplantation for patients with acute myeloid leukemia in untreated first relapse or in second complete remission.

PURPOSE: This study compares outcomes of autologous bone marrow transplantation (ABMT) in patients with acute myeloid leukemia (AML) in untreated first relapse (REL1) or in second complete remission (REM2). PATIENTS AND METHODS: Forty-seven patients with AML in REL1 (n = 21) or in REM2 (n = 26) were treated with busulfan (BU) and cyclophosphamide (CY) with or without total-body irradiation (TBI) followed by ABMT. All REL1 patients and four REM2 patients had marrow stored during first remission (REM1). Twenty-seven had marrow stored with and 20 without treatment in vitro with 4-hydroperoxycyclophosphamide (4-HC). Eighteen patients received BU and CY and 29 received BU, CY, and TBI. REL1 patients relapsed within a median of 9 months (range, 2 to 26) after marrow harvest and were transplanted a median of 30 days (range, 9 to 87) from detection of relapse. RESULTS: With a median follow-up of 2.1 years (range, 0.4 to 5.3), 19 patients survive in remission (10 of 21 in REL1; nine of 26 in REM2). The actuarial probabilities of relapse-free survival at 2 years for patients transplanted in REL1 and REM2 were 45% +/- 22% and 32% +/- 18%, respectively (P = .33). The corresponding probabilities of relapse were 30% +/- 26% and 44% +/- 23%, respectively (P = .45). No conclusions could be drawn about the benefits of adding TBI to BU plus CY. There were no significant differences in neutrophil or platelet recovery or in posttransplant probabilities of relapse and nonrelapse mortality between patients who received marrow treated or not treated with 4-HC. CONCLUSION: These results suggest that ABMT may produce long-term leukemia-free survival in approximately one third of patients with AML in REL1 or in REM2. There is no apparent clinical advantage in attempting to obtain second remissions in relapsed patients before ABMT if marrow has been cryopreserved during REM1. Although a strategy of transplantation in REL1 has advantages for the patient, such an approach involves the storage of marrow, which may not be used, and is impractical without the coordinated support of the treating physician, the patient, and the marrow transplant center.

Acute Disease↗
PubMed1993

Autologous bone marrow transplantation for acute lymphoblastic leukemia.

Between December 1979 and February 1991, 89 patients with ALL received autologous BMT. Median patient age was 18.4 years. Ten patients were in first remission, 52 were in second or greater remission and 27 were in relapse at the time of transplant. Conditioning regimens utilized chemotherapy alone (5 patients) or in combination with 10-15.75 Gy total body irradiation (84 patients). Disease-free survival at 1 year is 50% for patients transplanted in first remission, 27% for those in > or = second remission and 8% for patients in relapse. Pre- and post-transplant variables were evaluated in univariate and multivariate analyses for their effect on survival and relapse. Factors significantly associated with improved survival were being transplanted in first remission and achieving a self-sustained platelet count > or = 20 x 10(9)/l in a shorter period of time. A decreased relapse rate after transplant was associated with a lower white blood count at diagnosis, being transplanted in first remission and not being transplanted in relapse.

Adolescent↗
PubMed1993

Interleukin-2 with or without lymphokine-activated killer cells as consolidative immunotherapy after autologous bone marrow transplantation for acute myelogenous leukemia.

IL-2 with or without autologous lymphokine-activated killer (LAK) cells, administered early after ABMT for AML may eradicate residual disease and reduce relapses. This paper reports 14 patients who received IL-2 or IL-2 plus LAK cells after ABMT for AML in first relapse or at a later stage, in two separate trials. Patients with AML in first relapse (n = 9), second CR (n = 3) or second relapse (n = 2) underwent ABMT after busulfan (BU), CY and total body irradiation (n = 11) or BU/CY alone (n = 3), with marrow that was (n = 6) or was not (n = 8) purged with 4-HC. In a previously-reported Phase I trial, eight patients received IL-2 (Roche) by continuous infusion at 0.3-3.0 x 10(6) U/m2/day x 5 days and, after 6 days of rest, 0.3 x 10(6) U/m2/day x 10 days. In a subsequent trial, five patients received IL-2 at 3.0 x 10(6) U/m2/day x 5 days, underwent leukapheresis for 3 days and received their LAK cells plus IL-2 (0.3 x 10(6) U/m2/day x 10 days). A sixth patient received only 2 days of IL-2, developed sepsis and died of multiorgan failure. All other patients had mild to moderate toxicity which was reversible. All patients developed neutrophilia, lymphocytosis and thrombocytopenia. IL-2 with or without LAK therapy was initiated 21-91 days (median 51 days) after ABMT. Severe thrombocytopenia (< 10 x 10(9)/l) occurred during the apheresis days.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Consequences of cryopreserving first remission autologous marrow for use after relapse in patients with acute myeloid leukemia.

Ninety-eight patients with AML had marrow harvested and cryopreserved at a median of 6 months (range 1-36 months) after achieving first CR with the intent of performing an ABMT at the first sign of relapse. Thirty-three of the 98 patients have not relapsed and 32 survive at a median of 64 months (range 10-105 months) after marrow storage. Sixty-five of the 98 patients relapsed at a median of 7 months (range 1-53 months) after marrow storage. The survival at 2 and 4 years for the 65 patients who relapsed was 22% and 8% respectively. Sixteen of 24 patients treated initially with chemotherapy were ultimately transplanted and two are surviving 21 and 41 months following ABMT and allogeneic marrow transplant respectively. There were no survivors among the eight patients treated with chemotherapy who were not transplanted. Thirty-eight of the 65 patients who relapsed proceeded directly to ABMT without attempts at remission induction, and eight survive disease-free 15-114 months following ABMT. One of the first 17 patients treated with cyclophosphamide and total body irradiation survives without relapse. The probabilities of relapse-free survival, non-relapse mortality, and relapse for the 17 most recent patients prepared with busulfan-containing regimens were 41%, 39% and 32% respectively. Surviving patients had longer first remissions (p = 0.08) and lower peripheral blood blast counts at the time of transplant (p = 0.02) when compared with patients who died. These data suggest that ABMT in untreated first relapse is a reasonable approach for the treatment of patients with AML who relapse.

Adolescent↗
PubMed1992

Marrow transplantation following escalating doses of fractionated total body irradiation and cyclophosphamide--a phase I trial.

Thirty-six patients with advanced hematologic malignancy were entered into a Phase I study designed to define the maximum tolerated dose of unshielded total body irradiation delivered from dual 60 Cobalt sources at an exposure rate of 8 cGy/min and given in fractions twice daily for total doses ranging from 12 Gy to 17 Gy. All patients received cyclophosphamide, 120 mg/kg administered over 2 days before total body irradiation. Allogeneic marrow was infused from HLA-identical siblings (n = 29) or one locus HLA incompatible family members (n = 3); three patients received cryopreserved autologous marrow and one patient received syngeneic marrow. The maximum tolerated dose of total body irradiation given as 2 Gy fractions twice a day was 16 Gy. One of eight patients receiving 12 Gy, none of four receiving 14 Gy, three of 20 receiving 16 Gy, and two of four receiving 17 Gy developed severe (Grade 3-4) regimen-related toxicity. The primary dose limiting toxicity was pneumonitis, followed by veno-occlusive disease of the liver, renal impairment, and mucositis. Five patients (14%) are alive, four disease-free 798-1522 days posttransplant. Twenty (56%) relapsed posttransplant. Further investigation of regimens containing 16 Gy of hyperfractionated total body irradiation is warranted to assess anti-tumor efficacy.

Adolescent↗
PubMed1992

Long-term survival from respiratory failure after marrow transplantation for malignancy.

Respiratory failure was measured as the institution of assisted mechanical ventilation for hypoxemic (oxygenation) or hypercarbic (ventilatory) failure after marrow transplantation. There were 348 (23%) marrow recipients who required mechanical ventilation for an average of 8 days (median, 5; range, 1 to 45). The average onset of mechanical ventilation was 39 days (median, 22; range, 0 to 172) after transplantation. Factors previously found to be associated with mechanical ventilation were tested in a Cox proportional hazards model. Older age, active malignancy at time of transplantation, and donor-recipient marrow HLA-non-identity were independent risks for assisted mechanical ventilation after marrow transplantation. Twenty-one percent (n = 72) of the marrow recipients receiving assisted mechanical ventilation for respiratory failure were extubated. Four percent (n = 15) were discharged from the hospital, and 3% (n = 10) survived 6 months after transplantation. All of these survivors were physically functional. Three had mild chronic respiratory symptoms and restrictive or obstructive airflow defects 1 yr after transplantation. Respiratory failure requiring assisted mechanical ventilatory support occurs in 23% of marrow recipients and is associated with functional survival at 6 months in 3%. Older age, active malignancy at time of transplantation, and donor-recipient marrow HLA-non-identity are risk factors for subsequent respiratory failure. In view of the poor prognosis associated with respiratory failure, these factors should be considered when counseling patients and families regarding this mode of treatment.

Adolescent↗
PubMed1992

Allogeneic marrow transplantation during untreated first relapse of acute myeloid leukemia.

PURPOSE: The purpose of this report was to review the Seattle experience in bone marrow transplantation (BMT) for acute myeloid leukemia (AML) during untreated first relapse. PATIENTS AND METHODS: Through 1990, 126 patients were transplanted during untreated first relapse of AML. Several preparative regimens were used, two of which involved more than 20 patients. Regimen 1 (29 patients) consisted of cyclophosphamide (CY) 120 mg/kg and 15.75 Gy of fractionated total-body irradiation (TBI) with methotrexate (MTX) given intermittently during a 102-day period to prevent graft-versus-host disease (GVHD). Regimen 2 (22 patients) consisted of the same CY and TBI treatment and a combination of MTX and cyclosporine (CSP) for GVHD prophylaxis. The remaining 75 patients were treated with 17 other transplant regimens. Outcome was compared for patients who were treated with regimen 1, regimen 2, and any other regimen. RESULTS: The 5-year probabilities of relapse-free survival (RFS), relapse, and nonrelapse mortality for 126 patients were .23, .57, and .44, respectively. With regimen 1, relapse (.26) was significantly less than for regimen 2 (.70; P = .004) or any other regimen (.76; P = .004). Regimen 1 patients developed more acute GVHD (.67) than regimen 2 patients (.26; P = .02) or patients on other regimens (.41; P = .02), and had increased nonrelapse mortality. Nevertheless, regimen 1 patients had a significantly higher 3-year RFS (.38) than those treated with regimen 2 (.18; P = .04) or any other regimen (.20; P = .05). CONCLUSIONS: For patients who received 120 mg/kg CY and 15.75 Gy TBI, relapse incidence was less and survival was better after GVHD prophylaxis with MTX alone than after a combination of MTX and CSP, despite a significantly higher incidence of acute GVHD. The results of treatment with regimen 1 justify future studies of the optimal timing of allogeneic BMT in the treatment of patients with AML.

Acute Disease↗
PubMed1992

Phase I study of busulfan and cyclophosphamide in preparation for allogeneic marrow transplant for patients with multiple myeloma.

PURPOSE: To study the toxicity and potential efficacy of busulfan (BU) and cyclophosphamide (CY) as a conditioning regimen before allogeneic bone marrow transplantation (ABMT) in patients with multiple myeloma (MM). PATIENTS AND METHODS: Twenty patients with MM underwent conditioning, which was followed by ABMT from 16 HLA-identical donors, three one-antigen-mismatched donors, and one HLA A, B, D-identical unrelated donor. Four levels of BU plus CY were evaluated. RESULTS: Severe regimen-related toxicity occurred in two of five patients who received BU 16 mg/kg and CY 120 mg/kg, in none of the four patients who received BU 14 mg/kg and CY 120 mg/kg, in one of eight patients who received BU 14 mg/kg and CY 147 mg/kg, and in two of three patients who received BU 14 mg/kg and CY 174 mg/kg. Twelve of 15 (80%) assessable patients achieved a complete remission with the disappearance of M-protein and the return of normal marrow morphology. Ten patients died of complications related to the ABMT, and two patients died of progressive or relapsed MM. Overall, eight of 20 patients were alive; seven (35%) were in complete remission 190 to 1,271 days after ABMT. CONCLUSIONS: The maximum-tolerable dose given in this setting was BU 14 mg/kg and CY 147 kg/mg. These results suggest that this regimen may have significant antimyeloma activity. Further phase II studies are warranted.

Adult↗
PubMed1992

Marrow transplantation for treatment of multisystem progressive Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) embraces disorders characterized by the presence of marrow-derived abnormal Langerhans cells. A small number of patients with multisystem disease, vital organ dysfunction and rapid disease progression are considered to have a poor prognosis despite various treatments. Antiproliferative and immunosuppressive therapy, in combination with marrow transplantation, could be the appropriate treatment for these poor-prognostic patients. Four patients with progressive LCH were treated with high dose chemotherapy and fractionated total body irradiation followed by either an allogeneic (n = 2) or autologous (n = 2) marrow graft. Two of them are alive and have been disease free for almost 2 and 4 years after marrow grafting, respectively. One of the two survivors is the recipient of an allogeneic and the other of an autologous marrow graft. Two patients died, one of intrapulmonary hemorrhage 14 days after transplantation with active disease at autopsy, and the other of relapse of the original disease 355 days after marrow grafting. For patients with multisystem progressive LCH, allogeneic and autologous marrow transplantation may offer an opportunity for long-term remission and disease-free survival.

Adolescent↗
PubMed1992

Etoposide, cyclophosphamide and fractionated total body irradiation as a preparative regimen for marrow transplantation in patients with advanced hematological malignancies: a phase I study.

Thirty-seven patients with advanced hematologic malignancy were entered into a phase I study designed to define a maximum tolerable dose (MTD) of etoposide (VP-16) and cyclophosphamide (CY) combined with 12 Gy fractionated total body irradiation (TBI) as preparation for marrow transplantation from an HLA-identical sibling (n = 13) or with cryopreserved autologous marrow (n = 24). Dose levels ranged from 36 mg/kg of VP-16 combined with 67 mg/kg of CY to 52 mg/kg of VP-16 combined with 103 mg/kg of CY followed by 12 Gy TBI. The MTD for allogeneic marrow recipients was 36 mg/kg of VP-16 + 52 mg/kg of CY followed by 12 Gy TBI and for autologous marrow recipients 44 mg/kg of VP-16 + 103 mg/kg CY followed by 12 Gy TBI. Pulmonary and liver toxicities were dose limiting. All of 31 evaluable patients transplanted in relapse achieved a complete remission. However, in all but three of these patients the disease relapsed 28-899 (median 110) days post-transplant. Currently, six of 24 autologous marrow recipients are surviving, three in remission 256, 340 and 764 days post-transplant. None of 12 allogeneic marrow recipients have survived. In conclusion, a preparative regimen combining 44 mg/kg of VP-16 + 103 mg/kg CY followed by 12 Gy TBI is well tolerated by autologous marrow recipients and 36 mg/kg VP-16 + 67 mg/kg CY followed by 12 Gy TBI is well tolerated by allogeneic marrow recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Successful allogeneic bone marrow transplantation in a 6.5-year-old male for severe aplastic anemia complicating orthotopic liver transplantation for fulminant non-A-non-B hepatitis.

We report the case of a 6.5-year-old male who received an unrelated orthotopic liver transplant for hepatic failure and encephalopathy following non-A-non-B hepatitis and subsequently developed severe aplastic anemia. For treatment of his aplastic anemia, he received a successful marrow transplant from his 9-year-old genotypically HLA-identical sister following conditioning with cyclophosphamide 200 mg/kg and anti-thymocyte globulin 90 mg/kg. Significant veno-occlusive disease of the liver and graft-versus-host disease did not occur. The patient remains alive without clinical chronic active hepatitis or need for blood product therapy. His hematocrit is 36%, white blood cell count 9.7 x 10(3)/mm3, and platelet count 1.7 x 10(5)/mm3 almost 2 years after marrow transplantation.

Anemia, Aplastic↗
PubMed1991

Toxicity and immunomodulatory effects of interleukin-2 after autologous bone marrow transplantation for hematologic malignancies.

Autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies is associated with high relapse rates. Interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells represent a potentially non-cross-resistant therapeutic modality that might prevent or delay relapses if used early after ABMT at a time when the tumor burden is minimal. However, high-dose chemoradiotherapy and ABMT might increase patients' susceptibility to IL-2 toxicity, and might interfere with immunologic responses to IL-2 in vivo. Therefore, to determine safety, tolerance, and immunomodulatory effects of IL-2 therapy early after ABMT, IL-2 was administered by continuous intravenous infusion to 16 patients 14 to 91 days (median, 33) after ABMT for acute leukemia, lymphoma, or multiple myeloma. Patients were sequentially assigned to escalating IL-2 "induction" doses (0.3 to 4.5 x 10(6) U/m2/d, days 1 to 5), and all patients received a nonescalating IL-2 "maintenance" dose (0.3 x 10(6) U/m2/d, days 12 to 21). Most patients exhibited mild to moderate fever, nausea, diarrhea, and/or skin rash with IL-2 infusions. The maximum tolerated "induction" dose was 3.0 x 10(6) U/m2/d; dose-limiting toxicities were hypotension and thrombocytopenia. All toxicities reversed on stopping the IL-2 infusions, and all patients completed "maintenance." Postinfusion lymphocytosis was exhibited by patients at all IL-2 dose levels. With the higher IL-2 doses, increased percentages of patients' PBMC expressed CD16 and CD56, with augmented lysis of K562 and Daudi, reflecting the induction of natural killer and circulating LAK effector activities. Increased LAK precursor activity was exhibited by patients at all IL-2 dose levels. Thus, the IL-2 therapy regimen was safely tolerated after ABMT, and pronounced immunomodulatory effects were observed with the higher IL-2 doses. These studies support the planned use of IL-2 and LAK cells after ABMT in an attempt to reduce relapses of advanced hematologic malignancies.

Adolescent↗
PubMed1991

Allogeneic marrow transplantation in patients with chronic myeloid leukemia in the chronic phase: a randomized trial of two irradiation regimens.

A randomized trial was performed to compare two regimens of total body irradiation in patients with chronic myeloid leukemia treated by allogeneic marrow transplantation while in the chronic phase. All patients received cyclophosphamide 120 mg/kg followed by total body irradiation and marrow from HLA-identical siblings. Cyclosporine and methotrexate were used for prophylaxis against acute graft-versus-host disease. Fifty-seven patients were randomized to receive 2.0 Gy fractions of irradiation daily for 6 days and 59 were randomized to receive 2.25 Gy fractions daily for 7 days. The probabilities of relapse at 4 years were 0.25 for the 12.0 Gy group and 0.00 for the 15.75 Gy group (P = .008). The actuarial probabilities of survival and relapse-free survival at 4 years were 0.60 and 0.58 among the patients who received 12.0 Gy compared with 0.66 and 0.66 for those who received 15.75 Gy. The 4-year probabilities of transplant-related mortality were 0.24 and 0.34 respectively (P = .13) while the probability of moderate to severe acute graft-versus-host disease was 0.33 for the 12.0 Gy group and 0.44 for the 15.75 Gy group (P = .15). The lower relapse probability in the patients receiving the higher dose of total body irradiation did not result in improved survival because mortality from causes other than relapse was increased.

Adult↗
PubMed1991

Busulfan and cyclophosphamide as a preparative regimen for bone marrow transplantation in patients with prior chest radiotherapy.

In a previous study, we reported that patients with hematologic malignancies who had received prior chest radiotherapy had a 32% risk of developing fatal interstitial pneumonia (IP) when prepared for bone marrow transplantation (BMT) with a regimen containing total body irradiation (TBI). To determine if avoidance of TBI would lessen the incidence of fatal IP, 37 patients who had received prior chest radiotherapy in excess of 2000 cGy were prepared with busulfan (BU, 4 mg/kg x 4 days) and cyclophosphamide (CY, 60 mg/kg x 2 days) followed by autologous (n = 15) or allogeneic (n = 22) BMT. Thirty-five of these patients had recurrent or refractory hematologic malignancies and most were heavily pretreated. Results were compared with the group of similar patients (n = 25) previously treated at our institution with a CY/TBI conditioning regimen. Among those treated with BU/CY, two patients (5%) developed fatal interstitial pneumonia, 12 (32%) died of other transplant related toxicities and 13 (35%) died of relapse. Seven (19%) patients remain alive and well. Among those treated with CY/TBI, eight (32%) died of pneumonia, six (24%) died of relapse, nine (36%) died of other causes and two (8%) remain alive and well. The 5% incidence of fatal interstitial pneumonitis in the chemotherapy conditioned group was significantly less than the 32% incidence in the previously treated CY/TBI group (p = 0.005). However, long-term survival and relapse probabilities were not significantly better than seen previously with CY/TBI, although a trend towards improved survival was observed in the BU/CY group. Avoidance of TBI appeared to lower the incidence of fatal pneumonitis in patients with prior chest radiotherapy.

Adolescent↗