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Biomedical subjects

G L Phillips

Publications and source records attributed to G L Phillips.

At least 145 records · Page 8Linked to original sources
PubMed1985

Treatment of metastatic malignant melanoma with intensive melphalan and autologous bone marrow transplantation.

Twenty patients with metastatic malignant melanoma were treated with melphalan (180-225 mg/m2 iv over 3 days) followed by re-infusion of previously harvested and cryopreserved autologous bone marrow. Granulocyte (greater than 500/microliter) and platelet (greater than 20,000/microliter) count recovery occurred a median of 14 days (range, 12-22) and 19.0 days (range, 12-28) after bone marrow transplantation, respectively. Three patients died due to hemorrhage or infection. One of these patients and another (who ultimately achieved a complete response), both with brain metastases, developed intralesional hemorrhage when the platelet count was only moderately reduced. Complete responses occurred in six patients and ranged from 4 to 14 months, with a median of 5 months. Six patients achieved a partial remission lasting 2-5 months. High-dose melphalan and autologous bone marrow transplantation are a promising therapy for patients with metastatic malignant melanoma.

Adult↗
PubMed1985

High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study.

High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.

Acute Disease↗
PubMed1984

Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow.

Twenty-seven patients with malignant lymphoma in whom primary chemotherapy had failed and the prognosis was poor were treated with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. The median time to recovery of more than 500 neutrophils per microliter and more than 10,000 platelets per microliter was 18 and 24 days, respectively. Complete remission was achieved in 15 patients (56 per cent), five of whom were in continuous remission at this writing 19 to 71 months after transplantation without further therapy and one of whom was alive in a subsequent remission at 20 months. Fifteen patients died of lymphoma, three of interstitial pneumonitis, two of sepsis, and one of congestive heart failure. This experience shows that intensive therapy and autologous-marrow transplantation can produce prolonged remissions in patients with malignant lymphoma in whom conventional chemotherapy has failed.

Adolescent↗
PubMed1984

Intensive chemotherapy, total body irradiation, and autologous marrow transplantation for chronic granulocytic leukemia-blast phase: report of four additional cases.

Four patients with Philadelphia chromosome (Ph1)-positive chronic granulocytic leukemia (CGL) in blast phase received cyclophosphamide, total body irradiation, and autologous marrow transplants using cryopreserved marrow from the stable phase. Two patients fully reestablished stable-phase leukemia that lasted for 26 and six months; the first patient developed transient Ph1-negative hematopoiesis after transplantation. Three patients eventually died of recurrent blast-phase leukemia. Previous studies using autologous marrow for CGL have reported an occasional long survivor, but incomplete engraftment and especially the rapid recurrence of blast-phase leukemia have been responsible for the overall poor results. The latter problem complicates even normal marrow transplantation, indicating the inadequacy of the current therapeutic regimens used for treating blast-phase leukemia and the possibility of improving results with more effective regimens and autologous marrow transplantation. Although it is unknown whether the reestablishment of Ph1-negative hematopoiesis after transplantation contributes to improved survival, this interesting phenomenon must be investigated further.

Adult↗
PubMed1983

Detection of postmenopausal women at risk for endometrial carcinoma by a progesterone challenge test.

Currently, there exists no convenient, inexpensive screening test for the detection of postmenopausal women at risk for developing adenocarcinoma of the endometrium. After the administration of a progesterone challenge test (PCT) to asymptomatic postmenopausal women, the presence or absence of withdrawal bleeding may aid in detecting premalignant lesions of the endometrium. Of 30 such women who had endometrial sampling followed by a PCT, 25 had no withdrawal bleeding and all had nonpathologic histology. Five patients exhibited withdrawal bleeding. Of these five, three had unsuspected adenomatous hyperplasia (p less than 0.001). It is concluded that a PCT may be a reliable screening test for detecting those women at greater risk for developing endometrial hyperplasia or adenocarcinoma.

Adenocarcinoma↗
PubMed1983

Intensive 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), NSC #4366650 and cryopreserved autologous marrow transplantation for refractory cancer. A phase I-II study.

One hundred forty-three patients with refractory cancer were treated with intensive BCNU (600-2850 mg/m2) and autologous marrow transplantation to determine the maximum tolerated dose and antitumor effects of this regimen. Recovery from severe pancytopenia in less than 4 weeks after transplantation occurred in 92.8% of evaluable patients, suggesting the efficacy of the autologous marrow in limiting the prolonged myelosuppression anticipated with intensive BCNU. Serious extramedullary toxicity was encountered at BCNU 1200 mg/m2, where a 9.5% incidence of fatal interstitial pneumonitis and a 3.0% incidence of fatal hepatic necrosis was observed. Higher BCNU doses, 1500 to 2850 mg/m2, were associated with a 35.3% incidence of fatal hepatotoxicity. Fatal encephalomyelopathy was encountered in two patients given BCNU 2250 and 2850 mg/m2. One patient who received the highest cumulative dose of BCNU (3450 mg/m2 in 2 courses) died of cardiac necrosis. Other serious extramedullary toxicities were not encountered, even in the 14 patients who survived from 1 to nearly 5 years after BCNU therapy. Antitumor responses occurred in 40.0% of evaluable patients; a dose effect could not be evaluated due to patient heterogeneity. The BCNU doses associated with acceptable toxicity, 600 to 1200 mg/m2, produced a 37.5% total and an 11.3% complete response (CR) rate, including five patients with prolonged CRs of 1 to nearly 5 years. Notable among the CRs was the 25.0% CR rate in previously untreated metastatic melanoma, and the production of CRs in malignant disease in the central nervous system (CNS) including melanoma, lung cancer, adenocarcinoma of unknown primary, acute leukemia and glioblastoma multiforme. It is concluded that augmented doses of BCNU can be given when autologous marrow transplantation is used to limit myelosuppression. Lung and liver toxicity prevent the use of BCNU doses greater than 1200 mg/m2; neurotoxicity, and perhaps cardiotoxicity, are manifestations of the highest doses used in this study. The antitumor activity of BCNU 600 to 1200 mg/m2 remains to be determined for most neoplasms; these results suggest improved results in melanoma and CNS malignancy compared to conventional-dose BCNU therapy.

Adolescent↗
PubMed1983

Aspiration does not influence interpretation of bone marrow biopsy cellularity.

Alterations of hematopoietic cellularity have been described in preaspirated marrow biopsy specimens. In this study, the extent of aspiration-induced artifacts was evaluated by comparing preaspirated and nonaspirated marrow biopsy specimens obtained from individual patients. Fourteen patients (28 specimens) were studied. One specimen, containing only cortical bone, was not evaluable. Of the remaining specimens, estimation of hematopoietic cellularity was not disturbed by preaspiration. Provided an adequate sized biopsy specimen is obtained, this study demonstrates that aspiration can be performed immediately before biopsy without altering the interpretation of hematopoietic cellularity. This makes a simple one-step aspiration-biopsy technic possible, without loss in diagnostic accuracy. In addition, without the need for repositioning to a different site on the iliac crest, patient tolerance should be improved.

Biopsy, Needle↗
PubMed1983

Intensive melphalan chemotherapy and cryopreserved autologous bone marrow transplantation for the treatment of refractory cancer.

Thirty-three adult and pediatric patients with refractory malignancies were treated with escalating doses of melphalan (120-225 mg/m2 IV over 3 days) followed by reinfusion of previously harvested and cryopreserved autologous marrow. The hematological and nonhematological toxicities and the therapeutic effects of this regimen were evaluated. Increasing doses of melphalan did not alter the rate of decline nor the recovery of peripheral blood counts. Granulocyte (greater than 500/microL) and platelet count (greater than 20,000/microL) recovery occurred in a median of 19 (range 12-54) and 24 (range: 12-54) days after bone marrow transplantation, respectively. Five patients experienced severe infection, three of which were fatal, and one patient died due to thrombocytopenic hemorrhage. Toxicity to the gastrointestinal system was dose limiting. The maximum tolerated dose of melphalan was 180 mg/m2; only three of 24 patients experienced severe stomatitis, esophagitis, and diarrhea at this level or less, while eight of nine patients at 225 mg/m2 were affected (p less than 0.005). Administration of cyclophosphamide (300 mg/m2 IV) 1 week before melphalan therapy did not reduce the incidence of severe gastrointestinal toxicity. Plasma melphalan concentration peaked 30-60 min after infusion (4.8-11.5 micrograms/mL) but declined rapidly. Cerebrospinal fluid concentration was 10% of the corresponding plasma concentration and was undetectable at 3 hours. Antitumor responses occurred in nine of 13 patients with malignant melanoma (five complete and four partial remissions), and ranged 2-12+ months with a median of 5 months. Four of six neuroblastomas demonstrated responses (three complete and one partial remission( lasting a median of 7.5 (range: 5-10) months. Other tumors in which this regimen had activity included breast cancer and Ewing's sarcoma. The overall response rate for the 33 patients was 30% complete remissions (10 patients) and 21% partial remissions (seven patients). High dose melphalan and autologous bone marrow transplantation is a promising therapy for patients with malignancies for which no effective treatment is known or for patients whose cancer is refractory to conventional therapeutic agents.

Adolescent↗
PubMed1983

High-dose cytosine arabinoside therapy for refractory leukemia.

Fifty-seven patients with refractory acute leukemia were treated with high-dose cytosine arabinoside to establish the maximum tolerated dose and duration and to determine the antileukemic activity. The maximum tolerated regimen was found to be 3 g/sq m every 12 hr for 6 days. At this dose, nonhematologic toxicity was limited to conjunctivitis in approximately half of the patients, and liver toxicity (transient elevations in transaminase, alkaline phosphatase, or bilirubin) was frequently observed, but neither was dose-limiting. Extending the duration of treatment to 8 days resulted in excessive diarrhea and skin toxicity (painful erythema with bullae), while increasing the dose to 4.5 g/sq m q. 12 hr for 6 days resulted in severe cerebellar toxicity. Myelosuppression was severe, but was not related to the intensity of treatment; granulocyte recovery occurred a median of 28 days (range 22-40 days) after initiating therapy, and platelet recovery occurred after a median of 25 days (range 16-41 days). Antileukemic activity was evaluable in the 46 patients who survived at least 3 wk. Complete remissions were obtained in 1 of 6 patients with chronic myelogenous leukemia (CML) in accelerated phase and 1 of 3 acute lymphoblastic leukemia (ALL) patients. A more detailed analysis of response was possible for the 37 evaluable patients with acute nonlymphoblastic leukemia: 70% of these patients responded, with 51% complete remissions. The median unmaintained response was 4 mo (range 2-26+ mo). The complete response rate was higher in patients who received at least 12 doses of high-dose cytosine arabinoside compared to shorter regimens [17/28 (61%) versus 2/9 (22%), p less than 0.05]. Resistance to cytosine arabinoside in conventional doses was documented in 11 patients, 5 of whom responded (2 complete remissions) to high-dose regimens. We conclude that high-dose cytosine arabinoside in the maximally tolerated regimen of 3 g/sq m every 12 hr for 6 days has substantial antileukemic activity in patients refractory to standard therapy. Durable unmaintained remissions can be achieved, even in patients who fail to respond to cytosine arabinoside in conventional doses.

Acute Disease↗
PubMed1982

Veno-occlusive disease of the liver after high-dose mitomycin C therapy and autologous bone marrow transplantation.

Twenty-nine patients with refractory malignancies underwent intensive therapy with mitomycin C (60, 75, or 90 mg/m2 IV) and autologous marrow transplantation. Six patients developed the clinical syndrome of hepatic veno-occlusive disease (VOD) characterized by progressive abnormalities in liver function, abdominal pain, and ascites 15-70 days after mitomycin C therapy. Postmortem material was available in 16 patients, including four patients who had the clinical syndrome. VOD of the central and sublobular hepatic veins was noted in these four patients. VOD was discovered incidentally at autopsy in one of 12 patients without antemortem clinical evidence of disease. Two patients with abnormalities of liver function but without ascites or right upper quadrant pain had no evidence of VOD at autopsy. Although not statistically significant, there was a greater incidence of VOD with increasing doses of mitomycin C. When bone marrow toxicity of mitomycin C was overcome by autologous bone marrow transplantation, the development of VOD appeared to be the limiting factor in dose escalation.

Adult↗
PubMed1982

Bone marrow transplantation with high-dose cytosine arabinoside.

Eleven patients received allogeneic bone marrow from all HCA-identical sibling for the treatment of acute leukemia. The preparative regiment included high-dose cytosine arabinoside (Ara-C), 3 g/m2q 12 h for 12 doses, and 1000 rad single-fraction total body irradiation (5 patients) or 1200 rad fractionated total body irradiation (6 patients). The 5 patients receiving the 1000 rad single-fraction regimen were transplanted in relapse, while the 6 patients receiving the 1200 rad fractionated program were transplanted during remission. Both regimens were well-tolerated, but the single-dose radiation regimen was associated with more severe skin problems. Bone marrow engraftment was documented in 10 of 10 evaluable patients, occurring 2-3 weeks after marrow infusion. No recurrences have been observed during the brief follow-up time.

Bone Marrow Transplantation↗
PubMed1981

Central nervous system toxicity of high-dose systemic cytosine arabinoside.

Forty-nine adult patients with acute leukemia in relapse, refractory to conventional therapy, were studied. Increasing quantities of i.v. bolus high-dose cytosine arabinoside (cytarabine) were administered using the following schedules: 3 g/m2 every 12 hrs for 4-16 consecutive doses, or 4.5 g/m2 every 12 hrs for 12 consecutive doses. Patients ages ranged 16-76 year (median: 38). Thirty-seven patients had previously received either induction or maintainance therapy with conventional doses of cytarabine. Cerebral or cerebellar dysfunction attributable to cytarabine was observed in eight patients and appeared 6-8 days (mean: 6.6) after the first dose and lasted 3-7 days (mean: 4.7). None of 12 patients receiving up to 24 g/m2 total dose of 48 g/m2 developed reversible neurologic dysfunction. Four of six patients receiving 54 g/m2 developed CNS toxicity (irreversible in two cases), a significantly greater incidence compared to toxicity in patients receiving less than or equal to 48 g/m2 total dose (P less than 0.01). CNS toxicity was dose-related since patients treated for 12 consecutive doses of 4.5 g/m2 had significantly greater CNS toxicity than 12 consecutive doses at 3 g/m2 (P less than 0.04). Systemic cytarabine doses less than 54 g/m2 can be administered with minimal CNS side-effects.

Adolescent↗
PubMed1981

Recovery, life span, and function of stored plateletpheresis units.

Plateletpheresis units collected using the Haemonetics Model 30 or the IBM 2997 cell separator were stored for 24 h at 22 degrees C. Autologous recovery and life span measurements averaged 64 +/- 13% (1 SD) and 8.9 +/- 1.3 (1 SD) days. The hemostatic effectiveness of these preparations were satisfactory; the corrected increment 4-6 h and 18-24 posttransfusion was 20,400 and 13,400/microliter/m2, respectively, and the bleeding time showed improvement in each patient. There was no significant difference in these parameters between collection devices.

Blood Platelets↗