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Biomedical subjects

R L Krigel

Publications and source records attributed to R L Krigel.

29 records · Page 2Linked to original sources
PubMed1989

Exacerbation of epidemic Kaposi's sarcoma with a combination of interleukin-2 and beta-interferon: results of a phase 2 study.

Epidemic Kaposi's sarcoma (EKS) is the most common neoplastic manifestation of acquired immune deficiency syndrome (AIDS). The underlying immune deficiency can be partially reversed in vitro with interleukin-2 (IL-2). The type 1 interferons (IFN), alpha and beta, inhibit the growth of the etiologic agent of AIDS, the human immunodeficiency virus, have antitumor activity against Kaposi's sarcoma, and are synergistic with IL-2 in stimulating natural killer cell activity. Four patients with EKS were treated three times weekly with simultaneous intravenous injections of recombinant IL-2 (5 X 10(6) Cetus units/m2) and recombinant IFN-beta (6 X 10(6) units/m2). All patients had generalized disease, were without systemic symptoms, had no prior opportunistic infection, and had stable disease at the initiation of therapy. No patient had an objective response. Three patients exhibited rapid disease progression within 2-4 weeks of starting treatment, necessitating discontinuation of therapy and early closure of the study. This adverse result may have resulted from the significant levels of gamma-interferon (IFN-gamma) that can be generated with this dose and schedule of IL-2. Investigators using IL-2 should monitor IFN-gamma levels and avoid intermediate to high-dose bolus IL-2 therapy in patients with EKS.

Acquired Immunodeficiency Syndrome↗
PubMed1988

A phase I study of recombinant interleukin 2 plus recombinant beta-interferon.

Interleukin 2 (IL-2) therapies have antitumor activities against several neoplasms. In vitro these activities are enhanced by beta-interferon (IFN-beta). Therefore, we initiated a Phase I trial with a combination of IL-2 and IFN-beta three times weekly. The IFN-beta was administered i.v. Initially, the IL-2 was administered s.c. However, neutralizing antibody to the IL-2 developed in five patients, and the route of administration of the IL-2 was changed to i.v. Forty-seven patients were entered on the study. The maximum tolerated doses for the combination given i.v. were 5 x 10(6) units/m2 of IL-2 and 10 x 10(6) units/m2 of IFN-beta. Dose-limiting toxicities were profound fatigue/decreased performance status, anorexia/weight loss, depression, and arthralgias. Hypotension, exfoliative skin rash, thrombocytopenia, diarrhea, temperature greater than 40.6 degrees C, and peripheral edema were rarely dose limiting. Thirty-two patients were evaluable for response. After 4 weeks of treatment, 21 patients had stable disease, three patients had a minor response, and one patient had a partial response. Significant lymphokine-activated killer cell (LAK) activity was seen in seven patients (22%) and required 5 x 10(6) units/m2 of IL-2. Those who had progressive disease had significantly less LAK activity than those with either stable disease or a response. This therapy also induced more than 60 units/ml of endogenous gamma-interferon 4 h after the i.v. IL-2 administration. This study demonstrates that (a) intermittent i.v. bolus IL-2 therapy can generate LAK activity, (b) LAK activity may be associated with an antitumor response, (c) significant levels of gamma-interferon are induced by this therapy, and (d) IL-2 and IFN-beta given three times weekly i.v. is both tolerable and biologically active. The recommended Phase II dose is 5 x 10(6) units/m2 of IL-2 plus 6 x 10(6) units/m2 of IFN-beta.

Adult↗
PubMed1988

Metastatic extramedullary plasmacytoma: a case report and review of the literature of a rare pseudocarcinoma.

Extramedullary plasmacytomas are unusual plasma cell tumors arising outside the bone marrow. Most extramedullary plasmacytomas are solitary, but occasionally they disseminate, usually in conjunction with systemic myelomatosis. The authors report a case of disseminated extramedullary plasmacytoma with a picture suggestive of metastatic pancreatic carcinoma. This unusual presentation reconfirms the need for tissue diagnosis in all suspected cases of pancreatic carcinoma and demonstrates that extramedullary plasmacytoma can be an aggressive cancer without any sign of osseous or systemic disease.

Aged↗
PubMed1988

Treatment of epidemic Kaposi's sarcoma with a combination of interferon-alpha 2b and etoposide.

A prospective clinical trial of concomitant interferon-alpha 2b and etoposide was conducted in 24 previously untreated patients with epidemic Kaposi's sarcoma. Eight of 21 evaluable patients (38%) achieved either a complete response (1 patient) or a partial response (7 patients). None of the responders had a prior history of opportunistic infection. Hematologic toxicity was severe, and 8 patients developed an opportunistic infection. The combination of interferon-alpha 2b and etoposide has modest activity, but no additive or synergistic activity was evident in the dose and schedule utilized in this study. The exact role for interferon-alpha in epidemic Kaposi's sarcoma, both as a single agent and in combinations, remains to be determined.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Therapeutic trial of interferon-gamma in patients with epidemic Kaposi's sarcoma.

An epidemic form of Kaposi's sarcoma associated with the acquired immune deficiency syndrome has been recently described. Seven homosexual men with biopsy-documented epidemic Kaposi's sarcoma were treated with a human interferon-gamma preparation. All patients had generalized disease. Only one patient had received prior chemotherapy, and one other patient had recovered from a prior opportunistic infection. Interferon-gamma was administered in a dose of 500,000 U intramuscularly daily, with two 10-day induction courses, separated by a 2-week medication-free period. This was followed by maintenance therapy in the same dose twice weekly. Toxicities consisted of a flu-like illness with high fevers, shaking chills, myalgias, and arthralgias. There were no complete or partial responses. All patients exhibited disease progression, with a rapid progression of previously stable disease necessitating discontinuation of therapy in three patients. We conclude that low doses of this human interferon-gamma preparation are ineffective in epidemic Kaposi's sarcoma.

Adult↗
PubMed1984

Treatment of epidemic Kaposi's sarcoma with etoposide or a combination of doxorubicin, bleomycin, and vinblastine.

An epidemic of disseminated Kaposi's sarcoma in male homosexuals has recently been described. Forty-one evaluable patients with epidemic Kaposi's sarcoma were treated with etoposide. The majority of these patients had early stage disease, no prior opportunistic infections, and no prior therapy. Twelve patients (30%) achieved complete remission, 19 (46%) partial remission, and ten (24%) no response. With follow-up time to 31 months, the median response duration is nine months. The median survival of patients with complete and partial remissions has not been reached. A combination of doxorubicin (Adriamycin, Adria Laboratories, Columbus, Ohio), bleomycin, and vinblastine (ABV) was used in 31 evaluable patients with epidemic Kaposi's sarcoma. The majority of these patients had late stage disease, prior opportunistic infections, or had failed prior treatment. Seven patients (23%) achieved complete remission, 19 (61%) partial remission, and five (61%) no response. With follow-up time to 24 months, the median response duration is eight months. The projected median survival for all patients treated with ABV is nine months. Both regimens were well tolerated, with an overall response rate of 76% for etoposide and 84% for ABV. However, while successfully treating the Kaposi's sarcoma, the underlying immune deficiency in these patients has persisted. Future treatments of Kaposi's sarcoma will need to focus on reversing the underlying immune incompetence as well as controlling the malignant manifestations of Kaposi's sarcoma arising in relation to the acquired immune deficiency syndrome.

Adult↗
PubMed1983

Ribonucleotide content of mononuclear cells from normal subjects and patients with chronic lymphocytic leukemia: increased nicotinamide adenine dinucleotide concentration in chronic lymphocytic leukemia lymphocytes.

The ribonucleotide content of lymphocytes obtained from normal subjects and patients with chronic lymphocytic leukemia (CLL) was determined by means of high-performance liquid chromatography. The levels of normal B- and T-cells were compared to each other as well as those of their CLL counterparts. Unfractionated CLL lymphocytes, predominantly B-cells, had significantly lower levels of adenosine-5'-triphosphate, cytidine-5'-triphosphate, uridine-5'-triphosphate, cytidine-5'-diphosphate, and guanosine-5'-phosphate, while the concentration of nicotinamide-adenine dinucleotide was significantly higher than in normal unfractionated lymphocytes which consisted mainly of T-cells. For enriched populations: (a) CLL B-cells had much lower adenosine-5'-triphosphate (3439 versus 5689) (pmol/1 X 10(7) cells), cytidine-5'-triphosphate (107 versus 313), guanosine-5'-triphosphate (462 versus 978), and uridine-5'-triphosphate (633 versus 1214) than normal B-cells; (b) CLL T-enriched subpopulations had significantly lower ribonucleoside triphosphates, adenosine-5'-triphosphate (3217 versus 5468), cytidine-5'-triphosphate (119 versus 209), guanosine-5'-triphosphate (422 versus 826), and uridine-5'-triphosphate (504 versus 969) than normal T-cells. The lower ribonucleoside triphosphate levels found in unfractionated CLL lymphocytes, therefore, are the result of differences between the CLL and normal B-cells as well as between CLL and normal T-cells. These findings establish a framework for studying the reasons underlying the decreased ribonucleoside triphosphate levels in unfractionated CLL lymphocytes. T-helper and T-suppressor lymphocytes showed similar ribonucleotide patterns. Nucleoside and base levels were significantly higher in normal monocytes than in normal lymphocytes. The only compound found to be increased in the CLL B-lymphocytes when compared to their normal counterparts was nicotinamide-adenine dinucleotide. The level in CLL lymphocytes was 404 versus 209 pmol/10(7) cells for normal B-lymphocytes. No correlation was found between any ribonucleotide levels and the expression of 5'-nucleotidase activity.

B-Lymphocytes↗
PubMed1983

Kaposi's sarcoma: a new staging classification.

Reports of an unusual form of Kaposi's sarcoma in young homosexual men in North America have demonstrated that previous classification systems for this disease are incomplete. We describe the clinical characteristics of 49 homosexual men with Kaposi's sarcoma and propose a new staging for the disease. There appear to be four clinically distinct forms of Kaposi's sarcoma: stage I--the more typical locally indolent lesions occurring predominantly in elderly males in North America and Europe; stage II--a locally invasive and aggressive form seen almost exclusively in equatorial Africa; stage III--a disseminated mucocutaneous form, often with lymph node involvement, seen primarily in African children and North American male homosexuals; and stage IV--a disseminated, mucocutaneous form with visceral involvement also seen in African children and North American male homosexuals. These stages are further subtyped as to the presence or absence of the systemic signs of unexplained fever and/or weight loss. Further longitudinal follow-up of these recently diagnosed cases will hopefully document that this proposed staging system correlates with survival data and is useful in the evaluation of treatment regimens for uniformly defined patient groups.

Adult↗