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Biomedical subjects

R Kurzrock

Publications and source records attributed to R Kurzrock.

At least 91 records · Page 5Linked to original sources
PubMed1995

Muir-Torre syndrome.

The Muir-Torre syndrome is an autosomal dominantly inherited genodermatosis with malignant potential that is characterized by the presence of at least one sebaceous gland tumor (adenoma, epithelioma, or carcinoma) and a minimum of one internal malignancy. The syndrome has been documented in 147 individuals. Associated features in some of the Muir-Torre syndrome patients are colorectal carcinomas and genitourinary neoplasms. More than half of the 292 visceral cancers described in Muir-Torre syndrome patients were colorectal carcinomas; nearly 60% of these tumors were located at or proximal to the splenic flexure. The presence of even a single Muir-Torre syndrome-associated sebaceous tumor warrants serious consideration for further evaluation of that individual for the syndrome. Therefore, initial and periodic examination for internal malignancy should be performed in individuals with such tumors and patients with the syndrome. Also, family members of Muir-Torre syndrome patients should be screened for Muir-Torre syndrome-associated cutaneous lesions and visceral cancers.

Adenoma↗
PubMed1995

Response to interferon-alpha in patients with hairy cell leukemia relapsing after treatment with 2-chlorodeoxyadenosine.

2-Chlorodeoxyadenosine (2-CdA) has recently established itself as an extremely effective therapy for patients with hairy cell leukemia. To date, the issue of how to treat patients relapsing after 2-CdA has not been adequately addressed. In our initial study, 41 of 46 patients achieved an objective response (complete or partial remission). The only persistent toxicity associated with this agent appears to be significant suppression of CD4+ lymphocyte counts, albeit without evidence of clinical sequelae at a median follow-up of 30 months (range, 7-43). Eight patients have developed recurrent disease 3-23 months (median, 16 months) after 2-CdA. Because of progressive cytopenias, three of these patients were treated with interferon-alpha (IFN-alpha) (3 x 10(6) units subcutaneously three times per week), commencing 2, 9 and 16 months after the documentation of relapse. All three patients have shown an objective response with reduction of marrow hairy cells and amelioration of neutropenia and thrombocytopenia (two patients, complete remission; one patient, partial remission). Responses were maintained while on IFN-alpha, but two patients relapsed shortly (3 and 4 months, respectively) after discontinuation of IFN. There was no significant toxicity. Prior to commencing IFN-alpha, 22-36 months after 2-CdA, these patients' absolute CD4+ counts were suppressed (mean 211/microliters, s.d. +/- 85/microliters), but have not significantly changed after 10, 11 and 18 months of IFN-alpha therapy (mean 225/microliters, s.d. +/- 93/microliters). These results suggest that in hairy cell leukemia patients relapsing after 2-CdA, IFN-alpha may be a reasonable therapeutic option, especially if persistent CD4+ lymphocytopenia is present.

Adult↗
PubMed1995

KBM-7, a human myeloid leukemia cell line with double Philadelphia chromosomes lacking normal c-ABL and BCR transcripts.

A human myeloid leukemia cell line, KBM-7, was developed from a patient in the blastic phase of chronic myeloid leukemia (CML). We characterized its morphology, immunophenotype, cytogenetics, and proliferative capacity. Developed in the absence of exogenous lymphokines, KBM-7 in vitro cloning capacity actually decreased when colony-stimulating factors were added. The cells had an aberrant immature myeloid phenotype, a doubling time of 22 h in suspension cultures and a high cloning efficiency in semisolid system (24 +/- 3)%. Early passages contained one near-haploid (predominant) and one hyperdiploid stem line. Gradually the hyperdiploid stem line became predominant, reaching an average of 49 chromosomes per cell. Cells from passage 89 had two Philadelphia chromosomes [t(9;22)(q34;q11)] and lacked normal copies of chromosomes 9 and 22. Detailed molecular characterization of the breakpoint in the t(9;22)(q34;q11) revealed that KBM-7 had the BCR 2/ABL II splice junction. The cells had high protein kinase (p210BCR-ABL) activity and carried two identified variants of an ABL-BCR message. There was no evidence that normal BCR or c-ABL messages were expressed, assessed with the reverse-transcriptase polymerase chain reaction. When KBM-7 cells were heterotransplanted into nude mice without immunosuppressive pretreatment, one of three mice injected with 1 x 10(7) cells and all mice injected with 1 x 10(8) cells developed slowly growing granulocytic sarcomas within 6-8 weeks. These tumors were locally invasive but did not metastasize. We conclude that the KBM-7 cell line will be of value for investigating molecular events underlying neoplastic transformation in CML, in particular for studying the effects of BCR-ABL and ABL-BCR on the proliferation of CML cells in the absence of normal BCR and c-ABL messages.

Animals↗
PubMed1995

Interleukin-1 and its inhibitors: a biologic and therapeutic model for the role of growth regulatory factors in leukemias.

Production of growth factors may provide a mechanism for disease evolution in some leukemias. Interleukin-1 is a plelotropic cytokine with the ability to synergize with other growth factors as well as to stimulate their production and release. Autocrine and/or paracrine secretion of interleukin-1 has been implicated in the pathogenesis of both chronic and acute myelogenous leukemia. Recently, a series of both specific and nonspecific IL-1 inhibitory molecules have been identified. These include IL-1 receptor antagonist, soluble IL-1 receptors, IL-1-converting enzyme inhibitor, IL-4, IL-10 and IL-1-antisense. Early experiments demonstrating the ability of some of these molecules to inhibit acute and chronic myelogenous leukemia growth suggest that clinical trials of these compounds may provide a novel management approach in these malignancies. Here we review the potential biologic and therapeutic role of IL-1 and its inhibitors in the myeloid leukemias.

Animals↗
PubMed1994

Altered levels of interleukin-1 beta and interleukin-1 receptor antagonist in chronic myelogenous leukemia: clinical and prognostic correlates.

We have recently demonstrated that interleukin (IL)-1 beta levels are elevated in advanced chronic myelogenous leukemia (CML) and that IL-1 inhibitors can suppress CML clonogenic growth. To further assess the clinical implications of increased IL-1 beta expression in CML, we analyzed IL-1 beta and IL-1 receptor antagonist (IL-1RA) levels in leukocyte lysates from a series of CML patients and from normal volunteers. Both IL-1 beta and IL-1RA were measured by enzyme-linked immunosorbent assays (ELISAs), with the lower limits of sensitivity of the assays being 20 pg/mL and 6.5 pg/mL, respectively. The median IL-1 beta level in the 81 CML patients tested was higher (115.8 pg/2.4 x 10(7) cells; range, 0 to 2,000 pg/2.4 x 10(7) cells) than the median level in 25 control samples (10.8 pg/2.4 x 10(7) cells; range, 0 to 95.5 pg/2.4 x 10(7) cells) (P < .01). IL-1 beta was bioactive, as demonstrated with a bioassay based on cytotoxicity to a melanoma cell line (A375). For survival analysis, elevated IL-1 beta levels were defined as those exceeding the mean + 2 SD of normal levels (83 pg/2.4 x 10(7) cells). The survival of the 44 patients with elevated IL-1 beta levels was significantly shorter than that of those who had low IL-1 beta levels (median, 44 v 58 months; P = .049 by Wilcoxon-Gehan method). An association between IL-1 beta and CML prognostic criteria shows that IL-1 beta levels were significantly higher in patients in accelerated/blastic crisis phases of the disease (364.0 pg/2.4 x 10(7) cells) compared with patients in chronic phase (102.0 pg/2.4 x 10(7) cells) (P < .01), and that high IL-1 beta levels correlated with increased blasts in the marrow and peripheral blood (P < .01). In contrast, while IL-1RA levels did not differ between chronic-phase CML patients (median, 471.7 pg/2.4 x 10(5)) and healthy volunteers (median, 454.4 pg/2.4 x 10(5)), patients with accelerated/blast crisis disease had significantly lower levels of IL-1RA (median, 218.7 pg/2.4 x 10(5); P = .03). Finally, although IL-1 beta has been previously shown to increase IL-1RA levels, there was no correlation between IL-1 beta and IL-1RA levels in our CML patients.(ABSTRACT TRUNCATED AT 400 WORDS)

Bone Marrow↗
PubMed1994

2-Chlorodeoxyadenosine therapy in patients with T-cell lymphoproliferative disorders.

Mature T-cell lymphoproliferative disorders comprise a heterogenous group of diseases for which there is no standard therapy. These disorders are uncommon, and are usually treated similarly to their B-cell counterparts, but with less success. Nucleoside analogues have proven effective in indolent B-cell disorders but have been less well explored in T-cell malignancies. We treated 22 patients with mature T-cell lymphoproliferative diseases with 2-chlorodeoxyadenosine (2-CDA) administered as a continuous infusion at a daily dose of 4 mg/m2 over 7 days. Nineteen of the patients had received prior therapy with a median number of prior regimens of three. Eleven patients had leukemia or large granular lymphocytosis, eight patients had mycosis fungoides, and three had T-cell lymphoma. Nine patients (41%) responded to 2-CDA. Four of the patients had responses that were complete remissions, and three of these four patients remain in remission at 23, 24, and 23 months. The only important toxic effects were fever or infection, seen during 38% of courses. In conclusion, 2-CDA appears to be an effective therapy in T-cell lymphoproliferative disorders and deserves wider evaluation in this subset of patients.

Adult↗
PubMed1994

2-chlorodeoxyadenosine induces durable remissions and prolonged suppression of CD4+ lymphocyte counts in patients with hairy cell leukemia.

A number of effective treatments are available for patients with hairy cell leukemia (HCL). 2-Chlorodeoxyadenosine (2-CdA) induces more than 80% complete responses, but is associated with profound suppression of CD4+ lymphocyte counts. However, the duration of each is uncertain. We have analyzed a previously reported cohort of 40 patients who had responded to 2-CdA. Eight patients (20%) have relapsed at a median of 16 months (range, 3 to 23 months). The remaining 32 patients were observed for a median of 30 months (range, 7 to 43 months). No patients have died. At 3 years, the actuarial disease-free survival rate is 77% (95% confidence interval, 70% to 84%). The median CD4+ lymphocyte count before therapy was 743/microL (range, 58 to 2,201/microL). The median CD4+ nadir after treatment was 139/microL (range, 25 to 580/microL). There was a single opportunistic infection and no second malignancies observed. Although there was evidence of some improvement in CD4+ lymphocyte counts on sequential testing, CD4+ counts remained significantly lower than baseline (P < .0001) at a median of 23 months after therapy (median, 237/microL; range, 25 to 514/microL), and were also lower than baseline (P < .002) in those patients with more than 1 year of follow-up (median, 27 months; range, 13 to 42 months). The median time to reach an absolute CD4+ lymphocyte count of 365/microL, the lower limit of the normal range, was 40 months. Although responses to 2-CdA are durable in the majority of patients with HCL, the uncertain long-term consequences of the observed CD4+ lymphocytopenia suggest caution in the broad application of this therapy.

CD4-Positive T-Lymphocytes↗
PubMed1994

Leukemia inhibitory factor in long-term adherent layer cultures: increased levels of bioactive protein in leukemia and modulation by IL-4, IL-1 beta, and TNF-alpha.

In the current study, we used a monoclonal antibody-based enzyme-linked immunosorbent assay and bioassay to assess leukemia inhibitory factor (LIF) protein levels, activity, and function in supernatants of 59 adherent layers derived from acute and chronic myelogenous leukemia, myelodysplastic syndrome, and hairy cell leukemia patients and from normal controls. We demonstrate that biologically active LIF protein is constitutively produced and secreted by cultured bone marrow stromal cells from all of the studied subjects. Furthermore, various cytokines can alter endogenous LIF protein levels. Twenty-four h of exposure to recombinant human (rh) interleukin (IL) 4 (100 units/ml) significantly decreased LIF protein levels in adherent layer conditioned media [median base line level, 2.6 ng/ml; range, 1.6-8.0 ng/ml; median post rhIL-4 exposure levels, 1.9 ng/ml; range, 0.9-5.8 ng/ml (n = 7; P = 0.022)]. In contrast, rhIL-1 beta and rh tumor necrosis factor alpha consistently increased LIF protein levels. In the samples exposed to 50 units/ml rhIL-1 beta, median base line LIF level was 2.6 ng/ml; median post-LIF level was 9.0 ng/ml (n = 8; P = 0.014). In the two samples exposed to rh tumor necrosis factor alpha (200 units/ml), LIF levels increased from baseline levels of 2.6 and 2.7 ng/ml to postexposure levels of 7.7 and 12.2 ng/ml, respectively. Finally, the presence of LIF may be relevant to both normal and malignant hematopoietic processes as evidenced by: (a) LIF protein levels in adherent layer conditioned media were significantly elevated in samples from patients with a spectrum of hematological neoplasms [acute myelogenous leukemia: median level, 3.0 ng/ml (range, 1.6-11.0 ng/ml); myelodysplastic syndrome: median level, 4.5 ng/ml (range 1.4-15.5 ng/ml); hairy cell leukemia; median level, 3.5 ng/ml (range 2.2-10.3 ng/ml); chronic myelogenous leukemia-chronic phase: median level, 4.35 ng/ml (range 0.3-19.0 ng/ml); and chronic myelogenous leukemia-blast crisis: median level, 6.25 ng/ml (range 0.7-20.3 ng/ml)] as compared to samples from normal individuals (median level, 2.0 ng/ml; range, 0.7-4.6 ng/ml; P < 0.05); and (b) in normal controls, in vitro abrogation of endogenous LIF bioactivity by neutralizing antibody decreased the number of committed granulocyte-macrophage hemopoietic progenitors.

Blast Crisis↗
PubMed1994

Clinical manifestations of vasculitis in patients with solid tumors. A case report and review of the literature.

Vasculitis is characterized by inflammatory changes and necrosis of blood vessels. Involvement of arteries and veins of diverse sizes throughout the body is possible and results in a multiplicity of clinical manifestations. Primary and secondary forms of vasculitis exist. Secondary vasculitis has been linked to several processes, including infections, drugs, and allergic, rheumatologic, and neoplastic disease. The majority of patients with malignant neoplasm-associated vasculitis who have been described had hematologic neoplasms. We report a patient with adenocarcinoma of the colon and vasculitis and review the 36 cases of vasculitis in patients with solid tumors documented in the world literature. The most common malignant neoplasms were non-small-cell lung cancer and prostate, breast, colon, and renal cancer. Cutaneous leukocytoclastic vasculitis and nerve and muscle microvasculitis were the most frequently observed vasculitic subtypes. Importantly, in 71% of the cases, manifestations of vasculitis appeared before or concurrent with the initial recognition or the relapse of the tumor. Management strategies that met with success in at least half the patients in whom they were used included corticosteroids, cyclophosphamide, and treatment of the underlying cancer. Prognosis may be primarily related to the ability to control the malignant neoplasm, as most of the patients who died did so because of tumor progression.

Adenocarcinoma↗
PubMed1994

Interleukin 4 alters human bone marrow stroma and modulates its interaction with hematopoietic progenitors.

To investigate the functional activity of interleukin 4 (IL-4) on human marrow stroma formation, normal bone marrow (BM) samples were cultured in "Dexter-type" long-term cultures in the presence and absence of IL-4. IL-4 (0.001 to 1.0 micrograms/ml) added at the initiation of culture and once weekly when the cultures were fed effaced the culture architecture. In four-week old confluent cultures smooth muscle-like and endothelial-like cells were rare, the fibronectin network and cobblestone areas were absent, and a preponderance of monocyte-macrophages characterized the adherent layer. Exposure to IL-4 reduced the numbers of CD34+ cells, colony-forming unit granulocyte-macrophage (GFU-GM) cells and burst-forming unit-erythroid (BFU-E) cells in the adherent layer, and increased their numbers in the nonadherent layer. In five of eight IL-4-containing cultures the concentrations of macrophage colony-stimulating factor (M-CSF) were increased and in two of eight IL-4-treated cultures the concentrations of tumor necrosis factor-alpha (TNF-alpha) were significantly elevated as compared to those in control cultures, whereas there were no consistent differences in the levels of either IL-6 or transforming growth factor-beta (TGF-beta). IL-1 beta and granulocyte-macrophage CSF (GM-CSF) were not detected in any culture. These data suggest that IL-4 suppresses stroma formation and alters its structure and cellular composition.

Antigens, CD↗
PubMed1994

What is the contribution of molecular studies to the diagnosis of BCR-ABL-positive disease in adult acute leukemia?

The detection of BCR-ABL transcripts by polymerase chain reaction and hybridization protection assay was investigated in 59 adults with acute leukemia in whom the Philadelphia chromosome (Ph) abnormality was not documented by cytogenetic analysis. These included 35 patients with acute lymphocytic leukemia (ALL) and 24 with acute myelogenous leukemia (AML). Overall, three patients were found to have Ph-related molecular abnormalities; one had p190 and two had p210 disease. All three patients had ALL and were among 16 patients with insufficient metaphases by cytogenetic analysis, yielding an incidence of 19% in the latter category. Based on a 32% incidence of insufficient metaphases in our adult ALL population, we project an additional detection rate of 6% Ph-positive ALL by molecular studies and an overall incidence of 20% (14% + 6%) Ph-positive or BCR-ABL-positive ALL. None of the remaining patients with ALL and none of the 24 patients with AML investigated had BCR-ABL-positive disease. We conclude that molecular studies are useful in detecting BCR-ABL-positive disease in a subset of patients with Ph-positive ALL who are not identified by cytogenetic analysis because of insufficient metaphases.

Acute Disease↗
PubMed1994

Persistence of dormant leukemic progenitors during interferon-induced remission in chronic myelogenous leukemia. Analysis by polymerase chain reaction of individual colonies.

Interferon-alpha induces durable cytogenetic remissions in about one-quarter of newly diagnosed patients with chronic myelogenous leukemia (CML). Even so, after short-term follow-up, previous studies have shown that residual leukemic cells can be detected by the polymerase chain reaction (PCR) in all of these individuals. The objectives of our study were therefore to obtain long-term follow-up data on residual disease in a cohort of complete responders and to determine if leukemic cells with clonogenic potential are present in patients despite the absence of relapse. We performed (a) serial analysis of blood and/or bone marrow for a reverse transcriptase PCR amplified BCR-ABL transcript at times well beyond the point that cytogenetic remission was first attained and (b) reverse transcriptase PCR of individually plucked myeloid and erythroid colonies for the presence of the same transcript. Seven CML patients who had previously attained complete cytogenetic remission while on interferon-alpha were investigated. Six of the seven patients were in complete cytogenetic remission at the time of analysis, whereas one patient had early evidence of cytogenetic relapse. With ongoing therapy, five patients with the longest follow-up eventually achieved PCR negativity at time periods of 27, 32, 36, 49, and 67 mo after a complete cytogenetic remission was first noted. Even so, residual disease was detected in progenitor cells derived from two patients, each of whom had been in continuous cytogenetic remission for approximately 2.5 and 3.5 yr, respectively. Progenitors expressing BCR-ABL transcripts were also detected in the patient with early cytogenetic relapse. These observations demonstrate that residual disease resides in colony-forming cells that should have the potential to repopulate the bone marrow. However, the presence of a minority of Ph-positive CML progenitor cells for a very long period of time is still compatible with durable remission, confirming that a situation of tumor dormancy may be induced in CML by interferon therapy.

Adult↗
PubMed1993

Sweet syndrome in patients with solid tumors.

BACKGROUND: Sweet syndrome (acute febrile neutrophilic dermatosis) may occur as a cutaneous paraneoplastic syndrome. This condition has been associated with hematologic malignancies and, to a lesser extent, with solid tumors. METHODS: The authors report two patients with malignancy-associated Sweet syndrome: a 66-year-old man in whom the onset of Sweet syndrome preceded the diagnosis of an adenocarcinoma of unknown primary by 3 months and a 69-year-old woman in whom a workup after the appearance of Sweet syndrome skin lesions revealed an unsuspected recurrent squamous cell carcinoma of the larynx. The authors review the reports of the other 39 patients with solid tumor-associated Sweet syndrome that have been published in the world literature. RESULTS: The most common malignancies were carcinomas of the genitourinary organs (37%), breast (23%), and gastrointestinal tract (17%). Typical clinical features and laboratory findings in these patients included tender erythematous plaques located on the upper extremities (97%); elevated erythrocyte sedimentation rate (95%); anemia (83%); fever (79%); and neutrophilia (60%). The symptoms and lesions of Sweet syndrome resolved after treatment with corticosteroids, potassium iodide, or colchicine. Sweet syndrome preceded the initial diagnosis of cancer or the detection of asymptomatic metastatic, persistent, or recurrent tumor, or a hematologic malignancy (in an individual with a previously diagnosed solid tumor) in 61% of the patients. In the other 39% of patients, diagnosis of Sweet syndrome followed the development of a solid tumor. CONCLUSION: The search for a neoplasm of the genitourinary organs and breast cancer in women and a gastrointestinal tract carcinoma in men should be emphasized in the evaluation for a solid tumor in patients with Sweet syndrome without a prior diagnosis of malignancy.

Adenocarcinoma↗
PubMed1993

Biological properties and growth in SCID mice of a new myelogenous leukemia cell line (KBM-5) derived from chronic myelogenous leukemia cells in the blastic phase.

The establishment and the biological properties of a new leukemic cell line (KBM-5) derived from a patient in the blastic phase of chronic myelogenous leukemia are described. The cells exhibited multiple copies of the Philadelphia chromosome, and a high level of p210Bcr-Abl kinase activity was detected with rabbit anti-Abl and anti-Bcr (exon 3) peptide antisera. Use of specific primers and polymerase chain reaction followed by Southern blotting revealed that KBM-5 cells carried a bcr3-ABLII splice junction. While a normal BCR message was detected, no normal ABL message was found. The cells were phenotypically myeloid with monocytic differentiation. The high cloning efficiency in semisolid media was independent of the presence of exogenous colony-stimulating factors. In vitro exposure to induces of differentiation, such as retinoic acid, dimethyl sulfoxide, or hemin, failed to influence the growth rate of the cells and their level of differentiation. KBM-5 cells are highly resistant to the antiproliferative action of recombinant alpha- and gamma-interferons. Although sensitive to recombinant tumor necrosis factor alpha, they were completely resistant to natural killer cell action. KBM-5 cells constitutively expressed mRNA for tumor necrosis factor alpha but not for gamma-interferon, other interleukins, or hematopoietic growth factors. The KBM-5 cells that were transplanted into SCID mice manifested metastatic potential and tissue invasiveness similar to the way leukemic cells in humans do. This new KBM-5 cell line represents a helpful model for examining in vitro and in vivo modulation of the growth and properties of leukemic cells by using biological and chemotherapeutic agents.

Aged↗
PubMed1993

Heterogeneity in lineage derivation of Philadelphia-positive acute lymphoblastic leukemia expressing p190BCR-ABL or p210BCR-ABL: determination by analysis of individual colonies with the polymerase chain reaction.

The molecular hallmark of Philadelphia chromosome-positive acute lymphoblastic leukemia (ALL) is the expression of 1 of 2 alternate forms of the aberrant BCR-ABL protein-p210BCR-ABL or p190BCR-ABL. The presence of BCR-ABL message provides a target for analyzing the lineage derivation of this disease. We, therefore, studied myeloid and erythroid progenitor involvement in Philadelphia chromosome-positive ALL. Bone marrow low-density cells from Philadelphia chromosome-positive ALL patients (5 with the p190BCR-ABL and 2 with the p210BCR-ABL anomaly) were cultured in the mixed colony culture assay. cDNA from individually plucked colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies was then analyzed using the hybridization protection assay in conjunction with the polymerase chain reaction to detect BCR-ABL molecular aberrations. Colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies from 1 of 5 p190BCR-ABL-positive patients and 1 of 2 p210BCR-ABL-positive patients expressed BCR-ABL transcripts, whereas colony-forming unit-granulocyte-macrophage and burst-forming unit-erythroid colonies from the other patients did not. Our study suggests that the origin of both p190BCR-ABL- and p210BCR-ABL-positive ALL is heterogenous with involvement of either a pluripotent precursor or a lymphoid lineage-committed hematopoietic progenitor.

Adolescent↗
PubMed1993

Serum interleukin 6 levels are elevated in lymphoma patients and correlate with survival in advanced Hodgkin's disease and with B symptoms.

Several cytokines including gamma-interferon, tumor necrosis factor alpha, interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) are pyrogenic and can inhibit lipogenic processes. Because patients with lymphoma often suffer from fever, weight loss, and night sweats (B symptoms), the etiology of which is unknown, the authors investigated serum levels of these cytokines in normal volunteers and in patients with Hodgkin's and non-Hodgkin's lymphoma. Sixty serum samples from patients with Hodgkin's disease (28 patients) or non-Hodgkin's lymphoma (32 patients), as well as 20 samples from normal volunteers, were collected. The majority of patients had advanced (Stage III or IV) or relapsed disease. The assay for gamma-interferon was a specific and sensitive radioimmunoassay (lower limit of detection = 0.1 unit/ml); the assays for tumor necrosis factor alpha, IL-1 beta, and IL-6 were enzyme-linked immunoassays with lower limits of sensitivity of 10 pg/ml, 20 pg/ml, and 22 pg/ml, respectively. There were no statistically significant differences in gamma-interferon, tumor necrosis factor alpha, or IL-1 beta levels between lymphoma patients and normal subjects. In contrast, 20 of 57 patients (35%) with lymphoma as compared with 0 of 19 normal volunteers (0%) had detectable serum IL-6 levels (P < 0.005, chi 2 test). Interestingly, 17 of 29 lymphoma patients with B symptoms (59%) as opposed to 3 of 28 lymphoma patients without B symptoms (11%) had detectable serum IL-6 levels (P < 0.001, chi 2 test); the median IL-6 level was 28.9 pg/ml (B symptoms present) versus undetectable (no B symptoms) (P < 0.005, Mann-Whitney U test). Analyzing Hodgkin's and non-Hodgkin's lymphoma groups separately revealed similar results. IL-6 levels showed no significant correlation with time from diagnosis, beta 2-microglobulin, or lactate dehydrogenase levels. However, analysis by the method of Kaplan and Meir demonstrated that the median survival of Hodgkin's disease patients with detectable IL-6 levels (> or = 22 pg/ml) was 10 mo, whereas the median survival has not been reached at a median follow-up time of 37.5 mo in those patients with lower values (Wilcoxon P value = 0.0012). There were too few patients in each subset of non-Hodgkin's lymphoma to determine the correlation between IL-6 and survival but, considered as a single group, a statistically significant correlation was not found.(ABSTRACT TRUNCATED AT 400 WORDS)

Actuarial Analysis↗