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M Krailo

Publications and source records attributed to M Krailo.

44 records · Page 3Linked to original sources

Results of initial lymph node biopsy in homosexual men with generalized lymphadenopathy.

Persistent, generalized lymphadenopathy (PGL) is considered part of the acquired immunodeficiency syndrome (AIDS)-related complex. The clinical course is usually benign, although some patients may evolve to AIDS. Characteristic features on lymph node biopsy have been described. Recently, large series of PGL have been reported in which many study patients have not undergone initial diagnostic biopsy. The value of such biopsy has been questioned. We report the clinical, pathologic, and laboratory findings in six homosexual men initially considered as potential candidates for study of the natural history of PGL. They were excluded by initial lymph node biopsy, which revealed small-cleaved lymphoma in two, focal Kaposi's sarcoma in two, disseminated mycobacterium tuberculosis in one, and histoplasma encapsulatum in one. The clinical and laboratory data from these six patients were compared with those from 34 patients with biopsy-proven PGL; no statistically significant difference in any prebiopsy clinical parameter was found. We conclude that initial lymph node biopsy may reveal changes other than reactive hyperplasia in homosexual men with generalized lymphadenopathy.

Acquired Immunodeficiency Syndrome↗

Suramin antiviral therapy in the acquired immunodeficiency syndrome. Clinical, immunological, and virologic results.

The human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) requires reverse transcriptase for viral replication. We treated 12 patients who had acquired immunodeficiency syndrome and active HTLV-III/LAV viremia with suramin, a potent competitive inhibitor of reverse transcriptase, in six weekly induction doses of 1 g, followed by weekly maintenance doses of 500 mg. Three of eleven evaluable patients had complete inhibition of viral reverse transcriptase levels, lasting at least 18 weeks in each. Two additional patients had marked reduction in reverse transcriptase activity. Nadir serum suramin levels at the end of the induction phase correlated with the level of reverse transcriptase reduction. Toxicity included hepatic transaminase elevation, fever, malaise, rash, proteinuria, paresthesias, reversible neutropenia, and adrenal insufficiency. Objective clinical improvement was documented in 1 patient, but no patient had improvement in immune function and 7 patients had recurrent opportunistic infections. Although suramin may suppress HTLV-III/LAV viremia, its significant toxicity and lack of effect on immune variables indicate that alternative therapy will be required.

Acquired Immunodeficiency Syndrome↗

A comparison of imaging, clinical, and pathologic aspects of space-occupying lesions within the brain in patients with acquired immune deficiency syndrome.

Patients with acquired immune deficiency syndrome (AIDS) often have central nervous system mass lesions. Since clinical signs, symptoms, and results of imaging techniques are generally nonspecific, brain biopsy has been considered to be the optimal method for establishing a definitive diagnosis. In an effort to define better the imaging characteristics of such lesions, we retrospectively analyzed 24 patients with AIDS who had intracerebral space-occupying lesions, with subsequent definitive histologic diagnosis and/or a diagnostic response to empiric therapy for toxoplasmosis. We employed computerized tomography (CT), double-dose-delay CT (DDD-CT), and nuclear magnetic resonance imaging (NMRI) of the brain. Sixteen patients had toxoplasmosis, seven had high-grade non-Hodgkins lymphoma, and one had progressive multifocal leukoencephalopathy that was due to herpes simplex virus II (HPML). Toxoplasmosis generally occurred as multiple, small (2 cm or smaller), hypodense or isodense lesions with variable enhancement. Malignant lymphomas appeared as single lesions, always larger than 3 cm, which were isodense or hyperdense, with internal enhancement. The combined radiologic criteria of size, multiplicity, and pre- and postcontrast appearance were useful in differentiating these two pathologic processes. The best single discriminant of toxoplasmosis versus lymphoma was the average lesion size of less than 3 cm. In our experience, diagnostic brain biopsy may be averted when lesions typical of toxoplasmosis are seen. DDD-CT and NMRI may be useful in identifying lesions that are not seen optimally on routine CT.

Acquired Immunodeficiency Syndrome↗

Retrovirus and malignant lymphoma in homosexual men.

We report malignant lymphoma in 27 homosexual men, of whom 22 had high-grade lymphomas (B-cell immunoblastic sarcoma or small non-cleaved lymphoma) and five had low-grade disease. Antibody to human T-cell lymphotropic virus type III (HTLV-III) was present in 13 (87%) of 15 with high-grade lymphoma and in two (40%) of five with low-grade disease. In contrast, only one (9%) of 11 "control" heterosexual patients with high-grade lymphoma had antibody to HTLV-III, while such antibody was found in none of 40 asymptomatic heterosexual controls and in 17 (55%) of 31 asymptomatic homosexual men. Of the homosexual lymphoma patients, 85% presented with disease in extranodal sites, including the central nervous system and rectum, and 81% had reversed T-helper/suppressor ratios. Median survival, despite treatment, is eight months. The acquired immunodeficiency syndrome-related lymphomas in homosexual men are extranodal, high-grade, B-lymphoid tumors, associated with exposure to HTLV-III and unusual clinical characteristics.

Acquired Immunodeficiency Syndrome↗

Prognostic implications of blast cell morphology in childhood acute lymphoblastic leukemia: a report from the Childrens Cancer Study Group.

The Childrens Cancer Study Group (CCSG) has evaluated French-American-British (FAB) morphology in newly diagnosed children with acute lymphoblastic leukemia (ALL) since 1975. A modification of the FAB system was used in which individual lymphoblast cells were scored and designated as either L1 or L2 on the basis of distinctive morphologic characteristics. L1 ALL was defined as less than 10% L2 cells and greater than 90% L1 cells; L2 ALL was defined as greater than or equal to 10% L2 cells and less than 90% L1 cells. FAB morphology was an independent predictor of overall survival (P = 0.02) in CCSG-141 and a highly significant predictor of successful induction of complete remission and event-free survival in the CCSG-160 series (P = 0.00001). These studies involved nearly 3900 patients. Two concordance studies have been performed. In the first (1981) study, overall concordance between the FAB reference laboratory and member institutions was 76% using a two-category system (L1, non-L1), 86% for L1 cases, and 47% for non-L1 cases. In the second (1984) concordance study, the use of more stringent, semiquantitative definitions of L1 and L2 lymphoblasts did not improve overall (75%), L1 (89%), or non-L1 (46%) concordance. The results of reference laboratory classification more powerfully predicted event-free survival than did member institutions (P = 0.016 vs P = 0.125). Quality control factors (slide preparation, cellularity, staining quality, and discipline of the reviewer) did not influence concordance. These results justify the continued assignment of patients to protocols of the CCSG-100 series on the basis of the modified FAB classification. The biological significance of the FAB morphologic variants remains to be determined.

Child↗

Limitations of numerical ratios for defining monoclonality of immunoglobulin light chains in B-cell lymphomas.

Hematopathologists sometimes rely upon the "monoclonality" of immunoglobulin light chains of B-cells as an indicator of malignancy in lymph node biopsies. The validity of using the ratio of kappa to lambda light chains for defining monoclonality has not been statistically established, however. We examined with flow cytometry 57 unequivocal B-cell lymphomas and 49 benign lymphoid hyperplasias. Our purpose was to define and study the optimal numerical criteria for discriminating between B-cell lymphomas and benign hyperplasia on the basis of the kappa:lambda ratio. The data indicate that ratios less than .7 or greater than 5.5 are the optimum for discriminating between lymphoma and benign hyperplasia, but they have a false negative rate of approximately 27% and a 6% false positive rate. The reasons for the relatively low sensitivity are discussed. We conclude that kappa:lambda ratios are a fairly specific but insensitive parameter for distinguishing between B-cell lymphoma and benign lymphoid hyperplasia.

Antibodies, Monoclonal↗

Comparison of the antiemetic effect of high-dose intravenous metoclopramide and high-dose intravenous haloperidol in a randomized double-blind crossover study.

Metoclopramide is an effective antiemetic for cisplatin-induced vomiting when given in parenteral high-dose regimens but not oral low-dose regimens. Metoclopramide was compared to haloperidol, also given in a high-dose parenteral regimen. Patients received two cycles of cisplatin at a dose greater than or equal to 70 mg/m2. Metoclopramide (2 mg/kg intravenous) was given every two hours for five doses beginning one half hour before cisplatin. Haloperidol (3 mg intravenous) was given on the same schedule. A randomized double-blind crossover design was used to control subjective bias and to compare the same patient's experiences. Twenty-eight patients completed both study arms. Excellent control of vomiting was achieved with both drugs. Metoclopramide resulted in 1.92 vomiting episodes (range, 0-5) with 36% having no vomiting. Haloperidol resulted in 3.04 vomiting episodes (range, 0-8) with 20% having no vomiting. Significantly fewer vomiting episodes were noted with metoclopramide rho = .006, paired sign test). However, responses to the two drugs were well correlated (Spearman's rho = .39, P = .03). Metoclopramide and haloperidol are both excellent antiemetics when given in sufficient dosage by an effective route. Metoclopramide does show a mild advantage. However, the positive correlation in response to these agents suggests a common mechanism of action. The ability to identify related antiemetics will be useful in the design of rational combination antiemetic therapy.

Adult↗

Phase I trial of anti-B4-blocked ricin in pediatric patients with leukemia and lymphoma.

Monoclonal antibodies, specific for antigens expressed on lymphoid malignancies, which have been conjugated to toxins such as ricin, hold promise in the therapy of childhood leukemia and lymphoma. Anti-B4-blocked ricin (anti-B4-bR) is such an agent, and a phase I study of this agent was conducted in children with relapsed or refractory B-lineage leukemia and lymphoma. Anti-B4-bR was given as two 7-day continuous infusions separated by 7 days. Twenty patients were enrolled and 19 received the drug. Two dosage levels (30 and 40 microg/kg per day) were evaluated. Forty micrograms per kilogram per day was the maximally tolerated dose. Dose-limiting toxicity was capillary leak syndrome. Grade 3 reversible elevation in transaminases was also encountered. Human antimouse antibodies or human antiricin antibodies were detected in five patients. No complete remissions or partial remissions were seen.

Adolescent↗