Small cell carcinoma of the lung treated with irradiation and chemotherapy. Autopsy confirmation of long-term disease-free survival

A patient survived clinically disease free for 68 months following combination chemotherapy and radiotherapy for small cell carcinoma of the lung. No evidence of tumor was found at autopsy. To our knowledge, this represents the first documentation by autopsy of a greater than five year disease-free survival following treatment of small cell cancer of the lung.     

A randomized, controlled, phase II trial comparing escalating doses of subcutaneous interleukin-2 plus antiretrovirals versus antiretrovirals alone in human immunodeficiency virus-infected patients with CD4+ cell counts >/=350/mm3

A total of 73 patients with baseline CD4+ cell counts >/=350 cells/mm3 who were receiving combination antiretroviral therapy (ART) were randomized to receive subcutaneous interleukin-2 (IL-2; n=36) in addition to ART or to continue ART alone (n=37). Subcutaneous IL-2 was delivered at 1 of 3 doses (1.5 million international units ?MIU, 4.5 MIU, and 7.5 MIU per dose) by twice-daily injection for 5 consecutive days every 8 weeks. After 24 weeks, the time-weighted mean change from baseline CD4+ cell count was 210 cells/mm3 for recipients of subcutaneous IL-2, compared with 29 cells/mm3 for recipients of ART alone (P<.001). There were no significant differences between treatment groups for measures of plasma human immunodeficiency virus RNA (P=.851). Subcutaneous IL-2 delivered at doses of 4.5 MIU and 7.5 MIU resulted in significant increases in CD4+ cell count (P=.006 and P<.001, respectively), compared with that seen in control patients. These changes were not significant in the 1.5 MIU dose group compared with that in the control patients (P=.105). Side effects that occurred from subcutaneous IL-2 administration were generally low grade, of short duration, and readily managed in an outpatient environment.     

Afibrinogenemia and hypobetalipoproteinemia in a kindred

A 3-year-old boy with minor bleeding problems had no plasma fibrinogen measured by both clottable assay and immuno-precipitation. Low normal fibrinogen levels were present in the mother and father. Markedly decreased plasma cholesterol and apolipoprotein B levels were found in the father, proband's brother, and the paternal side of the kindred. The proband and his mother had normal plasma total cholesterol and apolipoprotein B levels. These findings are compatible with autosomal dominant transmission of hypobetalipoproteinemia and autosomal recessive transmission of afibrinogenemia. Two members of the father's family had plasma cholesterol levels below the fifth percentile but elevated levels of fibrinogen (6.0 and 4.4 g/L). Both have symptomatic coronary heart disease. Finding coronary heart disease with very low cholesterol but elevated fibrinogen levels is consistent with fibrinogen levels being an independent risk factor for coronary heart disease.     

Syngeneic bone marrow transplantation and adoptive transfer of peripheral blood lymphocytes combined with zidovudine in human immunodeficiency virus (HIV) infection

OBJECTIVE: To examine the role of syngeneic bone marrow transplantation and peripheral blood lymphocyte infusions combined with zidovudine in the treatment of patients with human immunodeficiency virus (HIV) infection. DESIGN: A partially randomized outpatient trial. SETTING: Outpatient and inpatient facility of the Clinical Center of the National Institutes of Health, a research-based referral facility. PATIENTS: Sixteen patients with HIV infection (15 symptomatic, 1 asymptomatic). INTERVENTIONS: Symptomatic patients were treated with zidovudine, 500 mg orally every 4 hours for 12 weeks, combined with six peripheral blood lymphocyte infusions (four at week 10, two at week 12) and bone marrow transplantation (at week 12) using HIV-seronegative identical twins as donors. After transplantation, patients were randomly assigned to receive either zidovudine, 100 mg every 4 hours, or placebo for 12 months. The asymptomatic patient received zidovudine for the first 12 weeks, discontinuing therapy after transplantation. Immunologic and virologic monitoring were done monthly. MEASUREMENTS AND MAIN RESULTS: Immediately after lymphocyte infusions and bone marrow transplantation, there was an increase in the mean (+/- SE) CD4 cell percent (19.1% +/- 3.1% to 28.1% +/- 3.0%), an increase in the fraction of patients with delayed-type hypersensitivity responses to tetanus toxoid (4 of 13 to 11 of 13) and the development of delayed-type hypersensitivity to keyhole-limpet hemocyanin (a primary immunogen to which only the donor had been immunized) in 8 of 12 patients tested. No significant clinical improvement was noted, however, and there was no overall sustained immunologic improvement. No differences in CD4 cell percents, delayed-hypersensitivity skin tests, HIV cultures, or p24 antigenemia were seen between patients treated with zidovudine or placebo after transplantation. CONCLUSIONS: Although they establish the feasibility of combining zidovudine with cellular immune reconstitution in treating patients with HIV infection, our results show that any benefits from such combination therapy are at best transient. Future attempts at cellular immune reconstitution may need to use improved antiretroviral regimens as well as immunization of donors with HIV-specific antigens.     

A clonally distinct recurrence of Burkitt's lymphoma at 15 years

A human immunodeficiency virus-negative male was successfully treated for two occurrences of Burkitt's lymphoma, 15 years apart. As consolidation of his second remission, he underwent high-dose chemotherapy with peripheral blood stem cell transplantation. In an effort to prove whether the second lymphoma was a relapse of the first or a second primary lymphoma, we obtained paraffin-embedded material from both lymphomas. DNA was extracted from this material and amplified by polymerase chain reaction (PCR) using consensus JH and VH region primers. Analysis of the PCR products, which mostly reflects VDJ joints, showed two sharp bands of different molecular size, proving the monoclonal nature of the lymphomas and suggesting that each had different Ig gene rearrangements. Sequencing of both PCR products showed a marked dissimilarity in nucleotide sequence in the clonally unique VDJ joint region, providing strong evidence for the separate cellular genesis of each lymphoma. These results suggest that late relapses of Burkitt's lymphoma should be examined for clonal distinctiveness. If the second lymphoma is distinct from the primary one, it might be treated as a primary lymphoma rather than as recurrent disease.     

Cryptococcosis in the acquired immunodeficiency syndrome

The clinical course and response to therapy of 27 patients with cryptococcosis and the acquired immunodeficiency syndrome were reviewed. Cryptococcosis was the initial manifestation of the syndrome in 7 patients, and the initial opportunistic infection in an additional 7. Meningitis was the commonest clinical feature (18 patients). Blood cultures and serum cryptococcal antigen were frequently positive. In patients with meningitis, leukocyte count, protein level, and glucose level in cerebrospinal fluid were frequently normal; cerebrospinal fluid India ink test (82%), culture (100%), and cryptococcal antigen (100%) were usually positive. Only 10 of 24 patients had no evidence of clinical activity of cryptococcal infection after completion of therapy; 6 of these 10 had relapses shown by clinical findings or at autopsy. Standard courses of amphotericin B alone or combined with flucytosine were ineffective. Cryptococcosis in patients with the syndrome is a debilitating disease that does not respond to conventional therapy; earlier diagnosis or long-term suppressive therapy may improve the prognosis.     

Laboratory methods in the diagnosis and prognostic staging of infection with human immunodeficiency virus type 1

Laboratory evaluation of infection with human immunodeficiency virus type 1 (HIV-1) may involve detection of antibodies to HIV-1, direct detection of HIV-1 itself, and measurement of an individual's immunologic status at the time of presentation. The ELISA is currently the preferred initial screening test, although a variety of other rapid immunoassays have also been developed. Methods defining the antigenic specificity of the antibody response, such as the western blot, have become standard confirmatory tests in this setting. CD4+ cell enumeration and the HIV-1 antigen capture assay are useful in predicting the course of HIV-1 infection and in monitoring antiretroviral therapies. Newer techniques of HIV-1 co-cultivation permit the characterization of viral isolates and the stratification of patients and facilitate monitoring of the effects of antiretroviral agents. The polymerase chain reaction is of value in identifying HIV-1 infection in individuals with inconclusive serologic results. Judicious use of other laboratory tests, including surrogate markers such as beta 2-microglobulin, also provides prognostic information potentially useful in clinical management of HIV-1-infected patients.