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Children with hematologic malignancies are at an increased risk of invasive fungal infections and a greater risk has been seen with exposure to building construction. Prophylaxis with high-dose (IV) liposomal amphotericin B (L-AmB) 10 mg/kg once weekly was initiated in our high risk children based on previous pharmacokinetic studies. This treatment regimen was associated with a 26% incidence of adverse infusion reactions.

Background: Empirical treatment with antifungal drugs is often used in haematology patients at high risk of invasive aspergillosis. We compared a standard diagnostic strategy (culture and histology) with a rapid biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) for directing the use of antifungal treatment in this group of patients., Methods: In this open-label, parallel-group, randomised controlled trial, eligible patients were adults undergoing allogeneic stem-cell transplantation or chemotherapy for acute leukaemia, with no history of invasive fungal disease. Enrolled patients were randomly assigned (1:1) by a computer-generated schedule to follow either a standard diagnostic strategy (based on culture and histology) or a biomarker-based diagnostic strategy (aspergillus galactomannan and PCR) to direct treatment with antifungal drugs. Patients, were followed up for 26 weeks or until death. Masking of the use of different diagnostic tests was not possible for patients, treating physicians, or investigators. The primary endpoint was empirical treatment with antifungal drugs in the 26 weeks after enrolment (for the biomarker-based diagnostic strategy, a single postive galactomannan or PCR result was deemed insufficient to confirm invasive aspergillosis, so treatment in this context was classified as empirical). This outcome was assessed by an independent data review committee from which the study allocations were masked. Analyses were by intention to treat and included all enrolled patients. This study is registered with ClinicalTrial.gov, number NCT00163722., Findings: 240 eligible patients were recruited from six Australian centres between Sept 30, 2005, and Nov 19, 2009. 122 were assigned the standard diagnostic strategy and 118 the biomarker-based diagnostic strategy. 39 patients (32%) in the standard diagnosis group and 18 (15%) in the biomarker diagnosis group received empirical antifungal treatment (difference 17%, 95% CI 4-26; p=0·002). The numbers of patients who had hepatotoxic and nephrotoxic effects did not differ significantly between the standard diagnosis and biomarker diagnosis groups (hepatotoxic effects: 21 [17%] vs 12 [10%], p=0·11; nephrotoxic effects: 52 [43%] vs 60 [51%], p=0·20)., Interpretation: Use of aspergillus galactomannan and PCR to direct treatment reduced use of empirical antifungal treatment. This approach is an effective strategy for the management of invasive aspergillosis in high-risk haematology patients., Funding: Australian National Health and Medical Research Council, Cancer Council New South Wales, Pfizer, Merck, Gilead Sciences., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We report a protracted course of disseminated candidiasis due to Candida tropicalis in a 17-year-old man with acute lymphocytic leukemia. Despite adequate antifungal therapy (amphotericin B), C. tropicalis was recovered from biopsy specimens 25 days (skin) and 109 days (kidney) after the first positive blood cultures. While blood cultures became negative for C. tropicalis 11 days after the initiation of treatment, mannanemia persisted and became negative only after 130 days of antifungal therapy. Thus, antigen assays provided indicators of antifungal response. Differential diagnosis was difficult for this patient with the observation of persistent lesions in image studies. With positive results of antigen assays, an invasive procedure might be avoided and preemptive antifungal treatment could be initiated in a timely manner. Anti-mannan antibody remained undetectable up to 164 days after first positive blood culture despite the patient's recovery from neutropenia and recruitment of neutrophils in the tissue (skin).

Background: Hodgkin disease and myeloma were recently included in the classification of posttransplant lymphoproliferative disorder (PTLD). However, because their incidence is low, not much is known about their particular features., Methods: The incidence, characteristics, risk, and prognostic factors of myeloma, Hodgkin disease, and lymphoid leukemia using the United States Renal Data System from 1991 to 2000 among 66,159 Medicare patients were analyzed., Results: In all, 1,169 recipients developed a lymphoid disease: 823 (1.2%) non-Hodgkin's lymphomas (NHL), 160 (0.24%) myelomas, 60 (0.1%) Hodgkin lymphomas, and 126 (0.2%) lymphoid leukemias. Older age was associated with an increased risk of myeloma and leukemia. The incidence of hepatitis C virus infection was higher in recipients with myeloma (6.9 vs. 3.9%, P=0.05). Induction therapy was associated with a greater risk of myeloma and leukemia, but not Hodgkin disease. Azathioprine was associated with a lower risk of myeloma, and tacrolimus with a lower risk of Hodgkin disease. According to the type of malignancy, ten-year survival rates were significantly different: 42, 26, 55 and 39% respectively for NHL, myeloma, Hodgkin disease, and leukemia., Conclusion: These results support specific features and risk factors related to the occurrence of each type of lymphoid-proliferation and suggest for the first time a possible association between hepatitis C virus and myeloma in kidney transplant recipients.

In two young children with leukaemia, a girl and a boy aged 5 and 4 years, respectively, an invasive infection due to Moraxella catarrhalis was diagnosed at the time of granulocytopenia. They were treated with antibiotics. The first child developed pneumonia and recovered, the other developed severe septic shock and died. M. catarrhalis is a Gram-negative diplococcus, frequently colonising the upper respiratory tract in young children. In childhood this pathogen mainly causes infections such as otitis media and sinusitis, while in adults it primarily causes laryngitis, bronchitis and pneumonia. Immunocompromised patients or patients with chronic cardiopulmonary disease have an increased risk of severe infections.

Background: This study was carried out to assess the isolation rate of bacterial and fungal causative agents in Mexican neutropenic adults with hematological neoplasia., Methods: A prospective observational survey involving 120 consecutive episodes of febrile neutropenia during 1 year was carried out. These episodes were observed in 630 patients discharged with diagnoses of leukemia or lymphoma, or after bone-marrow transplantation., Results: At least one pathogen was isolated in 42 of 120 episodes (35%), and was present in 39 patients with acute myeloid leukemia (AML) (43%), acute lymphoblastic leukemia (ALL) (23%), and in patients who underwent bone-marrow transplantation (20%). Primary bacteremia was the most frequent cause of fever (24 episodes, 57%), followed by intravascular device-related infections (5 episodes, 17%), and soft-tissue infections (5 episodes, 15%). Escherichia coli (33%) was the most frequently isolated agent of primary bacteremia, followed by coagulase-negative Staphylococcus (29%), and Klebsiella oxytoca (16%). Fungal infection was responsible for five events (4%): two episodes of pneumonia (Penicillium marneffei and Aspergillus fumigatus, one event each); two cases of fungemia, one due to Candida tropicalis and one to Rhodotorula gluttinis, and one cryptococcal meningitis event., Conclusions: The isolation rate, approximately 30%, was in accordance with previous reports; similar percentages of Gram-positive and Gram-negative isolates were found. A remarkably low rate of viridans group streptococci and fungal agents was observed, despite the fact that neutropenia is the main risk factor for infection due to these agents. Studies reporting local microbiological findings are necessary because they support an antibiotic choice for prophylaxis or therapy more accurately than reports from other areas.

Bacillus species are being more frequently recognized as pathogens in immunocompromised hosts or in patients with cancer and central venous catheters. Only nine cases of Bacillus licheniformis infection have been reported in the English-language literature since 1966. In a retrospective study we describe six patients and 17 episodes of B. licheniformis bacteremia over a 5-year span. All six patients had either a Hickman or a Broviac catheter in place for more than 3 months. Five of the six patients had multiple clinically significant episodes of bacteremia due to B. licheniformis. The six patients ranged in age from 4 years to 62 years. Two patients had leukemia or lymphoma and three patients had solid tumors, but only one patient was neutropenic. No deaths were related to B. licheniformis bacteremia. B. licheniformis should be considered as a potential pathogen in immunocompromised patients, especially when bacteremia is associated with the presence of long-term central venous catheters. Mortality due to B. licheniformis bacteremia is low, but recurrent bacteremia due to this organism causes significant morbidity and usually necessitates removal of the catheter.

We describe the first case of an Epstein-Barr virus (EBV)-associated natural killer-large granular lymphocyte (NK-LGL) leukemia in the United States to the best of our knowledge. A 29-year-old woman of Japanese descent developed EBV infection after a blood transfusion as indicated by a rise in serum antibody titers. Peripheral blood and bone marrow aspirate smears demonstrated increased LGLs. Flow cytometry showed that these cells expressed NK-associated surface antigens. Cytogenetic analysis of the bone marrow aspirate showed two distinct but related clones with multiple copies of a modified 7 marker chromosome. Death followed colonic perforation. Findings at necropsy included bone marrow lymphocytosis and erythrophagocytosis, a mononucleosis-like lymphadenitis, atypical hepatitis with a mixed, predominantly T-cell infiltrate, interstitial pneumonitis, and multiorgan system vasculitis with perforation of the transverse colon. Epstein-Barr virus transcripts were identified in lymphocytes infiltrating liver and peripheral nerve by in situ hybridization. In addition, Southern blot analyses showed monoclonal bands superimposed on oligoclonal ladders of EBV termini in liver and lymph node. The identical episomal form of EBV was found in the bone marrow, lymph node, and liver. No immunoglobulin (Ig), T-cell receptor beta, or T-cell receptor gamma chain gene rearrangements were identified. These studies support the hypothesis that the LGL population was a neoplastic EBV-related clonal proliferation of NK cells.

A 70-year-old man from an endemic area of human T-cell lymphotropic virus type I (HTLV-I) developed rapid generalized lymphadenopathy and abdominal tumours. The white blood cell count was 198.3 x 10(9)/l with 93% lymphocytes, 66.3% of which expressed large granular lymphocytes (LGLs). Bone marrow and lymph nodes were also infiltrated by LGLs. Surface markers were positive for CD4, CD25 and HLA-DR, and negative for CD3, CD8, CD16, CD56 and CD57. A monoclonal integration of HTLV-I proviral DNA was demonstrated on these LGLs by Southern blot hybridization analysis. This fact indicates that some adult T-cell leukaemia/lymphoma may morphologically present LGL leukaemia.

Clonal disease of large granular lymphocytes (LGLs) may arise from either CD3+ LGLs (LGL leukemia) or CD3- LGLs (natural killer [NK] cell leukemia). Other patients have chronic LGL proliferations that cannot be proven to be clonal (lymphoproliferative disease of granular lymphocytes [LDGL]). It was recently shown that clonally expanded CD3- LGLs from Japanese patients contain Epstein-Barr virus (EBV) DNA sequences, arguing for a direct causative role for EBV in NK cell leukemia. The aggressive clinical course and other clinical features of these Japanese patients differ markedly from the clinical features of LGL leukemia and CD3- LDGL patients in the United States and Europe, suggesting different pathogenic mechanisms. Therefore, we performed serologic and DNA hybridization studies for EBV in 31 patients from the United States and Europe (18 with LGL leukemia and 13 with chronic CD3- LDGL). All patients had serologic evidence for past infection with EBV. We did not detect EBV DNA sequences in peripheral blood mononuclear cell DNA from any of these patients in Southern blot hybridization analyses. EBV DNA sequences were detected after polymerase chain reaction amplification of peripheral blood mononuclear cell DNA in only 2 of 18 LGL leukemia patients and 4 of 13 chronic CD3- LDGL patients. These results argue against a direct causative role for EBV infection in LGL leukemia or chronic CD3- LDGL occurring in the United States and Europe.

We studied a patient with large granular lymphocyte (LGL) leukemia for evidence of human T-cell leukemia/lymphoma virus (HTLV) infection. Serum from this patient was positive for HTLV-I/II antibodies by enzyme-linked immunosorbent assay (ELISA) and was confirmed positive in Western blot and radioimmunoprecipitation assays. Results of a synthetic peptide-based ELISA showed that the seropositivity was caused by HTLV-II and not HTLV-I infection. Analyses of enzymatic amplification of DNA from bone marrow sections using the polymerase chain reaction (PCR) were positive for HTLV-II specific gag, pol, env, and pX gene sequences. Cloning and sequencing of amplified products showed that the HTLV-II pol and pX sequences in patient DNA differed from the sequences of 17 other HTLV-II isolates examined in our laboratory. HTLV infection may have a role in some patients in the pathogenesis of LGL leukemia.

To investigate the mechanisms of measles virus (MV) establishment and maintenance of persistence in lymphoid cells, we have established a long-term persistent infection with MV, Edmonston strain, in the human T lymphoblastoid cell line MOLT4, which has been in continuous culture for over 8 years. In this culture, designated MOMP1, more than 98% of cells display viral antigens. The MOMP1 culture is immune to superinfection with MV and is not cured by anti-MV antibodies. No evidence of defective interfering particles was obtained. The persistently infected culture releases an infectious virus showing a miniplaque and thermoresistant modified phenotype that, unlike the parental virus Edmonston strain which produces a lytic infection with extensive cell fusion, establishes an immediate persistence in MOLT4 cells with neither significant loss of cell viability nor cell fusion. This suggests that the modification in the virus suffices to maintain the state of persistence without requiring a coevolution of the host cell during the infection, as has been reported in other persistent virus infections.

A 32-year-old female was admitted to our hospital because of abdominal fullness, jaundice and pretibial edema in November, 1987. Leukocyte count of peripheral blood showed 13300/microliters with 84% leukemic cells and bone marrow was normocellular with 63.6% leukemic cells. Leukemic cells had azurophilic large granules with basophilic cytoplasm and positive for CD 2, OKIa 1, NKH-1 and negative for CD 3, CD 4, CD 8, CD 16. T cell receptor (TCR) genes for beta, gamma and delta chain and immunoglobulin heavy chain gene were in germ line configuration. These cells also had natural killer (NK) activity and antibody dependent cell mediated cytotoxicity (ADCC) activity. These observations suggested that they were derived from NK cell lineage. It is often difficult to demonstrate their clonalities in lymphoproliferative disorder of granular lymphocytes (LDGL). In the present case, the analysis of EBV genome using termini probe demonstrated polyclonal bands, while we found constant chromosome abnormalities; 47 XX, +3. From these observations, this case was considered to have several clones, and one of which could be detected by chromosome analysis. The analysis of EBV genome using termini probe may be useful to demonstrate their clonalities in LDGL in addition to conventional chromosome analysis.

In the AKR strain of mice a high incidence of spontaneous lymphoid leukemia develops before 12 months of age. Genetic, viral, and endocrine factors interact during development to produce the syndrome. Many of the deficiencies of AKR mice are associated with gene action in chromosome 17, at or near the major histocompatibility locus. It is suggested that low steroid levels and high thyroxin levels during an early period of development are an essential part of the syndrome. Specifically, induction of a polymerase enzyme and regulation of the extent of its action by hormones are postulated to favor appearance of C-type particles and accumulation of a population of undifferentiated lymphoid stem cells. Immunodeficiency and leukemic transformation result.

19 (34%) of 56 Jamaicans with lympho-proliferative neoplasia had antibody to the human T-cell leukaemia/lymphoma virus (HTLV) in their sera. 17 of those positive had either non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukaemia. Of 16 consecutive patients presenting with NHL, 11 (69%) were HTLV seropositive. Virus-positive patients with NHL, among whom females were over-represented, had the clinical features and poor survival typical of adult T-cell leukaemia/lymphoma. HTLV-associated leukaemia/lymphoma is a distinct clinicopathological entity, and the high incidence in this series suggests that HTLV is an important cause of lymphoreticular neoplasia in Jamaica.

Proviral DNA of adult T-cell leukemia virus (HTLV-I) was examined by the standard Southern blotting method in lymph nodes of 45 patients with anti-HTLV-I antibody (ATLA)-positive adult T-cell leukemia/lymphoma (ATLL). Six of these patients revealed no monoclonal proviral HTLV-I DNA in tumor cells. These six patients showed typical flower cells in peripheral blood; they comprised five cases of the smoldering type and one of lymphoma type. They showed a longer clinical course than ATLL patients with integrated proviral HTLV-I DNA. Five of the six patients were alive from 8 to 36 months after onset; the other patient died 9 months after onset. Histologically, they exhibited features of T-cell malignancy but with absence of the typical cerebriform giant cells that are usually present in ATLL. The tumor cells represented T-cell markers, usually CD4, but CD25 was negative. Rearrangement of the T-cell receptor gene C beta was found in four of the six cases. On the basis of these results, cases of ATLL with no monoclonal proviral HTLV-I DNA should be clinicopathologically differentiated from those with integrated proviral DNA.

A lymphocytic leukemia induced by the oncogenic DNA simian virus 40 (SV40) in an inbred LSH/SsLak Syrian golden hamster was evoked to produce infectious SV40 by fusion of the leukemia cells with grivet monkey kidney (GMK) cells and by exposure of the leukemia cells to the chemical inducers mitomycin C and cycloheximide. Plaque-purified viable substrains of the rescued SV40 when studied by restriction endonuclease digestion of viral DNA were found to contain small deletions within the Hind III restriction fragment C. These deletions lay near the viral origin of DNA replication. Ten plaque-purified substrains of the rescued virus identified by immunofluorescence as being SV40 were found, when compared to the wild-type SV40, to replicate slowly and to form small plaques. Although these substrains transformed NIH/3T3 cells as efficiently as the wild-type SV40 in tissue culture, they were generally less oncogenic in vivo--7 of the 10 failed to induce tumors. The 3 oncogenic SV40-rescued substrains were not found to exhibit "lymphocytotropism," i.e., the capacity to infect and neoplastically transform preferentially hamster lymphocytes. Thus the hamster lymphocytic leukemia originally induced by the wild-type SV40 was most likely a chance-stochastic event rather than the result of tropism-determinism mediated by the virus, as is usually the case with leukemogenic RNA viruses.

Hepatitis B surface antigen (HBsAg) was detected by a monoclonal antibody radioimmunoassay in sera from five of 43 children (11.6%) with acute leukemia, who were negative by conventional assay. None of the nine positive sera had evidence of reactivity for HBV-DNA or DNA-polymerase activity. No correlation was found between the presence of HBsAg in serum by monoclonal RIA and the behaviour of anti-viral antibodies. Twenty-two children could be studied for liver HBsAg by immunofluorescence, and nine of them (40.9%) were positive, including three patients having HBsAg reactivity in serum. These data indicate that monoclonal antibodies increase the sensitivity of RIA for the detection of serum HBsAg in children with acute leukemia, who previously have frequently been found to have an atypical hepatitis B virus (HBV) serology.

Extremely early and high rate of spontaneous occurrence of nonthymic leukemias was observed in SL/Kh mice, a subline of SL mice. In a cohort of 68 females and 21 males, the cumulative incidence at 6 months of age was 88% in females and 48% in males, and at 12 months it was 100% in females and 94% in males. There were two types of leukemias with distinct in vivo homing behavior: the major type (72/86) proliferated in lymph nodes and the spleen, and the minor type (14/86) proliferated predominantly in the bone marrow cavity. In the minor type, paraplegia due to spinal compression by growing leukemia cells in vertebrae was a characteristic clinical manifestation and this was faithfully reproduced by intravenous injection of the leukemia cells from bone marrow. Both types of leukemias were histologically poorly differentiated lymphoblastic leukemias of null cell type, since none of 8 immunocytological and 4 cytochemical differentiation markers allowed either positive identification of their normal derivation or distinction between them. In contrast to AKR mice with a high incidence of thymic leukemias, spontaneous expression of xenotropic virus was observed not only in the thymus but also in the spleen and bone marrow. In addition to the high level of expression of eco- and xenotropic viruses, viruses with dual-tropic host range were isolated sporadically from preleukemic and leukemic lymphoid tissues. Possible factors determining the type of leukemias in SL/Kh mice are discussed.

Partially purified extracts from 33 human tumors of several histologic types were used as competing antigens in a radioimmunoassay for the p30 protein of an endogenous primate type C virus (M7). Antigens immunologically related to the p30 protein of the M7 virus were detected in two tumors. Like viral p30 antigens previously identified in tissues of several other primates, the antigens found in human tumors crossreact with the p30 protein of the feline RD-114 virus but are unrelated by similar immunologic criteria to the p30 proteins of several other mammalian type C viruses. Gel filtration shows that most of the antigenic activity co-chromatographs with authentic p30 protein. These results, along with those showing nucleic acid sequences related to those of an endogenous primate type C virus in the DNA of human cells, make it clear that humans, like other primates, have type C viral sequences in their genome and can, in some circumstances, express at least one type C viral protein.

The evidence has been obtained indicating the presence of the antigen of leukocyte leukosis virus (LLV) in specimens from patients with leukosis. Immunofluorescence tests with rabbit immune serum to LLV revealed specific fluorescence of the cytoplasm of cells in 19 out of 32 bone marrow punctates and leukocytes in 10 out of 12 blood smears from patients with acute leukosis and chronic myeloleukosis. In these tests, the difference from analogous control materials (from donors, patients with polyarthritis, reticulosclerodermia, mveloma, etc. is highly statistically significant. By the CFT, antibody to LLV-infected cells were detected in 60.8% of patients with leukosis and 18.5% of donors. When examined by the gel precipitation test with the appropriate test-systems LLV antigen was found to contain no group-specific antigen of murine leukosis virus or antigen of oncornaviris D from HEp-2 continuous cell line.

The ability of leukemic leukocytes to support the replication of herpes simplex virus (HSV) was studied. Mononuclear leukocytes (MNL) from the peripheral blood of patients with a variety of lymphoid leukemias were isolated on Ficoll-Hypaque gradients and infected with HSV at a multiplicity of infection of 5 to 10. No virus growth was detected in cells from patients with chronic lymphocytic leukemia (9), acute lymphocytic leukemia (1), or lymphosarcoma cell leukemia (2), HSV replication did occur in hairy cell leukemic MNL from all of 4 patients studied. Maximal titers of 10(3.7) to 10(4.7) PFU/ml occurred 1 to 7 days after incubation. By electron microscopy, herpesvirus particles were seen in the nuclei of these infected cells after 3 days of culture, but none was seen in the cells not exposed to virus. Fluorescent antibody examination confirmed the presence of HSV antigens in the nuclei of infected hairy cells. No difference in the adsorption or penetration of the virus was found with the various MNL studied. Productive infection of the cells thus appeared to depend on the ability of the leukocyte ;o support a later stage of infection, either uncoating or replication of the virus.

On a model of experimental pneumonia in mice caused by the L-forms of bacteria against the background of diminished immunity a study was made of the therapeutic efficacy of penicillin, lincomycin, lysozyme and gamma-globulin. Lincomycin, particularly in combination with biologically-active preparations, proved to be expedience for the treatment and prophylaxis of pneumonia caused by the mentioned bacteria; a rapid arrest of pneumonic process occurred and more animals survived. In the greater percentage of cases the use of penicillin was accompanied by generalization of the process.

Advantages in the use of indirect immunofluorescence for the identification of terminal transferase (TdT) in single cells may be offset by lack of specificity, as compared to the biochemical assay of the enzyme, especially in analyses of lymphocyte populations. False positive results were obtained in 15/15 tonsillectomy samples and in 9/27 specimens from children with acute lymphoblastic leukemia in remission, perhaps due to antihuman lymphocyte activity in the rabbit heteroantisera which are used in the indirect immunofluorescence technique. This phenomenon may be more pronounced in 'activated' normal lymphocytes. Such reactions are not due to antibodies directed against adenovirus, papovavirus or EB virus antigens, although these are common constitutents of human tonsillar cells. Additional problems with TdT heteroantisera may result from immunization with non-TdT determinants in calf thymus extracts, as was manifest in human non-lymphoid (KB) cells cultured in fetal bovine serum. These difficulties will be overcome only by production of a monoclonal antibody using human TdT as the antigen.

The prevalence of oral colonization with C. albicans was studied in 40 children with acute lymphoblastic leukaemia (ALL) and 40 matched normal children. Colonization was more common in the ALL group (25% colonized) than the normal group (7.5% colonized). Total saliva IgA levels were lower in the ALL group, but low levels did not correlate with oral colonization. The three normal children with oral colonization all had anti-C. albicans IgA in their saliva, as had seven of the ten colonized ALL patients.

Human T-cell lymphotropic virus type I (HTLV-I) is a human retrovirus that can transform T-helper lymphocytes and is etiologically associated with adult T-cell lymphoma/leukemia. Mycosis fungoides represents a primary cutaneous lymphoma of helper T-cell origin, while chronic lymphocytic leukemia is generally considered to be a neoplastic B-lymphocyte disorder. Our patient had HTLV-I with coexistent mycosis fungoides and B-cell chronic lymphocytic leukemia. The concurrent lymphoid proliferations may represent HTLV-I-associated abnormalities of immunoregulation.

The production and nature of alkaline phosphatase were studied in Epstein-Barr viral nuclear antigen-positive, surface membrane immunoglobulin negative-cell lines established from two patients, one with acute myeloid leukemia and one with acute lymphoblastic leukemia. The acute myeloid leukemia-derived cells contained myeloid alkaline phosphatase, while the acute lymphoblastic leukemia-derived cells contained lymphoid alkaline phosphatase. The presence of the myeloid-specific enzyme in a surface membrane immunoglobin--negative cell line suggests that the line is composed of myeloid precursor cells and that such cells may be susceptible to infection with Epstein-Barr virus.

Nine patients with chronic lymphocytic leukemia (CLL), with pulmonary involvement confirmed by biopsy, presented with progressive cough and/or shortness of breath and had interstitial infiltrates on chest radiographs. Biopsies showed a dense lymphocytic infiltrate that followed bronchovascular bundles. We considered CLL the predominant finding, and the cause of the patient's pulmonary disease, in eight cases; in one, a histologically nonspecific organizing pneumonia was the main lesion and CLL was an incidental finding. Culture results were available in six cases and were negative except in one case with presumed contaminants. A granulomatous reaction was present in five cases and was necrotizing in two, although culture results were negative. The only case with a recognizable organism had noninvasive fungal hyphae growing in many of the small airways. All of the patients' respiratory symptoms improved after chemotherapy and/or steroid therapy, and the chest radiographs also showed clearing.

Fifty consecutive episodes of septicemia were studied in 41 children who had acute lymphoblastic leukemia. Seventy-six percent of these episodes occurred when the absolute granulocyte count was 200/mm3 or less and were caused by gram-negative enteric and gram-positive mucocutaneous bacteria. In eight patients, Streptococcus pyogenes was isolated at the time when ALL was diagnosed. Multiple anaerobic and aerobic isolates from a single blood culture were associated with abdominal distress, whereas Streptococcus pneumoniae and Hemophilus influenzae septicemia occurred in associated with respiratory illnesses. When patients with severe compromise of anatomic barriers or respiratory disease were excluded, 94% of all patients with septicemia had an AGC of less than 200/mm3. The data provide guidelines for treatment for febrile patients with ALL based upon the AGC, the phase of the disease, and on the presence of associated respiratory or abdominal findings.

As part of epidemiologic studies of human T-lymphotropic virus (HTLV)-I-associated malignancies in Jamaica, the authors evaluated 26 patients with non-Hodgkin's lymphoma for the presence of integrated HTLV-I provirus in their malignant cells. Fifteen of 26 patients had integrated provirus. All 15 also were HTLV-I antibody positive. Eleven patients did not have integrated provirus, and all 11 were antibody negative. All of the antibody-positive cases had onset of their disease in adulthood (age range, 21-57 years) as opposed to the broad age range of negative cases (4-66 years). Clinical features which were more common in provirus positive than negative patients included leukemic phase, skin involvement, and hypercalcemia, which are all features frequently seen in HTLV-I-associated adult T-cell leukemia/lymphoma (ATLL). The presence of skin involvement, circulating malignant cells, abnormal liver function tests, or the presence of two or more of these four features were statistically significantly different between virus-positive and virus-negative cases. Although the survival of positive cases (6 months) was shorter than that of negative cases (9 months), this was not statistically significant. The only significant determinant of survival was hypercalcemia, with those who developed hypercalcemia at some point in their disease course, independent of their HTLV-I status, surviving a mean of 5 months as compared to a mean of 17.5 months in those who never became hypercalcemic. The six HTLV-I-positive lymphomas that underwent cell typing were all primarily OKT4 positive, whereas two HTLV-I antibody-negative cases that were typed were B-cell lymphomas.

The electron microscopic examinations of the short-term cultures of mononuclear cells from patients with T-cell acute lymphoblastic leukemia were conducted for the detection of viral particles. The viral particles which correspond in their morphology to C type retroviruses are observed in the intercellular space of the culture.

Five gibbon ape leukemia virus substrains (two from gibbons with lymphocytic leukemia and three from gibbons with myelogenous leukemia) were examined for unique genomic sequences specific for each form of leukemia. By using sequential adsorption procedures, the genome from each gibbon ape leukemia virus was fractionated into four sets of distinct nucleotide sequences. Based on their hybridization specificities toward DNAs of leukemic tissues, these sequences were designated as follows: (i) "COM," (ii) "LYM" or "MYE," (iii) "UNI," and (iv) "UND." The COM fraction represented sequences common to all of the viral genomes. The LYM fraction, which was isolated only from gibbon ape leukemia viruses associated with lymphocytic leukemia, represented genomic sequences associated with lymphocytic leukemia since the RNA hybridized at a 4- to 15-fold-higher rate to infected tissue DNA from lymphocytic leukemic gibbons than to infected tissue DNA from myelogenous leukemic gibbons. The MYE fraction, which was isolated only from gibbon ape leukemia viruses associated with myelogenous leukemia, represented genomic sequences associated with myelogenous leukemia since the RNA hybridized at a 5- to 15-fold-higher rate to infected tissue DNA from myelogenous leukemic gibbons than to infected tissue DNA from lymphocytic leukemic gibbons. The UNI fraction contained sequences unique to one virus substrain. The UND fraction contained sequences which varied depending upon the substrains involved in the adsorption procedures. These findings suggest that each gibbon ape leukemia virus examined in this study contains subgenomic sequences that are specifically identifiable only with the form of leukemia from which the virus was isolated.

Mycoplasma salivarium was recovered from the blood of a five-year-old girl who had leukemia and subsequently developed pneumonitis. The patient's pneumonitis failed to respond to nafcillin, a cell-wall-active antibiotic, but eventually she recovered from the pneumonia after a regimen of erythromycin. Sputum, oropharyngeal, and nasopharyngeal cultures revealed normal bacterial flora; a blood culture was negative for bacteria. Throat and sputum cultures were negative for mycoplasma; however, M salivarium was recovered from the patient's blood. The patient had a cold hemagglutinin titer of 1:250.