Autologous transplantation for diffuse aggressive non-Hodgkin's lymphoma in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.

PURPOSE: To evaluate the results of high-dose chemotherapy and autologous hematopoietic stem-cell transplantation (autotransplants) in patients with diffuse aggressive non-Hodgkin's lymphoma (NHL) who never achieve a complete remission with conventional chemotherapy. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 184 patients with diffuse aggressive NHL who never achieved a complete remission with conventional chemotherapy and subsequently received an autotransplant were evaluated. Transplants were performed between 1989 and 1995 and were reported to the ABMTR by 48 centers in North and South America. RESULTS: Seventy-nine (44%) of 184 patients achieved a complete remission or a complete remission with residual imaging abnormalities of unknown significance after autotransplantation. Thirty-four (19%) of 184 had a partial remission and 55 (31%) of 184 had no response or progressive disease. Eleven patients (6%) were not assessable for response because of early death. The probabilities of progression-free and overall survival at 5 years after transplantation were 31% (95% confidence interval [CI], 24% to 38%) and 37% (95% CI, 30% to 45%), respectively. In multivariate analysis, chemotherapy resistance, Karnofsky performance status score less than 80 at transplantation, age > or = 55 years at transplantation, receiving three or more prior chemotherapy regimens, and not receiving pre- or posttransplant involved-field irradiation therapy were adverse prognostic factors for overall survival. CONCLUSION: High-dose chemotherapy and autologous hematopoietic stem-cell transplantation should be considered for patients with diffuse aggressive NHL who never achieve a complete remission but who are still chemotherapy-sensitive and are otherwise transplant candidates.

Palliative treatment with low-dose continuous infusion 5-fluorouracil in recurrent and/or metastatic undifferentiated nasopharyngeal carcinoma type.

BACKGROUND: Low-dose protracted continuous infusion (CI) 5-fluorouracil (5-FU), as proposed by Lokich et al, has been reported to be active and well tolerated in colorectal and breast cancers. We initiated a phase II trial with CI 5-FU in heavily pretreated undifferentiated carcinoma of the nasopharyngeal type (UCNT) patients in February 1989. METHODS: Twenty-one UCNT patients with recurrent and/or metastatic disease were treated with CI 5-FU (300 mg/m2) for 6 consecutive weeks. Treatment was to be continued until disease progression. RESULTS: Toxicity was mild. Diarrhea and mucositis (WHO grade 2 or greater) were seen in 4 (20%) and 6 patients (30%), respectively. Myelosuppression was infrequent, with only one patient with bone marrow invasion, experiencing grade 3 leukopenia. Two complete and 3 partial responses were obtained in 20 evaluable patients (ORR:25%). The median time to progression was 4 months (range 2-14); The median survival for the whole population was 10 months (avg 2-41). CONCLUSION: This appears to be a useful palliative treatment for heavily pretreated UCNT patients.

[Undifferentiated carcinoma of the nasopharynx: epidemiological, clinical and therapeutic aspects]. / Carcinomes indifférenciés du nasopharynx: aspects épidémiologique, clinique et thérapeutique.

Undifferentiated carcinoma of the nasopharynx (UCNT) is a particular head and neck epidermoïd lineage tumor related to the Epstein-Barr Virus (EBV). It has geographically selective endemic epidemiologic features, without relation to external carcinogens. Its systemic agressiveness is the source of most disease related demises, since radiotherapy achieves excellent local control and a significant percentage of cure in patients with exclusive locoregional disease. Differences in the staging systems currently in use, the recent changes in imaging and radiotherapy technology, and the lack of distinction between UCNT and SCC of the nasopharynx in Western literature reports make for some difficulty in therapeutic results evaluation when analyzing available literature. Its chemosensitivity is a relatively recent acknowledged fact, and its use in metastatic patients results in a high percentage of objective responses, many of long duration. Neoadjuvant cisplatin based chemotherapy seems to be of benefit, but outstanding controversies in this regard will be soon answered through ongoing phase III trials. After a review of the current literature of all the above mentioned aspects of this fascinating nosologic entity, our own experience in over 250 patients seen during the past 8 years, both in metastatic and locoregional disease patients is analyzed.

The influence of guided imagery on chemotherapy-related nausea and vomiting.

The purpose of this study was to determine if the addition of guided imagery to a standard antiemetic regimen decreased nausea, vomiting, and retching occurrence and distress in patients receiving cisplatin-based chemotherapy. A convenience sample of patients (N = 28) was selected from an oncologist's patient population and randomized into two groups. Both groups received the same standard antiemetic regimen, while the experimental group additionally used a chemotherapy-specific guided-imagery audiotape. The Rhodes Index of Nausea and Vomiting Form 2 was used to measure the nausea and vomiting experience. Findings revealed no statistically significant difference in this measurement between the two groups when measured at five different times during chemotherapy administration. The Chemotherapy Experience Survey was used to evaluate the participants' overall perceptions of the chemotherapy experience. The guided-imagery group expressed a significantly more positive experience (p = 0.0001) with chemotherapy. These findings have definite implications for developing effective nursing interventions to promote patient involvement in self-care practices and to increase patient coping abilities during symptom occurrence.

The complementary roles of surface-immunoglobulin clonality and fluorescence intensity, mouse rosettes, and cd5 in the diagnosis of B-chronic lymphocytic-leukemia.

Peripheral blood from 77 cases of B-CLL was analyzed to evaluate the diagnostic value of SIg clonality and fluorescence intensity, mouse rosettes (MR), and CD5. Monoclonal SIg (L-chain restriction or H-chain restriction or both) was detected in 69 cases (89.61%), with weak fluorescence (mean channel number on flow cytometry <200) in 65 (94.2%); MR was positive in 66 (85.71%); CD5 positive in 64 (83.12%). The association of SIg intensity, MR, and CD5 was as follows: weak SIg/MR+/CD5+, 41 cases (53.25%); weak SIg/MR+/CD5-, 13 (16.88%); weak SIg/MR-/CD5+, 11 (14.29%); strong SIg/MR+/CD5+, 4 (5.19%); and undetected SIg/MR+/CD5+, 8 (10.39%). Thus, by performing the three markers and accepting either two or three positive results (weak SIg, MR+, CD5+) as sufficient for diagnosis, all 77 cases (100%) were diagnosed. The study demonstrated the complementary roles between L- and H- chains, and between SIg intensity, MR, and CD5 in immunophenotyping CLL.

Characterization of a cytosolic fucosylation pathway in Dictyostelium.

FP21 is a 21-kDa fucoprotein which fractionates with the cytosol after high-speed centrifugation of gently lysed Dictyostelium cells. Less than 0.7% of FP21 is associated with vesicles. In proliferating cells, 4 x 10(5) fucosyl moieties/cell are associated with FP21 as anionic, possibly O-linked oligosaccharides equal in size to 4.8 glucose units. FP21 is underfucosylated in a mutant strain (HL250) that depends on extracellular fucose for synthesis of GDP-fucose. To determine the cellular site of FP21 fucosylation, cytosolic and vesicular preparations from strain HL250 were compared for their ability to transfer fucose from GDP-fucose to FP21. Cytosolic preparations fucosylate endogenous FP21 in a time-, concentration-, and divalent cation-dependent fashion, with a Km for GDP-fucose of 1.4 microM. Activity in normal cell cytosol is dependent on exogenous mutant FP21, demonstrating that FP21 is normally fully fucosylated. Both mutant and normal cytosols are also able to alpha-fucosylate a type 1 glycolipid substrate (8-methoxycarbonyloctyl-Gal beta 1-3 beta GlcNAc), but not related substrates, with Km values for the type 1 glycolipid of 0.99 mM and for GDP-fucose of 1.6 microM. Competitive inhibition between FP21 and the type 1 glycolipid shows that the same enzyme fucosylates both substrates. Intact and permeabilized vesicle preparations from wild-type cells are unable to fucosylate FP21 or the type 1 glycolipid by a divalent cation-dependent mechanism, and thus are devoid of FP21-fucosyltransferase. Since control experiments showed that vesicle leakage is minimal during cytosol preparation, these results indicate that FP21 is synthesized and fucosylated in the cytosolic compartment, by an unusual soluble fucosyltransferase.

The spore coat of a fucosylation mutant in Dictyostelium discoideum.

Strain HL250 of Dictyostelium discoideum cannot convert GDP-mannose to GDP-fucose, resulting in an inability to fucosylate protein. This affects a group of proteins which are normally fucosylated intracellularly and then secreted via prespore vesicles to become part of the outer lamina of the spore coat. We have found that strain HL250 nevertheless accumulates typical amounts of these proteins, stores them normally in prespore vesicles, and secretes them normally to become a part of the spore coat. However, affected proteins are proteolyzed after germination, the spore coat is more accessible to penetration by a macromolecular probe, and germination is inefficient in older spores. These findings can be explained by a dependence of the integrity of the outer layer of the spore coat on protein-linked fucose.

Necrobiotic xanthogranuloma with paraproteinemia. Case report and a pathogenetic theory.

Necrobiotic xanthogranuloma with paraproteinemia is a clinical and histopathological entity characterized by xanthelasma-like lesions in the periorbital region and elsewhere, paraproteinemia, leukopenia, and an elevated erythrocyte sedimentation rate. Multiple myeloma has been reported as an accompanying feature in several cases. We examined a patient with necrobiotic xanthogranuloma and multiple myeloma in whom an IgG kappa monoclonal protein was identified in serum, urine, bone marrow, and bilateral periorbital lesions. We speculate that increased serum immunoglobulins complexed with lipid may be deposited in the skin, leading to a foreign body giant cell reaction and the subsequent characteristic histopathologic features of necrobiotic xanthogranuloma.

Acute myelogenous leukemia in pregnancy.

The experience with acute myelogenous leukemia treated with newer chemotherapeutic agents during pregnancy is limited. We have reported the case of a mother treated during the 24th week of pregnancy, and her infant delivered in the 29th week. At 14 months the infant is of low height and weight, but has a normal head circumference and developmental parameters.

Non-frozen preservation of committed hematopoietic stem cells from normal human bone marrow.

We examined the optimal conditions for maintaining normal human hematopoietic stem cells without cryopreservation. The effects of serum, HEPES, CPD and storage temperature were studied. Stem cell integrity (CFU-c, CFU-e, and BFU-e) was optimally maintained when the bone marrow cells were suspended in a medium containing 40% fetal calf serum, 25 mM HEPES, and 12.28% CPD and maintained at 4 degrees C. For example, under these storage conditions the recovery of functionally intact early erythroid stem cells, BFU-e, was 84% after 2 days, 44% after 4 days and 12% after 7 days. These results indicate that non-frozen short-term storage of human bone marrow may be of clinical utility in bone marrow transplantation.

Metastatic tumors of the orbit.

A wide variety of metastatic tumors can invade the orbit. The incidence of orbital metastases varies in different studies and may be increasing. The most common tumors in children and adults are enumerated. The clinical features are given and diagnostic techniques listed. The value of the carcinoembryonic antigen is shown by data and a case report. The prognosis and treatment of orbital metastases are detailed with specific reference to breast cancer. The estrogen receptor assay is described and its usefulness illustrated with a case report.

Ophthalmic manifestations of metastatic breast cancer.

Metastatic breast cancer is the most common primary tumor metastasizing to the ocular structures. An analysis of 30 patients demonstrated a wide spectrum of ophthalmic manifestations including cranial nerve involvement, brain involvement with papilledema, Horner's syndrome, and choroidal and orbital tumors. The mean age of patients presenting with an ophthalmic sign was 54 years and the mean interval from the diagnosis of breast cancer to the development of the ophthalmic sign was 4.9 years. The carcinoembryonic antigen (CEA) was useful in confirming the diagnosis of metastatic disease as it was elevated in 18 of the 22 patients in whom it was measured. The estrogen receptor assay, performed on metastatic tissue removed from the orbit, can indicate the sensitivity of the breast cancer to hormonal therapy.

Immune function of successfully treated lymphoma patients.

Immunologic function was evaluated in 12 patients with Hodgkin's disease and 5 patients with lymphocytic lymphoma who had been successfully treated with either chemotherapy, radiation therapy, or both of these modalities 3-42 mo previously. Only two of the patients were found to have total anergy to a battery of six recall skin test antigens and all were responsive to skin testing with phytohemagglutinin. However, 10 of 16 patients were unable to develop delayed cutaneous hypersensitivity to either of the neoantigens dinitrochlorobenzene or keyhole limpet hemocyanin. Four other patients developed reactivity to only one of these neoantigens for a total of 14 of 16 (88%) of the patients demonstrating some impairment in neoantigen response. Total lymphocyte, T-lymphocyte, B-lymphocyte, and null cell numbers, as well as serum immunoglobulins were quantitatively normal. Monocyte numbers, chemotaxis, and Fc receptor activity were normal. Monocyte staphylocidal activity at 60 min was modestly depressed and candidacidal activity was depressed in those receiving both chemotherapy and radiation therapy. Spontaneous (unstimulated) lymphocyte [3H]thymidine incorporation was low in the patients as a group and lymphoblastic transformation to specific antigens was impaired in 11 of 17 patients who had positive skin test reactions to the same antigen. Highly significant suppression of lymphoblastic transformation was noted after stimulation by the mitogens phytohemagglutinin, pokeweed, and concanavalin-A. The greatest impairment of mitogen response was seen in those patients receiving both chemotherapy and radiation therapy. These data demonstrate specific impairments of neoantigen processing, lymphocyte function, and to a lesser extent monocyte function in successfully treated patients with lymphoma. These impairments may contribute to the increased incidence of infections and second primary malignancies in these patients.