Therapy-related ovarian dysfunction in women treated for Hodgkin's disease.
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Biomedical subjects
Publications and source records attributed to M Lazzarino.
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We report the case of a 42-year-old man who presented with B-symptoms, moderate splenomegaly and multiple nodules in the liver. Histologically, lymphocytic infiltrates were seen in the portal spaces and sinusoids of the liver and in the paratrabecular areas of the bone marrow. After excision, the spleen showed minimal disturbance of architecture with an expansion of the follicular marginal zones. These findings were considered inconclusive for lymphoma and the patient was treated only with non-steroidal anti-inflammatory drugs for persisting fever. Five months after splenectomy, a bone marrow biopsy still showed diffuse lymphoid infiltrates. From then on, the patient's condition improved with no further evidence of disease. Ten years after splenectomy the case was reconsidered as a splenic marginal cell lymphoma, indolent variant. Immunohistochemical and gene rearrangement studies demonstrated the monoclonality of the splenic proliferation, supporting the diagnosis. A further bone marrow biopsy did not detect residual lymphoid infiltrates. This case confirms that splenic marginal zone cell lymphoma may have a deceptively favorable course, even when presenting at an advanced stage. Moreover, it indicates that extrasplenic localizations of the lymphoma may persist for a long while after splenectomy but may vanish over time without therapy.
BACKGROUND AND OBJECTIVE: The existence of an imbalance in T-cell subpopulations in patients (pts) affected by monoclonal gammopathies (MG) has been well established. This imbalance might be correlated with different control of plasma cell growth and, particularly in MM, with the severity of the disease. The aim of this study was to verify whether the alteration of the T lymphocyte subsets in bone marrow correlates with the diagnosis, clinical status and disease phase in patients with monoclonal gammopathies. METHODS: We performed a study on bone marrow (BM) T-cell subsets in 49 multiple myelomas (MM) and in 17 monoclonal gammopathies of uncertain significance (MGUS), using as controls 20 BM aspirates from normal subjects. RESULTS: The percentages of BM CD4 cells in MM pts at onset were slightly lower than in controls and in MGUS pts, who showed normal percentages of CD4. The percentages of CD8 cells were lower than in controls in both MM and MGUS (p = 0.02 and p = 0.007, respectively), and consequently the CD4/CD8 ratios were significantly higher than in normal subjects (p = 0.01 and 0.008, respectively). Analysis of BM T-cell subpopulations in MM pts showed a progressive decrease in the percentage of CD4 cells from stage I to stage III (I vs III p = 0.008) and an increase in CD8 cells, although not statistically significant. The same trend was observed when the different phases of MM (onset, plateau, progression) were analyzed: a lower percentage of CD4 cells and an increase of CD8 cells characterized the advanced phases. Treatment did not seem to alter significantly the distribution of T-cell subsets in MM patients. INTERPRETATION AND CONCLUSIONS: The imbalance in T-cell involving the bone marrow lymphocytic populations that exist in MG is somewhat different in MGUS and MM. In MM patients this disturbance is related to the disease stages and phases, reflecting an important role for T-cell subsets in tumor cell control.
BACKGROUND AND OBJECTIVE: During the past ten years, the study of retinoids has undergone a total transformation. The Italian Society of Experimental Hematology decided to discuss these advances at a meeting in Florence on April 18, 1996. INFORMATION SOURCES: The material examined in the present review includes articles and abstracts published in journals covered by the Science Citation Index and Medline. In addition, all the authors of the present article have been actively working in the field of retinoids and have contributed several papers. Summaries of their oral presentations at the Florence meeting are reported in the Appendix to this review article. STATE OF ART AND PERSPECTIVES: One of the most important advances has been the elucidation of new molecular mechanisms of control of gene expression by retinoids. A number of new retinoids have been synthesized by chemists, some of which are being screened for potential clinical use, and a few have already had a tremendous impact on clinical practice. The most important achievements have been obtained in acute promyelocytic leukemia. In 1988 a Chinese group working in Shanghai showed that using all-trans retinoic acid (ATRA) alone 94% of acute promyelocytic leukemic patients obtained complete remission through differentiation of the leukemic clone. This result transformed a dream into reality and allowed researchers to move from laboratory experience to clinical applications of this differentiating therapy. Expanding the spectrum of hematological malignancies that may respond to ATRA remains a challenge; however, several results show some activity of retinoids alone or in combination with other drugs in juvenile chronic myeloid leukemia (CML), myelodysplastic syndrome, cutaneous T-cell lymphoma and CML. Particularly interesting are the studies that explored the potential clinical synergism of ATRA-based combination therapies with growth factors, other differentiating agents such as vitamin D3, immunomodulators like interferons, or chemotherapeutic agents, in particular Ara-C, all of which show promising in vitro effects when used in combination with retinoids.