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C Rozman

Publications and source records attributed to C Rozman.

At least 109 records · Page 6Linked to original sources
PubMed1995

Patients with multiple myeloma requiring long-term dialysis: presenting features, response to therapy, and outcome in a series of 20 cases.

From January 1982 to December 1993, 30 patients with multiple myeloma (MM) required haemodialysis (HD) at our institution. The subgroup of 20 patients who survived more than 2 months on HD is the subject of this study. Four patients were already on HD, due to previous nephropathy, when MM was diagnosed. 13 patients presented with acute renal failure and were on dialysis from the time of diagnosis. The remaining three cases developed renal failure later in the course of the disease. The objective response rate was 40% (8/20). Only two patients could discontinue HD (one had a late partial recovery and one received a kidney graft). Mean hospitalization per year was 19.3 d. The subgroup of patients who survived < 1 year spent a mean of 38.3 d in hospital. Whereas in the subgroup with a survival > 1 year mean hospitalization days was 9.6 (P < 0.001). The median survival was 20 months and six patients survived for > 3 years. In summary, patients with MM and severe renal failure who survive the first 2 months on dialysis have an objective response rate to chemotherapy of 40% and a median survival of almost 2 years, with 30% long-term survivors.

Acute Kidney Injury↗
PubMed1995

Increased expression of the PRAD-1/CCND1 gene in hairy cell leukaemia.

The PRAD-1/CCND1 gene encodes Cyclin D1, a cyclin involved in cell cycle regulation at the G1-S transition. Over-expression of this gene is a highly specific molecular marker of mantle cell lymphomas (MCLs), but it may also be up-regulated in some chronic lymphoproliferative disorders, mainly chronic lymphocytic leukaemia. We have examined PRAD-1/CCND1 gene expression by Northern blot and Western blot analysis in a series of 18 hairy cell leukaemias (HCLs), nine other splenic malignant lymphoproliferative disorders, and three normal/reactive spleens. Over-expression of the mRNA PRAD-1/CCND1 gene was observed in 16/18 HCLs, including one case of hairy cell leukaemia variant, whereas this molecular alteration was not found in other cases examined. mRNA levels varied from case to case, but they were lower than those observed in MCLs. At the protein level, Western blotting analysis showed Cyclin D1 protein expression in the 11 HCLs analysed. No bcl-1 rearrangements were seen with the MTC, p94PS and PRAD-1 (lambda-P1-4) probes used, and no PRAD-1/CCND1 gene amplification was detected in any case. These findings indicate that PRAD-1/CCND1 is over-expressed at mRNA and protein levels in a high number of HCLs. However, the levels of expression are much lower than in MCLs, and this expression is not associated with bcl-1 rearrangements or PRAD-1/CCND1 gene amplification.

Blotting, Northern↗
PubMed1995

Allogeneic marrow grafts from donors with congenital chromosomal abnormalities in marrow cells.

To determine whether siblings with chromosomal abnormalities in marrow cells which are associated with cellular defects (e.g. Down syndrome or heterozygosity for Fanconi syndrome) are suitable donors for allogeneic bone marrow transplants, we have reviewed the patient files at the Fred Hutchinson Cancer Research Center (FHCRC) and carried out a survey among member centres of the International Bone Marrow Transplant Registry (IBMTR). The 57 of 253 (23%) member centres which responded to the survey reported seven transplants from donors with the following conditions: Down syndrome (n = 2), suspected heterozygotes for Fanconi syndrome (n = 3), and 47,XXX syndrome (n = 2), among a total of 5,561 allogeneic transplants from HLA-identical siblings. Adding the three cases seen at the Fed Hutchinson Cancer Research Center among 2,927 HLA-identical sibling transplants during 1992 resulted in 10 transplants among 8,488 cases transplanted overall: four with Down syndrome, four suspected of being heterozygous for Fanconi syndrome, and two trisomy X. Three out of four grafts from siblings with Down syndrome had complications, including poor graft function (n = 2) and graft failure (n = 1). Two of four recipients of marrow from presumed Fanconi syndrome heterozygotes presented with poor graft function and a third recipient developed graft failure after initial evidence of engraftment. The two patients given marrow from siblings with 47,XXX syndrome engrafted uneventfully. The experience reported here shows a low frequency of encountering an HLA-identical sibling donor who has chromosomal abnormalities in marrow cells consistent with Down syndrome or heterozygosity for Fanconi syndrome, about one case among 1,000 transplants. The much higher than expected incidence of graft problems with marrow from such a donor would make it reasonable to look either for an alternative marrow donor or consider an autologous transplant, in case a sibling marrow donor with Down syndrome or heterozygosity for Fanconi syndrome is encountered, although a donor with trisomy X seems acceptable.

Adolescent↗
PubMed1995

Presenting features, natural history, and prognostic factors in localized non-Hodgkin's lymphomas: analysis of 117 cases from a single institution.

Clinical features and prognostic factors were analyzed in a series of 117 patients with localized non-Hodgkin's lymphoma (stage I-II). Median age of the patients was 53 years and 52% were men; 22% had a lymphoma of low-grade histology and one-third presented with extranodal involvement. Eighty percent of the patients achieved a complete response (CR); stage of disease and histology were revealed as the most important factors for response. When analysis was restricted to intermediate/high-grade cases, stage showed a predictive value for response. With a median follow-up of 4.5 years, median overall survival was 12.0 years, with 73% and 62.5% of patients being alive at 5 and 10 years, respectively. Main initial parameters significantly related to a shorter survival were intermediate/high-grade histology, stage II, poor performance status, bulky disease, high serum LDH levels, increased ESR, and advanced International Index. In the multivariate analysis, stage, histology and performance status (PS) were statistically significant. Among intermediate/high-grade lymphoma patients, stage and PS provided prognostic value for survival. Twenty-six patients relapsed after CR; median survival after relapse was 2.7 years. Stage (I vs II) was the only predictive variable for relapse in both the whole series and the intermediate/high-grade subset.

Actuarial Analysis↗
PubMed1995

Multiple myeloma following essential thrombocythemia.

The association of essential thrombocythemia (ET) and multiple myeloma (MM) is exceedingly rare, with only four such cases reported in the literature until now. In this paper, a patient is reported who developed IgA-lambda MM more than five years after the diagnosis of ET, for which she had received alpha interferon and radioactive phosphor (32P). She died shortly afterwards despite melphalan and prednisone therapy. In four of the five patients in whom the above association has been reported, including the present one, MM appeared some time after ET was initially recognized, with three of them having received alkylating drugs as their treatment for ET. MM was heterogeneous with respect to the M--component type and the clinical course. The possible etiological & pathogenetic link between both these entities is discussed.

Aged↗
PubMed1995

[Granulocyte abnormal chromatin clumping syndrome: report of a new case and review of the literature].

Abnormal chromatin clumping syndrome (ACCS) is a rare granulocyte disease halfway between Ph'-negative chronic myelogenous leukaemia (CML) and the myelodysplastic syndromes. A new case of such syndrome is presented, the patient being a 65 year-old man with anaemia, thrombocytopenia and myelaemic leucocytosis with abnormal condensation of the neutrophils' chromatin. Marked granulocytic hyperplasia was present in the bone marrow with strikingly dysplastic features, along with a decrease of the remaining blood cell lines. Irregular nuclear outlines and heterochromatin clumps separated by euchromatin bands were seen in the more mature granulocytes upon ultrastructural studies. No cytogenetic abnormalities were found in the bone marrow, and no ber-abl gene rearrangement was present in white cells from peripheral blood. The clinical course was marked by persistence of the anaemia and increasing leucocytosis which required 6-mercaptopurine treatment. Acute myeloblastic leukaemia occurred one year later and the patient died shortly after. It was concluded, from this case and others reported in the literature, that, with regard to its clinical course and proliferative character, ACCS is closer to Ph'-negative, bcr-abl negative CML rather than to the myelodysplastic syndromes.

Aged↗
PubMed1995

Analysis of the clinical relevance of the breakpoint location within M-BCR and the type of chimeric mRNA in chronic myelogenous leukemia.

It has been suggested that the breakpoint location within the M-BCR segment of chromosome 22 and the type of chimeric mRNA BCR/ABL (b2a2 or b3a2) are associated with differences in the clinical and hematological characteristics of chronic myelogenous leukemia (CML). To assist in clarifying this matter, in a series of Ph-positive CML patients the relationship of both the breakpoint location within M-BCR (n = 71) and the type of chimeric mRNA BCR/ABL (n = 40) with the chronic phase duration, patients' survival, and thrombopoietic activity was analyzed. Median survival for patients with breakpoints in zones 1+2+3 (n = 38) and zones 4+5 (n = 31) was 62 and 75 months, respectively, the difference being not significant; patients with breaks in zones 1+2 (n = 19) and zones 3+4+5 (n = 50) had a median survival of 50 and 67 months, respectively (P also not significant). Moreover, no significant differences were found in the survival of patients with b2a2 (n = 16) and b3a2 (n = 24) mRNA junctions. Finally, no differences were observed in the platelet or megakaryocyte counts between patients with breakpoints in extremes 5' and 3' nor between patients with b2a2 and b3a2 mRNA. The above results are in agreement with those reported in most recent studies, confirming the lack of clinical relevance of molecular pattern in CML.

Adolescent↗
PubMed1995

Leukemia after true histiocytic lymphoma: another type of acute monocytic leukemia with histiocytic differentiation (AML-M5c)?

The case of a 44-year-old man diagnosed of a true histiocytic lymphoma who, after autologous bone marrow transplantation, developed leukemia with histiocytic cells is reported. Morphologic, cytochemical, immunophenotypic and genotypic characteristics of malignant cells are described, and the literature about this and related entities is reviewed. In addition, comparison with a recent report of malignant histiocytosis with leukemic involvement is established and its inclusion in the recently proposed subtype of monocytic leukemia with histiocytic differentiation (M5c), suggested.

Adult↗
PubMed1995

[Characteristics of patients with low grade malignant lymphoma and long survival].

PURPOSE: To analyse the initial and evolutive characteristics of the patients with low-grade lymphoma and long survival (> or = 12 years). MATERIAL AND METHODS: The initial data (clinical, laboratory, histologic type, stage) and the clinical course (response to therapy, response duration) of 52 patients with low-grade lymphoma diagnosed before 1980 were analysed. The statistical study was carried out by means of the chi-square test with Yates' correction and Student's t; the actuarial survival was estimated, and the duration of remission was assessed by the Kaplan and Meier method. Curves were compared by the log rank method. RESULTS: The 12-year survival as a whole was 32% (CI: 95%: 18.5%-45.5%). Of the 52 patients, 13 (25%) survived over 12 years. Nine were men and 4 women, with median age of 41 years (range: 22-68 years). Three cases had lymphocytic lymphoma and 10 had follicular lymphoma; 2 were in stage I-II and 11 in stage III-IV. Those patients who would become long-survivors had at diagnosis lesser frequency of spread lymph-node regional involvement (> or = 3 sites): 46% vs 81.8%, p = 0.04, as well as lesser percentage of bone-marrow involvement (38.4% vs 78.1%, p = 0.023). They were also better responders to treatment (CR+PR = 100% vs 71%, p = 0.013) and with longer duration (actuarial median duration of response 8 years vs 1.5 years, p = 0.005). CONCLUSIONS: According to the present analysis, low-grade lymphoma patients who have at diagnosis low tumoral involvement (not too extensive lymph-node involvement, disease-free bone-marrow) and show good response to treatment have a better prognosis and may hope for a longer survival.

Adult↗
PubMed1994

[Sepsis by Candida tropicalis in patients with granulocytopenia. A study of 10 cases].

The aim of the present study was to analyze the main clinical and evolutive characteristics of a series of 10 patients diagnosed with sepsis by Candida tropicalis over a 5-year period in a Hematology Unit. The mean age of the 10 patients was 23 years (range 13-66 years) with 6 males and 4 females. Eight patients had acute leukemia, 1 non-Hodgkin's lymphoma and another patient had severe bone marrow aplasia. All the patients presented intense granulocytopenia (< 0.5 x 10(9)/L), had intravenous catheters and were receiving wide spectrum antibiotics as treatment for bacterial infection. The diagnosis of the fungal infection was based on the growth of C. tropicalis in blood cultures together with the evidence of tissue involvement by the fungus. Fever (> 38 degrees C) was the initial symptom of the infection in all the patients, being accompanied by myalgia in 5 cases, pleuritic pain in 2 and septic shock in 1. Violaceous erthymatomous pustules disseminated over the trunk and limbs, the histologic study of which demonstrated the presence of C. tropicalis were observed in 9 patients. Septic metastasis were found in the liver (2 cases), serosae (2 cases), the psoas muscle and the brain (1 case), respectively. Eight patients underwent treatment with amphotericin B which was complemented with 5-fluorocytosin in 6, with death occurring in the remaining 2 patients prior to the start of treatment. Three patients died with active fungal infection (2 by cerebral hemorrhage and 1 by septic shock). In 2 patients the infection evolved to chronic systemic candidiasis and in the remaining 5 patients infection was resolved with hemoperipheral values returning to normal. Sepsis by Candida tropicalis is a severe complication in patients with granulocytopenia, being mainly characterized by fever, cutaneous papulae and, to a lesser extent, muscle pain. Amphotericin B alone, or in combination with 5-fluorocytosin constitute a treatment of choice in this infection, which nonetheless is associated with an undisdainful mortality.

Adolescent↗
PubMed1994

Refractory anemia with excess of blasts and isochromosome 12p in a patient with primary mediastinal germ-cell tumor.

Isochromosome(12p), a cytogenetic abnormality characteristic of germ-cell tumors, is exceedingly rare in hematologic disorders. The cytogenetic analysis of a patient diagnosed as refractory anemia with excess of blasts with an associated i(12p), who previously had a teratocarcinoma of the mediastinum, is presented. The cytogenetic analysis was performed at diagnosis of the hematologic malignancy, with all 30 metaphases in the bone marrow culture showing a 47,X, -Y, +8, +i(12)(p10) karyotype. The cytogenetic findings in this patient are compared with those published concerning the association of mediastinal germ-cell tumors and malignant hematologic disorders.

Adolescent↗
PubMed1994

PRAD-1/cyclin D1 gene overexpression in chronic lymphoproliferative disorders: a highly specific marker of mantle cell lymphoma.

The t(11;14)(q13;q32) translocation and its molecular counterpart bcl-1 rearrangement are frequently associated with mantle cell lymphomas (MCLs) and only occasionally with other variants of B-cell lymphoid malignancies. This translocation seems to activate the expression of PRAD-1/cyclin D1 gene located downstream from the major breakpoint cluster region of this rearrangement. However, the possible overexpression of this gene in other lymphoproliferative disorders independently of bcl-1 rearrangement is unknown. We have examined the overexpression of PRAD-1 gene in a large series of 142 lymphoproliferative disorders including 20 MCLs by Northern blot analysis. Cytogenetic and/or bcl-1 rearrangement analysis with 2 probes (MTC, p94PS) were performed in 28 cases. Strong PRAD-1 overexpression was observed in 19 of the 20 MCLs including 3 gastrointestinal forms and 4 blastic variants. t(11;14) and/or bcl-1 rearrangement was detected in 6 of the 12 MCLs examined. No correlation was found between the different levels of mRNA expression and the pathologic characteristics of the lymphoma. Among chronic lymphoproliferative disorders other than MCL, only 1 atypical chronic lymphocytic leukemia (CLL) with a t(11;14) translocation and bcl-1 rearrangement and the 2 hairy cell leukemias (HCLs) analyzed showed upregulation of PRAD-1 gene. The expression in the 2 HCLs was lower than in MCL, and no bcl-1 rearrangement was observed. These findings indicate that PRAD-1 overexpression is a highly sensitive and specific molecular marker of MCL but it may also be upregulated in some B-CLLs and in HCL.

Biomarkers, Tumor↗
PubMed1994

[Pulmonary cavitation as the initial manifestation of Hodgkin's disease].

Most of the patients with Hodgkin's disease (HD), have lymph nodes in the anterior mediastinum. Nonetheless, it is exceptional for one of these adenopathies to be cavitated at diagnosis. The case of a patient with HD presenting a cavitated anterior mediastinal mass as one of the initial symptoms. The differential diagnosis of localized masses in the anterior mediastinum and cavitated images in conventional thoracic radiology is discussed.

Adult↗
PubMed1994

[Diagnosis of paroxysmal nocturnal hemoglobinuria with cytofluorometric of molecules bound to the membrane by glycosylphosphatidylinositol groups].

BACKGROUND: Paroxysmal nocturnal hemoglobinuria (NPH) is a clonal disease in which a deficit in the expression of molecules bound to the cell membrane by glycosyl-phosphatidylinositol (MUGFI) groups has been demonstrated. The MUGFI are widely distributed and among them proteins regulating the action of complement may be found. The development of monoclonal antibodies (MoAb) against MUGFI may allow the introduction of a new diagnostic method in this disease and increase the sensitivity, particularly in transfused individuals. METHODS: The erythrocytic and leukocytic phenotype of 14 patients with NPH clonality demonstrated by the classic tests of sensitivity to the complement was analyzed by immunofluorescence techniques and flow cytometry with the use of MoAb which recognize MUGFI (CD55, CD59, CD14, CD16 and CD24). RESULTS: Cells with a decrease or absence of MUGFI were observed in all the patients. The defect was demonstrated in the red cells, monocytes and neutrophils of all the patients, while it was only observed in the lymphocytes of three patients. The percentage of cells with a decrease in MUGFI was variable (2-100%) as well the pattern of deficiency against the different MoAb used. The MoAb with greatest sensitivity for the detection of clonal population were the CD59 in erythrocytes, the CD14 in monocytes and the CD24 in neutrophils. The CD16 was normal in one patient and the CD55 in two. The transfusion of packed red cells did not influence the abnormal leukocyte pattern, with abnormalities even being observed in the erythrocytary CD59. The Ham test was negative in those cases in which the percentage of negative CD59 erythrocytes was lower than 5% of the total erythrocytic population. CONCLUSIONS: The study of glucosylphosphatidylinositol by flow cytometry and monoclonal antibodies is a useful technique for the detection and quantification of the nocturnal paroxistic hemoglobinuria clone even in transfused patients.

Adult↗
PubMed1994

Benign hematopoietic progenitors in chronic myeloid leukemia: current status and future prospects.

Many patients with chronic myeloid leukemia (CML) retain a certain degree of normal hematopoiesis at disease presentation. This fact, suspected on the basis of cytogenetic findings, has been confirmed by long-term bone marrow cultures (LTBMC) and the combined use of phenotypic and molecular studies. Based on the lack of HLA-DR expression, it has been possible to recognize a benign subpopulation within the stem-cell compartment in CML. Different in vitro techniques have been developed for the selection of these benign progenitors, including LTBMC, marrow incubation with cytolytic drugs or interferon, positive selection based on their phenotypic characteristics, and exposure to synthetic antisense oligodeoxynucleotides. In vivo selection with interferon or intensive chemotherapy is also possible. The primary goal of the selection of benign hematopoietic progenitors is their use for autotransplantation. To date, a few hundred CML patients have been submitted to the latter procedure using bone marrow or peripheral blood. The fact that the majority of them show evidence of persistent disease emphasizes the necessity for better selection methods of the benign progenitors, for intensifying the conditioning regimen to reduce the tumor burden as much as possible, and for the use of adjuvant therapy post-transplantation. Future trends include the refinement of positive selection methods, negative selection by taking advantage of the different stromal adhesiveness of the benign and malignant progenitors, or the use of autologous natural killer cells, antisense oligodeoxynucleotides, or specific antibodies to the bcr/abl junction region, and retroviral marking to determine the origin of relapse in autologous transplantation.

Bone Marrow↗
PubMed1994

Multiple deletions of mtDNA in two brothers with sideroblastic anemia and mitochondrial myopathy and in their asymptomatic mother.

Two brothers presented with a clinical picture characterized by sideroblastic anemia, mild pancreatic insufficiency and progressive muscle weakness. The presence of an associated permanent basal lactic acidemia raised the suspicion of a mitochondrial disease. A muscle biopsy performed in both siblings proved the presence of a significant number of ragged-red fibers, and respiratory chain enzymatic determinations demonstrated a reduced activity of complexes I, III and IV. Mitochondrial DNA studies disclosed the presence of multiple deletions both in skeletal muscle and, to a lesser extent, in leukocytes. Similar, but not identical deletions were also present in the leukocytes and muscle from their mother. Deletions were flanked by short direct repeats. We conclude that such patients suffer from a familial form of mitochondrial disease clinically resembling Pearson's syndrome, with a probably autosomal dominant inheritance.

Adult↗