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C Rozman

Publications and source records attributed to C Rozman.

At least 127 records · Page 7Linked to original sources
PubMed1994

Long-term survivors in chronic granulocytic leukaemia: a study by the International CGL Prognosis Study Group. Italian Cooperative CML Study Group.

The purpose of the present work were to identify the initial characteristics associated with long-term survival in chronic granulocytic leukaemia (CGL) and to analyse the accuracy of prognostic models in identifying long-term survivors. 813 Philadelphia (Ph) chromosome-positive, nonblastic CGL patients from six American and European institutions, the majority treated conventionally, with a minimum follow-up > 10 years, were studied. Stepwise logistic regression was performed to ascertain the association between the initial clinicohaematological variables and survival > or = 8 years, and a prognostic index was derived. The usefulness of both Sokal's and the new prognostic index to identify long-term survivors was assessed by calculating their positive and negative predictive accuracies, sensitivity and specificity. Median survival of the series was 45 months (range 1-255), with 784 patients (96.4%) having died and 109 (13.4%) surviving 8 years or longer. Younger age, smaller spleen, platelets < or = 600 x 10(9)/l, and lower blood blast percentage were associated with survival > or = 8 years; platelets < or = 600 x 10(9)/l and lower blood blast percentage were the predictive factors in patients 50 years old or younger. Two-thirds of long survivors belonged to Sokal's low-risk group, but the positive predictive accuracy and specificity for prolonged survival of Sokal's index were very low. This was also the case for the new predictive index.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Impact of response to treatment on survival in multiple myeloma: results in a series of 243 patients.

Two hundred and forty-three patients diagnosed with multiple myeloma (MM) in a single institution over a 22-year period and treated with standard chemotherapy were analysed in an attempt to determine the impact of response to therapy on survival. The overall response rate in 229 evaluable patients was 50.1% (34.9% objective response plus 15.2% partial response). Median survivals of patients with objective and partial response were 43.4 and 42.8 months, respectively, versus 19 months for nonresponders. Median survival of 14 patients who achieved a complete remission was 42 months, whereas in 21 rapid responders (< or = 2 months) median survival was 43.3 months. A significant correlation between response and survival was observed with the landmark (P = 0.0169), the Mantel & Byar (P = 0.0001) and the Cox regression model (P < 0.0001) methods. These results indicate that, in responding patients, neither the degree of response nor the response kinetics has a significant influence on survival. However, the response to therapy is associated with a significantly longer survival in MM patients.

Adult↗
PubMed1994

Applicability of the International Index for aggressive lymphomas to patients with low-grade lymphoma.

PURPOSE: Variables used to build up the International Index for aggressive lymphomas (age, performance status, stage, extranodal involvement, and lactic dehydrogenase [LDH]) are also important in low-grade lymphoma. To assess the prognostic value of this index in low-grade lymphoma, we have applied it to a series of 125 patients. PATIENTS AND METHODS: One hundred twenty-five patients with low-grade lymphoma who were diagnosed at a single institution over a 20-year period and treated with standard chemotherapy were studied. End points of the study were response to therapy and survival according to the International Index. In addition to the International Index, main initial and evolutive variables were evaluated. Univariate and multivariate methods were used. RESULTS: After applying the International Index, the patients divided into four risk groups: low (36% of cases), low-intermediate (32%), high-intermediate (20.8%), and high (11.2%), with complete response (CR) rates in the four groups being 60%, 35%, 23%, and 21%, respectively. Ten-year overall survival rates for the risk groups were as follows: low, 73.6%; low-intermediate, 45.2%; high-intermediate, 53.5%; and high, 0% (P < .001). When the International Index was included in a multivariate analysis, along with the main initial variables, International Index (P < .001) and sex (male, worse) (P = .038) were the only parameters related to survival. When response to therapy was also included, achievement of CR (P < .0001) and International Index (P < .001) were the most important factors. In patients who achieved a CR, the International Index was the only parameter related to survival (P = .051). The results were the same when the International Index was applied to the subset of 107 patients with follicular lymphoma. CONCLUSION: In this study, the International Index has been found to be an important prognostic tool in low-grade lymphomas. Such an index could be used to predict prognosis not only in aggressive, but also in low-grade lymphomas.

Actuarial Analysis↗
PubMed1994

Current approaches to the treatment and management of chronic lymphocytic leukaemia.

Chronic lymphocytic leukaemia (CLL) patients in early clinical stage (Binet A; Rai 0) with nondiffuse bone marrow histopathology and low stable blood lymphocyte levels have long survival rates and should not be treated unless the disease progresses. In contrast, patients with poor prognostic features, such as advanced clinical stage (Binet B, C; Rai III, IV), diffuse bone marrow infiltration or high and rapidly increasing blood lymphocyte levels, have a median survival of less than 5 years and need therapy. Chlorambucil is still the mainstay for CLL treatment. Compared with chlorambucil, combination chemotherapy produces higher remission rates but no increases in survival. New agents such as fludarabine and 2-chlorodeoxyadenosine are already the treatment of choice for patients failing standard therapies, and their role as front-line therapy is being investigated in randomised trials. Whatever the treatment used, however, cure is rarely achieved. Certain situations (e.g. autoimmune cytopenias, hypersplenism) require special treatment approaches (e.g. corticosteroids, splenectomy). Bone marrow transplants, albeit experimental in CLL, warrant investigation in younger patients with poor prognosis.

Antineoplastic Agents↗
PubMed1994

Giant parallel tube arrays (PTAs), a new type of lymphocyte inclusion.

In a 56-year-old male patient, receiving chemotherapy after radical surgery for bladder carcinoma, an unusual type of cytoplasmic inclusion was discovered in about 30% of peripheral blood lymphocytes. This was a single, large (about 2 microns in diameter), round or ovoid body, darker than the nucleus and reddish-violet in May-Grünwald-Giemsa stain. The examination with transmission electron microscope demonstrated that such inclusions were made up of giant parallel tube arrays (PTAs). The absolute lymphocyte count was normal, but there was an expansion of CD3+, CD4-, CD8+, CD11b, TCR alpha beta lymphocytes. The lymphocytes bearing the inclusion were CD3+ and CD8+. DNA studies suggested an expansion of T-cell population with clonal rearrangement of TCR beta and TCR gamma. This case can be classified as an asymptomatic disorder of large granular lymphocytes, with unusual morphology. Giant PTAs should be taken into account in the differential diagnosis of lymphocyte cytoplasmic inclusions.

CD3 Complex↗
PubMed1994

Different response to recombinant human granulocyte-macrophage colony-stimulating factor in primary and secondary graft failure after bone marrow transplantation.

The efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) in graft failure after bone marrow transplantation (BMT) has been evaluated in 25 patients. rhGM-CSF was administered intravenously at a dose of 5 or 10 micrograms/kg. Fourteen patients (seven allogeneic BMT [allo-BMT], seven autologous BMT [ABMT]) were treated for primary bone marrow failure (no granulocyte recovery after BMT), and 11 cases (all allo-BMT) received rhGM-CSF for secondary bone marrow failure (absolute neutrophil count lower than 0.5 x 10(9)/L after a previously sustained granulocyte recovery). Two allo-BMT and three ABMT patients with primary bone marrow failure achieved a granulocyte response to rhGM-CSF. In contrast, nine patients with primary graft failure did not respond to rhGM-CSF (four ABMT, three HLA-identical T-depleted BMT, one minor mismatch BMT, one unrelated BMT). Ten of 11 allo-BMT patients treated for secondary bone marrow failure attained an ANC higher than 0.5 x 10(9)/L, but most became severely neutropenic again at a median time of 4 weeks. The possible cause triggering graft failure (graft-vs.-host disease [GVHD], cytomegalovirus [CMV] infection) remained unsolved in most of these cases. Actuarial probability of survival of the entire series was 16 +/- 9% at 15 months. The severity of graft failure and the presence of other concomitant complications in most of our patients may justify these poor results. In conclusion, rhGM-CSF had less efficacy in patients with primary bone marrow failure than in those with secondary bone marrow failure. In the latter setting, measures addressed to correct the initial cause of graft failure are mandatory.

Adolescent↗
PubMed1993

[Alpha interferon treatment of idiopathic myelofibrosis].

Idiopathic myelofibrosis is a chronic myeloproliferative syndrome for which there is no effective treatment. The good results obtained with interferon in other chronic myeloproliferative syndromes have led their being tested in idiopathic myelofibrosis, but to date the experience is scarce. Four patients out of a total of 12 diagnosed with idiopathic myelofibrosis over a period of 3 years were selected for interferon treatment. Patients with low leukocyte or platelet counts or with contraindication for administration of the drug were excluded. Alpha-2b interferon was administered at an initial dose of 3 MU/day which was increased at 4-6 weeks to 5 MU/day in cases of insufficient response and if tolerance so permitted. In patients in whom favorable response was observed a maintenance schedule was initiated with low doses of interferon. Treatment was discontinued in two patients due to bad tolerance at 6 and 8 weeks of initiation of treatment with no response having been observed until that time. In the other patients favorable response was reported to interferon after 5 months of treatment with disappearance of the symptomatology, normalization of the hemo-peripheral values and a marked reduction of splenomegaly. This responses was accompanied by a decrease in bone marrow fibrosis in one case and total disappearance of the same in the other patient. Alpha-2b interferon constitutes an effective therapy for a selected number of patients with idiopathic myelofibrosis. Greater experience would allow the identification of the subgroup of patients who may benefit from this type of treatment.

Adult↗
PubMed1993

[Acquired aplastic anemia: a stereological analysis of bone marrow fatty tissue and its clinical correlations].

BACKGROUND: To analyze the changes of the number and size of bone marrow adipocytes in aplastic anaemia. To discover possible clinical and haematological factors which may be associated with predominant expansion of the number or size of adipocytes. To analyze the prognostic value of the adipocyte number and size. METHODS: The adipose tissue of 25 plastic-embedded bone marrow specimens corresponding to patients with aplastic anaemia was studied stereologically. The correlation study between the results obtained and clinical and haematological data was carried out. RESULTS: The expansion of the adipose tissue is due to the predominant increase of the adipocyte number in some cases and of the adipocyte size in others. Among different clinical and haematological factors, only a lower age is significantly associated with a predominant increase of adipocyte number. In the prognostic stratification performed according to three different systems, neither the adipocyte number nor the size showed a statistically significant association. CONCLUSIONS: In the aplastic anaemia, the younger patients expand their bone marrow adipose tissue by increasing predominantly the adipocyte number, whereas in the older patients this occurs by predominantly increasing the adipocyte size (may be due to the decrease in proliferative potential). On the other hand, both the adipocyte number and size lack prognostic significance.

Adipocytes↗
PubMed1993

[Hodgkin's disease and non-Hodgkin's lymphoma occurring simultaneously].

The simultaneous appearance of Hodgkin's disease and a non Hodgkin's lymphoma is very infrequent and has classically been considered as coincidental. Nevertheless, recent clinical observations suggest that neoplastic cells which lead to Hodgkin's disease are of lymphoid origin. The case of a "discordant" lymphoma formed by a laterocervical Hodgkin's disease and a large cell gastric lymphoma is presented. The coexistence of these two diseases, as herein presented, supports the lymphoid origin of Hodgkin's disease.

Female↗
PubMed1993

Chronic lymphocytic leukaemia treatment.

Advances in the understanding of the natural history and prognosis of chronic lymphocytic leukaemia (CLL) and the introduction of new drugs and strategies have renewed interest in the treatment of this disease. Clinical trials in patients stratified according to risk factors are useful to determine the efficacy of different treatments. These advances currently allow treatment of CLL patients to be decided on a more rational basis. Patients in early clinical stage (Binet A, Rai 0) with non-diffuse bone marrow histopathology, and low, stable blood lymphocyte levels have a long survival and should not be treated unless the disease progresses. On the contrary, patients with poor prognostic features, such as advanced clinical stage (Binet B, C; Rai III, IV), diffuse bone marrow infiltration or high and rapidly increasing blood lymphocyte levels have a median survival inferior to 5 years and should be treated. Chlorambucil is still the mainstay for treatment of CLL but new agents such as fludarabine and 2-chlorodeoxyadenosine offer great promise. These agents are already the treatment of choice for patients failing standard therapies and its role as front-line therapy is being investigated in randomized trials. Whatever the treatment used, however, cure is rarely achieved. A number of situations (e.g. autoimmune cytopenias, hypersplenism) merit special treatment approaches (e.g. corticosteroids, splenectomy). Bone marrow transplants, albeit experimental in CLL, warrant investigation in younger patients with poor prognosis.

Aged↗
PubMed1993

Hepatic veno-occlusive disease after bone marrow transplant.

Hepatic veno-occlusive disease (VOD) is a non-thrombotic obliteration of the lumina of small intrahepatic veins. VOD has been reported after exposure to a wide variety of pathogens. It has been suggested that the chemoradiotherapy used as the conditioning regimen for bone marrow transplant (BMT) is now the main cause of this disease. However, the pathogenesis of VOD after BMT is probably multifactorial. Endothelial injury of sinusoids and small hepatic veins is considered to be the initial event in genesis of VOD. This injury is followed by deposition of fibrin-related aggregates in the subendothelial zone. These aggregates, and the intramural entrapment of fluid and cellular debris, occlude progressively the hepatic venous outflow and generate a postsinusoidal intrahepatic hypertension. Clinically, VOD is characterized by jaundice, weight gain, ascites, painful hepatomegaly and platelet refractoriness developing early post transplant, although other posttransplant liver disturbances can produce a similar syndrome. VOD diagnosis is usually established by applying the clinical criteria proposed by the Seattle and Baltimore groups. When clinical diagnosis of VOD is uncertain, a transjugular liver study including a transvenous biopsy and measurement of the gradient between wedged and free hepatic venous pressure, is recommended in order to establish an accurate diagnosis. According to the literature data, the incidence of VOD ranges from 0 to 70% and its mortality from 20 to 50%. This very wide range is attributable to the different incidence of risk factors in the different series and to the differences in applying the diagnostic criteria.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Agents↗
PubMed1993

Stereological study of human bone marrow adipocytes. A comparison of four methods for estimating size distributions.

Several methods are available for estimating size distributions of spherical objects in tissue sections. In this article a comparative study of four stereological techniques applied to human bone marrow adipocytes was carried out. In the first part, four stereological methods (Giger-Riedwyl, Saltykov, Wicksell, and Cruz-Orive) were used for the evaluation of adipocyte size in a set of 50 human bone marrow specimens (20 normal controls, 10 aplastic, 10 hyperplastic and 10 dysplastic bone marrows). In the second part, a computer simulation model was employed for generating both control and test populations. The latter were analyzed by means of the four stereological methods and compared to the control. When applied to bone marrow specimens, no statistically significant differences were seen among the four methods. Results were very close between the Giger-Riedwyl and Saltykov methods, and between the Wicksell and Cruz-Orive methods. In the simulation model, Saltykov's method was the most accurate stereological technique for the studied conditions. Additional advantages of this method are that the assumption of Gaussian distribution is not required, and that a higher relative weight is assigned to the largest classes, in which accurate definition is easier in the microphotographs. However, since the differences among the four methods are very small, they may all be considered as valid for the stereological study of human bone marrow adipocytes.

Adipocytes↗
PubMed1993

Chronic lymphocytic leukaemia: prognostic factors and natural history.

In the past 20 years, important progress has been made in the understanding of the natural history and prognosis of chronic lymphocytic leukaemia (CLL). Based on the notion that the clinical manifestations of CLL are due primarily to the progressive accumulation of lymphocytes over time, several prognostic factors have been identified. The prognostic value of parameters reflecting tumour burden (i.e. lymphadenopathy, splenomegaly, anaemia and/or thrombocytopenia due to bone marrow failure), first identified empirically, has been confirmed in multivariate analyses of large series of patients. Furthermore, clinical staging systems that group the most relevant of these factors have also been developed. Patients in early stage (Binet A; Rai 0) have a long survival which, in some cases, may match that of the general population. In contrast, patients with advanced stage (Binet C; Rai III or IV) have a median survival < 2 years. The major limitation of staging systems is that they do not give information about the likelihood of progression for patients in early stage. Nevertheless, haemoglobin level, blood lymphocyte count, lymphocyte doubling time and bone marrow infiltration pattern are useful to identify subsets of patients in early stage with different progression and survival rates, with the 'smouldering' form of the disease being identified fairly accurately. With all these advances, therapy in CLL can now be indicated on a more rational basis. However, further biological insight is needed to elucidate the mechanism accounting for the different forms of the disease.

Bone Marrow↗
PubMed1993

Comparative study of spleen pathology in drug abusers with thrombocytopenia related to human immunodeficiency virus infection and in patients with idiopathic thrombocytopenic purpura. A morphometric, immunohistochemical, and ultrastructural study.

A morphometric and immunohistochemical study was performed to assess the spleen's alterations in patients with autoimmune thrombocytopenia and in drug abusers with thrombocytopenia (DAT) related to human immunodeficiency virus (HIV) infection. A total of 34 patients were included in the study: 20 DAT patients and 14 with idiopathic thrombocytopenic purpura (ITP). Twenty HIV-negative splenectomy patients without thrombocytopenia were included as controls. Spleen weight in DAT patients (323.25 +/- 149.96 g, mean + standard deviation) was significantly increased compared with the ITP (164.28 +/- 29.79 g, P < 0.0001) and control (175.50 +/- 49.14 g, P < 0.0001) groups. The mean diameter of lymphoid follicles in the spleens of DAT patients (446.83 +/- 99.16 microns, was significantly higher than in those of the control patients (370.87 +/- 55.30 microns, P = 0.019). In control patients' spleens, the number of platelets in Billroth's cords was significantly higher (59.54 +/- 32.72/10(4) microns 2) than in those of the DAT (2.13 +/- 1.42/10(4) microns 2, P < 0.0001) and ITP (P < 0.0001) patients. The number of macrophages and ceroid histiocytes per 10(4) microns 2 of red pulp was significantly increased in both DAT (5.14 +/- 1.90) and ITP (7.48 +/- 4.38) patients compared with the control patients (3.66 +/- 1.10, P < 0.0001) and P = 0.06, respectively), and in ITP patients compared with DAT patients (P = 0.0136). The number of granulopoietic precursors per 10(4) microns 2 of red pulp was higher in the spleens of DAT (1.41 +2- 1.46, P < 0.0001) and ITP (0.92 +/- 0.75, P < 0.0001) patients compared with those of the control group. Transmission electron microscopy studies demonstrated platelet phagocytosis by macrophages of Billroth's cords and presence of myeloid metaplasia in spleens of DAT and ITP patients. Immunohistochemical studies showed a depletion of CD4+ lymphocytes in the T zone of splenic white pulp and an increased number of CD8+ lymphocytes in red pulp of DAT patients' spleens compared with those of ITP and control patients. There were no significant alterations in dendritic reticular cell network in the DAT group compared with the ITP and control groups.

Adolescent↗