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Biomedical subjects

F Cervantes

Publications and source records attributed to F Cervantes.

At least 91 records · Page 5Linked to original sources

[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↗

Prognosis of chronic myeloid leukemia: studies from the Barcelona Group.

Individual and multicenter efforts have facilitated the recognition of different parameters with prognostic value at presentation of chronic myeloid leukemia (CML). Interest is currently focused on the prognostic evaluation of features obtained from molecular analysis, and isolation of data with evolutive predictive value. The site of breakpoint within the M-BCR has been suggested as a prognostic factor in some studies. A recent analysis from our group failed to demonstrate differences in either duration of chronic phase or survival between patients with 5' and 3' breakpoints. We have confirmed in a sequential study that a decrease in the expression of some myeloid differentiation antigens of the blood granulocytes can be a prognostic indicator along CML evolution. Our more recent study, separating blast crises on immunological and molecular grounds, confirms lymphoid cases as a distinct subgroup and shows a trend for an association between megakaryoblastic blast crisis and 3' location of the breakpoint.

Adult↗

Large-cell lymphoma: a study of prognostic factors and assessment of five recently proposed predictive systems.

The main initial and evolutive variables of 133 patients with large-cell lymphoma treated with adriamycin-containing regimens were evaluated for prognostic significance. At the time of analysis, 66 patients had died with the median survival of the series being 48.9 months. Variables associated with poor prognosis in the univariate study were: lymphoma of immunoblastic subtype, advanced Ann Arbor stage, presence of B-symptoms, poor performance status, bulky disease (> or = 10 cm), involvement of two or more extranodal sites, bone marrow infiltration, and high serum LDH levels. In the multivariate analysis, Ann Arbor stage (p < 0.001), bulky disease (p = 0.004), performance status (p = 0.018), and histologic subtype (p = 0.021) retained their prognostic value. After excluding those patients with localized disease (stage I), the Ann Arbor staging system lost prognostic significance in favor of bone marrow infiltration (p = 0.009) and serum LDH (p < 0.001). However, when response to treatment was included in the regression model, it proved to be the most important prognostic factor (p < 0.001), followed by serum LDH (p = 0.004). On the other hand, when the analysis was restricted to complete responders, serum LDH at diagnosis was the only parameter useful to predict survival (p = 0.008). Finally, five recently proposed prognostic classifications were useful to separate different risk-groups of patients when applied to the series.

Aged↗

[Multiple myeloma after monoclonal gammopathy of uncertain significance. Study of 10 patients].

PURPOSE: To analyse the clinical, biological and evolutive characteristics of 10 patients with multiple myeloma (MM) previously diagnosed of monoclonal gammopathy of uncertain significance (MGUS). PATIENTS AND METHODS: Ten patients with diagnostic criteria of MM, included in a series of 114 subjects with MGUS, IgG (92 cases), IgA (21 cases) or biclonal IgG+IgA (1 case), diagnosed between 1970 and 1990, comprise this study group. RESULTS: The actuarial risk of developing MM in the series of 114 MGUS was 7.25% (95% CI: 1.5-13) and 16.1% (05% CI: 4.7-27.5) at 5 and 10 years of follow-up, respectively. MM occurred suddenly, both on clinical and biological grounds, in 8 of the 10 patients. The median period between the diagnosis of MGUS and the onset of MM was 48 months (range, 12-153). IgG MM appeared in 5 instances and IgA MM in 5 others. Bone pain (7 cases) and hypercalcaemic encephalopathy (2 cases) were the commonest clinical manifestations. Osteolytic lesions were found in the x-ray scan in 9 patients. Eight patients received chemotherapy, objective response being seen in five of them. The median survival since the diagnosis of MM was 18 months (range, 0.1-95). The causes of death in 8 deceased patients include disease progression (4 cases), pneumonia (3 cases) and neoplasm of the bladder (1 case). CONCLUSIONS: This analysis shows the difficulties in predicting the outcome of MGUS, since most of the MM seen here occurred abruptly and after a highly variable length of time. Thus, patients with MGUS must be followed-up for undetermined time.

Actuarial Analysis↗

[Initial iron deposits in idiopathic myelofibrosis. Analysis of 20 patients].

PURPOSE: To analyse the status of iron deposits at diagnosis in patients with idiopathic myelofibrosis (IM). PATIENTS AND METHODS: The study included twenty consecutive patients with IM. Haemoglobin, MCV, serum iron and serum ferritin were determined in each case. Perls stain was used to evaluate iron deposits in bone marrow samples attained by aspiration or biopsy. An attempt was made to correlate the semiquantitative estimation of bone marrow iron with the peripheral blood values connected with iron deposits. RESULTS: Anaemia was present in 15 patients, but in most cases MCV and serum iron were normal. Iron deposits in bone marrow aspirate could be evaluated only in one patient as in the remainders no material was obtained. The semiquantitative estimation of iron in bone marrow biopsy samples showed diminished or absent deposits in 15 cases (75%). In contrast, none of the patients had decreased serum ferritin levels. No correlation was found between bone marrow iron and the peripheral blood values related to iron deposits. CONCLUSION: Most IM patients have decreased bone marrow iron deposits at diagnosis. However, as in chronic myelogenous leukaemia and in essential thrombocytopenia, such finding does not mean a true iron deficiency status.

Bone Marrow↗

Immunophenotypic characteristics of blast crisis of chronic myeloid leukaemia: correlations with clinico-biological features and survival.

Blast cells from 40 patients with Philadelphia-positive chronic myeloid leukaemia (CML) in blast crisis were analysed by immunophenotypic methods. In 27 cases, BCR gene studies were also performed. By light microscopy morphology and cytochemistry the cases were classified as follows: undifferentiated (n = 7; 17.5%), myeloid (n = 27; 67.5%), and lymphoid (n = 6; 15%). On the basis of the immunological markers, the cases were reclassified as: myeloid (n = 17; 42.5%), megakaryoblastic (n = 17; 42.5%), and lymphoid (n = 6; 15%). The seven cases initially considered as undifferentiated by morphological and conventional cytochemical criteria were classified as myeloid (four cases) and megakaryoblastic (three cases) by marker analysis. The monoclonal antibody anti-myeloperoxidase (anti-MPO) was the most sensitive myeloid associated marker in these cases, being positive in five of them. A significant proportion (27%) of non-lymphoid blast crisis cases were CD7-positive, and myeloid markers were positive in the four lymphoid CML-CB cases studied. Analysis of the clinico-haematological characteristics on the various subgroups of patients showed that patients with lymphoid blast crisis had shorter duration of the chronic phase, more frequent extramedullary blastic involvement, more favourable response to therapy, and longer survival. Finally, a trend for an association between megakaryoblastic involvement of blast crisis and breakpoint localization in the 3' extreme of the M-bcr segment was also noted.

Adolescent↗

Sequential study of myeloid differentiation antigens of neutrophil granulocytes in different phases of chronic myeloid leukaemia: natural history and prognostic significance.

In an attempt to contribute to the knowledge of the natural history of Philadelphia-chromosome-positive chronic myeloid leukaemia (CML) and its prognosis, we analyzed sequentially the myeloid differentiation antigens of peripheral blood neutrophil granulocytes (NG) in different evolutive stages of the disease. Four monoclonal antibodies (CD15, CD24, 31D8, and 13F6) were used, and a total number of 116 sequential studies were performed in 43 patients. At diagnosis, there is a significant decrease of NG expressing myeloid differentiation antigens, which recover to nearly normal levels after initial control of the disease. The onset reduction is probably due to the circulation of incompletely mature NG. In accelerated/blastic phase NG expressing myeloid differentiation antigens decrease again, probably due to a true antigen loss. This reduction could herald by a few months the development of accelerated/blastic phase. In such a case, its predictive strength is higher than that of the well recognized initial prognostic parameters in CML. These results indicate that the sequential study of NG myeloid differentiation antigens may contribute to both a better understanding of the natural history of CML and the evolutive prognosis of this disease.

Adult↗

Ph-positive chronic myeloid leukemia mimicking essential thrombocythemia and terminating into megakaryoblastic blast crisis: report of two cases with molecular studies.

Two patients with chronic myeloid leukemia (CML) presenting with the hematologic features of essential thrombocythemia (ET) are reported. At diagnosis they showed extremely high platelet counts (4985 and 2800 x 10(9)/l, respectively) and moderate leukocytosis (21 and 17 x 10(9)/l, respectively). In both cases, in addition to the Philadelphia chromosome (Ph), a rearrangement within the major breakpoint cluster region on chromosome 22 was demonstrated, with the breakpoint in the 3' extreme. In patient 1 the disease initially responded to radioactive phosphorus and hydroxyurea, but during the evolutive course a progressive increase in the white blood cell counts was noted, reaching values typical of the chronic phase of CML, and the patient eventually died from blast crisis 45 months after diagnosis. In patient 2, although good control of the platelet counts was achieved with hydroxyurea, the disease also evolved into a blast crisis four months after diagnosis. In both cases monoclonal antibodies and electron microscopy studies demonstrated the megakaryocytic nature of the blast cells. The above features are not consistent with the present and similar cases being Ph-positive ET. Instead, they should be regarded as a special form of CML characterized by a marked protagonism of the megakaryocytic component.

Aged↗

[Long-term survival in chronic myeloid leukemia: frequency and fundamental characteristics in a series of 100 patients].

PURPOSE: To analyse the frequency and the main clinico-haematologic characteristics of the patients with Ph'-positive chronic myelogenous leukaemia (CML) with long survival. MATERIAL AND METHODS: Of a series of 100 patients with CML diagnosed in the chronic phase and treated in the conventional way at the "Farreras Valentí" School of Haematology between 1969 and 1982, and followed-up for at least 10 years, those surviving more that 8-10 years since the diagnosis were considered eligible for this study. Their clinico-haematological characteristics at diagnosis were compared to those of the remaining patients by means of the Student's t and Mann-Whitney's U tests, plus chi square with the Yates correction. The actuarial survival in the series was assessed according to the Kaplan and Meier method. The Sokal prognostic index was calculated in the longest survivors. RESULTS: The median survival of the series was 45 months (range: 4-171). Ninety-one patients died, 2 are alive in chronic phase and in 7 others the follow-up has been lost in the chronic phase. Eight patients survived more than 10 years and 14 more than eight years. Of these, six were men and eight women, 10 were under 50 years of age, one-half lacked splenomegaly at diagnosis and only 2 had Ph' chromosome mosaicism. According to the Sokal prognostic index, six of these patients were in the low-risk group, four were of intermediate risk, and four others were in the high-risk group. None of them had aplasia due to busulphan during the follow-up. When comparing the initial features of the patients surviving 8-10 years with those of the remainders, only the presence of a lower percentage of blast-cells (p = 0.03) and a lower number of blasts in peripheral blood (p = 0.01) in the former achieved statistically significant difference. CONCLUSIONS: These findings confirm the difficulty in identifying the CML patients with expected long survival at diagnosis. High numbers of cases must be analysed in order to attain definite conclusions in this regard.

Adolescent↗

[Ferrokinetic studies in the initial evaluation of idiopathic myelofibrosis: results in 18 patients].

BACKGROUND: Since there is no effective treatment for idiopathic myelofibrosis (IM) the determination of possible factors which are involved in the appearance of anemia in this disease may be important from a practical point of view. METHODS: The results of the initial ferrokinetic study analyzed in 18 patients with IM included plasma clearance (T1/2) and globular incorporation (U max) of 59Fe in addition to the uptake of 59Fe in the sacrum, spleen and liver in 16 patients. The clinical-hematologic and histologic data of the different groups of patients identified according to the results of the study were compared. RESULTS: Three ferrokinetic patterns were observed: 1) normal or increased erythropoiesis (8 patient), 2) inefficient erythropoiesis (7 patients), and 3) aplastic pattern (3 patients). The only difference observed between the three groups was the existence of lower levels of Hb and reticulocytes in the subjects with aplastic type pattern. In contrast, although there was an inverse correlation between the medullar and extramedullar uptake of iron (p = 0.018) no relation was observed between the latter and the size of the spleen or liver. CONCLUSIONS: The results obtained in this study indicate that IM behaves heterogeneously from a ferrokinetic point of view.

Adult↗

[Molecular analysis of chronic Philadelphia chromosome negative myeloid leukemia: study of 6 cases].

BACKGROUND: Patients with Philadelphia negative (Ph-) chronic myeloid leukemia (CML) constitute a small proportion of the total number of patients with CML. Molecular analysis of these cases has permitted recognition that some cases present a breakpoint in the bcr region of chromosome 22, that is, the alteration constituting the substrate of the Ph chromosome. To date, the number of patients analyzed to this regard is low. METHODS: Six patients with Ph negative CML who constituted part of a series of 96 patients diagnosed with CML over a period of 6 years were studied. Analysis of the BCR gene in the DNA of the leuko-concentrate of peripheral blood was carried out with the Southern Blot technique, using the 3' and 5' probes and Transprobe and the restriction enzymes Bgl II, Eco RI, Hind III and Bam HI. The principal clinical-hematological characteristics of the patients were analyzed. RESULTS: Breakpoints were observed in the bcr region of chromosome 22 in 3 of the 6 patients, all of whom presented typical CML clinical-hematological features. CONCLUSIONS: Half of the patients with Philadelphia negative (Ph-) chronic myeloid leukemia (CML) have a breakpoint in the bcr region of chromosome 22, a similar molecular pattern to the Ph positive CML and their clinical-hematological profile is indistinguishable from those with CML.

Adult↗

[Chronic myeloid leukemia after chemotherapy treatment for non-Hodgkin's lymphoma].

A 52 year old male presenting chronic myeloid leukemia (CML) Philadelphia chromosome positive (Ph) four years after the diagnosis of a non Hodgkin's lymphoma is described. The patient had received high total doses of alkylating drugs (cyclophosphamide and chlorambucil) as part of chemotherapy treatment for a diffuse mixed lymphoma. At four years of diagnosis of the lymphoma the appearance of hepatosplenomegaly, leukocytosis with myeloma and basophilia and thrombocytosis were observed. These alterations augmented progressively until a cytogenetic study of the bone marrow two years late established the diagnosis of CML upon demonstrating the presence of the Ph chromosome with no other karyotypic anomalies being observed. The explorations carried out at that time confirmed that the lymphoma continued to be in remission. The CML initially responded to treatment with busulphan. However, following a year and a half the disease evolved to a phase of acceleration and the patient died a few weeks later due to pneumonia with no signs indicative of lymphoma activity having been detected since the diagnosis of the CML.

Alkylating Agents↗

[Behçet's disease with an onset prior to the appearance of chronic myeloid leukemia].

The case of a Ph-positive female patient with chronic myeloid leukemia (CML) is reported. The patient presented a cutaneous-mucous picture prior to the appearance of the hemopathy consisting of genitals ulcers, buccal aphthae and nodular cutaneous lesions the study of which demonstrated panniculitis. The lesions improved with the administration of low doses of prednisone and colchicine. The CML evolved to a blastic crisis of a monocytic phenotype at 14 months of diagnosis leading to death of the patient. The cutaneous-mucous picture was catalogued as Becçet disease (BD) according to the criteria of the International Study Group for Behçet Disease. Given the lack of serologic tests or pathognomonic histologic lesions the difficulty in the diagnosis of BD is commented upon and the differential diagnosis of this disease, particularly with respect to the Sweet syndrome, is discussed.

Behcet Syndrome↗

Chronic systemic candidiasis in acute leukemia.

In the past few years a new syndrome of invasive Candida infection, the so-called hepatosplenic or chronic systemic candidiasis (CSC), has been recognized with increasing frequency in neutropenic patients. From January 1985 to December 1990, ten of 305 acute leukemia (AL) patients treated at our institution were diagnosed as having CSC. In contrast, during the same period this type of Candida infection was not observed in any patient with hematological diseases other than AL treated in our center, including 277 patients who underwent bone marrow transplantation. All patients with CSC had fever and hepatomegaly, and five complained of abdominal pain. Seven patients had neutrophilic leukocytosis and six an increased serum alkaline phosphatase activity. Abdominal computed tomography and ultrasound study showed typical lesions in eight and seven patients, respectively. In four patients a laparoscopy-guided needle liver biopsy displayed yellowish nodules on the liver surface, and the histologic study revealed large granulomas with yeasts and pseudohyphae. All patients were given amphotericin B (mean: 4.6 g, range: 1-12.5 g) and 5-fluorocytosine, and five received fluconazole. No patient died as a direct consequence of CSC and in six the infection resolved. Finally, once controlled, the infectious complication did not preclude subsequent intensive antileukemic therapy, including bone marrow transplantation.

Adolescent↗

The value of detecting surface and cytoplasmic antigens in acute myeloid leukaemia.

The immunophenotype of leukaemia cells from 60 patients with acute myeloid leukaemia (AML) was analysed with the APAAP technique using a panel of anti-myeloid and lymphoid associated monoclonal antibodies (McAb). Cells from all cases, including three with negative cytochemical features, were labelled by at least one of the anti-myeloid McAb CD13, anti-myeloperoxidase (anti-Mpo), and/or CD14. The most sensitive marker was CD13, since it was positive in 90% of cases. In two out of three AML cases defined as M0-AML, CD13 was expressed in the cytoplasm but not on the membrane; in these three cases peroxidase (Mpo) was not detected by conventional cytochemistry, but could be demonstrated in all of them using the McAb anti-Mpo. The simultaneous expression of CD14 and CD68 McAb was often confined to the M4 and M5 FAB AML subtypes (92% cases) as compared to the others: M1, M2, M3 (18% cases). Lymphoid antigens were rarely positive (TdT+: 13%, CD7+: 15%, CD19+: 5%) and none of the AML cases were CD3+ or CD10+. By contrast, CD4 was expressed in blasts from 44% of cases and this was not restricted to AML with a monocytic component (M4, M5) but also found in other subtypes. There were no significant differences in the clinical or prognostic features according to the positivity or negativity with TdT and CD4. By contrast, expression of CD7 was associated with refractoriness to the treatment or short complete remission duration, although the number of patients is too small to draw firm conclusions. Our findings support the clinical and diagnostic relevance of immunophenotypic studies in AML.

Acute Disease↗

Malignant transformation and life expectancy in monoclonal gammopathy of undetermined significance.

The actuarial probability of malignant transformation and the impact on expected survival were analysed in a series of 128 persons diagnosed with monoclonal gammopathy of undetermined significance (MGUS) over a 20-year period. At a median follow-up of 56 months the M-component remains stable in 101 patients (78.9%), 14 patients (10.9%) have died from non-related disorders and 13 (10.2%) have developed malignant transformation of MGUS (multiple myeloma, 10; primary amyloidosis, two; Waldenström's macroglobulinaemia, one). The actuarial probability of malignant transformation at 5 and 10 years was 8.5% and 19.2%, respectively. When different presenting features were analysed for predictive value of the malignant transformation, the IgA type of MGUS was the only variable associated with a higher probability of such an event (P less than 0.025). Although no significant difference was observed between the survival probability of persons with MGUS and that of the control population, the development of malignant transformation was associated with a shorter survival (P less than 0.001).

Adult↗