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Biomedical subjects

F Cervantes

Publications and source records attributed to F Cervantes.

At least 19 recordsLinked to original sources

[Cytolytic activity by lymphokines (LAK activity) in chronic myeloid leukemia].

BACKGROUND: Recent studies indicate that patients with chronic myeloid leukemia (CML) have a population of benign cytolytic cells (natural killer or NK) in their peripheral blood which may expand and activate in vitro in the presence of interleukin-2 (IL-2) leading to cytolytic cells activated by lymphokine or LAK cells (lymphokine-activated killer). METHODS: Thirteen patients with CML in the chronic phase of a median of 8 months (range: 1-43) in length and 13 healthy individuals were studied. The NK cells were separated from the peripheral blood by centrifugation by density gradient, elutriation and depletion in flasks with the CD5 and CD8 monoclonal antibodies. The resulting cell solution was cultivated in medium with IL-2 (1,000 U/ml) for 16 days with the count, phenotypic study and cytotoxicity tests of non adherent cells (LAK) being thereafter performed. RESULTS: Following the separation, the CD56+/CD3- cells constituted 6.9 +/- 2.4% of the total of the patients with CML. At day 16 of the culture, the non adherent cells of the CD56+/CD3- phenotype (LAK cells) were found to be 57.9 +/- 4.4% of the total (expansion = 31 +/- 10.4 fold with respect to the initial number of NK cells). The LAK cells showed intense cytotoxic activity versus the killer-sensitive K562 cell lines (76.2 +/- 4.2% of lysis to the effector/target cell proportion 20:1 and 5.6 +/- 1.3% to the proportion 0.08:1) and Raji killer-resistant (65.7 +/- 4.3% and 3.8 +/- 1.6%, respectively). Thus, the grade of LAK cell expansion and their cytotoxicity in patients with CML were significantly lower than in healthy individuals. CONCLUSIONS: Chronic phase patients with chronic myeloid leukemia may generate, in vitro, a population of LAK cells with intense cytotoxic activity in the peripheral blood.

Adult

[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

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

[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

Neutrophilic pustulosis associated with chronic myeloid leukemia: a special form of Sweet's syndrome. Report of two cases.

Two subjects with Ph-positive chronic myeloid leukemia (CML) in whom pustular Sweet's syndrome was diagnosed are reported. The first patient was a 47-year-old woman who developed fever, painful ulcers of the oral mucosa and vagina and generalized pustulous skin lesions 2 years after the diagnosis of CML. Histologically, the skin lesions consisted of dense neutrophilic infiltrates with perifollicular disposition. The microbiologic studies were negative. The lesions showed a favorable response to corticosteroids, but fever recurred with every attempt of tapering prednisone; it finally disappeared with the addition of oral cyclophosphamide. The second patient was a 45-year-old man who developed fever and disseminated pustules with histologic features consistent with Sweet's syndrome and negative microbiologic studies at 2.5 years after diagnosis of CML. The picture showed a dramatic response to prednisone and did not recur after the drug was discontinued. In both patients, CML remained stable after resolution of Sweet's syndrome.

Cyclophosphamide

Polycythaemia vera following non-Hodgkin's lymphoma.

A patient with non-Hodgkin's lymphoma (NHL) who developed polycythaemia vera (PV) is reported. Diffuse large-cell NHL was diagnosed and he was subsequently treated with combination chemotherapy including high dose cyclophosphamide and procarbazine. Four and a half years after chemotherapy splenomegaly developed, coincidently with the appearance of high Hb values, RBC and platelet counts. The screening tests for PV were consistent with this diagnosis, while the search for lymphoma activity was negative. To the best of our knowledge, the present case represents the first well-documented instance of PV following NHL.

Humans

[Granulocyte alkaline phosphatase activity in the chronic phase and blastic crisis of chronic myeloid leukemia. Sequential study of 43 patients].

PURPOSE: To evaluate in a sequential fashion the activity of the leukocyte alkaline phosphatase (LAP) in the chronic phase and the blastic crisis of chronic myelogenous leukaemia (CML). MATERIAL AND METHODS: This study is comprised of 43 patients diagnosed of CML according to standard criteria. The initial LAP scores were compared with those recorded in the blastic crisis, using cytochemical methods. The statistical analysis was performed with Student's test and chi-square. RESULTS: The LAP activity at diagnosis was low in 40 of the 43 cases (93%), the score being 0 in 20 instances. In the blastic crisis low scores were found in 27 patients (63%), while LAP activity appeared normal or increased in 16 others (37%). When the LAP scores of the two phases of the disease were compared the differences were found statistically significant (p less than 0.0001 and p less than 0.0007, respectively). CONCLUSIONS: These results confirm that the onset of the blastic crisis of CML is often accompanied by an increase of the LAP activity, although this last persists low in the majority of the patients.

Adolescent

[Chronic myeloid leukemia beginning as thrombocythemia. Analysis of 5 cases].

The clinico-haematological and evolutive features of five patients with Ph'-positive chronic myelogenous leukaemia (CML) whose initial profile suggested the diagnosis of essential thrombocythaemia (ET) were analysed. The patients were women with severe thrombocytosis (greater than or equal to 1000 x 10(9)/L) and moderate leucocytosis (less than 25 x 10(9)/L), and only two of them had splenomegaly. Increased basophil count in peripheral blood was present in all cases, and peripheral myelocytosis was seen in three. The molecular analysis showed rearrangement of the BCR gene in the three patients on which it was performed. Increasing leucocyte count was seen in the three patients with extended follow-up, this reaching values in accordance with CML. Finally, the three patients who died suffered a blastic crisis. The analysis of this series, along with others reported in the literature, suggests that such cases correspond to atypical forms of CML rather than actual TE patients.

Adult

[T lymphoid blast crisis of Philadelphia chromosome-positive chronic myeloid leukemia: analysis of 3 cases].

BACKGROUND: To investigate the frequency of the T lymphoid phenotype in the blast crisis of chronic myelocytic leukemia (CML) with positive Philadelphia chromosome (Ph) and to evaluate the major clinical and hematologic features of the patients with this phenotype. METHODS: The presence of the TdT enzyme was assessed and specific monoclonal antibodies to the different hemopoietic lines were used to evaluate blast cells in 38 patients with blast crisis during Ph-positive CML. RESULTS: T lymphoid phenotype was found in three of the 38 patients, corresponding in all cases to immature T cells. In one patient, the blast crisis was the presenting feature of CML and in two the localization of the blast crisis was lymphadenopathic. In the two patients who could be followed up a favorable response to chemotherapy regimens including vincristine and prednisone was observed. CONCLUSIONS: Although uncommon, T lymphoid blast crisis in CML should no longer be considered exceptional. This phenotypic finding suggests that, at least in some cases, CML originates in a pluripotential stem cell common to all hemopoietic cells, including T lymphocytes.

Adult

[Tuberculosis in chronic myeloproliferative syndromes: its incidence and principle characteristics in a series of 562 patients].

BACKGROUND: Incidence analysis of tuberculosis in a series of 562 patients with chronic myeloproliferative syndrome (CMPS). 344 had chronic myelocytic leukemia, 91 polycythemia vera, 70 idiopathic myelofibrosis and 57 essential thrombocythemia. METHODS: The association between CMPS and tuberculosis was evaluated with the "patient-year" test, using as a control group for the incidence of tuberculosis the population of Catalonia in 1982 from data published by the Catalan government. The comparison with this group was made on the basis of observed/expected distribution. RESULTS: 9 cases of tuberculosis were found, representing a significantly higher frequency than in the general population (observed/expected relation 18.16; p less than 0.000001). In patients with idiopathic myelofibrosis the incidence was clearly higher than in the rest of CMPS. In all patients tuberculosis developed some time after the diagnosis of CMPS. In 4 patients the disease was miliary. In only one of the 5 cases where the microorganisms could be typified it was found to correspond to an atypical mycobacterium. In six patients tuberculosis had an unfavorable outcome despite therapy. CONCLUSIONS: In patients with CMPS the incidence of tuberculosis was higher than in the normal population, with a high frequency of miliary forms.

Chronic Disease

Immune hemolytic anemia and renal failure associated with rifampicin-dependent antibodies with anti-I specificity.

A 50-year-old woman with primary biliary cirrhosis developed immune hemolytic anemia and renal failure while receiving rifampicin for the treatment of refractory pruritus. Serological studies revealed the presence of rifampicin-dependent antibodies of the IgM class that, when tested against a wide panel of erythrocytes, had anti-I specificity. Subsequently, rifampicin was withdrawn and prednisone treatment instituted, this resulting in a rapid resolution of the hemolysis, whereas hemodialysis was required for recovery of the renal function. A role is suggested for the anti-I specificity of the antibodies in the development of renal failure associated with rifampicin therapy.

Anemia, Hemolytic