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Biomedical subjects

F Cervantes

Publications and source records attributed to F Cervantes.

At least 145 records · Page 8Linked to original sources

A new prognostic system for multiple myeloma based on easily available parameters.

The prognostic significance of different presenting features in 180 patients with multiple myeloma (MM) from a single institution was analysed. Out of eight variables isolated from the univariate analysis only two (blood urea and serum albumin), were significant in the multivariate model. Derived from these two simple variables, the relative risk of each patient was calculated, and subsequently two subpopulations of patients could be recognized. The first group included patients with a very active myeloma and a high risk of death soon after diagnosis, their median survival being of only 11.6 months, and the second one comprised patients with low risk of death during the first year and a median survival of 28 months. A hazard function derived from two-thirds of the patient population (training group) was successfully validated in the remaining subset of patients (test group). Finally, the three major available myeloma staging systems (Durie & Salmon's, Merlini et al's, and the one proposed by the British Medical Research Council) were tested in the present series, and only the latter one showed prognostic validity.

Actuarial Analysis↗

Acute transformation of chronic myelomonocytic leukaemia: a multivariate study of predictive factors.

In an attempt to determine the possible predictive value of the main clinical and haematological initial features of chronic myelomonocytic leukaemia (CMML) on the evolution to acute leukaemia, as well as the real impact of such an event on survival, 35 such patients were submitted to multiple regression analyses. At the time of the study 30 out of the 35 patients had died, with a median survival of 8.2 months for the whole series. 12 patients (34%) developed acute leukaemia, between 1.5 and 42.1 months from diagnosis of CMML, the actuarial median time of acute transformation being 29.4 months. The initial bone marrow blast cell percentage was the only factor influencing the development of acute leukaemia. On the other hand, the multivariate survival study showed that acute transformation introduced in the model as a time-dependent variable had a clear-cut unfavourable influence on the outcome of CMML patients, as did palpable spleen, advanced age and marked monocytosis.

Adult↗

Is the histological classification of chronic granulocytic leukaemia justified from the clinical point of view?

By means of morphometric techniques, in 100 untreated Ph'-positive chronic granulocytic leukaemia (CGL) patients the main features from the initial bone marrow biopsy were analyzed, with particular attention being paid to morphological and quantitative study of megakaryocytes. The number of megakaryocytes per mm2 of marrow tissue showed a mean value of 25.3 (SD +/- 18.8), and was positively correlated with either platelet counts, blood percentage of basophils and blast cells, or spleen and liver size. Based on the number and morphological characteristics of megakaryocytes, patients were classified as having granulocytic CGL (67 cases) or the so-called chronic megakaryocytic-granulocytic myelosis (33 cases), but except for higher platelet counts and blood percentages of basophils and blast cells in the latter, no relevant clinical, evolutionary or prognostic differences were observed between the groups. Such results cast doubt on the validity of histological classification of CGL from the clinical point of view.

Bone Marrow↗

Prognostic evaluation of initial bone marrow histopathological features in chronic granulocytic leukemia.

In 100 patients with nonblastic Ph1-positive chronic granulocytic leukemia (CGL) the main features from the initial bone marrow biopsy were correlated with other clinical and hematological parameters and analyzed for prognostic significance. The mean number (+/- SD) of megakaryocytes per square millimeter of marrow tissue was 25.9 +/- 18.8. Marked reticulin fibrosis was observed in 19% of the patients but in only 5 cases it was diffuse, whereas collagen deposition was found in 10 patients. Reticulin fibrosis correlated significantly with white blood cell count and peripheral blood blast cell percentage, but not with platelet count. Actuarial survival studies demonstrated that marked diffuse reticulin fibrosis (p = 0.0005) and more than 15 megakaryocytes/mm3 of marrow tissue (p = 0.01) were associated with a poorer prognosis. However, they lost their prognostic influence when included in a multivariate regression model together with the patients' relative risk according to the currently most widely accepted CGL prognostic system. Such results indicate that bone marrow biopsy features add little prognostic weight to known prognostic indicators in CGL.

Adult↗

Central nervous system involvement demonstrated by immunological study in prolymphocytic variant of chronic lymphocytic leukemia.

A patient with the prolymphocytic variant of B cell chronic lymphocytic leukemia (CLL/PL) who developed meningeal leukemic involvement is reported. He had been diagnosed as having CLL/PL 2.5 years earlier, and treated successively with splenectomy, continuous chlorambucil and CHOP chemotherapy. While receiving the latter treatment, the patient developed persistent cephalalgia and vomiting, without signs of neurological focality. A lumbar puncture yielded a cerebrospinal fluid (CSF) showing lymphoid cells of prolymphocytic appearance and the immunological cell markers demonstrated the clonality of these cells. Intrathecal methotrexate and arabinosyl cytosine treatment was administered, this leading to the disappearance of the abnormal cells from the CSF and the resolution of the clinical symptoms.

Biomarkers, Tumor↗

[Extramedullary blast crisis in chronic myeloid leukemia].

Out of 113 cases of blastic crisis (BC) of Ph'-positive chronic myeloid leukaemia (CML), 13 had extramedullary involvement, this being the first BC manifestation in 5 instances. The median interval between extramedullary BC and bone marrow BC in these last was 2 months. Lymph nodes were the commonest extramedullary site of BC (8 cases), followed by osteoperiosteal and central nervous system (CNS). Lymph node BC occurred as generalised lymphadenopathy in most cases. Osteoperiosteal BC was seen as severe bone pain on osteolytic areas, whereas CNS blast crisis occurred as meningeal leukaemia in one case and chloroma in another. Lymphoid phenotype of blast cells was found in only 2 instances. The median survival of the patients after the onset of extramedullary involvement was 3 months.

Adult↗

[Chronic myelomonocytic leukemia and solid neoplasms: is it a causal or a fortuitous association?].

Out of a series of 36 patients with chronic myelomonocytic leukaemia (CMML), five cases are reported with the association of this hemopathy to solid neoplasms. In two patients this last was a cutaneous tumour, while the remainders had, respectively, papilloma of the bladder, carcinoma of the sigma, and cutaneous T-cell lymphoma. These neoplasms were diagnosed in all cases prior to the discovery of CMML. When applying the "patient/year" method, significantly higher frequency of solid tumours was found for CMML patients, which would support the hypothesis that this myelodysplasia could be regarded as a paraneoplastic condition.

Aged↗

[Erythroblastopenia associated with chronic myelomonocytic leukemia].

A patient is presented in whom the diagnoses of chronic myelomonocytic leukaemia (CMML) and erythroblastopenia were simultaneously established. Besides the conventional criteria for both haemopathies, the culture of bone-marrow precursor cells showed lack of growth of the erythroid stem cells. 6-Mercaptopurine given as therapy for CMML failed to induce any favourable changes in erythroblastopenia, which in turn improved with prednisone. Nevertheless, the patients died five months after diagnosis due to acute transformation of the CMML.

Aged↗

Chronic neutrophilic leukemia with marked myelodysplasia terminating in blast crisis.

A case of chronic neutrophilic leukemia (CNL) is reported. The patient had a history of bleeding, and showed sustained mature neutrophilic leukocytosis, hepatosplenomegaly, a high leukocyte-alkaline phosphatase score, elevated serum vitamin B12 and uric acid, and the presence of Döhle bodies in the neutrophils. In addition to the above typical features, marked myelodysplastic changes in the erythroid and megakaryocytic series were observed in the bone marrow. Three months after the diagnosis of CNL had been established, the hematological picture evolved into a blast crisis of monocytic type. Such findings give support to the statement of CNL as a distinct entity belonging to the spectrum of the myeloproliferative disorders.

Blast Crisis↗

Trisomy of the long arm of chromosome 1 in patients with hematologic malignancies and solid tumors: report of six cases.

Complete or partial trisomy of the long arm of chromosome #1 was observed in six patients with malignant disorders. Four patients suffered from hematologic diseases (two cases of refractory anemia with excess of blasts and one case each of acute myeloblastic leukemia and Burkitt lymphoma), and two had solid tumors (retinoblastoma and Ewing's sarcoma). In all cases the excess material included the distal part of chromosome #1. Such material was translocated to chromosomes #16 (three patients), #3, #9, and Y (one patient each), and this was accompanied by additional cytogenetic changes in five of the six patients. The present and other previously published observations support the hypothesis of the localization of genes responsible for malignant growth in the distal segments of chromosome #1.

Adult↗

Bone marrow lymphoid nodules in myeloproliferative disorders: association with the nonmyelosclerotic phases of idiopathic myelofibrosis and immunological significance.

The presence of lymphoid nodules in bone marrow biopsy was investigated at diagnosis in 200 patients with chronic myeloproliferative disorders (MPD). Twelve out of 51 patients with idiopathic myelofibrosis (IM) showed such a feature (23.5%), versus two out of 100 with Ph1-positive chronic myeloid leukaemia, two of 32 with polycythaemia vera, and one of 17 with essential thrombocythaemia, the difference between IM and the remaining MPD being statistically significant (P less than 0.0001). When IM patients were compared for their initial characteristics according to the presence or not of bone marrow lymphoid nodules, patients with such a histological finding showed significantly lower values for either WBC counts, number of primitive cells in the blood, and serum lactic dehydrogenase levels. Moreover, it was observed that virtually all patients with lymphoid nodules were in the nonmyelosclerotic phases of IM. Finally, among the 14 of 32 IM patients (44%) investigated for circulating immune complexes who gave a positive test, a significant association between this immunological abnormality and bone marrow lymphoid nodules was found. The above results reinforce the immunological significance of the finding of bone marrow lymphoid nodules in IM and give support to the hypothesis of an immune component in the pathogenesis of the disorder.

Adult↗

Liver involvement at diagnosis of primary myelofibrosis: a clinicopathological study of twenty-two cases.

Liver biopsies were carried out at diagnosis in 22 patients with primary myelofibrosis. Pathological changes were semiquantitatively evaluated and correlated with either liver function tests, peripheral blood features, bone marrow biopsy changes or patient survival. Hepatic myeloid metaplasia (HMM), primarily consisting of the presence of morphologically abnormal megakaryocytes, was found in all cases. Other remarkable pathological changes included increased reticulin network, sinusoidal widening not related to the intensity of HMM, and iron overload in the absence of previous blood transfusions. High serum alkaline phosphatase was the most frequent biochemical abnormality, and reflected rather the presence of sinusoidal widening than the degree of HMM. The number of immature myeloid cells was the only peripheral blood parameter positively correlated with the degree of HMM. No relationship could be established between bone marrow changes and the degree of HMM. Finally, patients with mild HMM survived longer than those showing marked HMM.

Adolescent↗

Longitudinal study of serum ferritin concentrations in chronic granulocytic leukaemia.

In 60 patients with Ph1-positive chronic granulocytic leukaemia (CGL) the serum ferritin concentration was measured as a part of the initial evaluation of the disease. The mean value (+SD) was 285 +/- 368.6 ng/ml, normal or slightly increased values being obtained in most cases. In 38 patients serum ferritin was again determined in clinical remission following busulphan treatment. Although the levels generally remained within the normal range, a significant decrease was observed with respect to the initial values (p = 0.0000004), suggesting that serum ferritin at presentation of CGL may be partially influenced by the disease activity. Finally, a further determination of serum ferritin concentration was made in a subgroup of 21 patients when they were diagnosed as being in the accelerated or blastic phases of CGL. Although no substantial increase was found with respect to the values obtained at presentation, a significant increase (p = 0.0008) was observed when accelerated-blastic phase ferritin levels were compared with those obtained in clinical remission. Although in patients in blast crisis no correlation was found between blast cell mass and serum ferritin, the differences observed between the different phases could indicate that in CGL serum ferritin concentrations roughly parallel the disease activity.

Adolescent↗

Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia.

Of 661 patients with Philadelphia chromosome (Ph)-positive, nonblastic chronic granulocytic leukemia, 58 had cytogenetic abnormalities in addition to the Ph at the time of diagnosis. Twenty patients had reduplication of the Ph in one or more metaphases. Twenty-one patients with a single Ph exhibited hyperdiploidy in one or more metaphases. Eleven patients had two or more hypodiploid metaphases as their only numerical abnormality. The remaining six patients had a variety of abnormalities. Many patients had more than one type of abnormality. Survival of patients in the different subgroups was similar, but these 58 patients had a shorter course than the 603 patients without additional cytogenetic abnormalities (P less than .02). Survival curves for the two populations did not diverge until the 2-year point, after which the annual death rate among patients with additional cytogenetic abnormalities was approximately 40% higher than that of patients without such abnormalities. The two populations had similar relative risk values according to a hazard ratio formula previously described by the International CGL Prognosis Study Group. Thus, they would have been expected to have essentially identical survival curves. We conclude that the presence of additional cytogenetic abnormalities at the time of diagnosis constitutes an independently significant prognostic feature with an unusually delayed influence on survival.

Adolescent↗