Chronic lymphoproliferative disorders.
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Antineoplastic Combined Chemotherapy Protocols↗
Biomedical subjects
E Montserrat
Publications and source records attributed to E Montserrat.
[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↗
[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↗
Autologous bone marrow transplantation for non-Hodgkin's lymphoma in first remission.
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Adolescent↗
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↗
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↗
Intensive therapy of chronic lymphocytic leukaemia.
In contrast to advances in understanding the biology and natural history of CLL, progress in treatment has been slow. Considerable data indicate that response to therapy is associated with increased survival. Also, more intensive therapy is associated with increased responses. However, few data suggest that this translates into increased survival or cure, even in patients seemingly free of CLL cells using sensitive detection techniques. Preliminary results with allogeneic and autologous bone marrow transplants are promising but controlled or randomized trials are needed to determine survival and/or cure. Several considerations suggest that intensive therapy should be reserved for young persons with adverse prognostic features failing conventional treatment.
Adult↗
B-type large-cell primary splenic lymphoma with massive involvement of the red pulp.
A B-type large-cell primary splenic lymphoma with massive red-pulp involvement was diagnosed in a 64-year-old woman presenting with malaise, fever, anemia, atypical lymphoid cells in peripheral blood, and splenomegaly. This case differs from most splenic lymphomas both macroscopically and microscopically. At macroscopic examination, the spleen was homogeneously red without tumoral nodules or masses. Microscopically, the cords of the red pulp were extensively invaded by tumor cells maintaining patient sinuses. The white pulp was reduced by expansion of the red pulp. To our knowledge only few additional cases of splenic lymphoma with similar features have been previously described. The differential diagnosis of this unusual form of lymphoma with other lymphoproliferative disorders is briefly discussed.
Antineoplastic Combined Chemotherapy Protocols↗
Occult cancer in patients with acute pulmonary embolism. A prospective study.
We prospectively studied 78 consecutive patients with acute pulmonary embolism (PE) to determine the most appropriate workup study for searching for hidden cancer. After a careful physical examination, the following tests were performed: erythrocyte sedimentation rate (ESR), complete blood cell counts, biochemistry, carcinoembryonic antigen levels, chest radiograph, upper gastrointestinal endoscopy, and abdominal ultrasound. If a malignant lesion was suspected, further appropriate tests were performed. After hospital discharge, periodic follow-up was performed on all patients in our outpatient clinic. A malignant lesion was detected in 9 of 78 patients: in 7 of them, cancer was diagnosed during the hospital admission because of acute PE. All but one of these 7 patients were asymptomatic, except for PE symptoms. In three of them some abnormalities on physical examination led to the diagnosis of cancer; in the remaining three patients the diagnosis was suspected from abnormal results of blood tests. Cancer was detected several months after hospital discharge in two additional patients: an esophageal cancer was diagnosed 5 months later in one of the 23 patients who refused endoscopy; and a colonic carcinoma was detected 21 months after hospital discharge in a patient in whom colonoscopy was not performed at the time of hospital admission. When considered overall, cancer was more commonly found in patients with "idiopathic" PE as compared with patients with known risk factors for PE development (6 of 21 patients vs 3 of 51 patients; p < 0.05). On the other hand, one patient died because of massive recurrent PE after a biopsy sample was obtained because of a prostatic node. Gross hematuria had developed shortly after biopsy, and any attempt to increase heparin doses was followed by recurrent hematuria. According to our experience, any decision about procedures that potentially involve bleeding should be carefully individualized in patients with acute PE.
Acute Disease↗
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↗
[Immunophenotyping study of bone marrow fractions obtained by elutriation in allogeneic bone marrow transplantation].
PURPOSE: Bone marrow transplantation (BMT) is an effective treatment for acute and chronic leukaemias. Lymphocyte depletion of donor bone marrow for preventing GVHD has been associated with a higher incidence of relapse after allogeneic BMT. This association suggests an antileukaemic effect of donor lymphocytes. In vitro studies show that cytotoxic T lymphocytes (CD3+ CD56+) and NK cells (CD3-CD56+) have an antileukaemic effect. To know which specific subpopulation of lymphocytes are depleted by counterflow centrifugation or elutriation, we analysed B, T, NK cells and hematopoietic precursors in the marrow fractions after this procedure. PATIENTS AND METHODS: Eight patients (6 CML, 1 ALL, 1 B-CLL) received an allogeneic BMT with lymphocyte depletion of the bone marrow graft using elutriation. After a Percoll gradient, donor marrow mononuclear cells (MNC) were separated with this method in five fractions (F1 to F5). RESULTS: Lymphocyte depletion of donor marrow was in average of 1.7 log. This depletion was also selective, the last fraction containing higher number of cytotoxic T lymphocytes and NK cells than the other fractions. Recovery of CD34+ cells in the four fractions concerning to post-Percoll marrow was 84%, most of them being in the last fraction. CONCLUSIONS: The use of elutriation for lymphocyte depletion is a good method for graft manipulation with the feasibility to adjust a lymphocyte/Kg. dose. Elutriation may be effective in reducing the incidence and severity of graft versus host disease and preserving the antileukaemic effect.
Adult↗
[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↗
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↗
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↗
[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↗
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↗