Comprehensive clinical, molecular and histopathological analysis of bone marrow in chronic myeloproliferative neoplasia. / Análisis integrado clínico, molecular e histopatológico de la médula ósea en las neoplasias mieloproliferativas crónicas.

OBJECTIVES: To analyse the possible correlation between molecular changes in the JAK2, MPL and CALR genes, the morphological pattern of bone marrow and the clinical-haematologic profile of patients. PATIENTS AND METHODS: We conducted a retrospective study that included 140 patients diagnosed with Philadelphia-negative myeloproliferative neoplasia (Ph-MPN) in a single centre. RESULTS: In essential thrombocythaemia (ET), the patients with the JAK2 V617F mutation presented more leucocytes and neutrophils than patients who presented the CALR mutation, who had more platelets and a greater need for cytoreductive therapy. These findings support the fact that the mutational state in ET appears to define subtypes of patients with substantially different clinical courses and prognoses. In myelofibrosis, the mutational state appears to influence the histopathological changes found in the bone marrow biopsy, which did not occur in polycythaemia vera or ET.

Splenic marginal zone lymphoma--a clinicopathological study in a series of 16 patients.

Splenic marginal zone lymphoma (SMZL), characterized in the WHO classification of lymphoid tumors, is a rare disorder comprising less than 1% of lymphoid neoplasms; only a few series concerning this entity have been published. Although this type of lymphoma is well defined histologically, its histogenesis remains obscure. Moreover, specific biological markers are still lacking and immunophenotype profile is not specific. These and other reasons, such as the existence of cytogenetic subtypes, have led to some authors to suspect that SMZL constitutes a heterogeneous entity. We have analyzed a series of sixteen SMZL cases from four hospitals in our community, from a clinical, biological and pathological point of view. When compared with those reported in the literature, our findings show three main differences: our patients less frequently showed an intrasinusoidal bone marrow infiltration pattern; the presence of a serum monoclonal component was rarely seen; and CD5-positive SMZL cases appear to be more common than previously thought.

[Peritoneal tuberculosis as a complication in a case of unclassifiable myelodysplastic/myeloproliferative disease]. / Tuberculosis peritoneal como complicación en un caso de síndrome mielodisplásico/mieloproliferativo inclasificable.

We report the case of a 68-year-old male with a diagnosis of unclassifiable myelodysplatic/myeloproliferative disease (WHO classification), under prolonged steroid treatment and unsuccesful chemotherapy response, who developed progressive asthenia, thoracic pain, minimal efforts dyspnea, and abdominal distension, that initially was suspicious of splenic rupture. Exploratory laparotomy showed multiple peritoneal implants, and a diagnosis of peritoneal tuberculosis was obtained from local biopsy. Definitive diagnosis included a positive result to culture and PCR urine test, together with a possible pleural and splenic tuberculous affectation. Response to tuberculostatic treatment was successful. To the best of our knowledge, this is the first reported case with such characteristics.

Essential thrombocythemia in young individuals: frequency and risk factors for vascular events and evolution to myelofibrosis in 126 patients.

The frequency of vascular events and evolution to myelofibrosis (MF) in young individuals with essential thrombocythemia (ET) is not well known. The incidence and predisposing factors to such complications was studied in 126 subjects diagnosed with ET at a median age of 31 years (range: 5-40). Overall survival and probability of survival free of thrombosis, bleeding and MF were analyzed by the Kaplan-Meier method and the presence of the Janus Kinase 2 (JAK2) V617F mutation correlated with the appearance of such complications. The JAK2 mutation (present in 43% of patients) was associated with higher hemoglobin (Hb) (P<0.001) and lower platelets at diagnosis. With a median follow-up of 10 years (range: 4-25), 31 thrombotic events were registered (incidence rate: 2.2 thromboses/100 patients/year). When compared with the general population, young ET patients showed a significant increase in stroke (odds ratio 50, 95% CI: 21.5-115) and venous thromboses (odds ratio 5.3, 95% CI: 3.9-10.6). Thrombosis-free survival was 84% at 10 years, with tobacco use being associated with higher risk of thrombosis. Actuarial freedom from evolution to MF was 97% at 10 years. In conclusion, young ET patients have thrombotic events, especially stroke and venous thrombosis, more frequently than generally considered, whereas they rarely transform to MF.

[Indurated erythema as the presenting form of a case of chronic myelomonocytic leukemia]. / Eritema indurado como forma de presentación de un caso de leucemia mielomonocítica crónica.

Chronic myelomonocytic leukemia (CMML) is an oncohematologic disease with a mixed nature, myeloproliferative and myelodysplastic, and presenting features are usually the consequence of peripheral blood cytopenias (anemic syndrome, infections or bleeding). Specific or non-specific cutaneous involvement in patients with myelodysplastic syndromes or chronic leukemias is exceptional, and it takes place often in advanced stages of the disease, as a preample of a transformation from chronic illness to acute leukemia. Recognition and early diagnosis of the skin lesion by cutaneous biopsy, in every patient with myelodysplastic or myeloproliferative disease, have therapeutic and prognostic significance. We describe a patient who presented with a non-especific cutaneous lesion, Bazin's erhythema induratum, as initial manifestation of chronic myelomonocytic leukemia; we also comment diagnostic, therapeutic and clinical evolution aspects.

HIV-associated primary body-cavity-based lymphoma: clinico-biologic features in three patients diagnosed at the same institution.

Primary effusion lymphoma (PEL) is a recently individualized form of non-Hodgkin lymphoma (WHO classification) that mainly develops in HIV infected males, more frequently in homosexuals and advanced stages of the disease (total CD4+ lymphocyte count below 100-200/mL). Occasionally, it appears in others immunodepressive states (such as solid organs postransplant period) and even, although very rarelly, in immunocompetents patients. From a pathogenetic point of view, PEL has been related to Kaposi's sarcoma-associated herpes virus (also named human herpesvirus 8) and to the clinical antecedent of Kaposís sarcoma. Relative unfrequency of this disease, the absence of wide casuistics allowing a better characterization, and its unfavorable outcome, support the need of a deeper knowledge. We present here the clinical-biological findings of three patients that were diagnosed of pleural PEL in our institution in the last two years.

Deoxycoformycin in the treatment of patients with hairy cell leukemia: results of a Spanish collaborative study of 80 patients.

BACKGROUND: Deoxycoformycin (DCF) has been reported to produce high response rates in patients with hairy cell leukemia (HCL), but to the authors' knowledge data regarding experience with such therapy in a large HCL series are scarce. METHODS: Between 1988-1997, DCF (4 mg/m(2)/day, every 2 weeks) was administered to 80 HCL patients in 32 Spanish institutions. In 35 of 78 evaluable patients DCF was the first-line therapy; the remaining 43 patients had received other therapies. Pretreatment variables influencing the achievement of complete remission (CR) and event free survival were identified by multivariate analyses. RESULTS: The median number of cycles administered was 7 (range, 1-22 cycles). A CR was obtained in 56 patients (72%) and a partial remission was obtained in 13 patients, for an overall response rate of 88%. In the multivariate analysis previous splenectomy and an Eastern Cooperative Oncology Group (ECOG) performance status > or = 2 were the parameters adversely influencing CR achievement. With a median follow-up of 31.2 months (range, 0.4-126.5 months), disease recurrence was observed in 11 of the CR patients, 5 of whom showed a further response to DCF. An ECOG performance status > or = 2 was the only pretreatment variable associated with a shorter event free survival. Seven patients died, four during the treatment period. The actuarial median event free survival was 46 months (95% confidence interval, 22.5-69.5 months), and 48.7% of the 56 patients who achieved a CR were expected to be alive and disease free at 5 years. Hematologic toxicity (marked neutropenia [22 cases], anemia [6 cases], and thrombocytopenia [1 case]) was the main side effect, followed by nausea and emesis (5 cases); 14 patients required hospitalization. CONCLUSIONS: The results of the current study confirm the effectiveness and acceptable toxicity of DCF in the treatment of patients with HCL.

[Neutrophil mobilization test with intravenous hydrocortisone in the study of chronic idiopathic neutropenias. Experience with 19 cases and usefulness of a new diagnostic index]. / Prueba de movilización de los neutrófilos con hidrocortisona intravenosa en el estudio de las neutropenias crónicas idiopáticas. Experiencia en 19 casos y utilidad de un nuevo índice diagnóstico.

BACKGROUND: Some patients with chronic benign neutropenia present granulocytes distribution disorders within their different physiologic pools, and this situation can be exposed by granulocyte mobilization tests. Stimulation with hydrocortisone is the best known test, but its performance and interpretation are not well standardized. Granulocyte mobilization test with hydrocortisone was performed in 19 patients with chronic peripheral idiopathic granulocytopenia, by applying homogeneous criteria. PATIENTS AND METHOD: The test included an injection of intravenous hydrocortisone 200 mg after a first basal blood neutrophil determination, and a second neutrophil count four hours after steroid administration. Following data were registered: basal blood neutrophil count (BNC), final blood neutrophil count (FNC), difference between both counts or increment (INCR), and the ratio = 60% of INCR/2.0 (109/1) BNC, which we name demargination index (DI). RESULTS: Three response patterns (three patient groups) were observed: pattern I, with FNC > 2.0 109/1 and DI >/= 1 (false neutropenia with hypermargination component); pattern II, with FNC > 2.0 (109/1) and DI < 1 (false neutropenia with pathogenic mechanisms others than hypermargination), and pattern III, with FNC < 2.0 (109/1) and DI < 1 (true neutropenia). There were no significant differences in BNC or INCR when groups I and II were compared, but we found differences in FNC (p = 0.026) and DI (p = 0.026). Comparison between groups I and III showed differences in all four parameters (BNC P = 0.07, FNC p < 0.001, INCR p = 0.02, and DI p < 0.001). No differences were found between groups II and III. CONCLUSIONS: Granulocyte mobilization test with intravenous hydrocortisone 200 mg and a four-hours interval between basal and final neutrophil counts, allows differentiation between false neutropenia with hypermargination component and true neutropenia.

Sensitization to Blomia kulagini in a general population of a subtropical region of Spain (Canary Islands).

The Blomia genus has been described as allergenic in man. The present study aimed to assess the prevalence of B. kulagini sensitization in a large population of allergic subjects without occupational exposure in a subtropical region (Canary Islands, Spain). Secondarily, a new standardized B. kulagini extract was evaluated. The study population comprised 207 patients. RAST for B. kulagini was positive in 76.2% of patients, and 47 of them were selected for the biologic standardization. When the prick test was performed with the nonstandardized extracts, results were positive in 76.6%, whereas when the test was repeated with the standardized extract, sensitivity rose to 95.7%. The conjunctival provocation test was positive in 78.3% of 46 evaluated patients. The bronchial provocation test was positive in 18 sensitized patients and negative in five controls. In conclusion, B. kulagini is an important cause of sensitization among the occupationally unexposed population of the studied area and should be included in allergy diagnostic tests. For reliable prick tests, the use of standardized extracts is mandatory.

CHOP vs. ProMACE-CytaBOM in the treatment of aggressive non-Hodgkin's lymphomas: long-term results of a multicenter randomized trial.(PETHEMA: Spanish Cooperative Group for the Study of Hematological Malignancies Treatment, Spanish Society of Hematology).

From May 1985 to May 1989, 175 patients with previously untreated aggressive non-Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM. Eligibility criteria included follicular large-cell diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor stage II, III or IV. One hundred and forty-eight patients were evaluable. There were no significant differences between the 2 treatments in response rate (83.5% [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr). Furthermore, there were no significant differences between the 2 regimens when response rates and outcome were analyzed for different prognostic subgroups. Toxicity was not significantly different between the 2 regimens, although only 1 patient died as result of treatment-related toxicity in the CHOP arm compared to 6 patient in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas. This trial gives support to the notion that CHOP still is the standard chemotherapy for aggressive lymphomas, and that new treatment approaches for these lymphomas should be compared to CHOP.

Deletion of exon b3 of the BCR gene in CML: easy breakpoint mapping by a two-round PCR.

We have performed the molecular analysis for the detection of the BCR-ABL and ABL-BCR fusion genes in 50 patients with myeloproliferative disorders. All patients diagnosed with CML (13 out of 50) were positive for the BCR-ABL hybrid. Six CML patients (46%) showed ABL-BCR amplifications of the Ib-BCR type. All rearrangements but one were concordant. The aberrant case presented a deletion of exon b3, in addition to the alternative Ib-BCR and Ia-BCR. Its possible origin and relevance are briefly discussed.

[Low grade non-Hodgkin's lymphoma after combined therapy for Hodgkin's disease]. / Linfoma no Hodgkin de bajo grado tras terapéutica combinada por enfermedad de Hodgkin.

The most serious complication of curative therapy for Hodgkin's disease is the development of a second malignancy. A patient who developed a low grade non-Hodgkin's lymphoma three years and a half after combined-modality therapy for Hodgkin's disease, is described. It is exceptional this type of non-Hodgkin's lymphoma as a second neoplasm after cytotoxic treatment for Hodgkin's disease. Pathogenic relationships between both processes are discussed.