Dolor en hematología clínica / Pain in clinical hematology

Objetivo: El objetivo de esta revisión es una puesta al día acerca del tratamiento del dolor así como los cuidados paliativos aplicables a pacientes con patología hematológica, oncológica o no. En hematología hay diversas entidades nosológicas y causas que pueden requerir alivio del dolor u otros síntomas molestos para el paciente. Generalmente, se admite que sólo un 5% de los pacientes afectados de enfermedad hematológica maligna presenta cuadros de dolor, mientras que en otros tipos de cáncer (pulmón, próstata y mama que cursan, con frecuencia, con metástasis ósea) el porcentaje llega al 70-80% de los pacientes. El dolor puede venir motivado por la propia enfermedad, por infiltración leucémica o mielomatosa, destrucción ósea (75-80%), por los tratamientos empleados (15-19%), mucositis en neutropénicos, posmetotrexato, talidomida (parestesias), bortezomib (Velcade ®), imatinib (Glivec®), trasplante de médula ósea, neurotoxicidad de citostáticos (vincristina, cisplatino) y radioterapia. El dolor no tiene relación con el cáncer en un 3-5% de casos (debilidad muscular y mialgia, úlceras por decúbito, neuralgia postherpética, procedimientos diagnósticos, etc.). Clásicamente la drepanocitosis, que no es una enfermedad prevalente en España, se encuentra entre las enfermedades hematológicas benignas que producen crisis de dolor. En nuestra experiencia, 10 años después de nuestra primera revisión sobre el tema, el porcentaje de enfermos hematológicos que requieren atención específica al problema del “dolor” (entendido como “dolor total” la afectación de tipo físico, emocional, espiritual, social, laboral, familiar, etc.) se puede incrementar si englobamos no sólo a los pacientes con dolor, sino también a aquellos con síntomas más o menos desagradables durante el curso de su enfermedad...(AU)

Objective: The present review aims to provide an update on the pain management and/or palliative care provided to patients with hematological disease, whether malignant or not. In hematology, several entities may require alleviation of pain or other distressing symptoms. It is generally acknowledged that only 5% of patients with malignant hematological disease experience pain, while this percentage ranges from 70 to 80% in other types of cancer (lung, prostate and breast, which frequently lead to bonemetastases). Pain may be caused by the disease itself, due to leukemic or myelomatoid infiltration, bone destruction (75-80%), the therapies administered (15-19%), mucositis in neutropenic patients, methotrexate, thalidomide (paresthesias), bortezomib (Velcade®), imatinib (Glivec®), bone marrow transplantation, neurotoxicity of cytostatic agents(vincristine, cisplatin) and radiotherapy. Pain is unrelated to malignant disease in 3-5% of patients (muscular weakness and myalgia, decubitus ulcers, postherpetic neuralgia, diagnostic procedures). Classically, sickle cell disease, which is not a prevalent disease in Spain, is included among the benign hematological diseases that produce pain exacerbations. According to our experience, 10 years after our previous review on the topic, the percentage of hematological patients requiring specific management of “pain” (understood as “global pain” = physical, emotional, spiritual, social, occupational, familial...) can increase if, in addition to patients with pain, we also include those with unpleasant symptoms of varying severity throughout the course of their disease. The World health Organization (WHO) estimates that 9 million new cases of cancer occur each year, that there are 6.7 million annual deaths from cancer and that almost 25million persons are still alive 3 years after diagnosis. Pain is moderate to intense in 40-50% of patients and very intense or intolerable in 25-30%...(AU)

Characterization of antibodies directed against platelet cryptantigens detected during the immunological study of 356 consecutive patients with presumed autoimmune thrombocytopenia (AITP).

Cryptic antigens are detected by antibodies present in a wide spectrum of patients with or without thrombocytopenia, and even in healthy individuals. They are produced for unknown reasons and do not react with antigens of native platelets, but only with altered platelets. Cryptantigen antibodies may not only result in spuriously low platelet counts, but also in 'falsely' positive tests for platelet antibodies. We report our experience in the characterization of the different types of antibodies directed against cryptantigens of platelets: EDTA-dependent antibodies, PFA-dependent antibodies, EDTA-PFA-dependent antibodies and cold agglutinins. These antibodies were detected in the course of the serological study of 37 patients from a group of 356 (10%) whose blood was sent to our laboratory for platelet antibody testing. Pseudothrombocytopenia was diagnosed in 24 cases. Twenty-one of these showed EDTA-dependent or EDTA-PFA-dependent platelet agglutination and three were due to the presence of cold agglutinins. In 13 patients the thrombocytopenia was genuine. Eleven of these presented EDTA-dependent or EDTA-PFA-dependent antibodies in their serum and in the two remaining cases PFA-dependent antibodies were found. Cryptantigen antibodies were also detected in 9 out of 228 (4%) blood donors who were used as healthy controls in the platelet immunofluorescence test. In the light of the results obtained we put forward some guidelines to detect the presence of these antibodies and establish an accurate serological and clinical diagnosis of the autoimmune thrombocytopenias.

Combined autoimmune cytopenias.

BACKGROUND: Autoimmune neutropenia (AIN) can occur in association with autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenic purpura (ITP), although these associations have not been studied in detail. METHODS AND RESULTS: Twenty cases of AIN were found in a group of 55 adults with unexplained neutropenia over a five-year period. Eight subjects with AIN had an associated AIHA and/or ITP (AIN+ITP, n = 2; AIN+AIHA, n = 2; AIN+ITP+AIHA, n = 4). Thorough investigations identified no underlying disease in four patients, and none has appeared during follow-up. Of the other 4, one was found to have been suffering from systemic lupus erythematosus when the combined immunocytopenia was diagnosed, one patient from idiopathic myelofibrosis, one from a combined variable immunodeficiency and the other from disseminated tuberculosis. These last three conditions, while sometimes associated with autoimmune cytopenias, has not been previously reported together with combined immunocytopenias. All patients responded to immunosuppressors, although severe infectious complications occurred in two, leading to death from Pneumocystis carinii pneumonia and to irreversible neurologic damage from Listeria monocytogenes meningitis, respectively. CONCLUSIONS: We conclude that combined autoimmune cytopenias are frequently observed in patients with AIN, and a thorough search for associated conditions can lead to unsuspected diagnoses.

[Peripheral T-cell lymphoma. Morphologic, immunophenotypic and immunogenotypic studies of 10 cases]. / Linfoma T periférico. Estudios morfológicos, inmunofenotípicos e inmunogenotípicos de diez casos.

We describe the histopathology, immunophenotype and immunogenotype of 10 cases of peripheral T-cell lymphoma. The majority of patients showed disseminated disease at the time of diagnosis. From a histopathological view point the cases were classified into 5 types: T zone lymphoma (4 cases); Lennert lymphoma (2 cases); pleomorphic lymphoma, small all type (2 cases); pleomorphic lymphoma of medium-sized cell type (1 case); pleomorphic lymphoma of large cell type (1 case). In most of them the neoplastic cells demonstrated a mature T-cell phenotype: CD3+, CD4+, CD8-, CD43+, CD45RO+, CD45RA-, CD20- and surface immunoglobulins. All cases studied displayed gene rearrangements for the T-cell receptor beta chain while the immunoglobulins genes remained in germinal configuration. Antibodies against the human T-cell lymphotropic virus type I were not found in the 9 samples studied.

Immunophenotype of blast cells in acute myelofibrosis.

The immunophenotype of peripheral blood blast cells from six patients with acute myelofibrosis was studied using a panel of monoclonal antibodies directed against granulocytic, erythroid, megakaryocytic and lymphoid antigenic determinants. In all patients most of the blast cells were labeled with anti-HLA-DR and with the early myelomonocytic antibodies My7 (CD13), My9 (CD33) and B1-3C5 (CD34) (3/3). In three cases, platelet antibodies Edu3 (CD41) and GPIIIa (CD61) reacted with about 30% of blast cells. TdT was positive in two out of six samples studied. Lymphoid markers T3 (CD3), Leu9 (CD7), J5 (CD10), B4 (CD19) and B1 (CD20) were negative in all cases. These results suggest that blast cells are mainly of immature myelocytic origin. However, the coexistence of megakaryoblasts cannot be ruled out in the cases with a proportion of cells that are positive with Edu3 and GPIIIa antibodies.

Use of monoclonal anti-actin as a megakaryocyte marker in paraffin wax embedded bone marrow biopsy specimens.

Monoclonal anti-actin was used as a marker of megakaryocytes in Zenker's fixed, paraffin wax embedded bone marrow tissue, using an immunoperoxidase staining method. Twenty bone marrow samples were studied, including controls, and different myeloproliferative and myelodysplastic syndromes. The results were compared with those obtained using factor VIII related antigen (F VIII RAg) immunolabelling. Anti-actin is as good a marker for megakaryocytes as anti-FVIIIRAg and is potentially clinically useful when morphological identification is difficult, when bone marrow aspiration is unsuccessful, or when quantitative evaluation of tissue sections is required.

Acute erythroblastic leukemia. Cytological, cytogenetic and phenotypic studies in one case.

We report the clinical, cytological, immunophenotypic, and cytogenetic findings in one patient with acute erythroblastic leukemia. Blast cells were identified by their reactivity with the early erythroid antibodies FA6-152 and carbonic anhydrase I. The leukemic blasts had no specific differentiating features identifying them as erythroblasts even at an ultrastructural level. Cytogenetic studies revealed multiple chromosome aberrations: 45,XX,i(11q),-16,-17,-21,+der(21)t(21;?)(q22;?),+mar 1.