Importancia del diagnóstico precoz en policitemia vera y trombocitemia esencial. Experiencia de un centro / Relevance of early diagnosis in polycythemia vera and essential thrombocythemia: a single center's experience

Objetivos: Describir la proporción de pacientes con policitemia vera (PV) o trombocitemia esencial (TE) y trombosis previa al diagnóstico que presentaban eritrocitosis o trombocitosis antes de la trombosis. Pacientes y métodos: Revisión retrospectiva de 63 pacientes con PV y 130 con TE. Resultados: En PV, encontramos eritrocitosis previa en 7 (11,1%) de los 17 casos (27%) con trombosis previa al diagnóstico. En TE, encontramos trombocitosis previa en 10 (7,7%) de los 25 casos (19,2%) con trombosis previa al diagnóstico. La mediana de tiempo entre el hallazgo analítico y la trombosis fue de 8,2 meses y 11,8 meses para PV y TE, respectivamente. En ambas entidades, los pacientes con trombosis previa al diagnóstico tenían una supervivencia significativamente menor. Conclusión: Una proporción significativa de pacientes con trombosis previa al diagnóstico de PV y TE presenta eritrocitosis o trombocitosis previa al episodio de trombosis, lo que permitiría anticipar el diagnóstico y el tratamiento (AU)

Objectives: This work aims to describe the proportion of patients with polycythemia vera (PV) or essential thrombocythemia (ET) and thrombosis prior to the diagnosis who had erythrocytosis or thrombocytosis prior to thrombosis. Patients and methods: This is a retrospective review of 63 patients with PV and 130 with ET. Results: In regard to PV, we found prior erythrocytosis in 7 (11.1%) of the 17 cases (27%) with thrombosis prior to diagnosis. In ET, we found prior thrombocytosis in 10 (7.7%) of the 25 cases (19.2%) with thrombosis prior to diagnosis. The median time between the laboratory finding and thrombosis was 8.2 months and 11.8 months for PV and TE, respectively. In both entities, patients with thrombosis prior to diagnosis had significantly lower survival. Conclusion: A significant proportion of patients with thrombosis prior to the diagnosis of PV and ET present erythrocytosis or thrombocytosis prior to the episode of thrombosis. This could allow for anticipating diagnosis and treatment (AU)

Relevance of early diagnosis in polycythemia vera and essential thrombocythemia: A single center's experience.

OBJECTIVES: This work aims to describe the proportion of patients with polycythemia vera (PV) or essential thrombocythemia (ET) and thrombosis prior to the diagnosis who had erythrocytosis or thrombocytosis prior to the thrombosis. PATIENTS AND METHODS: This is a retrospective review of 63 patients with PV and 130 with ET. RESULTS: In regard to PV, we found prior erythrocytosis in 7 (11.1%) of the 17 cases (27%) with thrombosis prior to diagnosis. In ET, we found prior thrombocytosis in 10 (7.7%) of the 25 cases (19.2%) with thrombosis prior to diagnosis. The median time between the laboratory finding and thrombosis was 8.2 months and 11.8 months for PV and TE, respectively. In both entities, patients with thrombosis prior to diagnosis had significantly lower survival. CONCLUSION: A significant proportion of patients with thrombosis prior to the diagnosis of PV and ET present with erythrocytosis or thrombocytosis prior to the episode of thrombosis. This could allow for anticipating diagnosis and treatment.

SNP-based mapping arrays reveal high genomic complexity in monoclonal gammopathies, from MGUS to myeloma status.

Genetic events mediating transformation from premalignant monoclonal gammopathies (MG) to multiple myeloma (MM) are unknown. To obtain a comprehensive genomic profile of MG from the early to late stages, we performed high-resolution analysis of purified plasma cells from 20 MGUS, 20 smoldering MM (SMM) and 34 MM by high-density 6.0 SNP array. A progressive increase in the incidence of copy number abnormalities (CNA) from MGUS to SMM and to MM (median 5, 7.5 and 12 per case, respectively) was observed (P=0.006). Gains on 1q, 3p, 6p, 9p, 11q, 19p, 19q and 21q along with 1p, 16q and 22q deletions were significantly less frequent in MGUS than in MM. Although 11q and 21q gains together with 16q and 22q deletions were apparently exclusive of MM status, we observed that these abnormalities were also present in minor subclones in MGUS. Overall, a total of 65 copy number-neutral LOH (CNN-LOH) were detected. Their frequency was higher in active MM than in the asymptomatic entities (P=0.047). A strong association between genetic lesions and fragile sites was also detected. In summary, our study shows an increasing genomic complexity from MGUS to MM and identifies new chromosomal regions involved in CNA and CNN-LOH.

[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.

Conditioning regimens in autologous stem cell transplantation for multiple myeloma: a comparative study of efficacy and toxicity from the Spanish Registry for Transplantation in Multiple Myeloma.

High-dose chemoradiotherapy conditioning regimens for autologous stem cell transplantation (ASCT) are generally held to give similar results in multiple myeloma (MM), but no specific comparative study has been published. We addressed this issue by comparing the main high-dose chemoradiotherapy regimens used in the Spanish Registry. Patient cohorts included 315 cases treated with 200 mg/m2 melphalan (MEL200), 127 patients with 140 mg/m2 melphalan plus total body irradiation (MEL140 + TBI) and 121 cases with 12 mg/kg busulphan plus 140 mg/m2 melphalan (BUMEL). After ASCT, granulocyte and platelet recovery time was similar in all conditioning groups. There were no differences in transplant-related mortality. All regimens yielded a similar response in reference to pre-ASCT MM status, although BUMEL produced a slightly better overall response when compared with the other regimens (97% vs. 89% and 92%, P = 0.003). The 5-year overall survival (OS) with BUMEL was 47% [95% confidence interval (CI) 26-68] compared with 43% (CI 31-54) for MEL140 + TBI and 37% (CI: 18-56) for MEL200. The median survival for the BUMEL group was 64 months compared with 45 and 37 months for the MEL200 and MEL140 + TBI groups respectively. These differences were non-significant (P = 0.2). The median event-free survival (EFS) was better for BUMEL (32 months) than for MEL200 (22 months) or for MEL140 + TBI (20 months). The differences in EFS between BUMEL and the other conditioning regimens reached statistical significance (P = 0.01). Nevertheless, the adjusted multivariate analysis for OS and EFS revealed that the conditioning regimens had no independent prognostic value. We concluded that three different conditioning regimens, commonly used for ASCT in MM, have a similar antimyeloma effect. However, the trend for better results observed in our series with BUMEL requires a prospective trial.

Nutritional assessment of drug addicts.

OBJECTIVE: To discern if factors such as organic pathology, sex, duration and/or intensity of drug addiction, alcohol abuse, hepatitis B infection, anorexia with poor food and drink consumption, or disturbance of social and familial networks, are related to an impaired nutritional status in hospitalized drug addicts. DESIGN: Cross-sectional prospective study. SETTING: Detoxication unit and internal medicine unit of a university hospital. PATIENTS: 140 drug addicts without acute organic pathology and 18 with acute organic pathology related to drug addiction. The immunological study was compared with a control group composed of 50 healthy and well-nourished individuals (26 women and 24 men), age-matched with our patients. RESULTS: Drug addicts without organic pathology were under-nourished: 92.4% weighed under the mean weight for the population and 55.7% had had a weight loss above 5%. The distribution of mid-upper arm circumference (MUAC), triceps skinfold (TSF) measurement and mid-arm muscle area (MAMA) compared with the percentiles for the population showed a shift towards lower values. We found a high percentage of patients with a high lymphocyte count (55%). Despite the high lymphocyte count, delayed hypersensitivity was depressed in our patients. Of our patients, 66.4% exhibited anorexia at admission. The mean calorific intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. However, in most cases, malnutrition (usually marasmus-like malnutrition) was not very severe; only 30% of the drug addicts weighed less than 80% of the mean weight for the population, or admitted to a weight loss above 10%, and by subjective nutritional assessment, only 18% were deeply malnourished. Otherwise, the nutritional status was very poor in drug addicts with acute organic pathology. We also found a worse nutritional status in our patients related to female sex, intensity of drug addiction, anorexia with poor food and drink consumption, and disturbance of the social and familial networks. CONCLUSIONS: Many drug addicts suffer from calorie and protein malnutrition. This mainutrition is related to female sex, intensity of drug addiction, anorexia and poor food and drink consumption, and disturbance of the social and familial links. Acute organic pathology leads to a significant worsening of the nutritional status of drug addicts.

[The beneficial effect of 1,25-dihydroxycholecalciferol on the excess of blasts and the myelofibrosis in 2 cases of chronic myeloproliferative syndrome]. / Efecto beneficioso del 1,25-dihidroxicolecalciferol sobre el exceso de blastos y la mielofibrosis en 2 casos de síndrome mieloproliferativo crónico.

The active metabolite of vitamin D3 1.25 dehydroxycholecalciferol (1.25DHCC) is a potent inducer of monocytic differentiation of the myeloid blasts "in vitro". Likewise the inhibiting role of vitamin D3 on bone marrow fibrosis by, among others, a stimulating effect of macrophagic activity is known. However, these actions have seldom been clinically demonstrated. Two cases of chronic myeloproliferative syndromes in which treatment with 1.25DHCC was effective are presented. In the first case, one patient with polycythemia vera with myelofibrosis and focal blastosis in the bone marrow achieved disappearance of the excess of blasts and a reduction in the fibrosis (grade III to grade I) upon treatment. In the second case, idiopathic myelofibrosis, also with focal blastosis in the bone marrow biopsy, there was no regression of the fibrosis but the blastosis did disappear. It was concluded that 1.25DHCC may constitute an interesting treatment in this group of diseases through the following two mechanisms: limitation of the fibrosis and delay of blast transformation.

Nutritional assessment of drug addicts. Relation with HIV infection in early stages.

OBJECTIVE: To assess the nutritional status of drug addicts without acute organic pathology, in order to determine the prevalence of malnutrition and to discern if early HIV infection is associated with a poor nutritional status in this group of patients. DESIGN: Prospective study. SETTING: Detoxication unit of a university hospital. PATIENTS: 140 drug addicts without acute organic pathology. 31 patients were HIV+. No one fulfilled the definition of AIDS. RESULTS: We found that drug addicts were undernourished: 92.4% weighed under the mean populational weight and 55.7% had a weight loss above 5%. The distribution of mid upper arm circumference (MUAC), triceps skinfold (TSF) and mid arm muscle area (MAMA) was lower than a reference normal population. Food intakes were poor; 66.4% of our patients complained of anorexia on admission. The mean caloric intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. The mean protein intakes were 39.3 +/- 3.3 g/day in females (0.76 +/- 0.07 g/kg/day) and 49.7 +/- 2.7 g/day in males (0.77 +/- 0.04 g/kg/day). When we compared nutritional parameters between HIV+ and HIV- patients we found no differences. CONCLUSIONS: Nutritional impairment in drugs abusers with early stages of HIV infection should be attributed to drug abuse rather than to HIV infection.

Bone marrow trephine biopsy: anterior superior iliac spine versus posterior superior iliac spine.

Bone marrow biopsy (BMB) is generally performed either on the anterior superior iliac spine (ASIS) or the posterior superior iliac spine (PSIS), the choice between these two sites depending largely upon practice at individual centres. No previous study has attempted to ascertain which of these two sites is preferable for needle BMB. We studied 72 biopsies, of which 36 were of the PSIS and 36 of the ASIS, measuring the length of the cylinder and the area of the histologic section. We asked those patients who had undergone BMB at both sites which had been the less painful. The cylinders obtained from the PSIS were found to have a significantly greater length and area than those obtained from the ASIS (P < 0.00001). Of the 13 patients who underwent BMB at both sites, 11 reported the PSIS biopsy to have been distinctly less painful (P = 0.012). We conclude that needle BMB of the PSIS provides samples of greater length and area, and is less painful, than that of the ASIS.

Bone marrow fibrosis: histomorphometric analysis and interobserver reproducibility of a simple optical method of assessing its intensity.

A histomorphometric analysis of the length of reticulin fibres per area of haemopoietic bone marrow was performed on 59 trephine iliac crest biopsies. The values obtained were found to correlate with the degree of fibrosis as determined by a simple optical method based on the degree of microscopic magnification required for recognition of the presence of reticulin fibres. The mean length of fibre (microns/10,000 micron2) for the three degrees of fibrosis defined by the optical method were: 241.8 +/- 16.6 for grade I, 713 +/- 85.6 for grade II, and 1827.9 +/- 230.4 for grade III (P < 0.001). In a series of 67 biopsies, the overall interobserver agreement of the optical method was found to be good (Spearman's r = 0.99; P < 0.001) and there was good individual agreement for each of the three degrees of fibrosis (improved kappa test). There was a small amount of overlap between the extreme values of adjacent optical degrees. These results suggest that the optical method described here can be recommended as a practical technique for the routine evaluation of myelofibrosis.

[Masked Philadelphia chromosome: diagnostic implications in a case of chronic myeloid leukemia presenting in blast crisis]. / Cromosoma Filadelfia enmascarado: implicaciones diagnósticas en un caso de leucemia mieloide crónica de presentación en crisis blástica.

We present a female patient with acute non-lymphoblastic leukemia (ANLL) and with haematologic features suggestive of its evolution from chronic myeloid leukaemia (CML), in which a bone marrow karyotype showing a "masked" Philadelphia (Ph) chromosome due to a variant translocation of complex type t(9;9;22)(q32;q34;q11) was found. We comment the peculiarities of this special Ph chromosome as well as the differential diagnostic problems between ANLL Ph(+) and CML with onset in blastic crisis.

AML with unusual chromosomal changes. Translocation (15;21) and 5q- in the presence of two normal chromosomes 5.

We performed serial cytogenetic studies of the bone marrow (BM) of a patient with acute myeloblastic leukemia (AML) and noted abnormal karyotypes 47,XY,+del(5)(q12q34),t(15;21)(q21;q22)/47,XY,+del(5)(q12q34 ) during the second relapse. Although a case of this t(15;21) was recently observed in a female patient with acute nonlymphocytic leukemia (ANLL) of subtype M4 of the French-American-British (FAB) classification, the present article constitutes the first report of its occurrence in association with ANLL of subtype M1-M2. Furthermore, the presence of the 5q- accompanied by two chromosomes 5 of normal appearance is very rare and of great interest.

[Bone marrow biopsy in non-Hodgkin's lymphoma: experience with 259 samples]. / Biopsia medular en los linfomas no Hodgkin: experiencia sobre 259 muestras.

A study performed on 259 cases of bone-marrow biopsy specimens from 121 patients with non-Hodgkin's lymphoma (NHL) is presented after an introduction dealing with several well-known facts. Specific involvement of the initial samples was present in 53.45% of the cases. Such involvement was more frequent in stages III and IV, although no difference was found between the clinical forms, A or B. Stage progression due to positive bone-marrow biopsy occurred in 26% of the patients, and in 25% of these it was from stages 0 to II onto stage IV. Low-grade lymphomas showed higher bone-marrow involvement than high-grade ones (p = 0.025); specific involvement significantly influenced survival in only high-grade lymphomas, not in the low-grade ones, when the series was considered as a whole. Absolute compatibility between lymph-node and bone-marrow cellularity was found in 71% of the cases, and in 85% was taken into account. Six possible histological lesions are described herein, while for practical purposes, the use of 5 patterns of involvement is recommended, namely, interstitial, nodular, patchy, mixed nodular-patchy, and diffuse. Patchy pattern associated to low-grade and skin-involvement lymphomas. Although those patterns had non-significant influence on survival, this last was found when comparing diffuse pattern with the remainders; similarly, the diffuse pattern correlated with significantly lower haemoglobin rates. Finally, fibrosis was present in 58% of the positive biopsies and in 94% of the lesions, it being thus considered as a marker of bone-marrow involvement.