Refractory anemia with ringed sideroblasts associated with thrombocytosis: comparative analysis of marked with non-marked thrombocytosis, and relationship with JAK2 V617F mutational status.

The World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues (2001) defined a provisional entity named refractory anemia with ringed sideroblasts associated to marked thrombocytosis (RARS-MT). Diagnosis of RARS-MT requires more than 15% of ringed sideroblasts in bone marrow aspirate and the existence of a thrombocytosis in blood, with a platelet count above 600 x 10(9)/L. Nevertheless, controversy exists regarding this platelet count "cut-off" value and, when RARS-MT was defined, the JAK2 mutation and its importance in the study of myeloproliferative disorders was unknown. We present the results of a Spanish retrospective multicentric study, which includes 76 cases of RARS with associated thrombocytosis (platelet count above 400 x 10(9)/L) at diagnosis (RARS-T), 36 of them with a platelet count above 600 x 10(9)/L. Our aim was to analyze their clinical, analytical and morphological characteristics, and to establish correlations with the JAK2 mutational status.

Influence of highly active anti-retroviral therapy on response to treatment and survival in patients with acquired immunodeficiency syndrome-related non-Hodgkin's lymphoma treated with cyclophosphamide, hydroxydoxorubicin, vincristine and prednisone.

Combined highly active anti-retroviral therapy (HAART) with protease and reverse transcriptase inhibitors has modified the natural history of opportunistic infections and neoplasms in human immunodeficiency virus (HIV)-infected patients. We analysed the influence of HAART on the response to treatment and survival in a series of 58 patients with acquired immune deficiency syndrome (AIDS)-related non-Hodgkin's lymphoma (NHL) treated with CHOP (cyclophosphamide, hydroxydoxorubicin, vincristine and prednisone). Two groups of patients were included: (i) forty-one patients diagnosed with NHL between 1988 and 1996 who were not treated with HAART; (ii) seventeen patients diagnosed since 1996, who were receiving or commenced HAART when NHL was diagnosed. The response rate to CHOP was higher in group 2 (13 out of 17 cases; 75%) than in group 1 (14 out of 41 cases; 34%) (P = 0.003). The 2-year probability of event-free survival (EFS) [95% confidence interval (CI)] for group 1 was 0.5 (0.24-0.74), whereas for group 2 it was 0.85 (0.61-0.90) (P = 0.024). The lymphoma-free survival (LFS) was also significantly different for both groups (2-year LFS probability 0.53 vs. 1.0, P = 0.04). The median (95% CI) overall survival (OS) for group 1 was 7 months (range, 3-10.8 months), whereas it was not reached in group 2 (P = 0.0015). In the multivariate analysis for remission attainment, the only variables with a higher probability to achieve complete remission (CR) were HAART (P = 0.01) and International Prognostic Index score 1 (P = 0.02). The only statistically significant variable in the multivariate analysis for EFS was HAART (P = 0.049) and the variables with prognostic value for OS in the multivariate analysis were B symptoms (P = 0.01) and HAART (P = 0.003). Patients with AIDS-related NHL treated with CHOP and HAART had a higher CR rate than those treated only with CHOP. In this study, HAART was an independent prognostic factor for CR, OS and EFS in patients with AIDS-related NHL.

[Changes in the long arm of chromosome 3 (3q) in malignant myeloid hemopathies. A study of 10 cases]. / Alteraciones del brazo largo del cromosoma 3 (3q) en hemopatías malignas mieloides. Estudio de 10 casos.

BACKGROUND: Abnormalities of the long arm of chromosome 3 (3q) involving bands 3q21 and/or 3q26 occur in 2-6% of myeloid malignancies. Trilineage myelodysplasia, especially in the megakaryocytic line, is a characteristic feature. Additional abnormalities of chromosomes 5 and 7 are usually present. The response to treatment and prognosis are poor. PATIENTS AND METHODS: The main clinical, cytologic (bone marrow aspirate and biopsy) and cytogenetic characteristics as well as the response to the treatment in 10 patients with 3q abnormalities diagnosed in a single hospital in a period of 8 years are referred. RESULTS: Eight patients had acute non-lymphoblastic leukemia, being de novo in five of them. The median value of hemoglobin was 87 g/l (range: 51-148), white blood cells count 5.8 x 10(9)/l (1.2-47.1) and platelet count 34 x 10(9)/l (5-182). The morphological findings in the study of the bone marrow were: dyserythropoietic features (7 patients), dysgranulopoietic abnormalities (5 patients) and small-sized megakaryocytes with hypolobulated nuclei (8 patients). Fibrosis was observed in the 4 cases in which a bone marrow biopsy was performed. In addition to the 3q alteration, abnormalities of chromosomes 7 (4 patients), 5q (2 patients) and +8 (2 patients) were present. Four patients received intensive chemotherapy and in two of them a complete remission was achieved, but relapse occurred at 3 and 5 months, respectively. All patients have died, the median survival being 7 months. CONCLUSIONS: 3q abnormalities define a subtype of myeloid malignancies with characteristic clinical and morphological features. The response to therapy and survival are poor.

[The usefulness of the bone marrow examination in the etiological diagnosis of prolonged fever in patients with HIV infection]. / Utilidad del examen de la médula ósea en el diagnóstico etiológico de la fiebre prolongada en los pacientes con infección por el virus de la inmunodeficiencia humana.

BACKGROUND: To analyze the usefulness of bone marrow (BM) study in the diagnosis of fever of unknown origin (FUO) in patients infected by the human immunodeficiency virus (HIV) in a single center during a period of 42 months. PATIENTS AND METHODS: 182 episodes of FUO in 162 patients p3th HIV infection were studied. Age, sex, risk factor for HIV infection, hemoglobin level, counts of leucocytes, neutrophils, lymphocytes, CD4 positive lymphocytes, platelets and levels of hepatic enzymes, albumin and beta 2-microglobulin were studied. BM aspirate was performed in all episodes for cytologic and microbiologic examination, and BM biopsy was done in 43. Analysis of factors related with the probability of diagnosis by BM examination was carried out. RESULTS: The median age was 33 years (range, 22-70), and 123 were males. Drug abuse was the most frequent risk factor for HIV infection (63%). One hundred thirty patients had previous AIDS diagnosis before they were evaluated for unexplained fever. A specific diagnosis was achieved in 161 episodes (88%) and the most frequent diagnoses were Mycobacterium spp. (55%) and Leishmania spp. (14%) infections. Fifty-four episodes (30%) were diagnosed by BM examination, and in 36 (20%) BM study was the only diagnostic tool. Examination of the BM aspirate yielded the diagnosis in 40 out of the 178 episodes (13%), whereas BM biopsy was a diagnostic tool in 8 (19%); in 9 additional cases (21%) granulomas were observed. Microbiologic study of BM smears for mycobacterial infections was positive in 28 of the 143 episodes (19%), and the culture for Leishmania was positive in 2 out of the 42 cases. The presence of thrombocytopenia (< 75 x 10(9)/l) and elevated serum levels of aspartate-aminotransferase (AST) (> 100 U/l) were the factors associated with a high probability to obtain the diagnosis through BM study. CONCLUSIONS: In patients infected by the HIV and unexplained fever, BM examination is an useful procedure for the diagnosis, particularly in areas where infections by Mycobacterium spp. and Leishmania are prevalent. So that, in our setting, systematic use of this procedure is justified for diagnosis of FUO in those patients.

[Primary gastrointestinal lymphoma in patients infected with HIV: study of 15 cases in a series of 76 patients with non-Hodgkin's lymphoma and HIV infection]. / Linfomas gastrointestinales primarios en pacientes infectados por el virus de la inmunodeficiencia humana VIH: estudio de 15 casos de una serie de 76 enfermos con linfoma no hodgkiniano e infección por el VIH.

BACKGROUND: To analyze the main clinical and biological data and the response to therapy in 15 patients with primary gastrointestinal lymphoma (PGIL) from a series of 76 patients with HIV related non-Hodgkin's lymphoma (NHL) diagnosed in a single institution in a 13 years period. PATIENTS AND METHODS: The main clinical, biological and evolutive data were recorded. Pathologic diagnosis of PGIL was made according to the REAL classification. Clinical stage was determined by the Ann Arbor system modified by Rohatiner et al. Response to therapy as well as overall survival (OS) were studied. Results were compared with non-PGIL HIV-related NHL patients. RESULTS: Mean age of the series was 38 years. Thirteen patients were male, and 8 intravenous drug abusers. Then had bad performance status (ECOG 2-4) and 11 B symptoms. All patients had a high grade malignant PGIL and the localization was gastric in 10 cases. The most frequent symptoms were abdominal pain (11 cases), gastrointestinal bleeding (4) and dysphagia (3). Ten patients had advanced stages (IIE2-IV). The median CD4 cell count was lower in PGIL patients (92 x 10(6)/l vs 148 x 10(6)/l; p < 0.05). Thirteen patients received intensive chemotherapy with CHOP regimen (in 5 surgical procedures were previously made). Complete response (CR) was obtained in 4 patients (31%) and 1 of them relapsed. Median OS was 10 months vs 16 months non-PGIL HIV-related lymphoma patients (p < 0.05). CONCLUSIONS: PGIL in HIV patients often presented advanced stages and high grade of malignancy. The most common localization is the stomach, and these patients usually have bad performance status and a low CD4 lymphocyte count. Response to therapy is poor. In our series OS was worse in PGIL patients than in the rest of HIV-related NHL, possibly due to the high degree of immunosuppression in the formers.

Prophylactic platelet transfusion threshold during therapy for adult acute myeloid leukemia: 10,000/microL versus 20,000/microL.

BACKGROUND AND OBJECTIVE: The threshold for prophylactic platelet transfusions has been classically established at 20,000/microL. In 48 patients with de novo acute myeloblastic leukemia (AML) we analyzed the effect of reducing the threshold for prophylactic platelet transfusion from 20,000/microL (group A) to 10,000/microL (group B) after induction and consolidation chemotherapy. DESIGN AND METHODS: Forty-eight adult patients with de novo AML diagnosed in a single institution in a nine year period were enrolled in the study. Between January 1989 and December 1993 the patients received prophylactic platelet transfusions when their platelet count was below 20,000/microL (group A), and from January 1994 to March 1998 prophylactic platelet transfusions were indicated below 10,000/microL or between 10,000/microL and 20,000/microL if there was any consumption factor. RESULTS: The mean number (SD) of platelet transfusions during induction was 8.4 (5.3) in group A and 8.5 (5.5) in group B; and during consolidation 4.7 (3.4) in group A and 4.6 (3.8) in group B (p = n.s.). Excluding the cases with consumption factors from the analysis, group B patients required 34% fewer transfusions during induction and 15.5% fewer during consolidation (p = 0.04). There were no differences between groups regarding major bleeding episodes. INTERPRETATION AND CONCLUSIONS: Our data show that the threshold for prophylactic platelet transfusion can be safely set at 10,000 microL during induction and consolidation chemotherapy for adult patients with de novo AML.

The usefulness of the serum transferrin receptor in detecting iron deficiency in the anemia of chronic disorders.

BACKGROUND AND OBJECTIVE: Recent studies have shown that the serum transferrin receptor (sTfR) is a sensitive, quantitative measurement of tissue iron deficiency. The objective of the study was to evaluate the diagnostic efficiency of some laboratory tests, including sTfR measurements, in the diagnosis of iron depletion in patients with anemia of chronic disorders. DESIGN AND METHODS: The patient population consisted of 37 anemic patients: 10 hypoferritinemic patients (serum ferritin < 25 micrograms/L), and 27 anemic in-patients with hyperferritinemia (serum ferritin > 200 micrograms/L) and clinical/analytical criteria of anemia of chronic disorders, who were submitted to a bone marrow aspirate with iron stain. The sensitivity and specificity of serum TfR was evaluated according to the results of bone marrow iron status. Statistical analysis employed Student's t-test, one way analysis of variance and a logistic regression model using the Wald test. RESULTS: Serum TfR was high in all the patients with hypoferritinemic anemia. In 12 patients with low bone marrow iron, the mean sTfR was 5.63 mg/L. In 6 of these 12 patients the sTfR was normal. On the other hand, sTfR was high in 4/15 patients with normal or increased iron stores. On multivariate analysis the most sensitive predictor of true iron deficiency was MCH (mean corpuscular hemoglobin). No other variables remained independently significant, including sTfR, after the inclusion of MCH in this model. INTERPRETATION AND CONCLUSIONS: In our opinion, the iron status of patients with anemia of chronic diseases can not be accurately assessed by sTfR, as its sensitivity and specificity are low. In these patients, the gold standard for iron stores evaluation continues to be bone marrow aspirate and Perls stain.

International prognostic index is the best prognostic factor for survival in patients with AIDS-related non-Hodgkin's lymphoma treated with CHOP. A multivariate study of 46 patients.

BACKGROUND AND OBJECTIVE: The management of non-Hodgkin's lymphomas (NHL) in AIDS is difficult because of the poor bone marrow reserve and immunosuppression of these patients. Combination chemotherapy is the treatment of choice in the subset of patients with good performance status and mild immunosuppression. Several combination chemotherapy regimens have been used in these patients but the results have been poor. We have studied the clinical and biological features, response to treatment, outcome and prognostic factors of 46 patients with NHL and HIV infection, diagnosed in a single institution between January 1988 and June 1997. DESIGN AND METHODS: Forty-six patients with NHL and HIV infection were treated with CHOP. Patients with previously treated systemic NHL, primary CNS NHL, performance status > 2 and active AIDS-defining opportunistic or neoplastic diseases were excluded. The parameters evaluated were: age, sex, risk activity, basic hematologic and biochemical parameters, CD4 lymphocyte count, B symptoms, stage (Ann Arbor), histologic subtype (REAL classification), International Prognostic Index (IPI), response to treatment, relative dose intensity (RDI), relapse free survival (RFS) and overall survival (OS). Uni- and multivariate analyses of prognostic factors were performed. RESULTS: Median age was 35 years and 40 patients were male. CD4 lymphocyte count was lower than 0.1 x 10(9)/L in 18 out of 38 cases, hypoalbuminemia was registered in 24 (52%), serum LDH was higher than 400 U/L in 20 (43%) and beta 2-microglobulin was higher than the normal range in 9 out of 20 patients (45%). Complete response was achieved in 18 patients (40%). Twenty-six patients received G-CSF after chemotherapy. Grade 4 neutropenia and fever were significantly more frequent in patients who did not receive G-CSF. Serum LDH > 400 U/L and hypoalbuminemia were the only parameters associated with a lower probability to achieve complete response (p = 0.015 and p = 0.025, respectively). The median RFS was 26 (6-47) months and no variable was found to have statistically significant influence on it. The median OS was 9.2 (4.5-14) months, and IPI score 1 and ESR < 60 mm/h were the only parameters identified as good prognostic factors in the multivariate analysis (p = 0.03 and 0.049, respectively). INTERPRETATION AND CONCLUSIONS: In spite of patient selection, the response to CHOP treatment in patients with NHL and HIV infection remains poor. Episodes of neutropenic fever are less frequent when G-CSF is administered after CHOP. The IPI score 1 is the most important favorable prognostic factor for survival.

[Acute lymphoblastic leukemia in adults. Comparative study of clinicobiologic characteristics and of response to treatment in terms of age in a group of 41 patients]. / Leucemia aguda linfoblástica del adulto. Estudio comparativo de las características clinicobiológicas y de la respuesta al tratamiento en función de la edad en un grupo de 41 pacientes.

BACKGROUND: The aim of this study was to analyze the influence of age on the clinical and biological features as well as the results of treatment in 41 adult patients with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: The patients diagnosed with ALL from January 1989 to October 1995 in a single center were studied. Two groups of patients were analyzed based on age. The main clinical, hematologic and biochemical parameters, morphologic subtype and immunologic phenotype and the results of the cytogenetic study were analyzed. Likewise, the attainment of complete remission (CR), its duration and overall survival (OS) were also studied. Comparison of the cited variables and the results of treatment among the two groups of patients was performed. RESULTS: Group I was made of 19 (11 males, 8 females) patients > or = 50 years of age (mean age 65 +/- 9 years). Group II included 22 patients (11 males and 11 females) with a mean age of 28 +/- 11 years. Significant differences were only observed between the two groups in regard to the proportion of peripheral blood blasts (p < 0.02), serum LDH values (p = 0.05) and the performance status at the time of diagnosis ( p < 0.00007). In the patients in group 1 cytogenetic alterations were more frequent (10/16 vs 4/20, p < 0.02), being mainly pseudodiploid. Complete remission was achieved in 7/16 patients in group I and in 17/22 in group II (p < 0.02). The median duration of CR was 34 and 18 months, respectively. The median OS was 7 months in group 1 and 15 months in group II with an estimated survival at 5 years of 0% in group I and 38% in group II (p < 0.05). CONCLUSIONS: Patients with acute lymphoblastic leukemia over the age of 50 years have a worse general status and more cytogenetic alterations (particularly structural) than younger adult patients, presenting a lower probability of achieving complete remission and a shorter survival.

[Disseminated histoplasmosis and AIDS. Report of 4 cases]. / Histoplasmosis diseminada y sida. Aportación de 4 casos.

Disseminated histoplasmosis is frequent in patients with HIV infection from endemic zones of Africa and South America. It is infrequent in Europe. Four cases diagnosed as disseminated histoplasmosis among a total of 1,100 AIDS cases reported from 1984 to 1994 were reviewed. Four males with a mean age of 40 years were reviewed. Two were from Argentina, one from Gambia with HIV-2 infection and the remaining case was a Spanish man who had made numerous travels to endemic zones. Prolonged fever without an apparent focci in the previous weeks was the clinical manifestation at the onset in all the cases. Diagnosis was performed by bone marrow aspirate (1 case), histologic study of the cutaneous lesions (1 case) and on autopsy with the diagnosis not being suspected during life (2 cases). Tracheal ulcers and hyperferritinemia are the main peculiarities of the two cases presented. Antifungal treatment with amphotericin B and secondary prophylaxis with itraconazole were effective in one of the cases. It is important to take histoplasmosis into account in the differential diagnosis of prolonged fever in patients with HIV infection from endemic zones.

[Pseudotumorous cardiac infiltration in a patient with acute monoblastic leukemia]. / Infiltración cardíaca seudotumoral en un paciente con leucemia aguda monoblástica.

Although cardiac infiltration is common in advanced stage of acute leukaemia, it is not usually diagnosed at life and it is extremely rare for it to become pseudotumoral. A 25-years-old patient with an acute monoblastic leukaemia who had a leukaemic infiltration which affected the main part of the left ventricle at the time of diagnosis, is referred. The heart infiltration was detected by a two dimension echocardiography. In spite of a massive infiltration, heart failure was not present and the left ventricle's ejection fraction was 50%. Even though chemotherapy was administered, the patient died four days after diagnosis due to septic shock of respiratory origin. The most relevant autopsy finding was a widespread pseudotumoral infiltration of the left ventricle, the back side of the right ventricle and the interventricular wall. The pseudotumoral infiltration of the heart by acute leukaemia is uncommon and must be differentiated from granulocytic sarcoma. The usefulness of the different diagnostic procedures is discussed.