[Jejunal mucormycosis in a patient with Hodgkin's lymphoma]. / Mucormicosis yeyunal en paciente con linfoma de Hodgkin.

We report a case of intestinal mucormycosis in a 46-year-old male diagnosed with classical Hodgkin's disease, IV-B stage. During the first phase of chemotherapy he had a massive digestive bleeding event secondary to a jejunal ulcer, and zygomicosis mucor-type was diagnosed by endoscopic biopsy. The patient was treated with antifungal drugs and surgical resection of the intestine involved. At surgery a double covered perforation of the jejunum was seen. Pathological examination confirmed the previous diagnosis. After one year of follow-up the patient is doing well, and his lymphoma is on remission. To our best knowledge this is the second case of intestinal mucormycosis in a patient with Hodgkin's lymphoma reported in the medical literature.

Oral anticoagulant treatment: risk factors involved in 500 intracranial hemorrhages.

Intracranial bleeding is the most severe complication caused by anticoagulant or antiplatelet treatment. The increasing use of this therapy, especially in older people, makes the balance between clinical benefit and bleeding risk an important consideration. A retrospective study of all consecutive 500 intracranial hemorrhages in the West Valladolid area, approximately 220,000 people, during the period 1998 to 2004, was performed. In relation to mortality, predisposing conditions were included, such as age, antithrombotic treatment, arterial hypertension, cancer, blood diseases, vascular malformations, and traumatisms. The incidence of intracranial hemorrhage was 310 per 100,000 per year with a mortality of 30%. Higher mortality was found in antiplatelet-treated patients (44.9%) than in anticoagulated patients (31.1%). This may be related to a different mean age of 78 vs. 71 years. Arterial hypertension was the most frequent risk factor (45.1% in nontreated patients, 60% anticoagulated, and 75.5% antiplatelet). The relative risk of intracranial bleeding in anticoagulated patients was 11.2 (p < 0.001) with an incidence of 0.03% and a median of 14 months since treatment began. The median INR was 3.3. In 40% of the patients the previous five controls were in range. Strict consideration of indications criteria joined to a better control of risk factors may avoid intracranial bleeding episodes.

A randomized study of intermediate as compared with high doses of interferon-alpha for chronic myeloid leukemia: no differences in cytogenetic responses.

Interferon-alpha (IFN-alpha) is a therapy of unquestionable efficacy in chronic myeloid leukemia (CML) patients. The best dose of IFN-alpha in the treatment of CML still remains controversial. Our primary objective was to compare cytogenetic responses in patients treated with intermediate versus high doses of IFN-alpha. A multicenter randomized controlled trial was conducted involving 109 patients with untreated CML in chronic phase from 26 Spanish hospitals. Patients were assigned to receive either an intermediate (2.5 MU/m(2) per day) or high (5 MU/m(2) per day) target dose of IFN-alpha. Hydroxyurea was allowed in both groups. In total, 108 patients were analyzed, 53 in the intermediate- and 55 in the high-dose group. Median follow-up was 47.5 months. The dose of IFN-alpha actually given was lower in the intermediate-dose group (3.83 MU/day) than in the high-dose group (6.6 MU/day) ( p<0.001). The rate of complete cytogenetic response was 24.5% in the intermediate- and 12.7% in the high-dose group (NS). A partial cytogenetic response was obtained in 7.5% and 10.9%, respectively. Cox analysis did not reveal any influence of the randomization arm on cytogenetic response rate. Ten patients in each group discontinued IFN-alpha because of toxicity. Albeit not our primary objective, no differences were found in terms of survival or transformation rate between both groups. Median survival was 73 months; 64% of patients remained free of transformation at 5 years. In terms of cytogenetic response, intermediate doses of IFN-alpha are as effective as high doses in the treatment of CML.

Are myeloma patients with renal failure candidates for autologous stem cell transplantation?

INTRODUCTION: Renal function is one of the most important prognostic factors in multiple myeloma (MM). Patients with renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy schemes. The aim of this study was to analyze the outcome of MM patients with renal insufficiency undergoing autologous stem cell transplantation (ASCT), including the evaluation of the quality of PB stem cell collections, kinetics of engraftment, transplant-related mortality, response to high dose chemotherapy and survival. MATERIALS AND METHODS: From a total of 566 valuable patients included in the MM Spanish ASCT registry, three groups of patients were defined: group BA, patients with abnormal renal function at diagnosis but normal at transplant (73 cases); group BB, patients with abnormal function both at diagnosis and at transplant (14 cases); and group AA (control group, 479 cases), patients who constantly had normal renal function. RESULTS AND CONCLUSION: Patients from groups BA and BB presented with a significantly higher number of adverse prognostic factors, reflecting that we were dealing with high tumor MM cases, as compared with patients from group AA. The number of mononuclear cells, CD34+ cells and CFU-GM cells collected in patients with non-reversible renal insufficiency was similar to those harvested in MM patients with normal renal function. Moreover, neutrophil and platelet engraftments were identical in patients with and without renal failure (days +11 and +12, respectively). By contrast, transplant-related mortality (TRM) was significantly higher in group BB patients (29%) than in groups BA (4.1%) and AA (3.3%). In multivariate analysis only three variables showed independent influence on TRM: poor performance status (ECOG 3), hemoglobin <9.5 g/dl and serum creatinine > or =5 mg/dl. The response to high dose therapy was independent of renal function. Interestingly, 43% of patients from group BB showed an improvement in renal function (creatinine < 2 mg/dl) after transplant. The three-year overall survival from transplantation was 56, 49 and 61% for the BB, BA and AA groups, respectively, with a statistically significant difference favoring group AA (P<0.01). PFS did not differ significantly between the three groups of patients. In multivariate analysis the only unfavorable independent prognostic factors for overall survival were poor performance status either at diagnosis or at transplant, high beta(2)-microglobulin levels, and no response to transplant. According to these results, ASCT is an attractive alternative for MM patients with renal insufficiency, and it should not constitute a criterion for exclusion from transplant unless patients display poor performance status and very high creatinine levels (>5 mg/dl).

[Treatment with lymphoblastoid alpha interferon in patients with chronic myeloid leukemia refractory to recombinant interferon alpha 2]. / Tratamiento con interferón alfa linfoblastoide en pacientes con leucemia mieloide crónica resistente a interferón alfa 2 recombinante.

The results of the treatment with lymphoblastoid alpha interferon (IFN-alpha N1) in 10 patients with chronic myeloid leukaemia who had poor response to previous recombinant alpha interferon (rIFN-alpha) are presented. Eight of these patients had not developed anti-alpha 2 interferon antibodies, and 2 had non-neutralising anti-IFN antibodies. Three of the 10 patients received benefit from IFN-alpha N1 treatment. Two of them, with no response to rIFN alpha 2, attained complete haematologic response wit IFN-alpha N1. Cytogenetic responses although minimal, were achieved as well. The third patient, after receiving rIFN-alpha for 3 years with no response, had partial cytogenetic response after 4 months of treatment with IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN-alpha N1. These results suggest that IFN-alpha N1 when used in patients refractory to IFN alpha 2 without anti-IFn alpha 2 neutralising antibodies may be useful in a minority of patients, although the frequency of cytogenetic responses is low.

Magnetic resonance imaging features of chloroma of the shoulder.

A patient with a history of essential thrombocytosis presented with diffuse skeletal pain and restricted motion of the left shoulder. Magnetic resonance imaging (MRI) of the left glenohumeral joint showed a soft tissue mass that displaced the rotator cuff. Biopsy of the mass revealed chloroma. MRI is the method that best characterizes this lesion.

Southern technique and cytogenetics are complementary and must be used together in the evaluation of Ph1, M-BCR positive chronic myeloid leukemia (CML) patients treated with alpha interferon (IFN-alpha).

Cytogenetic analysis is the gold standard for the follow-up of CML patients. The sensitivity of cytogenetics is fairly similar to that of Southern detection of M-BCR rearrangement (5%); this last technique has the potential advantage of being independent of cell division and yield of metaphases. IFN alpha treatment can induce lack of growth of hemopoietic precursors and poor yield of metaphases has been observed. For this reason we decided to study the grade of concordance and complementarity between analysis of karyotype and detection of M-BCR rearrangement of Southern blot. We studied 43 Ph1 positive, M-BCR positive pre-BMT CML patients (48 samples) treated with IFN alpha 2a. Karyotype was done on bone marrow cells by direct method, culture, and banding. Southern technique was performed onto DNA from peripheral blood leukocytes treated with BgIII (and Xbal if necessary) and hybridized with the universal probe (Ph1/bcr-3, Transprobe 1) labelled with dCTP32. A highly significant association between both tests was obtained. Of 48 samples analyzed, 34 were evaluable by both methods and 28 gave the same result for both tests. The concordance between the tests was good (kappa index: 0.63). Of total samples 27.1% was not evaluable by cytogenetics; this figure was 31.2% in samples from patients who were previously in complete cytogenetic response. All of the specimens not evaluable by karyotyping were evaluable by Southern. One sample was not analyzable by Southern but it was evaluable by cytogenetic analysis. The information obtained by Southern technique was clinically relevant, and decisions were made according to its results. We conclude that both tests show a significant association and a good concordance, although they are not interchangeable. Cytogenetic and molecular studies are complementary and must be employed together in CML patients treated with alpha-interferon.

[Imipenem combined with teicoplanin or vancomycin in the initial empirical treatment of febrile neutropenia. Analysis of the primary response and of a global sequential strategy in 126 episodes]. / Imipenem combinado con teicoplanina o vancomicina en el tratamiento empírico inicial de la neutropenia febril. Análisis de la respuesta primaria y de una estrategia secuencial global en 126 episodios.

The results of empiric antibiotic therapy in 126 episodes of febrile neutropenia in patients with hematologic neoplasms postchemotherapy and bone marrow transplantation are presented. The main objective of this work was the study of the initial control of infection comparing two glycopeptidic antibiotics: vancomycin and teicoplanin combined with imipenem in first line of empiric therapy. The secondary objective was to analyze the overall control of infection during the complete episode of neutropenia using a sequential empiric antibiotic therapy course which included the addition of amikacin followed by intravenous amphotericin B when fever persisted or recurred without microbiological documentation. Both initial courses (no guidelines), imipenem + vancomycin (arm A) and imipenem + teicoplanin (arm B) resulted in a similar percentage of response at 72 hours, both in episodes of fever of unknown origin (FUO) (55% and 68%, respectively; p = NS) and in those microbiologically documented (54% and 34.5%, p = NS); 58% and 79% of these episodes, respectively, were caused by gram-positive organisms. About 60% of patients in both arm ultimately required the empiric addition of amikacin, with or without amphotericin B, because of persistence or recurrence of fever; the percentage of overall responses in both arm did not differ significantly, both in FUO (70% and 86%, p = NS) and in microbiologically documented episodes (71% and 45%, p = NS). The overall infectious mortality for the whole group was 1.58%. In conclusion, no significant differences were observed in the clinical response or in toxicity between the combination of imipenem with any of the two glycopeptides: vancomycin or teicoplanin, for the initial empiric therapy of febrile neutropenia. The sequential empiric use of amikacin followed by amphotericin B assured an adequate overall control of infection in a group of patients with prolonged severe neutropenia.

[Allogeneic bone marrow transplantation in chronic myeloid leukemia. The clinical results and risk factors in 70 patients]. / Trasplante alogénico de médula ósea en la leucemia mieloide crónica. Resultados clínicos y factores de riesgo en 70 pacientes.

BACKGROUND: The 10 year experience of a single center performing allogeneic bone marrow transplantation in 70 patients with chronic myeloid leukemia (CML) is analyzed. METHODS: Seventy patients transplanted for CML between November 1982 and October 1992 were evaluated. Fifty-two patients were in the first chronic phase (FC), 10 in an accelerated phase, 4 in blast crisis and 4 in the second chronic phase. The combination of cyclosporin and methotrexate was the most commonly used prophylactic schedule for graft versus host disease (GVHD) (60 cases) and T depletion was not performed in any case. The combination of cyclophosphamide (120 mg/kg) and total body irradiation was used in 48 patients with the remaining patients received busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg). The estimation of survival was performed using the Kaplan-Meier limit product method. The prognostic factors influencing survival, disease free period and relapse were evaluated by Cox multivariate models of proportional risk. RESULTS: Actuarial survival at four years was 40% (95% Cl: 26-58%). Multivariate analysis selected variables associated with lower survival, the presence of acute GVHD (relative risk-RR-4.75), advanced disease phase (RR: 3.26) and age over 30 years (RR: 3.57). Eleven patients had relapsed. Multivariate analysis found the absence of chronic GVHD (RR: 5.3) and advanced phase (RR: 1.91) to be associated to a higher probability of relapse. In a separate analysis of the 48 patients transplanted in chronic phase who received cyclosporin and methotrexate, the disease free survival was longer for those under the age of 30 years (71.4% vs. 36%) without acute GVHD (68.8% vs. 39.6%) and those transplanted from a male donor (64.6% vs. 30%). CONCLUSIONS: Advanced phase of the disease, the presence of acute graft versus host disease and the age and female sex of the donor are the main factors associated to shorter survival in allogeneic bone marrow transplant for chronic myeloid leukemia. In contrast, the presence of chronic graft versus host disease decreases the possibilities of relapse.

Hypertriglyceridemia may be severe in CML patients treated with interferon-alpha.

We analyzed serum triglyceride (TG) levels in 22 chronic myeloid leukemia (CML) patients treated with interferon-alpha (IFN-alpha). Hypertriglyceridemia was present in one-half of patients at diagnosis, and IFN-alpha treatment was associated with a further increase in 90% of the total group of patients. This increase was maximal during the first months of therapy. Four patients (18%) reached levels higher than 1,000 mg/dl. This is the first report describing this secondary effect in CML patients treated with IFN-alpha.

[Early bacterial infections in 103 patients treated with bone marrow transplantation]. / Infecciones bacterianas precoces en 103 pacientes tratados con trasplante de medula ósea.

PURPOSE: To analyse bacterial infections in the period immediately following bone-marrow transplantation. PATIENTS AND METHODS: A retrospective study of 174 febrile episodes appearing on 103 patients treated with bone-marrow transplantation in 1990 and 1991 was carried out, special attention being paid to the bacterial infections. RESULTS: Virtually all patients (100/103) had at least one febrile episode, and its infectious character was documented in 54% of the instances. Gram-positive germs were most commonly present, 85% of the bacteria isolated, and coagulase-negative staphylococci, especially St epidermidis, predominated (60%). Different species of streptococci, mostly of the viridans group, were isolated in 22% of the blood cultures attained in the first febrile episodes. The mortality due to infection in the series as a whole was 4.8%. CONCLUSIONS: Infections by gram-positive germs, especially coagulase-negative staphylococci, are commonly found among the patients subjected to bone-marrow transplantation. Increased streptococci infections, mostly of the viridans group, are also appreciated. These facts, along with decreased number of gram-negative infections, must be born in mind when designing initial antimicrobial coverage for these patients.