Identification of CD34+ cells in normal and pathological bone marrow biopsies by QBEND10 monoclonal antibody.

Monoclonal antibody QBEND10 is reactive with the CD34 antigen in aldehyde-fixed, decalcified, paraffin-embedded bone marrow biopsies. In normal bone marrow it stained endothelial cells lining arterioles and capillaries, sinusoidal (littoral) cells and 0.89% of all haemopoietic cells. QBEND10+ mononuclear cells were seen as isolated, randomly distributed mononuclear cells in normal and regenerating bone marrows. Conversely, QBEND10+ cells were increased and present in aggregates of three or more cells in 6/8 cases of acute leukemia; in two cases of CD34-negative leukemia and in two patients after complete remission no aggregates were seen. QBEND10 immunohistochemistry may therefore be useful for diagnosis and follow-up of myeloid leukemias. In addition, increased numbers of CD34+ cells arranged in clusters were seen in 4/9 cases of refractory anemia with excess blasts (RAEB), 1 case of chronic myelomonocytic leukemia, 3/3 cases of RAEB in transformation, and in 3/7 cases of chronic myelogenous leukemia: in all these cases, CD34 staining of the bone biopsy may have prognostic value. QBEND10+ endothelial cells were significantly increased in all the pathological conditions examined (1.43% of all nucleated cells versus 0.80% in normal bone marrow; p = 0.0063), but especially in myeloid leukemias and in two fibrotic syndromes examined.

Idarubicin in the therapy of acute myeloid leukemia: final analysis in 57 previously untreated patients.

Fifty-seven previously untreated adult acute myeloid leukemia patients received idarubicin (IDA) in sequential combination with cytarabine as induction therapy; post-remission treatment included two courses of IDA and cytarabine alternating with two courses of VP-16 and cytarabine. As late intensification, patients received either high-dose cytarabine or, in 10 cases, autologous bone marrow transplantation. Complete remission (CR) was achieved in 48 patients (84.2%), 41 after one induction course and seven after two courses. Median length of disease-free survival (DFS) was 26 months. Univariate analysis did not identify any of the investigated variables as having prognostic significance in predicting DFS. On the other hand, patients achieving CR after one induction course had a better DFS than those requiring two courses. Furthermore, the analysis of DFS slightly favors autologous bone marrow transplantation. In conclusion, the antileukemic activity of the present IDA protocol is testified by the high CR rate and by the possibility of minimizing the role of prognostic factors. The better outcome of patients achieving CR after one induction course further supports the opinion that the intensity of the induction treatment, offered by an agent as potent as IDA, might significantly influence DFS.

Cytogenetic and myelodysplastic alterations after autologous hemopoietic stem cell transplantation.

Secondary myelodysplastic syndrome/acute myelogenous leukemia (MDS/AML) are today considered a primary complication of autologous hematopoietic stem cell transplantation. In our Center, 83 autografted patients underwent bone marrow (BM) biopsy and cytogenetic analysis at fixed intervals. Twelve patients developed non-clonal cytogenetic abnormalities and 10 patients clonal abnormalities, five of whom (three - 7, one - 5 and one t(9;11)) developed secondary MDS/AML. MDS was also diagnosed in two patients with a normal karyotype. In brief, seven patients (three males, four females; median age 36 years) developed MDS/AML 12-48 months (median 14) after autografting. The FAB diagnosis was AML-M2 in one, chronic myelomonocytic leukemia in two and refractory anemia with excess of blasts in transformation in four cases. Two patients presented a BM biopsy picture of MDS with fibrosis; none of them experienced leukemic transformation. Four MDS patients died, three of leukemic transformation and one of BM insufficiency; the two remaining patients are still living and untransformed. Our data underline the leukemogenic role of previous treatments, even if it is not possible to exclude that underlying disease and/or conditioning therapy may be involved.

Multiple autoimmune events after autologous bone marrow transplantation.

A 36-year-old woman with RAEB-t and severe bone marrow fibrosis undergoing autologous BMT, developed a histologically documented GVHD-like skin rash. Thereafter, autoimmune thyroiditis, autoimmune thrombocytopenic purpura and autoimmune hemolytic anemia and a lupus anti-coagulant (LAC) were diagnosed. The patient is still alive, symptom-free and in first complete remission (CR); however, all of the autoantibodies are still detectable, with the exception being the anti-erythrocyte antibody. The most outstanding feature of the present case is the polymorphism of the autoimmune events, in the absence of a coexisting systemic autoimmune disease. This patient has achieved long-term disease-free survival (DFS) in first CR despite high-risk MDS and the repeated immunosuppressant therapy required because of the complications described above; a GVL reaction somewhat similar to the autoimmune events may have contributed towards maintaining disease control.

Histological alterations in bone marrow in patients with late engraftment after autologous bone marrow transplantation.

Bone marrow histology after bone marrow transplantation has rarely been studied. Here, we reviewed the pre- and post-transplant bone marrow biopsies (BMB) of 40 acute myelogenous leukemia (AML) patients autografted in our center, 28 with normal and 12 with delayed peripheral recovery. The two groups were comparable in terms of previous therapy, disease phase and the number of infused cells, and received the same conditioning regimen. In the former group, reduced bone marrow cellularity and mild reticulin abnormalities were usual histological findings; in the latter, five patients had the same pattern, but the other seven had an almost undetectable hematopoietic parenchyma and severe reticulin derangement. One of these seven patients died of reactivated hepatitis B virus infection; the others eventually achieved peripheral recovery, with none of them experiencing a relapse. Autografted AML patients are excellent subjects for histological investigations. They account for the majority of delayed engraftments, the contribution of extramedullary components to the timing of engraftment is minimal, and leukemia relapse cannot be ruled out. These results suggest that BMB is a useful investigation in the work-up of late engraftment. A high degree of reticulin derangement with an almost undetectable hematopoietic parenchyma appear to be the morphological hallmarks of late engraftment.

Haematopoietic abnormalities after autologous stem cell transplantation in lymphoma patients.

Haematopoietic reconstitution after autologous stem cell transplantation (ASCT) was evaluated at different times in 26 lymphoma patients. All of the patients showed a significant decrease in the number of both committed (CFU-C) and more primitive progenitor cells (LTC-IC). The expansion of bone marrow progenitor cells in a 'stroma-free' long-term liquid culture system supplemented with SCF, IL-3, IL-6 and GM-CSF from 19 transplanted patients was significantly reduced compared to normal controls. The stromal cell compartment, evaluated by means of a CFU-F assay, was also greatly reduced. The number of haematopoietic and stromal cell progenitors was, nevertheless, very similar to their pre-transplant values. Bone marrow histology, which was evaluated at different times after transplant, showed an increase in reticulin fibres, the dilatation of parenchymal sinusoids and some morphological evidence of trilineage dysplasia in 11 patients; however, the same abnormalities were seen in the majority of pre-transplant samples. No cytogenetic abnormalities were observed in 15 patients before transplant, but four subsequently developed persistent clonal karyotypic alterations and five showed non-clonal abnormalities that generally disappeared over time. Our data suggest that both the stromal and the haematopoietic compartments are somehow damaged after ASCT for lymphoma; however, these defects generally pre-exist the transplant conditioning regimen and seem to become less pronounced over time.

Myelodysplastic syndrome associated with bone marrow fibrosis.

Bone marrow biopsy (BMB) in myelodysplastic syndrome (MDS) frequently reveals a slight alteration in the reticulin stroma which does not have any clinical significance. However, in a minority of cases, full-blown bone marrow fibrosis (BMF) can be found. Primary MDS patients with BMF show distinct clinico-pathological features and an unfavourable prognosis mainly attributable to complications deriving from pancytopenia and continuous transfusions, while leukemic transformation occurs only rarely. Since BMF may characterize other hematological disorders, primary MDS with BMF should be included in the differential diagnosis particularly with malignant myelofibrosis (MM) and idiopathic myelofibrosis (IMF). Secondary MDS with BMF represent a variety of preleukemic conditions in subjects treated for previous neoplasias. Unlike the primary forms, they do not form a clearcut clinico-pathological entity.

The diagnostic and prognostic value of bone marrow immunostaining in myelodysplastic syndromes.

Immunohistochemistry has been introduced as a means of increasing the diagnostic accuracy of bone marrow biopsy (BMB) in myelodysplastic syndromes (MDS); more recently the possibility of coupling immunostaining with other investigational techniques has broadened the spectrum of applications to the biology and physiopathology of MDS. Using panels of monoclonal antibodies (MoAbs), various histological classifications of MDS have been proposed as an alternative to the FAB criteria. The use of lineage-specific MoAbs has allowed a deeper insight into the dysplastic features of early hematopoietic precursors. The study of various gene products involved in the regulation of cell growth, proliferation and sensitivity to antineoplastic drugs, has revealed significant differences between MDS and morphologically-related disorders, particularly acute myelogenous leukemias (AML); these can be considered markers of a biological difference between the two groups of disorders and deserve consideration when designing therapeutic strategies for MDS. Both an increase in the percentage of cell positivity for the CD34 glycoprotein and a tendency of positive cells towards forming aggregates have been shown to be reliable predictors of leukemic transformation and survival, irrespective of the FAB subtype; furthermore, CD34 positivity has also proved to be a better prognostic factor than the presence of the abnormal localization of immature precursors (ALIP) on BMB. Finally, the simultaneous occurrence of "large" and CD34 positive aggregates can be proposed as a means of recognizing MDS patients with an exceedingly unfavourable prognosis, and who are therefore suitable for early aggressive therapy.

Cost-Effectiveness Analysis of Induction Regimens Containing Anthracyclines in Adult Acute Myelogenous Leukemia.

A cost-effectiveness analysis was performed to evaluate the impact on hospital costs of two alternative regimens, idarubicin + cytarabine and daunorubicin + cytarabine, in the induction treatment of newly-diagnosed patients with acute myeloid leukemia (AML). In evaluating the economic effects the perspectives of both hospital doctors and administrators were taken into account in order to achieve better value for money spent. For this study, the comparative results from four recently published randomized clinical studies were used as the source of clinical data. Data on the duration of hospitalization, hospital procedures and AML treatment costs were obtained from the patient records of two haematological centers. The idarubicin induction regimen appeared to be more cost-effective than that of daunorubicin in achieving complete remission, especially when costs are linked to response rate. Although several methodological issues in terms of economic evaluation still need to be solved, this type of study might offer a social contribution to the problem of the efficient allocation of resources in the health care sector.

Autologous bone marrow transplantation in advanced Hodgkin's disease.

Autologous bone marrow transplantation (ABMT) has been proposed as an alternative treatment of resistant/refractory Hodgkin's disease (HD). Thirty-seven patients in various phases of HD underwent autografting in our Center: fourteen received a CBV conditioning regimen, the others BCNU or VP16 followed by cyclophosphamide and TBI. Three patients died before engraftment, 28 (75.67%) achieved CR and 6 showed persistent disease. As of March 1996, 18 patients had died and 13 were in continuous CR. The median event-free survival (EFS) and 3-year EFS chances were respectively 9 months and 31.3% in the series as a whole, 14 months and 40% in primary resistant disease, 9 months and 28.4% in responsive relapse, and 3 months and 22.2% in resistant relapse. As many of these patients had failed to respond to third-line therapies, their EFS figures are primarily attributable to the therapeutic efficacy of ABMT. Furthermore, since the EFS curves are better in patients seemingly characterized by a lower chance of chemoresistance, our data favour the use of ABMT in the earlier phases of HD.

Long-term results of autologous bone marrow transplantation in adult acute lymphoblastic leukemia.

Autologous bone marrow transplantation (BMT) is widely performed in both adult and high-risk pediatric acute lymphoblastic leukemia (ALL). Nevertheless, there is still a lack of definitive data concerning its real effectiveness in prolonging the survival of these patients. Between 1984 and 1992, 20 ALL patients in first, second and third complete remission (CR) underwent autografting in the BMT Unit of the University of Milan. This series included 3 children in CR after one or more hematological relapses while all the other patients were adult. Autologous bone marrow was harvested during the same disease phase as that in which the autologous BMT was performed. The conditioning regimen included high-dose Ara-C, cyclophosphamide and TBI 1000 cGy. Successful engraftment occurred in all patients; no early deaths or deaths in CR were recorded, making disease-free survival and event-free survival (EFS) curves superimposable. The overall chance of EFS at 72 months was 41%: 57% for patients in first CR, 53% for patients autografted after one or more isolated meningeal relapse, 14% for patients autografted after one or more hematological relapse. The present data do not provide any evidence to support a role for autologous BMT in prolonging EFS in first CR ALL patients. Nevertheless, the results after meningeal relapse seem to be favourable when compared with the disappointing prospects of these patients after conventional chemotherapy. The EFS after hematological relapse revealed by this study does not significantly differ from that reported in the majority of other studies: the efficacy of autologous BMT in these ALL patients is doubtful.

Long-term results in non randomized patients with acute myelogenous leukemia: a single institution experience.

Sixty-three non randomized adults with acute myelogenous leukemia were treated with an idarubicin-based protocol. The patients achieving complete remission received autologous bone marrow transplantation or (if > 50 years or refusing autologous bone marrow transplantation) high-dose Ara-C, as late intensification. Fifty-two patients (82.5%) achieved complete remission, 45 after one induction course and 16 of them underwent autologous bone marrow transplantation a median of 11 months later. As of December 1997 (median follow-up 112 months, range 50-135 months), 16 patients were still in complete remission (10 after autologous bone marrow transplantation, 6 after high-dose Ara-C) and 29 had relapsed (median time to relapse 14 months, range 2-75 months). Four patients died in complete remission. The median disease-free survival was 25 months; the 50-months and 10-year disease-free survival were 41% and 35% respectively. No significant differences were observed between the autologous bone marrow transplantation and high-dose Ara-C treated patients whose complete remission had lasted more than 11 months. The median disease-free survival in the autografted patients had not been reached after 120 months (the 50-month and 10-year disease-free survival chances were both 67%). Age was the only predictive variable for leukemic relapse. These long-term results confirm the antileukemic efficacy of an idarubicin-containing protocol, which led to high complete remission rates and favorably influenced disease-free survival. Furthermore, the efficacy of late intensification treatment with either autologous bone marrow transplantation or high-dose Ara-C is underscored. The disease-free survival chances after autologous bone marrow transplantation are comparable with those published for allogeneic bone marrow transplantation; however, disease-free survival of the patients receiving a high-dose Ara-C intensification regimen is not significantly worse than that seen after autologous bone marrow transplantation.

Improving fiberoptic intubation in the conscious patient using the new Janus mask / Mejora del procedimiento de intubación con fibra óptica y paciente despierto con la nueva máscara Janus

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Case report. Rosacea-like Tinea incognito.

We report a case of dermatophytosis of the face due to Microsporum canis that was exacerbated and altered clinically by a long-term application of topical corticosteroids. We considered this case a rosacea-like tinea incognito of the beard area.

Pityriasis versicolor of the face.

Pityriasis versicolor (p.v.) is a superficial mycosis occurring frequently on the face. Epidemiological and clinical data regarding cases of p.v. on the face over a period of 11 years are discussed and some explanation given for conditions which favour facial involvement. This study underlines that face lesions of p.v. are more common in children than in adults and in females than in males. The forehead is the site of facial involvement usually affected. Clinical features are variable but we often observed achromic or hypopigmented scaling lesions, smaller than trunk patches.

Case Report. Widespread tinea corporis due to Trichophyton rubrum.

We report the case of a 36-year-old man who presented large erythematous plaques involving the trunk, face and extremities, since one month. Some of these lesions had a psoriasis-like aspect, with abundant superficial scaling. Direct microscopic examination of scales removed from the plaques revealed numerous hyphae. Cultural examination lead to the identification of Trichophyton rubrum species. Our case of tinea corporis presented some peculiarities related both to the extension of the lesions and their clinical aspects.

Tinea capitis in adults.

Scalp ringworm is unusual after puberty. Etiological, epidemiological and clinical data regarding cases of tinea capitis in the elderly observed over a period of 15 years are discussed and some explanations are given for the conditions which favoured the mycotic infection of the scalp in adults. This study underlines that tinea capitis in the elderly is usually characterized by very variable and often atypical lesions and that female preponderance in adult cases of scalp ringworm is striking and unexplained. Moreover, all the dermatophytes we isolated from scalp lesions in children can cause tinea capitis in adults.

Dermatophytes and dermatophytoses in the Milan area between 1970 and 1989.

Between 1970 and 1989 we examined 13,019 patients with dermatophytoses in the Milan area, Northern Italy. The results obtained during the 1980-89 period were compared with those obtained in the years 1970-79. From the data collected, tinea corporis emerged as the most frequently observed dermatophytosis, followed by tinea pedis and unguium. As far as dermatophytes are concerned, the dermatological pattern is dominated by Microsporum canis and Trichophyton rubrum. Other species, such as Epidermophyton floccosum, T. mentagrophytes, M. gypseum, T. violaceum, T. verrucosum, T. tonsurans and T. schoenleinii, have progressively become less evident. Other mycetes, such as T. megninii, T. soudanense, M. langeroni, T. vanbreuseghemii, M. ferrugineum, sporadically isolated in the 1970-79 period, have disappeared in recent years. An analysis of the distribution and frequency of the dermatophytes according to the cutaneous area affected is reported.