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.

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.

Induction-consolidation with an idarubicin-containing regimen, unpurged marrow autograft, and post-graft chemotherapy in adult acute lymphoblastic leukaemia.

Between 1991 and 1993 we conducted a collaborative trial in adult acute lymphoblastic leukaemia, introducing an idarubicin (IDA)-containing regimen for induction and early consolidation, and increasing consolidation intensity with an autologous bone marrow transplantation phase (ABMT, patients aged <51 years) followed by further chemotherapy for 12 weeks and low-dose maintenance for 6 months (ABMT patients) or 18 months. 96 patients were evaluable for antileukaemic response after induction with vincristine-prednisone-L-asparaginase plus cumulative IDA 36 or 20 mg/m2 (IVAP-1 and IVAP-2), and for disease-free survival (DFS) after a minimum follow-up >3.5 years with an off-therapy interval >1.5 years. The response rate was 44% (7/16) with IVAP-1 and 90% (72/80) with IVAP-2 (P=0.0001), due to regimen-related toxicities. Post-remission therapy was administered as planned to most cases but protocol violation was registered in some patients eligible to ABMT and post-graft chemotherapy. The 5-year disease-free survival (DFS) rate was 31%. Multivariate analysis indicated that DFS was improved in patients receiving a transplant (11 allogeneic, DFS 70%; 32 ABMT, 36%; 37 neither, 17%; P < 0.001) and was negatively affected by high-risk features such as blast cell count >25x10(9)/l, T-cell or mature B-cell immunophenotype, and t(9;22)/t(4;11) (all P values <0.05). The 5-year DFS rate was 54% for 26 patients with no high-risk factor, 26% for 35 patients with any one, and 6% for 18 patients with any two (P<0.005). IVAP-2 brought about a high complete response rate and post-remission treatment including ABMT was feasible and modestly toxic. In spite of the short post-graft chemotherapy phase, the long-term DFS rate was good in cases with no high-risk feature. However, because autografting may be redundant in the standard-risk category, its role requires further investigation for high-risk cases.

Prognostic significance of bone marrow biopsy in essential thrombocythemia.

BACKGROUND AND OBJECTIVE: The diagnostic and prognostic value of bone marrow biopsy (BMB) has been widely investigated in patients with chronic myeloproliferative disorders (CMPD). The present study is based on a review of the results of routine BMBs taken from 93 essential thrombocythemia (ET) patients at the time of diagnosis. DESIGN AND METHODS: The common BMB histologic parameters and clinico-hematologic variables were considered for diagnostic and prognostic purposes. Clinico-pathologic correlations were looked for univariately. Moreover, the diagnostic significance of the histologic findings was tested by means of cluster analysis. Overall survival and event-free survival were considered as prognostic endpoints. RESULTS: There were no correlations between the clinic and pathologic findings, and none of the histologic and clinical parameters was predictive of survival or the occurrence of major clinical events. Cluster analysis of the BMB findings revealed two distinct morphologic patterns: one was clearly myeloproliferative; the other had somewhat dysplastic features. The event-free and overall survival rates in the latter group were significantly worse (p = 0.0377 and p = 0.0162 respectively), with major ischemic events accounting for most of the difference in event-free survival. INTERPRETATION AND CONCLUSIONS: These results have no clearcut counterpart in the literature, but we feel that dysplastic BMB findings could be included in the definition of ET prognostic scores in order to allow therapeutic strategies to be adapted to the level of risk.

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.

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.

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.

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.

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.

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.

Bone marrow histology and CD34 immunostaining in the prognostic evaluation of primary myelodysplastic syndromes.

The prognostic impact of bone marrow biopsy (BMB) histology and CD34 immunoreactivity was compared with that of the more conventional parameters (the FAB diagnosis, peripheral blood values, percentage of BM blasts and some common prognostic scores) in 100 MDS patients. Statistical correlations among the cytological, haematological, histological and immunohistochemical parameters and their relationship with clinical outcome were searched for. At univariate analysis, FAB classification (P < 0.001), pattern of blastic infiltration at BMB (P < 0.005), presence of CD34+ aggregates (P < 0.0005), percentage of blasts in BM aspirate (P < 0.0001) and percentage of CD34 positivity (P < 0.0001) proved to be linked to leukaemic transformation and, except for FAB classification, retained a high degree of prognostic significance in terms of survival. Leukaemic transformation occurred in 16/18 patients simultaneously presenting 'large' blastic infiltrates at BMB and CD34+ aggregates (P < 0.00001); 9/17 evaluable patients died within 12 months of diagnosis (P < 0.001)> Discriminant functions for leukaemic transformation and survival did not offer any advantage over univariate analysis in the prognostic work-up. The results indicate that the size of blastic aggregates and CD34 positivity allowed patients with a worse prognosis to be identified irrespective of their FAB subtype, but the prognostic impact is considerably greater when both parameters are simultaneously taken into account, as testified by the restricted and homogeneous subgroup of patients with both 'large' and CD34-positive aggregates.

Single-institution results of autologous bone marrow transplantation in acute myeloid leukemia.

BACKGROUND: Current results of autologous bone marrow transplantation (ABMT) suggest that this procedure may prolong disease-free survival (DFS) in patients with acute myeloid leukemia (AML). MATERIALS AND METHODS: Over the last ten years, 29 AML patients received unpurged autologous bone marrow (BM) after a conditioning regimen including Ara-C (3 g/m2/12h, days -9, -8), CTX (60 mg/kg/day, days -6, -5) and TBI (3.33 Gy/day, days -3 through -1). In 21 patients, ABMT was performed as late intensification after first CR. Eight more relapsing patients were autografted after the achievement of second CR. RESULTS: Three patients died from transplant-related complications. In the remaining patients, mean times to WBC and platelet recovery were, respectively, 23 days (range 13-55) and 55 days (range 22-790). Follow-up for censored patients ranged from 1 to 120 months. Relapse occurred in 7 patients (5 in first and 2 in second CR). Overall 5-year DFS and event-free survival (EFS) chances were, respectively, 67.3% and 60%, with no statistically significant differences between first (DFS = 67.3%, EFS = 60.3%) and second CR (DFS = 68.6%, EFS = 60%). DISCUSSION: Apart from obvious selection biases, our study suggests that outcome in first CR AML patients is improved by ABMT. Long-term DFS and EFS are clearly better than when conventional post-remission chemotherapies are used. The greater antileukemic potential of ABMT is further underlined by the results in patients autografted in second CR, when conventional chemotherapy is almost never curative.

CD34 immunohistochemistry of bone marrow biopsies: prognostic significance in primary myelodysplastic syndromes.

Bone marrow (BM) biopsies from 58 patients with primary myelodysplastic syndrome (MDS) were studied using QBEND10, a monoclonal antibody that recognizes the human progenitor CD34 antigen in routine aldehyde-fixed paraffin-embedded samples. FAB subtypes were RA (5 patients), RARS (9 patients), RAEB (20 patients), RAEBt (11 patients), CMML (3 patients). In addition, 10 MDS patients whose BM biopsies revealed heavy reticulum fibrosis were included. Neither the percentage of CD34+ cells nor the number of CD34+ aggregates (defined as clusters of 3 or more cells) correlated with the presence and morphology of abnormal localizations of immature precursors (ALIP). When all patients were considered, median survival was 69 months in those with less, and 25 months in patients with more than 1% CD34+ cells (P < 0.05). Median survival was 15 months in patients with CD34+ aggregates and 41 months in those without aggregates (P = 0.0017). When RAEB patients were considered median survival was 41 months in those with less than 1%, and 29 months in those with more than 1% CD34+ cells; the 4-year survival chance was 45% in the former and 18.3% in the latter group. Therefore, CD34 positivity of more than 1% identifies a subset of RAEB patients with shorter life expectancy. In addition, leukemic transformation was observed in 11 of 35 patients (31%) with no CD34 aggregates, but in 14 of 23 patients (60%) with aggregates (P < 0.05). CD34 immunostaining, which can be easily performed on routinely prepared BM biopsies, was found to be a powerful prognostic tool for predicting survival and outcome in MDS.

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.

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.

Prognostic relevance of histological findings on bone marrow biopsy in myelodysplastic syndromes.

Bone marrow biopsy (BMB) has aroused growing interest as a possible aid in the diagnostic and prognostic evaluation of myelodysplastic syndromes (MDS). Previous reports have pointed out that MDS patients with blastic aggregates or severe bone marrow (BM) fibrosis are characterized by a worse clinical outcome. BMBs of 106 MDS patients were retrospectively reviewed, and relationships among the different histological parameters as well as clinicopathological correlations were looked for. Three patterns of BM blastic infiltration ("diffuse," "cluster," and "large") were recognized. Overt leukemic transformation and overall survival were selected as prognostic end points. BM infiltration was "diffuse" in 18, "cluster" in 48, and "large" in 40 cases. RAEB-t patients accounted for about half of the "large" cases, and none had a "diffuse" pattern (p < 0.01). Nineteen patients showed extensive BM fibrosis; most of them were characterized by "cluster" blastic infiltration and megakaryocyte hyperplasia. Leukemic transformation occurred in 67% of "large" cases (p< 0.001) and in none of the "cluster" cases with severe BM fibrosis (p < 0.01); however, survival was equally poor in these two groups because of early leukemic transformation (large cases) and BM failure (cluster cases). The FAB classification did not significantly correlate with prognosis. Patients with "cluster" BM infiltration and severe fibrosis can be regarded as a true separate MDS subset characterized by unique clinicopathological and prognostic features. Because of the subacute clinical behavior of most cases, and the poor performance status of many elderly patients, there is still controversy as to the best therapeutic approach in MDS. Histological analysis allowed two groups of MDS patients to be identified, both characterized by poor life expectancy, who could benefit from early aggressive chemotherapy.

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.

Incidence and histological features of bone marrow involvement in malignant lymphomas.

Bone marrow biopsy (BMB) is a routine investigation in the diagnosis and staging of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), and there is evidence supporting its prognostic importance in some histological varieties. The histological characteristics of BMB in 433 NHL and 155 HD patients were reviewed for clinicopathological correlations; 36 of these cases were also studied by means of immunohistochemistry. BM infiltrates were discovered in 171 NHL patients. In 36 cases, the diagnosis of NHL was directly established by BMB; a discordance between lymph node and BM histology was observed in 38 of the other 135 cases. BM-positive centroblastic and immunoblastic NHL were significantly associated with larger infiltrates, BM fibrosis, and megakaryocytic hyperplasia. Leukemization at diagnosis was more frequent in low-malignancy NHL. No correlation was found between histology and prognosis, although immunohistochemistry revealed a B-cell phenotype in all but two cases. BMB was positive in 18 of the 155 HD patients and directly diagnostic in two; Reed-Sternberg and Hodgkin cells were CD-30 positive and surrounded by T-cell infiltration. The concordance between BM and lymph node histology was fairly satisfactory, although the relationships between BM infiltration and other histological parameters may reflect peculiar interactions with BM microenvironmental factors. The usefulness of BMB in the diagnosis of malignant lymphomas has been demonstrated, and further progress can be expected from the availability of reliable immunohistochemical markers of clonality reacting on paraffin-embedded BM sections.

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 blastic crisis of chronic myelogenous leukemia.

BACKGROUND: Blastic crisis (BC) is the terminal event in the natural history of most chronic myelogenous leukemia (CML) patients. Depletion of the normal stem cell compartment, as well as the proliferative advantage and frequent pharmacoresistance of the blastic clone, contribute to the poor prognosis of CML patients in this phase. Recent clinical trials have shown that idarubicin (IDR) in combination with cytosine arabinoside (ARA-C) is more active than daunorubicin at comparable doses in acute myelogenous leukemia (AML). Furthermore, IDR alone also exhibits antitumoral activity in the BC of CML. METHODS: Twelve Ph+ CML patients in BC (male 8, female 4; median age 45 yrs., range 19-55 yrs.) were treated with IDR 12 mg/m2/die for 3 consecutive days in sequential combination with Ara-C (1 hour i.v. infusion) 120 mg/m2/12 hrs. for 7 consecutive days. BC exhibited a myeloid phenotype in 9 and a lymphoid phenotype in 3 cases. Median duration of the previous chronic phase had been 36 months (range 6-180). RESULTS: Clearing of peripheral and bone marrow blasts was achieved in all but one patient. Three other patients were classified as resistant because of blastic regrowth, and 3 died of infection during postchemotherapeutic aplasia. Two patients achieved complete remission (CR) and 3 partial remission (PR). The median duration of response was 11 months (range 6-32). CONCLUSIONS: In BC of CML the IDR/Ara-C combination led to an encouraging rate of either partial or complete responses. The relatively long duration of unmaintained response was even more interesting, with the duration of PR approaching that of CR. These data suggest that IDR should be considered as one of the first-line drugs in the treatment of BC of CML.