The expression level of BAALC-associated microRNA miR-3151 is an independent prognostic factor in younger patients with cytogenetic intermediate-risk acute myeloid leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease whose prognosis is mainly related to the biological risk conferred by cytogenetics and molecular profiling. In elderly patients (⩾60 years) with normal karyotype AML miR-3151 have been identified as a prognostic factor. However, miR-3151 prognostic value has not been examined in younger AML patients. In the present work, we have studied miR-3151 alone and in combination with BAALC, its host gene, in a cohort of 181 younger intermediate-risk AML (IR-AML) patients. Patients with higher expression of miR-3151 had shorter overall survival (P=0.0025), shorter leukemia-free survival (P=0.026) and higher cumulative incidence of relapse (P=0.082). Moreover, in the multivariate analysis miR-3151 emerged as independent prognostic marker in both the overall series and within the unfavorable molecular prognostic category. Interestingly, the combined determination of both miR-3151 and BAALC improved this prognostic stratification, with patients with low levels of both parameters showing a better outcome compared with those patients harboring increased levels of one or both markers (P=0.003). In addition, we studied the microRNA expression profile associated with miR-3151 identifying a six-microRNA signature. In conclusion, the analysis of miR-3151 and BAALC expression may well contribute to an improved prognostic stratification of younger patients with IR-AML.

Plerixafor in patients with lymphoma and multiple myeloma: effectiveness in cases with very low circulating CD34+ cell levels and preemptive intervention vs remobilization.

This retrospective study presents data from 105 consecutive multiple myeloma and lymphoma patients who had PB CD34+ cell counts <10/µL on day 4 of steady-state G-CSF mobilization for autologous hematopoietic cell transplantation. Our results confirm the capacity of plerixafor to improve mobilization outcomes in this clinical setting. In addition, they show that the effectiveness of plerixafor, compared with G-CSF only, translates to patients with very low (<3.5/µL) circulating CD34+ cell counts: overnight CD34+ cell count expansion (5.3- vs 1.7-fold), overall CD34+ cell yield (2.29 vs 0.15 × 10(6) CD34+ cells per kg) and patients yielding ⩾2 × 10(6) CD34+ cells per kg (63% vs 3%). Furthermore, our data also show that preemptive plerixafor is significantly more effective and more efficient than in remobilization: CD34+ cell yield in the first apheresis (3.28 vs 2.0 × 10(6) CD34+ cells per kg) and overall (3.73 vs 2.44 × 10(6) CD34+ cells per kg), patients yielding ⩾2 × 10(6) CD34+ cells per kg in the first apheresis (85% vs 44%) and overall (92% vs 64%), all this requiring less days and doses of plerixafor treatment (1.08 vs 1.48). These data would advocate using plerixafor as an early preemptive intervention based on day 4 circulating CD34+ counts, including very high-risk patients with very low circulating levels.

Prognostic value of minimal residual disease (MRD) in acute myeloid leukemia (AML) with favorable cytogenetics [t(8;21) and inv(16)].

Most patients with acute myeloid leukemia (AML) and t(8;21) or inv(16) have a good prognosis with current anthracycline- and cytarabine-based protocols. Tandem analysis with flow cytometry (FC) and real-time RT-PCR (RQ-PCR) was applied to 55 patients, 28 harboring a t(8;21) and 27 an inv(16), including one case with a novel CBFbeta/MYH11 transcript. A total of 31% (n=17) of CR patients relapsed: seven with t(8;21) and 10 with inv(16). The mean amount of minimal residual disease (MRD) detected by FC in relapsed and nonrelapsed patients was markedly different: 0.3 vs 0.08% (P=0.002) at the end of treatment. The mean number of fusion transcript copies/ ABL x 10(4) also differed between relapsed and non-relapsed patients: 2385 vs 122 (P=0.001) after induction, 56 vs 7.6 after intensification (P=0.0001) and 75 vs 3.3 (P=0.0001) at the end of chemotherapy. Relapses were more common in patients with FC MRD level >0.1% at the end of treatment than in patients with < or = 0.1%: cumulative incidence of relapse (CIR) was 67 and 21% (P=0.03), respectively. Likewise, using RQ-PCR, a cutoff level of >10 copies at the end of treatment correlated with a high risk of relapse: CIR was 75% for patients with RQ-PCR >10 compared to 21% for patients with RQ-PCR levels < or = 10 (P=0.04). Combined use of FC and RQ-PCR may improve MRD detection, and provide useful clinical information on relapse kinetics in AML patients.

Adverse prognostic impact of CD36 and CD2 expression in adult de novo acute myeloid leukemia patients.

BACKGROUND AND OBJECTIVES: A consecutive series of acute myeloid leukemias (AML) patients was analyzed in conditions which reduce the inter-assay variations (the same flow cytometer, the same observers and the same panel of monoclonal antibodies) in order to investigate the prognostic information provided by flow cytometry. DESIGN AND METHODS: Two hundred and sixty-six bone marrow (BM) samples from 326 patients enrolled in the LMA-99 protocol from the CETLAM group were studied by multiparametric flow cytometry. Immunophenotyping studies were performed on erythrocyte-lysed BM samples. Antigen expression of leukemic cells was analyzed using triple stainings with fluorochrome-conjugated combinations of monoclonal antibodies. RESULTS: CD2 was positive in 21 cases (8%); an associated inv(16) was detected in eight CD2+ cases (38%). Two-year overall survival (OS) rate for CD2+/inv(16)+ patients was 75%, whereas it was 0% for CD2+/inv(16)- patients and 47% for CD2- patients (p=0.0001). CD36 was expressed in 37% of patients (n=98). Two-year leukemia-free survival (LFS) rate was 34% for CD36+ patients and 55% for CD36- patients (p=0.001). In the multivariate analysis, CD2+ (RR=8.4; p=0.0001) and adverse karyotype (RR=10.2; p=0.0001) were associated with a lower CR rate, CD36+ (RR=1.5; p=0.03), CD2+ (RR=2; p=0.04) and adverse karyotype (RR=4; p=0.0001) were associated with a lower OS and CD36+ (RR=2; p=0.002) and adverse karyotype (RR=3.5; p=0.005) predicted a lower LFS. CONCLUSIONS: CD2+ patients had a very poor OS when CD2/inv(16)+ cases were excluded. CD36 and CD2 expression at diagnosis can provide prognostically important information in adult de novo AML.

[Clinical value of positron emission tomography with F-18-FDG in the follow up of patients with cancer of the ovary]. / Valor clínico de la tomografía de emisión de positrones con F-18-FDG en el seguimiento de pacientes con cáncer de ovario.

BACKGROUND: Positron emission tomography with fluor-18-deoxyglucose (PET-FDG) is an efficient technique for the detection of tumoural tissue. The aim of the paper is to evaluate the PET-FDG in the diagnosis of residual disease or relapse in patients with cancer of the ovary. METHODS: A total of 24 patients, diagnosed and treated for cancer of the ovary with surgery and subsequent chemotherapy, were included. With 12 patients the study was carried out prior to second-look surgery, and with the other 12 after objectivising an increase of the tumoural marker in the follow up. Abdominal-pelvic CAT, determination of the seric levels of CA-125 and PET-FDG of thorax, abdomen and pelvis were carried out on all patients. The PET-FDG was evaluated in a qualitative way through the visual study of the images, and quantitatively through the SUV or standard uptake value. The definitive diagnosis was confirmed through an anatomopathological study in 13 cases and through clinical follow up in the rest with an average of 11.2+/-5.4 months (range 6-24). RESULTS: A CA-125 value higher than 35 UI/ml was considered positive, obtaining a sensitivity of 77% and a specificity of 100%. The sensitivity of the CAT was 23% and the specificity 91%. With the FDG-PET sensitivity was 92% and the specificity 90%. A SUV value >or= 3 was considered pathological, obtaining the same results as with the visual evaluation. The FDG-PET was positive in 5 patients with non-conclusive CAT, 4 with negative CAT and 2 with negative CA-125. CONCLUSION: These preliminary results suggest that the FDG-PET could be useful in the detection of disease in the follow up of patients treated for cancer of the ovary. The FDG-PET could be efficient in the differentiation between residual disease or recurrence, as opposed to sequels to the treatment, when the CAT is not conclusive due to anatomical distortion, since it permits the detection of tumoural lesions undetected by the radiological image techniques but metabolically active. The FDG-PET could be more sensitive than an increased marker value, and facing an increase of the latter it permits a non-invasive localisation of the disease.

Increased conventional chemotherapy does not improve survival in multiple myeloma: long-term results of two PETHEMA trials including 914 patients.

BACKGROUND: Melphalan and prednisone (MP) has been the standard treatment for multiple myeloma (MM) for the last 30 years. Combination chemotherapy at conventional doses has not shown a significant prolongation of survival when compared to MP. There are few data comparing conventional chemotherapy at standard doses with conventional treatment at higher doses. We present the long-term outcome of 914 patients from two randomized trials comparing three different dose intensity regimens. METHODS: From 1 January, 1985 to 31 December, 1989, 487 patients were randomized between MP (melphalan 9 mg/m(2) p.o. and prednisone 60 mg/m(2) days 1-4) and alternating VCMP (vincristine 1 mg i.v. on day 1, cyclophosphamide 500 mg/m(2) i.v. on day 1, melphalan 6 mg/m(2) p.o. on days 1-4, and prednisone 60 mg/m(2) on days 1-4) and VBAP (vincristine 1 mg i.v. on day 1, BCNU and doxorubicin 30 mg/m(2) i.v. each on day 1, and prednisone 60 mg/m(2) on days 1-4). From 1 January, 1990 to 31 May, 1994, 427 patients were randomized between VCMP/VBAP at the above detailed doses (VCMP/VBAP 'SD') and the same regimen increasing the doses of cyclophosphamide and doxorubicin from 500 to 1200 mg/m(2) and from 30 to 50 mg/m(2), respectively (VCMP/VBAP 'HD'). RESULTS: Increasing dose intensity produced a significantly higher partial response rate (31% vs 45% vs 51% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P < 0.01). However, a significantly early death rate was observed in the HD arm (7.7, 7.5 and 12.1% for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = 0.05). Median duration of response (20 vs 18 vs 19 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) and median survival (25 vs 31 vs 29 months for MP, VCMP/VBAP 'SD', and VCMP/VBAP 'HD', respectively; P = NS) were similar in the three groups. MP produced a higher degree of thrombocytopenia than combination chemotherapy at standard (P = 0.002) or high dose (P = 0.01), this leading to a significantly higher dose reduction in the MP arm (P < 0.001 and P = 0.003 for VCMP/VBAP 'SD' and VCMP/VBAP 'HD', respectively). CONCLUSION: In these trials the response rate significantly correlated with the regimen intensity. However, no significant differences in response duration and survival were found. This highlights the limited role of conventional chemotherapy in MM and the need for further trials, aimed at determining the impact of new treatment approaches such as high-dose therapy/autotransplantation.

An in vitro comparison of hollow ground and trocar points on threaded positive-profile external skeletal fixation pins in canine cadaveric bone.

OBJECTIVE: To compare the microstructural damage created in bone by pins with lathe-cut and rolled-on threads, and to determine the peak tip temperature and damage created by positive-profile external fixator pins with either hollow ground (HG) or trocar (T) tips during insertion. STUDY DESIGN: An acute, in vitro biomechanical evaluation. SAMPLE POPULATION: Twenty-seven canine tibiae. METHODS: Lathe-cut thread design with T point (LT-T), rolled-on thread design with T point (RT-T), and rolled-on thread design with HG point (RT-HG) pins were evaluated. Twenty pins of each type were inserted under constant drilling pressure into 12 canine tibiae (12 diaphyseal and 8 metaphyseal sites per pin type). Peak pin tip temperature, drilling energy, end-insertional pin torque, and pullout force were measured for each pin. For the histologic study, five pins of each type were inserted into cortical and cancellous sites in 15 additional tibiae. Entry and exit damage, and thread quality were assessed from 100 micron histologic sections by using computer-interfaced videomicroscopy. RESULTS: T-tipped pins reached higher tip temperature in both diaphyseal and metaphyseal bone compared with HG-tipped pins. RT-T pins had higher pullout strength (diaphyseal) and end-insertional torque compared with other combinations. No differences in drilling energy or insertional bone damage was found between the three pin types (P < .05). CONCLUSIONS: T-tipped pins mechanically outperformed HG-tipped pins. Pin tip and thread design did not significantly influence the degree of insertional bone damage. CLINICAL RELEVANCE: T-tipped pins may provide the best compromise between thermal damage and interface friction for maximizing performance of threaded external fixator pins.

[Positron emission tomography with F-18-FDG: a new tool in the evaluation of patients with head and neck tumors]. / Tomografía de emisión de positrones con F-18-FDG: una nueva técnica en la evaluación de pacientes con neoplasias de cabeza y cuello.

INTRODUCTION: Positron emission tomography using fluoro-deoxyglucose (PET-FDG) imaging has been shown to be effective in detecting and staging malignancies based on tumor glucose metabolism. The aim of the study was to evaluate the use of PET-FDG for the detection of metastatic lesions as well as early recurrence in patients with head and neck tumors. MATERIAL AND METHODS: Eleven patients were examined with PET-FDG to study the reliability of PET in assessing regional nodal status and in identifying distant metastasis (group I) and 37 patients who had previously received curative treatment and who presented differential diagnostic problems were imaged to differentiate between scar and residual or recurrent cancer (group II). PET-FDG studies were compared to results of computed tomography (CT) in 35 patients, magnetic resonance imaging (MRI) in 4 patients and both techniques in 6 patients. RESULTS: All PET-FDG studies were positive in group I, while CT failed to detect metastatic lesions in three patients. In group II PET-FDG accurately detected recurrent disease in 22/25 patients, while CT/MRI were negative in 4 cases and equivocal in 6 cases. However, there was a false positive PET study with equivocal CT in a patient with local infection. CONCLUSION: PET-FDG was highly effective in detecting metastatic cervical lymph nodes in head and neck tumours. It was most helpful in differentiating residual or recurrent tumour from scar sequelae and it enhanced the diagnostic accuracy when CT and MRI were equivocal due to anatomical distortions.

Biomechanical comparison of the trocar tip point and the hollow ground tip point for smooth external skeletal fixation pins.

OBJECTIVE: To compare the insertional characteristics of external fixator pins with hollow ground (HG), modified HG, and trocar (T) points. STUDY DESIGN: An acute, in vitro biomechanical evaluation. SAMPLE POPULATION: Thirteen radii from canine cadavers. METHODS: A total of 16 T-tipped and 16 HG-tipped pins were inserted into 8 canine radii. Ten pins of each modification of the HG tip (length of the cutting edge reduced by 0.127 mm and 0.254 mm, respectively) were inserted into another five radii. All pins were inserted with low-speed power drilling and 80 N drilling load. Differences between peak tip temperature, drilling energy, and pullout force were determined for each pin type at both diaphyseal and metaphyseal locations. RESULTS: HG-tipped pins showed a 40% lower tip temperature in diaphyseal bone, a 25% reduction in drilling energy in diaphyseal bone, and a reduction of pullout force in both diaphyseal (65%) and metaphyseal (50%) bone compared with T-tipped pins. HG 0.254-mm pins generated higher tip temperatures and had greater pullout than HG pins in diaphyseal bone. CONCLUSIONS: The HG tip was a more efficient design; however, the reduction in pullout force suggests that, because a better hole was drilled, radial preload is reduced. Reduction of the cutting edge by 0.254 mm increased the pullout force but also increased the temperatures. CLINICAL RELEVANCE: Thermal and microstructural damage are reduced by the HG tip, but pin-bone interface stability is also compromised. The use of a tip with 0.254 mm reduction in the cutting edge may optimize the biological and mechanical factors at the pin-bone interface.

Maintenance treatment with interferon alpha-2b in multiple myeloma: a prospective randomized study from PETHEMA (Program for the Study and Treatment of Hematological Malignancies, Spanish Society of Hematology).

The objectives of the present study were to investigate whether interferon alpha (IFN) maintenance could prolong response duration and survival in patients with multiple myeloma (MM) in objective response and to analyze the characteristics of relapse and subsequent survival. From January 1991 to November 1994, 92 patients from the Spanish Cooperative Group PETHEMA with MM in objective response after 12 courses of VCMP/VBAP chemotherapy were randomized to receive IFN maintenance vs no treatment until relapse. Prognostic factors at diagnosis were similar in both groups. IFN was administered at a starting dose of 3 mU/m2 three times per week. The IFN toxicity was moderate with granulocytopenia and fatigue being the most common adverse effects. Median duration of response from randomization until relapse was 13 months in the IFN group vs 7.7 months in the no treatment arm (P = 0.042). Median survival from randomization was 38.8 months for patients given IFN vs 32.7 months for those allocated to the no treatment arm (P = 0.12). Features at relapse were similar in patients who received IFN maintenance and in those assigned to no treatment. Finally, survival from relapse was identical in both groups. In summary, our results show a significant prolongation of response in patients maintained with IFN with no significant influence on survival. In addition, in our series features at relapse and subsequent outcome were similar in both groups.

Bilateral pigmented villonodular synovitis in a dog.

Villonodular synovitis is an extremely rare condition of the synovial membrane in the dog. A 10-year-old, neutered crossbreed was presented with bilateral, progressive hindlimb lameness. Periarticular swelling was noted in both stifle joints. No craniocaudal instability was noted. Radiographs showed massive intra-articular soft tissue proliferation in both joints, with no bony involvement. Arthrocentesis was unsuccessful. Exploratory arthrotomy of the left stifle revealed a greatly thickened, florid, proliferative synovial membrane. An incisional biopsy was carried out and the histopathological diagnosis was chronic active villonodular synovitis. A radical synovectomy was carried out in the right stifle joint 10 days later. Corticosteroid treatment was initiated 10 days after the second surgery and continued for six weeks, with a continuous clinical improvement. Eighteen months after discontinuation of the steroid therapy, the owners reported no recurrence of clinical signs although a mild stiffness was still present.

[Intense neutropenia of 14 years duration as the only manifestation of a myelodysplastic syndrome]. / Neutropenia intensa de 14 años de duración como única manifestación de un síndrome mielodisplásico.

Myelodysplastic syndromes (MDS) are a group of acquired hemopathies characterized by peripheral cytopenias due to ineffective hematopoiesis and a high risk of transformation into acute non lymphoblastic leukemia (ANLL) which, in most cases, usually occurs from 6 months to 4 years after diagnosis. A patient with extreme neutropenia with intense dysgranulopoiesis as the only manifestations of MDS is described. The patient was controlled over 14 years and presented multiple infectious episodes, in various locations, throughout the evolution, some being very severe and generally caused by gram-negative germs. Likewise, during this time the patient received different treatments (oxymetholone, prednisone and lithium carbonate) with no hematologic response being observed. The leukocyte count remained around 3 x 10(9)/L with a mean proportion of neutrophils of 12% with no variations being found in the bone marrow aspirates carried out throughout the evolution (total of 9). At 14 years the diagnosis of MDS evolved to ANLL. The patient died shortly after the acute transformation due to respiratory failure secondary to bilateral pneumonia. In this case three peculiar features are of note: the almost exclusive involvement of the granulopoietic series without either anemia or thrombocytopenia, the long evolution of AREB, with acute transformation 14 years after diagnosis and the severity of the infections, among which recurrent lingual granulopenic ulcers were of note.

[Alfa-2b interferon in the treatment of thrombocytosis associated to chronic non leukemic myeloproliferative syndromes]. / Interferón alfa-2b en el tratamiento de la trombocitosis asociada a síndromes mieloproliferativos crónicos no leucémicos.

BACKGROUND: The effect of interferons in the correction of thrombocytosis in chronic myeloproliferative syndromes is well known. In this study the efficacy of alpha-2b interferon in a regimen of induction followed by a phase of sequential maintenance to progressively decreasing doses was evaluated with the aim of knowing the minimum doses necessary to maintain response. METHODS: The response to treatment with alpha-2b interferon was prospectively studied in a group of 37 patients with chronic myeloproliferative syndromes with associated thrombocytosis (excluding chronic myeloid leukemia). Likewise, the toxicity of the treatment was analyzed. RESULTS: Sixty-seven percent of the patients responded (platelets lower than 600 x 10(9)/1) to the daily administration of 3 or 5 MU of interferon. Forty percent of the patients who responded to the daily schedule of administration maintained the response upon receiving 3 doses weekly for 4 months. Half of the 8 patients who received 2 weekly doses of interferon for 4 months continued maintaining the responses. Only two of the 4 patients who received one sole weekly dose during the following 4 months maintained the response. Only one of the 37 patients who initiated treatment underwent progression of the symptoms present at the beginning of the study. Toxicity was high and was the cause of 12 discontinuations of treatment (32% of the patients) during the daily treatment phase (9 patients) or during maintenance of 3 weekly doses (3 patients). No toxicity was observed in the schedule of one or two weekly doses. CONCLUSIONS: Alpha-2b interferon is effective in the treatment of thrombocytosis of the chronic myeloproliferative syndromes (excluding chronic myeloid leukemia) when administered daily and is ever less so when the doses are spaced at 3, 2 or 1 week. The toxicity of interferon treatment is high when administered at affective doses.

On the reliability of clinical criteria for the diagnosis of hepatic veno-occlusive disease.

Among 217 patients who received an allogeneic (136 cases) or autologous (81 cases) bone marrow transplant, the diagnosis of hepatic veno-occlusive disease (VOD) was established in 38 according to Seattle clinical criteria. Thirty-two underwent a transjugular liver biopsy and measurement of the hepatic venous pressure gradient (HVPG). The study was completed in 30 patients with no serious complications. Hepatic VOD was histologically confirmed in 18 patients (60%); the remaining 12 were classified as non-VOD. An increased HVPG discriminated well between VOD and non-VOD cases. Thus, hemodynamic data can considerably reinforce the accuracy of histological diagnosis. The predictive value of two vs. three clinical data of the Seattle criteria was analyzed. Among the 19 cases fulfilling two clinical data VOD was confirmed in only eight (42%), whereas VOD was proved in ten of 11 cases (91%) (p = 0.02) suspected on the basis of three clinical data. When reliability of the Baltimore clinical criteria was analyzed, the result was identical to that observed when three Seattle clinical data were present. The specificity of the latter classification was high (92%) while its sensitivity was relatively low (56%). In conclusion, clinical criteria are not reliable for either recognizing or excluding the diagnosis of VOD. Thus, a transjugular liver biopsy, associated with hemodynamic evaluation, is strongly recommended when VOD is clinically suspected.

Hematological recovery after autologous bone marrow transplantation in acute leukemia: predictive factors.

The kinetics of hematological recovery after autologous marrow transplantation have been studied in 70 patients with acute leukemia (38 acute nonlymphoblastic leukemia [ANNL] and 32 acute lymphoblastic leukemia [ALL]). The incidence of graft failure in this group was 3.2%, and a persistent severe thrombocytopenia was observed in 24% of the cases. Variables influencing engraftment have been studied using univariate and multivariate statistical analysis. Analysis of the entire group showed a correlation between graft colony-forming unit granulocyte-macrophage (CFU-GM) content and granulocyte recovery (p < 0.001). Marrow purging was associated with a delayed engraftment (p < 0.001). In ANLL patients, we found that high cummulated AraC doses before marrow cryopreservation correlated with poor granulocyte recovery after marrow infusion (p < 0.002). Platelet recovery was essentially affected by age, with shorter thrombocytopenia periods in younger patients (p < 0.001). Finally, excluding autotransplants with purged marrows, ALL patients showed better platelet recoveries than ANLL patients (p < 0.005). These findings will be useful to evaluate the risk of delayed engraftment after autologous bone marrow transplantation (ABMT) in patients with acute leukemia.

Transjugular liver biopsy in BMT.

With the aim of evaluating liver disturbances after BMT in 76 patients, the hepatic venous pressure gradient was measured and a transvenous liver biopsy was performed through the jugular vein. Catheterization was successful in 71 patients (93%). In 11 cases the procedure was performed twice, yielding a total number of 82 studies. In five (6%) liver biopsies were non-evaluable. Complications were rare (7%), minor and reversible. As a result of this procedure, the diagnosis was modified in 45%, with both the diagnosis and treatment being modified in 30% of patients. Veno-occlusive disease (VOD) was histologically demonstrated in 15 out of 26 patients (58%) in whom this complication was suspected and in two out of 33 (6%) in whom it was not. Acute GVHD of the liver was confirmed in 15 out of the 35 patients (43%) in whom this complication was suspected and in four of 24 (17%) in whom it was not. The hepatic venous pressure gradient was significantly higher in VOD than in liver GVHD. Whereas 14/17 (82%) patients with VOD had a gradient pressure higher than 9 mmHg, no patient with GVHD had a gradient above this value. We conclude that transjugular liver biopsy is an effective, safe, and useful technique to evaluate BMT related liver dysfunction.

Mitoxantrone and intermediate-dose cytosine arabinoside for poor-risk acute leukemias: response to treatment and factors influencing outcome.

Mitoxantrone (MIT, 12 mg/m2, i.v. 5 days) and intermediate-dose cytosine arabinoside (IDAC 1 g/m2/12 h, i.v. 3 days) was given to 43 patients with poor-risk acute leukemias (AL). Moderate or severe toxicity was infrequent. The proportion of complete remissions (CR) in the main patient categories was as follows: 15/18 (85 per cent) in acute myeloid leukemia (AML) in the first relapse, 2/6 in ALL in the first relapse, 0/2 in AML in relapse after bone marrow transplantation (BMT), 2/7 in AML refractory to first-line treatment (REF-AL), and 1/6 in postmyelodysplastic (PMD-AL) plus secondary AL (S-AL). The mortality rate during induction was 23 per cent. Median duration of CR was 24 weeks. The multivariate prognostic factor analysis on CR obtention showed that data concerning treatment for the first relapse and platelet count higher than the median of the series were favourable. On the contrary, PMD-AL, S-AL and REF-AL were unfavourable situations. A percentage of marrow erythroblasts superior to the median was a favourable prognostic factor for survival. Finally, the duration of CR after MIT-IDAC was directly related to the duration of previous CR. In conclusion, MIT-IDAC was highly effective to attain CR in AML in the first relapse. However, due to the poor long-term results in these patients, additional measures are recommended after CR.